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Brain and Cognition Abnormalities in Long-Term Anabolic-Androgenic Steroid Users
Abstract
Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans.
This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS).
AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053).
Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
... Emerging evidence from field studies suggests that prolonged high-dose AAS use is associated with aberrant brain aging. For instance, brain imaging has revealed that long-term AAS use is associated with structural, neurochemical (36), and functional brain differences (36)(37)(38), including smaller gray matter, cortical, and putamen volume and thinner cerebral cortex (37). In addition, compared with nonusing weightlifters, AAS-exposed weightlifters performed poorer on tests assessing working memory (12,39,40), executive functions (12,40,41), learning and memory (12,39,41), processing speed, and problem solving (12,40). ...
... Emerging evidence from field studies suggests that prolonged high-dose AAS use is associated with aberrant brain aging. For instance, brain imaging has revealed that long-term AAS use is associated with structural, neurochemical (36), and functional brain differences (36)(37)(38), including smaller gray matter, cortical, and putamen volume and thinner cerebral cortex (37). In addition, compared with nonusing weightlifters, AAS-exposed weightlifters performed poorer on tests assessing working memory (12,39,40), executive functions (12,40,41), learning and memory (12,39,41), processing speed, and problem solving (12,40). ...
... More evident brain aging in long-term AAS users is consistent with in vitro studies suggesting that various sorts of AASs might have neurotoxic effects (19)(20)(21)(22)(23)(24) and recent findings of impaired cognitive performance (12,39,40), smaller brain volumes (37), and metabolite abnormalities (36) in long-term AAS users. Older-appearing brains in AAS-dependent users compared with nondependent users is consistent with a megaanalysis pooling data from 23 cohorts, suggesting that dependence shares a common neural substrate across a range of substances, indicating smaller brain volumes and thinner cortex in dependent individuals relative to nondependent individuals (75). ...
Background
High-dose long-term use of anabolic-androgenic steroids (AAS) may cause a range of adverse effects, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging.
Methods
T1-weighted MRI (3D MPRAGE) scans were obtained from male weightlifters with a history of prolonged (n=130) or no (n=99) AAS use. We trained machine learning models on combinations of regional brain volumes, cortical thickness and surface area in an independent training set of 1838 healthy males (18-92 years) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval 3.5 years, n=76) MRI data, we used linear mixed effects (LME) models to compare the gap between chronological age and predicted brain age (the brain age gap, BAG) between the two groups, and tested for group differences in the rate of change in BAG. We tested for associations between apparent brain aging and AAS use duration, pattern of administration and dependence.
Results
AAS users had higher BAG compared to weightlifting controls, which was associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities or depression. While longitudinal analysis revealed no evidence of increased brain aging in the overall AAS group, accelerated brain aging was seen with longer AAS exposure.
Conclusions
The findings suggest that long-term high dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AAS.
... Although the glutamate/fMRI relationship has been most broadly studied in marijuana and nicotine users, both modalities also have been applied to the study of other SUD. For example, the dACC glutamine/ glutamate ratio, which may reflect increased glutamate turnover, was found to be elevated in long-term anabolic androgenic steroid (AAS) users relative to matched control subjects (Kaufman et al., 2015). In the same subjects, right amygdala rsFC with the dACC also was found to be disrupted in AAS users, an effect which may be related to observed deficits in their cognitive function (Kaufman et al., 2015). ...
... For example, the dACC glutamine/ glutamate ratio, which may reflect increased glutamate turnover, was found to be elevated in long-term anabolic androgenic steroid (AAS) users relative to matched control subjects (Kaufman et al., 2015). In the same subjects, right amygdala rsFC with the dACC also was found to be disrupted in AAS users, an effect which may be related to observed deficits in their cognitive function (Kaufman et al., 2015). Taken together, the above examples, in which fMRI and MRS were conducted in the same subjects, highlight the potential utility of MRS/fMRI in understanding the progression of the addiction process (initiation, maintenance, relapse) with several substances of abuse and suggest that the information gained by using a multimodal approach may help to identify biomarkers that could be used to predict efficacy of candidate medications. ...
... Several lines of evidence point to alterations in brain structure that increase the propensity for developing problems with substance abuse or are the result of neurotoxicity associated with long-term drug use (Acheson et al., 2014;Ersche et al., 2012;Battistella et al., 2014;Kaufman et al., 2015). Such anatomical abnormalities reported using DTI or volumetric measurements may be related to cognitive deficits often reported in SUD patients. ...
Over 200 in vivo magnetic resonance spectroscopy (MRS) studies of substance use and related disorders (SUD) were published this past decade. The large majority of this work used proton (¹H)-MRS to characterize effects of acute and chronic exposures to drugs of abuse on human brain metabolites including N-acetylaspartate, choline-containing metabolites, creatine plus phosphocreatine, glutamate, and GABA. Some studies used phosphorus (³¹P)-MRS to quantify biomarkers of cerebral metabolism including phosphocreatine and adenosine triphosphate. A few studies used carbon (¹³C)-MRS to quantify intermediary metabolism. This Mini-review discusses select studies that illustrate how MRS can complement neurocircuitry research including by use of multimodal imaging strategies that combine MRS with functional MRI (fMRI) and/or diffusion tensor imaging (DTI). Additionally, magnetic resonance spectroscopic imaging (MRSI), which enables simultaneous multivoxel MRS acquisitions, can be used to better understand and interpret whole-brain functional or structural connectivity data. The review discusses some limitations in MRS methodology and then highlights important knowledge gaps and areas for potential future investigation, including the use of ¹H- and ³¹P-MRS to quantify cerebral metabolism, oxidative stress, inflammation, and brain temperature, all of which are associated with SUD and all of which can influence neurocircuitry and behavior.
... Emerging evidence from field studies suggests that prolonged high-dose AAS use is associated with aberrant brain aging. For instance recent brain imaging findings show that long-term AAS-use is associated with structural, neurochemical (29), and functional brain differences (29)(30)(31), including smaller gray matter, cortical and putamen volume, and thinner cerebral cortex in widespread regions (30). Also, compared to non-using weightlifters, AAS-exposed weightlifters have been shown to perform poorer on tests assessing working memory (12,32,33), executive functions (12,33,34), learning and memory (12,32,34), processing speed and problem solving (12,33). ...
... Emerging evidence from field studies suggests that prolonged high-dose AAS use is associated with aberrant brain aging. For instance recent brain imaging findings show that long-term AAS-use is associated with structural, neurochemical (29), and functional brain differences (29)(30)(31), including smaller gray matter, cortical and putamen volume, and thinner cerebral cortex in widespread regions (30). Also, compared to non-using weightlifters, AAS-exposed weightlifters have been shown to perform poorer on tests assessing working memory (12,32,33), executive functions (12,33,34), learning and memory (12,32,34), processing speed and problem solving (12,33). ...
... Both uncorrected p-values and p-values adjusted using false discovery rate (64) are reported. As we were primarily interested in long-term exposure and since stricter inclusion criteria have previously been applied (29,65), sensitivity analyses were conducted on a narrowed sample where AAS users with less than two years of AAS use were omitted. ...
Background High-dose long-term use of anabolic-androgenic steroids (AAS) may bring a range of health consequences, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging.
Methods T1-weighted brain MRI data were obtained from male weightlifters with a history of prolonged (n=133) or no (n=105) AAS use. We trained machine learning models on combinations of regional brain volumes, cortical thickness and surface area in an independent training set of 1838 healthy males aged 18-92 years and predicted brain age for each participant in our study. We used linear models to compare the gap between chronological age and predicted brain age (the brain age gap, BAG) between the two groups, and, in a subsample with longitudinal data (mean interval 3.5 years), tested for group differences in the change rate of BAG. Moreover, we tested for associations between apparent brain aging and AAS use duration, administration pattern and dependence.
Results AAS users had higher BAG compared to weightlifting controls with strongest effects for frontal and insular regions. Higher BAG was associated with current AAS use, dependency, and longer history of AAS use. Group differences in BAG could not be explained by substance use, general cognitive abilities or depression. Longitudinal data revealed no group difference in the rate of BAG change.
Conclusions The findings suggest that long-term high dose AAS use may have adverse effects on brain aging, potentially linked to current and exaggerated use of AAS.
... AAS use is linked with negative physical health effects, such as testicular atrophy, liver toxicity, dermal scarring, cognitive problems, gynaecomastia, muscle damage, myocardial injuries, infertility [7], and BBVs [8]. AAS users are at greater risk than non-users of psychological risks such as: mania, delusions, aggressive behaviours, depression, suicide and anxiety [9][10][11][12][13][14]. Pilot studies have shown that lifetime AAS use may impact on some cognitive processes and the structural features of the brain [15][16][17]. ...
... One key purpose of a review is to identify gaps in the literature [61] and IPED users seemed to reject the 'medical model' that doctors are the experts as they give credibility to advice from people who have used [33] stating that doctors lacked credibility as they did not [1,2,4,8,12,13,15,16] Online forums* [3,8,17] Underground books/Magazines [1,8,13,16,18] Doctor(s)/Medical practitioner(s)/Nurse(s) [1,4,12,15] Gym contact(s)/Gym trainer(s)/Personal trainers [1,4,12,15,19] Dealer(s)/Supplier(s) [1-3, 11, 12, 15] Questions to anti-doping hotline/Online service on AAS [20] Internet/Specialist websites* [2-4, 12, 13, 15, 16, 18] Medical journals [1] NSP(s) [2,4,12,15] Steroid guides in gyms/Other sources [12,15,18] Research into cycling, stacking and types of substances Peers/Fellow users [2,13] Websites [16] Dealers [2] Online forums [17] Self-experimentation [16] Research into side effects and risk management People with 'hands-on' experience of use/ Steroid guides in gyms/ Underground books/Dedicated websites [18] Questions to anti-doping hotline/Online service on adverse side-effects/ Health risks [20] Doping tests Questions to anti-doping hotline/Online service on obtaining positive doping test and penalties [20] Any data given about access of services that is not linked to AAS/IPED use has not been included in this table. *It could be that when AAS users refer to websites they might also mean specialist forums have personal experience [36]. ...
... One key purpose of a review is to identify gaps in the literature [61] and IPED users seemed to reject the 'medical model' that doctors are the experts as they give credibility to advice from people who have used [33] stating that doctors lacked credibility as they did not [1,2,4,8,12,13,15,16] Online forums* [3,8,17] Underground books/Magazines [1,8,13,16,18] Doctor(s)/Medical practitioner(s)/Nurse(s) [1,4,12,15] Gym contact(s)/Gym trainer(s)/Personal trainers [1,4,12,15,19] Dealer(s)/Supplier(s) [1-3, 11, 12, 15] Questions to anti-doping hotline/Online service on AAS [20] Internet/Specialist websites* [2-4, 12, 13, 15, 16, 18] Medical journals [1] NSP(s) [2,4,12,15] Steroid guides in gyms/Other sources [12,15,18] Research into cycling, stacking and types of substances Peers/Fellow users [2,13] Websites [16] Dealers [2] Online forums [17] Self-experimentation [16] Research into side effects and risk management People with 'hands-on' experience of use/ Steroid guides in gyms/ Underground books/Dedicated websites [18] Questions to anti-doping hotline/Online service on adverse side-effects/ Health risks [20] Doping tests Questions to anti-doping hotline/Online service on obtaining positive doping test and penalties [20] Any data given about access of services that is not linked to AAS/IPED use has not been included in this table. *It could be that when AAS users refer to websites they might also mean specialist forums have personal experience [36]. ...
Background:
Since there is a paucity of research on support for people using Anabolic Androgenic Steroids (AAS), we aimed to identify and synthesise the available evidence in this field. Gaining an understanding of the support both accessed and wanted by recreational AAS users will be of use to professionals who provide services to intravenous substance users and also to those working in the fields of public health and social care, with the aim to increase engagement of those using AAS.
Methods:
A systematic scoping review of the literature to explore and identify the nature and scope of information and support both accessed and wanted by non-prescribed AAS users. Any support services or information designed to help people who use AAS were considered.
Results:
We identified 23 papers and one report for review, which indicated that AAS users access a range of sources of information on: how to inject, substance effectiveness, dosages and side effects, suggesting this is the type of information users want. AAS users sought support from a range of sources including medical professionals, needle and syringe programmes, friends, dealers, and via the internet, suggesting that, different sources were used dependent on the information or support sought.
Discussion:
AAS users tended to prefer peer advice and support over that of professionals, and access information online via specialist forums, reflecting the stigma that is experienced by AAS users. These tendencies can act as barriers to accessing services provided by professionals.
Conclusions:
Support needs to be specific and targeted towards AAS users. Sensitivity to their perceptions of their drug-use and the associated stigma of being classified in the same sub-set as other illicit drug users is relevant to facilitating successful engagement.
... This substance, indeed, has the characteristic to pass the blood-brain barrier freeing its actions directly on the nervous system inducing brain alteration [45]. Testosterone and AAS can act at this level via AR largely distributed in the cerebral cortex, hypothalamus, hippocampus, brain stem, and amygdala [46][47][48][49]. ...
... Analogous alterations were seen at the expense of the putamen, one of the structures of the basal ganglia, which can be associated with less total grey matter rather than a specific functional alteration in the area. On the contrary, a previous study on brain morphometry linked AAS use to an enlargement of the right amygdala [45] and of the nucleus accumbens [54]. Thinner cortex areas and augmentation in nucleus accumbens dimensions were proven even in cannabinoid and alcohol abuse [55,56], maybe explaining the anatomical substrate for the development of drug addictive behavior. ...
... ACC, lastly, does not conduct a concrete function but contributes to the cognitive, motor, and attentional control or to reward-based decisions [64,65]. Abnormalities in this region were also demonstrated with magnetic resonance spectroscopy (MRS) as a response to glutamate-turnover increase [45]. ...
Background and Objectives: Anabolic androgenic steroids (AASs) are a complex group of molecules that include both steroidal androgens and synthetic compounds, derived from testosterone. AASs are commonly used to support pharmacological therapy in cases of primary or secondary hypogonadism, major burns, and neoplastic cachexia. Their prolonged and supra-physiological consumption can provoke several adverse effects on various organs and systems. Among these, the physiopathological mechanisms that induce neuropsychiatric disorders related to AAS abuse are poorly known. For this reason, the proposed review aims to retrace the pathway of action of testosterone to focus on the effects on the central nervous system and specifically highlight the effects of AASs on neuropsychiatric and behavioral functions, as well as on lifestyle. Materials and Methods: This review was conducted using PubMed and Google Scholar databases. On these database websites, we searched for articles from 1 January 1980 to March 2019 using the key terms: “AAS,” “Anabolic Androgenic Steroids,” “brain,” and “neurology.” Results: The use of AASs through self-administration yields circulating androgens levels, inducing neuron apoptosis, which is linked to thinner cortex and, in general, less cortical volume. The same alterations affect the putamen. These differences were more evident when correlated with longer use. From a functional point of view, prolonged AAS consumption seemed to be related to lower connectivity between amygdala and frontal, striatal, limbic, hippocampal and visual cortical areas. On the other hand, AAS use seems to negatively condition the positive effects of the sport exercise, reducing its important anti-apoptotic and pro-proliferative functions on the hippocampus, implicated in anxiolytic control. Conclusion: This review clarifies the major aspects of the side effects related to AAS use/abuse highlighting the complex mechanisms on neuropsychiatric and cognitive pathological alterations and also the emotional and behavioral dysfunctions.
... Evidence exists for AAS harms more broadly [36][37][38][39][40], however, an emerging body of literature suggesting harms are compound-specific [7,12] and this fits more closely with the present findings. Trenbolone users in this study spoke about the way social harms emanated from their use of this compound, with reports of social challenges confirmed by their peers. ...
... The associated physical and psychological health issues of PIEDs depend on the types of substance used and their forms of administration [43]. Research has indicated long-term AAS use is associated with disruptions to brain areas involved in cognitive control and spatial memory (e.g., amygdala), which are thought to contribute to the psychiatric effects and cognitive dysfunction associated with AAS use [38]. The current data support the findings of Underwood [7] and further underscore the potential for trenbolone to be associated with the highest level of psychosocial harms when considered alongside other AAS, which may also substantiate the neurological harms highlighted in extant literature. ...
Introduction:
There are a variety of harms associated with anabolic-androgenic steroids (AAS), with some AAS associated with an increased risk profile for users. Despite potentially different risk profiles, these harms are seldom discussed with respect to specific compounds although recent ethnographic research has identified a need to do so. Specifically, myth has developed among users with trenbolone reportedly having more dramatic effects on individuals, with reports of aggression, violent behaviour and extreme mood disturbances, and this is reflected in extant literature. This paper aims to report on the narrative surrounding the use of trenbolone among AAS users.
Method:
As part of a larger qualitative study, a number of AAS users were interviewed regarding their usage practices. A narrative emerged regarding the physical and psychological harms which accompanied their AAS use of which trenbolone played a central role (N = 16).
Results:
Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues. AAS-using peers and family members of users reported the readily observable effect of trenbolone.
Discussion and conclusions:
Users should be cognisant of the potential for significant harms and health-care providers working with this group may consider more focused screening strategies. Future policy decisions regarding AAS may wish to consider the pivotal role trenbolone plays in adverse outcomes for this unique group of substance users.
... En el análisis sobre los resultados de estos estudios, se han presentan alteraciones en el funcionamiento cognoscitivo en los usuarios con un consumo prolongado o dependiente de EAA, específicamente en: memoria viso-espacial (Kanayama et al., 2013;Kaufman et al., 2015), memoria de reconocimiento de patrones (Kanayama et al., 2013), atención (Hildebrandt et al., 2014), memoria retrospectiva-prospectiva (Heffernan, 2015) y en tareas de funcionamiento ejecutivo como: planeación (Hildebrandt et al., 2014), inhibición Hildebrandt et al., 2014), velocidad de procesamiento (Bjornebekk et al., 2019), memoria de trabajo (Bjornebekk et al., 2019;Hauger et al., 2020), resolución de problemas (Bjornebekk et al., 2019;Hauger et al., 2020) y flexibilidad mental . ...
... Bjørnebekket al., 2019;Hauger et al., 2020;Vaskinn et al., 2020), seguido por Inglaterra con el 42.9% (n = 3;Heffernan et al., 2015;Kanayama et al., 2013;Kaufman et al., 2015) y Estados Unidos con el 14.2% (n = 1;Hildebrandt et al., 2014). ...
... En la revisión sistemática se incluyeron 7 estudios, de los cuales el 42.9% de las investigaciones fueron realizadas principalmente en Noruega (n = 3; Bjørnebekk et al., 2019;Hauger et al., 2020;Vaskinn et al., 2020), seguido por Inglaterra con el 42.9% (n = 3; Heffernan et al., 2015;Kanayama et al., 2013;Kaufman et al., 2015) y Estados Unidos con el 14.2% (n = 1; Hildebrandt et al., 2014). ...
... En el análisis sobre los resultados de estos estudios, se han presentan alteraciones en el funcionamiento cognoscitivo en los usuarios con un consumo prolongado o dependiente de EAA, específicamente en: memoria viso-espacial (Kanayama et al., 2013;Kaufman et al., 2015), memoria de reconocimiento de patrones (Kanayama et al., 2013), atención (Hildebrandt et al., 2014), memoria retrospectiva-prospectiva (Heffernan, 2015) y en tareas de funcionamiento ejecutivo como: planeación (Hildebrandt et al., 2014), inhibición Hildebrandt et al., 2014), velocidad de procesamiento (Bjornebekk et al., 2019), memoria de trabajo (Bjornebekk et al., 2019;Hauger et al., 2020), resolución de problemas (Bjornebekk et al., 2019;Hauger et al., 2020) y flexibilidad mental . ...
El consumo de sustancias esteroides anabólico-androgénicas (EAA) no se limita a su uso en el deporte profesional, actualmente se ha extendido a usuarios de gimnasio que practican deporte con fines estéticos. Sin embargo, poco se sabe de sus consecuencias en el funcionamiento cognoscitivo por su consumo prolongado y en dosis elevadas. Por lo tanto, se realizó una revisión sistemática de los estudios llevados a cabo durante la última década (2011-2021). Fueron incluidos siete artículos para su revisión de los que se destaca que, los usuarios de gimnasio de consumo prolongado o dependiente a sustancias EAA presentan déficits en ciertas funciones cognoscitivas (memoria y funciones ejecutivas) en comparación con usuarios no consumidores, consumidores a corto plazo o no dependientes. Aunque es necesario que se lleven a cabo investigaciones que realicen una evaluación integral de los diferentes procesos cognoscitivos, los resultados de estos estudios ofrecen evidencia importante para que profesionales de la salud y el público en general puedan atender, intervenir o prevenir las posibles consecuencias.
... The structural brain MRI data we know come from TM during shortmedium administration (around a year or less), 31,72 whereas data from AAS consumers are from longterm consumption. 73,74 Over 1-year's consumption of AASs by weightlifters is associated with a thinner cortex and smaller volumes of total gray matter, cerebral cortex, and putamen, 74 but right amygdala enlargement and higher Gln/Glu ratio have also been reported. 73 These reports suggest that the effects of testosterone and other AASs on brain structure depend upon the duration of the administration of these substances. ...
... 73,74 Over 1-year's consumption of AASs by weightlifters is associated with a thinner cortex and smaller volumes of total gray matter, cerebral cortex, and putamen, 74 but right amygdala enlargement and higher Gln/Glu ratio have also been reported. 73 These reports suggest that the effects of testosterone and other AASs on brain structure depend upon the duration of the administration of these substances. ...
Transgender men (TM) experience an incongruence between the female sex assigned when they were born
and their self-perceived male identity. Some TM seek for a gender affirming hormone treatment (GAHT) to induce a somatic transition from female to male through continuous administration of testosterone. GAHT
seems to be relatively safe. However, testosterone produces structural changes in the brain as detected by quantitative magnetic resonance imaging. Mainly, it induces an increase in cortical volume and thickness and subcortical structural volume probably due to the anabolic effects. Animal models, specifically developed to test the
anabolic hypothesis, suggest that testosterone and estradiol, its aromatized metabolite, participate in the control
of astrocyte water trafficking, thereby controlling brain volume.
... There is significant AAS abuse in the U.S. adolescent population, with 3-4 million Americans having used AAS at least once in their lifetime [12]. Adolescents who consume AAS during puberty subject their hormonally sensitive brains to risks, as the addition of exogenous hormones at supraphysiological levels induces behavioural detriments and changes in neural connectivity [13]. Behavioural symptoms experienced by chronic AAS abusers include major mood syndromes such as mania and major depression [14], increases in hostility and aggression, and changes in anxiety [15]. ...
... Similarly, our increases in both the ipsilateral and contralateral AMYG volume in response to Met treatment are consistent with clinical studies of long-term AAS users [13]. Increased androgen exposure in the AMYG has been associated with threat reactivity and aggressive behaviour [45,46], which may have been reflected in our dominance tube findings. ...
Background:
Repetitive mild traumatic brain injury (RmTBI) is increasingly common in adolescents. Anabolic-androgenic steroid (AAS) consumption among younger professional athletes is a significant risk factor for impaired neurodevelopment. Given the increased rates and overlapping symptomology of RmTBI and AAS use, we sought to investigate the behavioural and neuropathological outcomes associated with the AAS Metandienone (Met) and RmTBI on rats.
Methods:
Rats received either Met or placebo and were then administered RmTBIs or sham injuries, followed by a behavioural test battery. Post-mortem MRI was conducted to examine markers of brain integrity and qRT-PCR assessed mRNA expression of markers for neurodevelopment, neuroinflammation, stress responses, and repair processes.
Results:
Although AAS and RmTBI did not produce cumulative deficits, AAS use was associated with detrimental outcomes including changes to depression, aggression, and memory; prefrontal cortex (PFC) atrophy and amygdala (AMYG) enlargement; damaged white matter integrity in the corpus callosum; and altered mRNA expression in the PFC and AMYG. RmTBI affected general activity and contributed to PFC atrophy.
Conclusions:
Findings corroborate previous results indicating that RmTBI negatively impacts neurodevelopment but also demonstrates that AAS results in significant neuropathological insult to the developing brain.
... [4][5][6][7] While use of AAS among women has been identified, 8-10 the majority of AAS users are men. 11,12 Use of AAS has been associated with a range of medical and psychological sideeffects 13 including mental health disorders, 14,15 reduced brain volume 16,17 and cognitive function, [18][19][20] metabolic and endocrine disturbance, [21][22][23] and cardiovascular pathology. 24,25 AAS use is associated with use of other image and performance enhancing drugs and psychoactive substances use, [26][27][28] and such a poly-drug taking repertoire is common. ...
... The majority (n = 453, 80.5%) of the participants were inpatients and 108 (19.2%) were outpatients. Norway was country of origin for the majority of the sample 93.8% (512), whereas 3.3% (18) were born in other Nordic countries and 2.9% (16) originated from other countries. For these measures answers were missing for 7, 2 and 17 responses respectively. ...
Background
Anabolic androgenic steroid (AAS) use is associated with serious mental and physical health problems. Evidence indicates that AAS use among people who use psychoactive substances is higher than in the general population. This study aims to estimate lifetime AAS use among patients in substance use disorder (SUD) treatment, compare characteristics of AAS and non-AAS users and identify whether AAS use was addressed during treatment.
Methods
This cross-sectional survey included 563 (142 women, 24.2%) patients in 38 SUD treatment facilities in Norway. Respondents reported on AAS and substance use, and treatment experiences.
Results
Lifetime AAS use was reported by 156 (28.3%) SUD patients, thereof 35.6% of the men and 8.0% of the women. Lifetime AAS use was highest among men with stimulants (55.8%) as preferred substance, and lowest among men who preferred alcohol (14.6%). Initiation of AAS use due to getting thinner following substance use was reported by 44.5% of the AAS using men. AAS users reported more severe substance use than non-AAS users. More than half (58%) of all patients had not been asked about AAS use, and 42.4% of those who were asked, experienced that treatment providers lacked expertise about AAS.
Conclusion
Lifetime AAS use in this sample of SUD patients is common practice and comprise an underrecognized problem in SUD treatment. Given the deleterious implications to the individual and society that concomitant use of AAS may cause, it would be essential to raise the awareness about AAS use among SUD patients, and the level of competence among health professionals.
... These subjects exhibited increased amygdala volume and reduced functional MRI coupling in the resting state of the amygdala. It was suggested that prolonged use of such might negatively modulate functional and structural brain networks related to the amygdala 58 . This data emphasized the need for further investigation in this area to substantiate the involvement of anabolic steroids in cerebellar lesions, considering the importance of this region for the organisms' cognitive and motor capabilities. ...
The abuse of anabolic-androgenic steroids (AASs) is associated with high morbidity and mortality rates. The highest incidence of this malpractice documented in males (prevalence rate about 6.4%), a third of which develop adverse reactions. Accordingly, the objective was to review published studies about the neurological complications triggered by the indiscriminate use of AASs, with focus on the pathogenesis of lesions in the nervous system (NS). As a result it was observed that at NS, these stimulants actuate through a complex signaling systems that include the neuroendocrine alteration of the hypothalamic-pituitary-gonadal axis, modification of neurotransmitters and their receptors, as well as the induction of neuronal death by apoptosis in several pathways. These organic neurological alterations can lead to a clinical symptomatology with neurological, mood and sleep disorders. Consequently, varying adverse effects were observed analogous to the class of AAS utilized, how it was administered and time of use. Even though to date, only a few classes were submitted for scientific analyses, on dosages, mode of administration and specific exposure times. Furthermore, the illegal use and production of these drugs does not propitiate their appropriate application, quality control and purity. It was concluded that the abuse of AAS has inimically severe and complex effects, including serious neurotoxic issues.
... AAS use has been shown to influence several complex neuropsychiatric traits, and thus the current findings may be explained by additional factors which are more proximal to social cognitive behaviors, including structural and functional changes to relevant brain regions including the prefrontal cortex and amygdala (Hauger et al. 2019b;Hiser and Koenigs 2018;Kaufman et al. 2015;Westlye et al. 2017). Testosterone has been shown to decrease connectivity between the right amygdala and dorsolateral prefrontal cortex, and increase neural reactivity to fearful and angry expressions in the amygdala, with implications for emotional recognition and behavioral response (Derntl et al. 2009;Goetz et al. 2014;Votinov et al. 2020). ...
Rationale
Anabolic-androgenic steroids (AAS) are used to improve physical performance and appearance, but have been associated with deficits in social cognitive functioning. Approximately 30% of people who use AAS develop a dependence, increasing the risk for undesired effects.
Objectives
To assess the relationship between AAS use (current/previous), AAS dependence, and the ability to recognize emotional facial expressions, and investigate the potential mediating role of hormone levels.
Methods
In total 156 male weightlifters, including those with current (n = 45) or previous (n = 34) AAS use and never-using controls (n = 77), completed a facial Emotion Recognition Task (ERT). Participants were presented with faces expressing one out of six emotions (sadness, happiness, fear, anger, disgust, and surprise) and were instructed to indicate which of the six emotions each face displayed. ERT accuracy and response time were recorded and evaluated for association with AAS use status, AAS dependence, and serum reproductive hormone levels. Mediation models were used to evaluate the mediating role of androgens in the relationship between AAS use and ERT performance.
Results
Compared to never-using controls, men currently using AAS exhibited lower recognition accuracy for facial emotional expressions, particularly anger (Cohen’s d = −0.57, pFDR = 0.03) and disgust (d = −0.51, pFDR = 0.05). Those with AAS dependence (n = 47) demonstrated worse recognition of fear relative to men without dependence (d = 0.58, p = 0.03). Recognition of disgust was negatively correlated with serum free testosterone index (FTI); however, FTI did not significantly mediate the association between AAS use and recognition of disgust.
Conclusions
Our findings demonstrate impaired facial emotion recognition among men currently using AAS compared to controls. While further studies are needed to investigate potential mechanisms, our analysis did not support a simple mediation effect of serum FTI.
... Moreover, it is structurally and functionally connected to parts of the frontal cortex involved in executive functions and the so-called top-down cognitive control, which physiologically limits aggression [106]. The right amygdala has been observed to be enlarged in chronic AAS users, and functional magnetic resonance imaging (fMRI) results have shown its reduced connectivity at rest with the frontal cortex [107], which may impair top-down cognitive control and regulation of amygdala activity and reactivity [105]. Amygdala enlargement is associated with increased aggressive behavior in humans [108], and decreased resting-state connectivity between the amygdala and the frontal cortex during the fMRI is associated with an increased risk of violence [109]. ...
Anabolic-androgenic steroids (anabolic-androgenic steroids, AAS) are testosterone-derived compounds whose popularity and use are constantly growing. Chronic use of AAS leads to many hormonal and metabolic disorders in the human body, which often lead to permanent health damage. Changes affect the following systems: cardiovascular, musculoskeletal, reproductive, digestive, and nervous. We decided to collect the existing knowledge in the literature and enrich it with the latest research reports in the field of degenerative effects of AAS on the nervous system. The work aimed to increase public awareness of the dangers and consequences of AAS use and improve it with the latest research on the neurodegenerative effects of AAS. We hope that our work will contribute to raising public awareness and reducing the use of AAS.
... AAS use has been shown to influence several complex neuropsychiatric traits, and thus the current findings may be explained by additional factors which are more proximal to social cognitive behaviors, including structural and functional changes to relevant brain regions including the prefrontal cortex and amygdala (44,45,84,85). Testosterone has been shown to decrease connectivity between the right amygdala and dorsolateral prefrontal cortex, and increase neural reactivity to fearful and angry expressions in the amygdala, with implications for emotional recognition and behavioral response (86)(87)(88). ...
Background: Anabolic-androgenic steroids (AAS) are used to improve physical performance and to achieve a muscular appearance, with significant physical and psychiatric consequences. Approximately 30% of people who use AAS develop a dependence, increasing the risk for undesired effects, largely driven by endocrine dysfunction. AAS use has been associated with antisocial behaviors and decreased empathy, indicating impaired social cognitive abilities, but the potential mediating role of hormone levels is not well-established.Methods: In total 156 male weightlifters, including those with current (n=45) or previous (n=34) AAS use and never-using controls (n=77), completed the Emotion Recognition Task (ERT) as part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Participants were presented with morphed faces expressing one out of six emotions (sadness, happiness, fear, anger, disgust and surprise) and were instructed to indicate by a button press which of the six emotions the face displayed. ERT accuracy and response time were recorded and used as behavioral outcomes and evaluated for association with AAS use status, AAS dependence, and serum reproductive hormone levels. Mediation models were used to evaluate the mediating role of androgens in the relationship between AAS use and ERT performance. Results: Compared to never-using controls, men currently using AAS (“On”) exhibited lower recognition accuracy for facial emotional expressions, particularly anger (F=4.29, pFDR=0.03) and disgust (F=3.87, pFDR=0.05). Those with AAS dependence (n=47) demonstrated worse recognition of fear relative to men without dependence (t=-2.26, p=0.03). Recognition of disgust was negatively correlated with serum free testosterone index (FTI), however FTI did not significantly mediate the association between AAS use and recognition of disgust.Conclusions: Our findings demonstrate impaired facial emotion recognition among men currently using AAS compared to controls. While further studies are needed to investigate potential mechanisms, our analysis did not support a simple mediation effect of serum FTI.
... AAS consumers with a high cumulative history of AAS exposure are at risk for various physical problems [10], including hypogonadism [11], cardiovascular conditions [12,13], and cognitive deficiencies [14]. In addition, AAS use is associated with the use of (other) illicit substances and AAS dependence disorder [15]. ...
Introduction:
The use of anabolic androgenic steroids (AAS) and other image- and performance-enhancing drugs is a growing public health concern. AAS use is associated with various physical and mental harms, including cardiovascular risks, cognitive deficiencies, and dependence. The aim of this study was to determine whether patterns of AAS use and other variables are associated with the presence of an AAS use disorder (AASUD).
Methods:
An online survey was completed by 103 male AAS consumers visiting gyms. The association of different patterns of AAS consumption (cycling vs. continuous forms of AAS use), psychoactive substance use, mental health disorders, and sociodemographic variables with moderate-severe AASUD (fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ≥4 criteria) was investigated. The associations between duration of AAS use and the AAS dose with moderate-severe AASUD were investigated using logistic regression analysis with moderate-severe AASUD as the dependent variable.
Results:
Moderate-severe AASUD was present in 25 (24.3%) of the participants. AAS consumers meeting criteria for moderate-severe AASUD, compared to those that did not, in the last 12 months reported a longer duration of AAS use (in weeks), a higher average AAS dose (mg/week), and a greater number of AAS side effects. Duration of AAS use and the AAS dose were the only independent predictors, with an increase of 3.4% in the probability of moderate-severe AASUD with every week increase of the duration of AAS use in the last year (p < 0.05) and an increase in moderate-severe AASUD of 0.1% with every 10 mg increase in the average AAS dose per week (p < 0.05), respectively.
Conclusion:
Our findings show that moderate-severe AASUD is relatively frequent among male AAS consumers and is positively associated with the duration and average dose of AAS use in the last 12 months.
... The issue with illicit enhancement substances, however, is that the scientific literature regarding their harms, albeit growing, is lacking, including when it comes to steroids. Nevertheless, the evidence that does exist shows that there are various physical and psychological harms associated with steroid use with particular concerns around the increased risk of cardiovascular disease (Baggish et al., 2017), cognitive deficiencies (Kaufman et al., 2015), and steroid dependence (Kanayama et al., 2009). Taking a simple use versus non-use dichotomy, people who consume steroids are of course at a higher risk of health harms. ...
There is a long history and growing evidence base that the use of drugs, such as anabolic-androgenic steroids, to enhance human performance is common amongst armed forces, including in Australia. We should not be surprised that this might have occurred for it has long been predicted by observers. It is a commonplace of many recent discussion of the future of warfare and future military technology to proclaim the imminent arrival of Super Soldiers, whose capacities are modified via drugs, digital technology and genetic engineering, in ways that increase their performance exponentially. This is what some observers have referred to as the “Gladiator Model” wherein the aim is to create soldiers able to perform feats of which ordinary citizens are not capable. One key aspect of this “gladiator project” is the use of illicit drugs to enhance performance. Could we use drugs, such as steroids or amphetamines, to enhance performance? Should we use such drugs? In this paper we explore the ethics of creating Super Soldiers, and raise issues of consent, coercion and the extent to which such use is permitted or condemned by just war theory. We conclude that much will depend on the extent to which such use is harmful to the soldiers themselves and this is still an open question.
... The link between anabolic androgenic steroid (AAS) use and violence remains a topic of contention. While empirical studies demonstrate an association between AAS use and increases in self-reported aggression (Chegeni et al., 2021), risk-taking behaviour (Nelson et al., 2022) and disinhibition (Bjørnebekk et al., 2017;Kaufman et al., 2015), research documenting AAS use among violent offenders at the time of arrest is limited. ...
... Long-term use of AAS was found to be associated with amygdala enlargement and poorer visual spatial function in AAS using male weightlifters compared to weightlifters with no experience with AAS (Kaufman et al., 2015). With a similar design, Bjørnebekk et al. (2017) found that AAS users had a thinner cortex in various regions as well as reduced total gray matter, cerebral cortex, and putamen. ...
Objective
The purpose of this study was to investigate the psychiatric morbidity among men with abuse of anabolic steroids.
Methods
The design is a retrospectively matched cohort study. Five hundred and fourty‐five males, who tested positive for anabolic steroids in Danish fitness centers during the period January 3, 2006 to March 1, 2018, were matched with 5450 randomly chosen male controls. Data was cross‐referenced with seven national registers pertaining to information about education, employment status, and psychiatric comorbidity. Main outcomes and measures were prescription of psychopharmacological treatment.
Results
The incidence of treatment with anxiolytics (HR: 2.34, 95% CI: 1.62−3.38) and antipsychotics (HR: 2.69, 95% CI: 1.99−3.63) displayed a remarkable increase in the years following doping sanction, compared to the control group. The prevalence of antidepressant use was already markedly elevated several years before doping sanction, but also displayed a higher incidence in the years following sanction (HR: 1.65, 95% CI: 1.28−2.13). The associations remained highly significant after controlling for socioeconomic factors.
Conclusion
Anabolic steroids use is strongly associated with psychiatric morbidity.
... Spatial memory performance decreased in the testosterone-supplemented group relative to a eugonadal placebo group, whereas the hypogonadal group performed worse than either eugonadal group. 93 Some studies have demonstrated that long-term use of anabolic-androgenic steroids impairs spatial memory, 94,95 supporting the conclusion that supraphysiological levels of androgens have negative effects on memory. The dose-dependent effects of testosterone were also demonstrated by a study that analyzed both circulating testosterone and androgen receptor genotype. ...
... AAS may also dispose users to impaired cognitive functions or structural brain alterations, with one study that conducted structural MRI brain imaging on AAS users and nonusers noting a negative association between cortical thickness and brain volume and AAS use [67]. Notably, this is in the context of an association between AAS use and poorer performance on cognitive tests [68,69]. Furthermore, some commentators have raised the possibility of a link between supraphysiologic testosterone levels and dementia through androgenic induction of additional oxidative stress [70]. ...
Anabolic-androgenic steroids (AAS) encompass a broad group of natural and synthetic androgens. AAS misuse is highly prevalent on a global scale, with the lifetime prevalence of AAS misuse in males being estimated to be around 6%, with 15 to 25% of male gym attendees using it at any one time. AAS are associated with sudden cardiac death, neuropsychiatric manifestations, and infertility. The average AAS user is unlikely to voluntarily declare their usage to a physician, with around 1 in 10 actively engaging in unsafe injection techniques. The aim of this paper is to review the current evidence base on AAS with emphasis on mechanisms of action, adverse effects, and user profiles that are most likely to engage in AAS misuse. This paper also reviews terminologies and uses methods specific to the AAS user community.
... These structures play an important role in regulating main functions, such as emotion and cognition. 49,51 Bjørnebekk et al evaluated the association between long-term exposure to AAS and brain morphometry. 52 In this study, 150 participants, divided into 82 current or previous users of AAS and 68 nonuser controls, underwent magnetic resonance imaging scans of the brain. ...
Introduction
For several decades, testosterone and its synthetic derivatives have been used for anabolic and androgenic purposes. Initially restricted to professional bodybuilders, these substances gradually became more popular with recreational weightlifters. Considering its increasing prevalence, the consumption of anabolic androgenic steroids (AAS) has become a matter of great concern. Although most side effects are mild and reversible, some of them can cause permanent damage or can be potentially life threatening.
Objectives
To review and summarize medical literature regarding misuse and abuse of testosterone and other androgens, in order to provide evidence-based information on the main topics related to this subject, such as how to identify and how to deal with these patients, and to elucidate the multiple possible adverse effects secondary to this practice.
Methods
Key studies were retrieved from PubMed (1989–2021) with reference searches from relevant articles. Search terms included “hypogonadism”, “anabolic androgenic steroids”, “androgens”, “misuse AND testosterone”, “abuse AND testosterone”, and “side effects AND testosterone”.
Results
There is a significant lack of information in the peer-reviewed literature describing demographic data, implications for different organ systems and the management of current or former AAS users; however, androgen abuse has been already linked to a wide variety of cardiovascular diseases, metabolic, endocrine, neurological, psychiatric and liver disorders. Despite all this, most physicians still feel uncomfortable and hesitate to discuss the issue with patients.
Conclusions
The chronic use of high doses of AAS is associated with adverse effects in several organ systems; however, there are still many gaps in our knowledge about the long-term consequences of this practice and how to deal with these patients. Healthcare professionals have a crucial role in combating this public health problem, recognizing and preventing the spread of androgen abuse.
Linhares BL, Miranda EP, Cintra AR, et al. Use, Misuse and Abuse of Testosterone and Other Androgens. Sex Med Rev 2021;XX:XXX–XXX.
... However, Tabor et al. [23] found that rats treated with androgens demonstrated increased aggression and enlarged amygdala volumes. Notably, a previous study in humans also identified right amygdala enlargement in androgen users [40], though the sample size of this study was small and more recent findings have found no differences in amygdala volume between androgen users and controls [41]. In addition, polysubstance use may contribute to aggressive behaviour, as rats treated with combined cannabis and nandrolone demonstrated increased aggression, but those exposed to either substance alone did not [16 & ]. ...
Purpose of review:
The purpose of this review is to examine the recent evidence regarding the effects of exogenous androgens on the brain. Understanding these effects is of high importance, as the consequences of androgens on the reproductive and endocrine system are well documented, while fewer studies have focused on the neural and cerebral consequences of androgen use.
Recent findings:
Supraphysiological doses of androgens have been shown to contribute to neurodegeneration, decreased brain-derived neurotrophic factor, increased inflammation and decreased neuronal density in animal studies, which may correspond to changes in mood, cognition and aggression. Findings from human studies suggest that similar behavioural and cognitive deficits may occur as a result of prolonged use of androgens. Additional evidence suggests that androgen use, particularly in high doses, may contribute to brain ageing and cerebrovascular problems.
Summary:
Findings from recent human and animal studies indicate that androgen use likely contributes to brain alterations, which may cause the frequently observed deficits in cognitive and emotional functioning. Although exogenous testosterone in appropriate doses for therapeutic purposes likely have some neurobiological benefits for certain populations, supraphysiological doses may cause multiple mental and physical health problems, indicating a need for additional large-scale studies in humans.
... It is known that androgen receptors are present in most of the body parts including CNS and influence many neuronal functions through both classical genomic effects and also rapid membrane effects. Sustained use of AAS has an impact on those areas of the CNS that are involved in emotional and cognitive responses such as sexuality, anxiety, aggression, memory and development of drug dependence [17][18][19][20][21]. The Different brain regions associate with different neurodegenerative diseases. ...
... Resting T concentrations are related to posttraumatic stress (PTSD), in which higher T is associated with a lower risk for PTSD (139). Further, long-term use of AAS in former weightlifters was associated with poor cognitive function and negative changes in brain morphology (140,141). Approximately 30% of illicit AAS users will develop AAS dependence, and there is some overlap between AAS dependence and the mechanisms and risk for opioid dependence (142,143). Sudden discontinuation of exogenous AAS use in those who are dependent or have suppressed endogenous production may result in severe depression and suicidality (142,143). ...
This consensus statement is an update of the 1987 American College of Sports Medicine (ACSM) position stand on the use of anabolic-androgenic steroids (AAS). Substantial data have been collected since the previous position stand, and AAS use patterns have changed significantly. The ACSM acknowledges that lawful and ethical therapeutic use of AAS is now an accepted mainstream treatment for several clinical disorders; however, there is increased recognition that AAS are commonly used illicitly to enhance performance and appearance in several segments of the population, including competitive athletes. The illicit use of AAS by competitive athletes is contrary to the rules and ethics of many sport governing bodies. Thus, the ACSM deplores the illicit use of AAS for athletic and recreational purposes. This consensus statement provides a brief history of AAS use, an update on the science of how we now understand AAS to be working metabolically/biochemically, potential side effects, the prevalence of use among athletes, and the use of AAS in clinical scenarios.
... According to a recent study that performed a neuroimaging investigation of AAS users, smaller overall gray matter, cortical and putamen volume, and thinner cortex in widespread regions in AAS users compared to non-using weightlifters was observed [44]. Furthermore, another imaging study showed markedly increased right amygdala volumes; markedly decreased right amygdala and reduced dACCgln/glu and scyllo-inositol levels compared to nonusers [45]. Recent evidence, by administrating neuropsychological tests to weightlifters both AAS users and nonusers, demonstrated a cognitive disfunction due to long-term high AAS exposure [46]. ...
Anabolic-androgenic steroids (AASs) are a large group of molecules including endogenously produced androgens, such as testosterone, as well as synthetically manufactured derivatives. AAS use is widespread due to their ability to improve muscle growth for aesthetic purposes and athletes’ performance, minimizing androgenic effects. AAS use is very popular and 1–3% of US inhabitants have been estimated to be AAS users. However, AASs have side effects, involving all organs, tissues and body functions, especially long-term toxicity involving the cardiovascular system and the reproductive system, thereby, their abuse is considered a public health issue. The aim of the proposed review is to highlight the most recent evidence regarding the mechanisms of action of AASs and their unwanted effects on organs and lifestyle, as well as suggesting that AAS misuse and abuse lead to adverse effects in all body tissues and organs. Oxidative stress, apoptosis, and protein synthesis alteration are common mechanisms involved in AAS-related damage in the whole body. The cardiovascular system and the reproductive system are the most frequently involved apparatuses. Epidemiology as well as the molecular and pathological mechanisms involved in the neuropsychiatric side-effects of AAS abuse are still unclear, further research is needed in this field. In addition, diagnostically reliable tests for AAS abuse should be standardized. In this regard, to prevent the use of AASs, public health measures in all settings are crucial. These measures consist of improved knowledge among healthcare workers, proper doping screening tests, educational interventions, and updated legislation.
... Burke et al. 2017). In line with our results, long-term users of anabolic androgens show generally blunted amygdala rsFC with a widespread network that includes the medial prefrontal cortex and the STG relative to matched non-users (Kaufman et al. 2015;Westlye et al. 2017). This pattern also fits studies suggesting that T reduces threat sensitivity Enter et al. 2016) and decreases connectivity within emotionprocessing networks (Bos et al. 2016;van Wingen et al. 2010). ...
The steroid hormone testosterone (T) has been suggested to influence reactive aggression upon its action on the basolateral amygdala (BLA), a key brain region for threat detection. However, it is unclear whether T modulates resting-state functional connectivity (rsFC) of the BLA, and whether this predicts subsequent aggressive behavior. Aggressive interactions themselves, which often induce changes in T concentrations, could further alter BLA rsFC, but this too remains untested. Here we investigated the effect of endogenous T on rsFC of the BLA at baseline as well as after an aggressive encounter, and whether this related to behavioral aggression in healthy young women (n=39). Pre-scan T was negatively correlated with basal rsFC between BLA and left superior temporal gyrus (STG), which in turn predicted increased aggression. BLA-STG coupling at rest might thus underlie hostile readiness in low-T women. In addition, coupling between the BLA and the right superior parietal lobule (SPL), a brain region involved in higher-order perceptual processes, was reduced in aggressive participants. On the other hand, post-task increases in rsFC between BLA and medial orbitofrontal cortex (mOFC) were linked to reduced aggression, consistent with the established notion that the mOFC regulates amygdala activity in order to curb aggressive impulses. Finally, competition-induced changes in T were associated with increased coupling between the BLA and the right lateral OFC, but this effect was unrelated to aggression. We thus identified connectivity patterns that prospectively predict aggression in women, and showed how aggressive interactions in turn impact these neural systems.
... The result of this interaction can include several different consequences, such as an enhancement of the adverse effects of each drug, serious damage to different organs, and serious neurological or psychological complications [29,30]. It has been well described that AAS assumption generates an alteration in amygdala functions, with subsequent neurochemical abnormalities and visuospatial memory impairment [31]. ...
Anabolic-androgenic steroids (AASs) can be used to treat both hormonal diseases and other pathologies characterized by muscle loss (aging, cancer, and AIDS). Even if the adverse effects related to the misuse of AASs have been well studied in different systems and apparatuses, knowledge about brain damage is poor.
In this scenario, this experimental study aimed to analyze the role of several microRNAs (miRNAs) in brain damage after AAS misuse, to better comprehend the underlying mechanisms. The research hypothesis at the base of this experimental study is that the chronic use of AASs may be associated to brain damage with a dysregulation of these miRNAs. Moreover, miRNA expression values were compared among three different groups, “AAS” group, “Cocaine” group and “Aging” group, in order to define if AAS brain damage can be compared with the brain impairment linked to aging and/or cocaine assumption.
This experimental study revealed that the tested miRNAs (hsa-miR-21-5p, hsa-miR-34a-5p, hsa-miR-124-5p, hsa-miR-132-3p, and hsa-miR-144-3p) were overexpressed in all enrolled groups. In the light of the presented results, the identification of specific circulating and/or tissue biomarkers is challenging for the scientific community. Further studies with larger samples are needed to confirm these interesting findings.
... Common effects include anxiety, mood disturbances and reckless behaviour (Piacentino et al. 2015). Links have been found between cessation of AAS use and depression, and AAS-dependent users were more likely to report diagnoses of anxiety or major depressive disorder than non-dependent AAS users (Ip et al. 2012;Kaufman et al. 2015). While AAS use may be linked with mental health problems, the impact on individuals is idiosyncratic and unpredictable ; therefore, social workers should be alert for mental health-related problems, regardless of whether AAS is the cause of the mood disturbances or being used to alleviate them. ...
Non-prescribed anabolic–androgenic steroid (AAS) use has increased during recent years. Often used ‘recreationally’ and for aesthetic purposes, AAS are easily purchased over the internet and informally from gym-using peers. Social workers have a responsibility to support service users, to identify and manage risks and AAS use raises some noteworthy challenges to social work practice. This literature review aims to identify AAS-related knowledge social workers might require and consider its implications for social work practice. Although some of the evidence is inconclusive, particularly in relation to causal relationships between AAS use and behavioural change or polysubstance use implications, there are consequences that could cause significant short- and long-term harm to physical and/or psychological health to young people. Social workers should consider the possibility that a young person may be vulnerable to using AAS without being fully aware of the risks, as this could result in harm reduction and enhanced outcomes among this easily overlooked population. While rarely addressed in the existing social work literature, the risks associated with AAS usage, particularly in young people, necessitate more awareness and attention from social work practitioners particularly in today’s image conscious society.
... Finally, we conclude by exploring some of the negative policy consequences arising from the dominance of the "narrative of harm" and advance a regulatory approach grounded in rational reduced insulin sensitivity (e.g. see Rasmussen et al., 2017Rasmussen et al., , 2016, cardiovascular disease (Baggish et al., 2017) and cognitive deficiencies (Kaufman et al., 2015). Evidently, the potential for harm exists, however, such harms need to be contextualized. ...
... Finally, we conclude by exploring some of the negative policy consequences arising from the dominance of the "narrative of harm" and advance a regulatory approach grounded in rational reduced insulin sensitivity (e.g. see Rasmussen et al., 2017Rasmussen et al., , 2016, cardiovascular disease (Baggish et al., 2017) and cognitive deficiencies (Kaufman et al., 2015). Evidently, the potential for harm exists, however, such harms need to be contextualized. ...
... Finally, we conclude by exploring some of the negative policy consequences arising from the dominance of the "narrative of harm" and advance a regulatory approach grounded in rational reduced insulin sensitivity (e.g. see Rasmussen et al., 2017Rasmussen et al., , 2016, cardiovascular disease (Baggish et al., 2017) and cognitive deficiencies (Kaufman et al., 2015). Evidently, the potential for harm exists, however, such harms need to be contextualized. ...
المستخلص: هذه الدراسة الموسومة بـ: المنشطات في ميزان المصالح والمفاسد، تقوم على دراسة قضية المنشطات التي لم تبحث من قبل على شكل دراسة مقاصدية، وتدرس المنشطات عن طريق تعريف المنشطات وذكر أنواعها، وسوف يتم ذكر مصالح ومفاسد تناول المنشطات، وعليه سوف يتم الموازنة بين المصالح والمفاسد، وهذا ليساعد الفقيه على التوصل للحكم الشرعي. وقد اعتمد هذا البحث على المنهج الاستقرائي، والمقارن، والوصفي، وذلك لمناقشة المقاصد التي تدور حولها المنشطات. فبدأ البحث بالتمهيد للمنشطات بذكر التعريف والأنواع، وبعدها بذكر المصالح المتعلقة بالمنشطات ومدى صلتها ببعضها من حيث الثبوت ورتبتها، ثم مناقشة المفاسد من حيث وقوعها ورتبتها ومدى صلتها بالمنشطات، وفي النهاية تمت الموازنة بين مصالح ومفاسد تناول المنشطات، وهذا يعطي الفقيه المجتهد مفتاح الوصول للحكم الشرعي؛ لأن المنشطات المراد دراستها لا تخرج عن هذه الدائرة المقاصدية، فتعطي الفقيه النظرة الشمولية للمنشطات ليتمكن من تنزيل الحكم على كل منشط بعينه.
Background: The use of anabolic steroids is increasing in athletes due to body beauty and performance enhancement and is one of the major public health problems. The aim of study was to compare the characteristics of five major personality factors in male bodybuilding and fitness athletes with and without the use of anabolic-androgenic steroids. Materials and Methods: The research was practical in terms of purpose and in terms of strategy, it is a descriptive causal-comparative description. The statistical population of the present study included all male bodybuilding and fitness athletes in Yazd province. 105 athletes (50 with a history of use and 55 with no history of steroid use) with an age range of 18 to 48 years and at least two years of sports experience were selected as availabe. The instrument used was the personality questionnaire NEO-FFI. Kolmogorov-Smirnov test and independent t-test were used for statistical analysis. Results: The results showed athletes who use steroids have a higher score in the dimension of neuroticism and a lower score in the dimensions of extraversion, openness, adaptation and conscientiousness score than athletes who didnot use steroids. The results showed significant differences in the components of neuroticism (P=0/013), extraversion (P=0/02), adaptation (P=0/04) and conscientiousness (P=0/01). however, the difference between the components of openness to experience was not significant (P=0/26). Conclusion: The results showed that there is a significant difference between bodybuilding and fitness athletes with and without the use of anabolic steroids in the personality dimensions of neuroticism, extroversion, adaptability and conscientiousness.
Son yıllarda oldukça ön plana çıkan görsellik ve beraberinde getirdiği alışkanlıklar bazı fiziksel rahatsızlıkları ve psikolojik sendromları da ortaya çıkarmaktadır. Antrenman bağımlılığı, anabolik androjenik steroid kullanımı, performans arttırıcı ilaç kullanımı gibi davranışlar kas dismorfisi sendromunu meydana getirmektedir. Bu kapsamlı değerlendirmede gerek kas dismorfisinin getirdiği antrenman bağımlılığı, gerekse daha kaslı olmak için kullanılan steroid ve performans arttırıcı ilaçların psikolojik etkileri derlenmiştir. Henüz Amerika Psikiyatri Derneği tarafından hastalık kategorisinde sınıflandırılmamış kas dismorfisi ve beraberindeki sendromlar oldukça yaygın görülmektedir. Bu sendroma en yakın olan beden algı bozukluğu rahatsızlığı için farmakolojik tedavi ve bilişsel davranışçı terapi ön plana çıkmaktadır. Kas dismorfisi ve benzeri sendromların hastalık kategorisinde değerlendirilmesi için daha fazla kanıta dayalı kontrollü randomize araştırmalara ihtiyaç duyulmaktadır.
Anabolic androgenic steroids (AAS) are frequently used to improve physical appearance and strength. AAS are known to affect muscle growth, but many AAS-users also experience psychiatric and behavioral changes after long-term use. The AAS-induced effects on the brain seem to depend on the type of steroid used, but the rationale behind the observed effect is still not clear. The present study investigated and compared the impact of nandrolone decanoate and testosterone undecanoate on body weight gain, levels of stress hormones, brain gene expression, and behavioral profiles in the male rat. The behavioral profile was determined using the multivariate concentric squared field test (MCSF-test). Blood plasma and brains were collected for further analysis using ELISA and qPCR. Nandrolone decanoate caused a reduction in body weight gain in comparison with both testosterone undecanoate and control. Rats receiving nandrolone decanoate also demonstrated decreased general activity in the MCSF. In addition, nandrolone decanoate reduced the plasma levels of ACTH in comparison with the control and increased the levels of corticosterone in comparison with testosterone undecanoate. The qPCR analysis revealed brain region-dependent changes in mRNA expression, where the hypothalamus was identified as the region most affected by the AAS. Alterations in neurotransmitter systems and stress hormones may contribute to the changes in behavior detected in the MCSF. In conclusion, both AAS affect the male rat, although, nandrolone decanoate has more pronounced impact on the physiological and the behavioral parameters measured.
Use of anabolic androgenic steroids (AAS) is associated with adverse health effects. The factors that predispose to AAS use among athletes are poorly understood, but attention deficit/hyperactivity disorder (ADHD), which is known to occur among athletes more often than in the general population, is associated with risk behaviors, including substance abuse. We aimed to see if AAS use in male weightlifters was associated with ADHD symptoms, and test the link between ADHD symptoms and cognitive performance. Hundred and forty male weightlifters, 72 AAS users and 68 weightlifting controls (WLC), completed the Achenbach system of empirically based assessment (ASEBA) for ADHD symptoms and underwent cognitive examination. Self-reported ADHD symptom scores were significantly higher among AAS users compared to WLC, and scores in the range indicating clinically important ADHD was significantly more common in the AAS-using group. Age of onset of AAS use correlated inversely with ADHD scale score (r = − 0.35; p = 0.003). ADHD score correlated inversely with cognitive scores for working memory (r = − 0.25, p < 0.001), processing speed (r = − 0.24, p < 0.001), verbal learning and memory (r = − 0.19, p = 0.03), and problem solving (r = − 0.20, p = 0.02). AAS use among weightlifters is associated with ADHD symptoms and corresponding lower cognitive performance. Recognising a relationship between ADHD symptoms and AAS use may guide drug prevention strategies in sports.
Previous research has uncovered medical and psychological effects of anabolic–androgenic steroid (AAS) use, but the specific relationship between AAS use and risk-taking behaviors as well as between AAS use and psychopathic tendencies remains understudied. To explore these potential relationships, we anonymously recruited 492 biologically male, self-identified bodybuilders (median age 22; range 18–47 years) from online bodybuilding fora to complete an online survey on Appearance and Performance Enhancing Drug (APED) use, psychological traits, lifestyle choices, and health behaviors. We computed odds ratios and 95% confidence intervals using logistic regression, adjusting for age, race, education, exercise frequency, caloric intake, and lean BMI. Bodybuilders with a prior history of AAS use exhibited heightened odds of psychopathic traits, sexual and substance use risk-taking behaviors, anger problems, and physical problems compared to those with no prior history of AAS use. This study is among the first to directly assess psychopathy within AAS users. Our results on risk-taking, anger problems, and physical problems are consistent with prior AAS research as well as with existing frameworks of AAS use as a risk behavior. Future research should focus on ascertaining causality, specifically whether psychopathy is a risk associated with or a result of AAS use.
Background and Objectives
Anabolic‐androgenic steroid (AAS) use has become a major worldwide substance use disorder, affecting tens of millions of individuals. Importantly, it is now increasingly recognized that some individuals develop uncharacteristically violent or criminal behaviors when using AAS. We sought to summarize available information on this topic.
Methods
We reviewed the published literature on AAS‐induced behavioral effects and augmented this information with extensive observations from our clinical and forensic experience.
Results
It is now generally accepted that some AAS users develop uncharacteristically violent or criminal behaviors while taking these drugs. Although these behaviors may partially reflect premorbid psychopathology, sociocultural factors, or expectational effects, accumulating evidence suggests that they are also attributable to biological effects of AAS themselves. The mechanism of these effects remains speculative, but preliminary data suggest a possible role for brain regions involved in emotional reactivity, such as the amygdala and regions involved in cognitive control, including the frontal cortex. For unknown reasons, these effects appear idiosyncratic; most AAS users display few behavioral effects, but a minority develops severe effects.
Conclusion and Scientific Significance
Professionals encountering AAS users in clinical or forensic settings should be alert to the possibility of AAS‐induced violence or criminality and should employ strategies to assess whether AAS is indeed a contributory factor in a given case. Further research is needed to elucidate the mechanism of AAS‐induced violence and to explain why only a subset of AAS users appears vulnerable to these effects. (Am J Addict 2021;00:00–00)
The use of image and performance enhancing drugs (IPEDs), such as anabolic-androgenic steroids to grow muscle mass, is a growing public health concern in the UK and across the globe. An important indicator is the rapid rise of people who inject steroids accessing needle and syringe programmes (NSPs). However, NSP workers and other health professionals often report having a lack of knowledge regarding IPEDs, and not feeling confident when engaging with this group. Adding to this is a lack of evidence-based educational/training materials, making it difficult for health professionals to improve their skills in this area. Using a participatory action research approach (PAR), we collaborated with health professionals who had experience in working with this client group (n=52), particularly NSP staff, to address this knowledge gap. Consistent with our PAR approach, health professionals were involved in all stages of this research, from establishing the research questions through to disseminating the findings. To identify current best practices, a workshop was organised to collaboratively determine approaches to improve professional development in this area and to ultimately facilitate better engagement with people who use IPEDs. The participating health professionals described issues and solutions in relation to the collection of clinical data, staff training, client contact and service provision – with community engagement being mentioned as a key element to improve and create awareness of health services, and to strengthen community partnerships. By adopting a PAR approach, we have co-produced guidance on effective engagement with consumers that is both evidence-based and experience-informed.
The anabolic-androgenic steroids (AAS) are a family of hormones that comprise the natural male hormone testosterone and its many synthetic relatives. Once used almost exclusively by elite athletes, AAS have now spread to the general population, with some tens of millions of users worldwide. Contrary to popular belief, most AAS users are not competitive athletes, but take these drugs simply to gain muscle. Because widespread AAS use did not arise until the 1980s in the United States and about a decade or more later in other countries, even the oldest AAS users – individuals who started AAS as youths in the 1980s or 1990s – are only now reaching middle age. Thus, the long-term adverse effects of AAS are only beginning to be recognized, as more individuals enter the age of risk for these effects.
Introduction: Anabolic-androgenic steroids are one of the powerful drugs that cause long-term hormonal and psychological changes that can have a wide range of side effects for the athletes.
Objective: The purpose of this study was to compare the Behavioral Activation-Inhibition Systems and Sense of Coherence in Bodybuilders with and without Use Anabolic-Androgenic Steroids.
Materials and Methods: The method of this research is descriptive - comparative. The statistical population consisted of all bodybuilders with and without taking anabolic-androgenic steroids in Rasht in 2019, of which 140 individuals (70 natural bodybuilders and 70 steroids bodybuilders) were selected purposefully and included questionnaires of Carver & White (1994) behavioral activation-inhibition systems and sense of coherence Antonovsky (1993) responded by the participants. Data were analyzed using multivariate analysis of variance by SPSS 24.
Results: The findings of the present study showed that there was a significant difference between the two groups in the activation/inhibition system and the sense of coherence (P<0.01). Compared with natural bodybuilders, steroid bodybuilders had less behavioral inhibition (15.95) and sense of coherence (18.87) and more behavioral activation systems (37.77).
Conclusion: According to the results, we suggest that bodybuilders who have used steroids derivatives have many irreversible problems in their cognitive and physical functions. Therefore, coaches need to pay more attention to the psychological problems of the athletes and examine them before competitions.
Anabolic androgenic steroids (AASs) are prescribed for medical conditions related to low testosterone. Abuse of AASs has surged as they become recognised as potent image enhancement drugs. The primary goal of most abusers is to obtain a more attractive outward appearance. Abuse is complex. There are a vast range of AAS substances illegally available, the nature of their true composition is difficult to evaluate. Users follow dosing patterns which incorporate a number of different AASs, in addition to other pharmaceutical substances believed to complement the desired physical effects or manage unwanted effects. Animal work and medical case reports suggest potential to cause serious hepatotoxicity, plus possible neurotoxicity, nephrotoxicity and damage to the cardiovascular and reproductive systems. As the long‐term AASs users reach maturity, further controlled experimentation, with larger sample sizes, is required. Data gathering should be directed towards the most vulnerable group of AAS users, females and adolescent boys.
Background
Sport-related concussions (SRCs) are known to have short-term effects on cognitive processes, which can result in diverse clinical presentations. The long-term effects of SRC and repeated exposure to head impacts that do not result in SRC on specific cognitive health outcomes remain unclear.
Objectives
To synthesize and appraise the evidence base regarding cognitive health in living retired athletes with a history of head-impact exposure or SRC.
Data Sources
A systematic search of the EMBASE, PsycINFO, MEDLINE/PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science databases was conducted from inception to April 2018 using common key words and medical subject headings related to 3 components: (1) the participant (eg, retired athlete), (2) the primary outcome measure (eg, cognitive test used), and (3) the secondary outcome measure (eg, history of sport concussion).
Study Selection
Cross-sectional studies of living retired male or female athletes in which at least 1 cognitive test was used as an outcome measure were included. Two reviewers independently screened studies.
Data Extraction
Data extraction was performed using Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Methodologic quality was assessed independently by 2 reviewers using the Downs and Black tool.
Data Synthesis
The search yielded 46 cross-sectional observational studies that were included in a qualitative synthesis. Most included studies (80%, n = 37) were published in the 5 years before our review. A large proportion of these studies (n = 20) included retired American National Football League players. The other research investigated professional, university, high school, and amateur retired athletes participating in sports such as American and Australian football, boxing, field and ice hockey, rugby and soccer. The total sample consisted of 13 975 participants: 7387 collision-sport athletes, 662 contact-sport athletes, 3346 noncontact-sport athletes, and 2580 participants classified as controls. Compared with control participants or normative data, retired athletes display worse performance on 17 of 31 studies (55%) of memory), 6 of 11 studies (55%) of executive function, and 4 of 6 studies (67%) of psychomotor function and increased subjective concerns about cognitive function in 11 of 14 studies (79%). The authors of 13 of 46 investigations (28%) reported a frequency-response relationship, with poorer cognitive outcomes in athletes who had greater levels of exposure to head impacts or concussions. However, these results must be interpreted in light of the lack of methodologic rigor and moderate quality assessment of the included studies.
Conclusions
Evidence of poorer cognitive health among retired athletes with a history of concussion and head-impact exposure is evolving. Our results suggest that a history of SRC may more greatly affect the cognitive domains of memory, executive function, and psychomotor function. Retired athletes appeared to have increased self-reported cognitive difficulties, but the paucity of high-quality, prospective studies limited the conclusions that could be drawn regarding a cause-and-effect relationship between concussion and long-term health outcomes. Future researchers should consider a range of cognitive health outcomes, as well as premorbid ability, in diverse samples of athletes with or without a history of concussion or head-impact exposure to delineate the long-term effects of sport participation on cognitive functioning.
Over the past decade, the use of steroid medications has increased among athletes, especially bodybuilders who work professionally. Therefore, the present study was conducted to compare the dark trait personality and behavioral activation-inhibition system in bodybuilders with and without the use of anabolic-androgenic steroids. The present study was descriptive and casual-comparative. The statistical population of the study consisted of all male bodybuilders of Rasht in 2019. A sample of 150 (75 natural bodybuilders and 75 steroid bodybuilders) was selected purposefully, and then data were collected using Jonson & Webster (2010) personality dark trait questionnaire and Carver & White (1994) behavioral activation-inhibition system. Data were analyzed using multivariate analysis of variance. The results showed that there is a significant difference in the dark trait of personality and behavioral activation-inhibition system bodybuilders' with and without the use of anabolic-androgenic steroids. Based on this, it was found that steroid bodybuilders have a lower system of inhibition and a more active behavioral system than natural bodybuilders. Also, in the components of dark character traits, steroid bodybuilders showed more Narcissism, Machiavellianism and Psychopathy. According to the results, it is possible to control the activation/inhibition system and reduce the dark trait of personality in steroid bodybuilders by implementing programs and interventions.
Our goal is to understand the consequences of anabolic-androgenic steroid (AAS) abuse on cognitive function, using rats as a model. There is relatively little research on how AAS abuse impacts cognition. In the present study, rats were tested for their ability to use contextual information to guide decision-making in biconditional discrimination. The Stroop task is a classic human test for contextual decision-making. In rodents, biconditional discrimination challenges subjects to use contextual cues in the operant chamber to resolve the correct lever response when auditory and visual cues are incongruent. The hypothesis is that chronic high-dose testosterone impairs biconditional discrimination. Rats were trained in 24 trials/day over 14 days, in alternating sessions with each environment. On a flat floor with houselight illuminated, auditory cues (clicker vs tone) signified the active lever. On a barred floor with no light, visual cues from 2 stimulus lights (constant vs blinking) identified the active lever. Rats treated chronically with testosterone (7.5 mg/kg) were unimpaired in task acquisition, and all rats learned to select the correct lever in response to auditory or visual cues. During extinction, controls made significantly more correct than incorrect responses in congruent trials (p < 0.05 by paired t-test), but testosterone-treated rats failed to show a similar preference. This was reflected by significant interactions of drug x cue agreement (F1,18 = 5.21, p < 0.05) and drug x cue agreement x response accuracy (F1,18 = 8.95, p < 0.05). These results suggest that testosterone impairs cognitive flexibility, and demonstrates potential for AAS abuse to impair cognitive function in humans.
In 1935, testosterone was finally isolated and synthesized, and testosterone-analogs soon entered the world of sports. Today, the use of these performance-enhancing agents is no longer confined to the elite sports milieu, and the lifetime prevalence of anabolic steroid use among men is estimated to be around 6%. Unfortunately, these drugs are not without side effects, and the most common somatic adverse drug reactions are gynaecomastia, infertility, testicular dysfunction, and acne. Furthermore, the use of AAS is associated with a variety of psychiatric disorders and antisocial behaviour.
Background:
The use of Anabolic-Androgenic Steroids (AAS) has been associated with increased aggressiveness and violent behavior. We therefore investigated the proposed correlation between the use of AAS and criminality while controlling for important socio-economics covariates and for psychiatric comorbidity.
Methods:
The primary endpoints were prison sentences, and time to first prison sentence. A retrospective matched cohort study design consisting of 545 males, who tested positive for AAS in Danish gyms during the period January 3, 2006 to January 31, 2017. They were matched with 5450 randomly chosen male controls. Data were cross-referenced with national register information on education, employment status, substance abuse and psychiatric comorbidity. In addition, 638 males sanctioned because they rejected to participate in the doping control and 6380 controls were used as a replication cohort.
Results:
Already at baseline, 20.6% of the AAS users had a previous prison sentence whereas the rate was 3.7% in the control cohort (p < 0.0001). During the follow-up period the cumulative prevalence increased to 29.5% and 4.9%, respectively (unadjusted HR 9.15, 95% CI 6.33-13.20). The associations remained highly significant after controlling for socio-economic factors, drug abuse and psychiatric comorbidity. The results could be replicated in a similar cohort.
Conclusion:
Our study shows that AAS users have a 9-fold increased risk of being convicted of a crime compared to matched controls, randomly chosen from the general population. This association could not be explained by common socioeconomic factors or by psychiatric comorbidity.
AimsTo assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use.DesignCross-sectional, naturalistic.SettingOutpatient facility.ParticipantsTwenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiologic testosterone replacement, leaving 19 untreated users for the numerical comparisons below.MeasurementsThe Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations, and the International Index of Erectile Function (IIEF).FindingsCompared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes (estimated difference [95% confidence interval (CI)]: 2.3 [0.1, 4.5] ml; p = 0.042) and lower serum testosterone levels (estimated difference: 131 [25, 227] dL; p = 0.009), with five users showing testosterone levels below 200 ng/dL despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF Sexual Desire subscale (estimated difference: 2.4 [1.3, 3.5] points on a 10-point scale; p < 0.001). In the overall group of 24 treated plus untreated former users, 7 (29%) had experienced major depressive episodes during AAS withdrawal; 4 of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment.Conclusions
Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged, and associated with substantial morbidity. This article is protected by copyright. All rights reserved.
Several models have proposed that different medial temporal lobe (MTL) regions represent different kinds of information in the service of long-term memory. For instance, it has been proposed that perirhinal cortex (PRC), parahippocampal cortex (PHC), and hippocampus differentially support long-term memory for item information, spatial context, and item-context relations present during an event, respectively. Recent evidence has indicated that, in addition to long-term memory, MTL subregions may similarly contribute to processes that support the retention of complex spatial arrangements of objects across short delays. Here, we used functional magnetic resonance imaging and multivoxel pattern similarity analysis to investigate the extent to which human MTL regions independently code for object and spatial information, as well as the conjunction of this information, during working memory encoding and active maintenance. Voxel activity patterns in PRC, temporopolar cortex, and amygdala carried information about individual objects, whereas activity patterns in the PHC and posterior hippocampus carried information about the configuration of spatial locations that was to be remembered. Additionally, the integrity of multivoxel patterns in the right anterior hippocampus across encoding and delay periods was predictive of accurate short-term memory for object-location relationships. These results are consistent with parallel processing of item and spatial context information by PRC and PHC, respectively, and the binding of item and context by the hippocampus.
A growing translational literature suggests that adolescent exposure to anabolic-androgenic steroids (AASs) leads to increased aggression and impulsivity. However, little is known about the cognitive effects of AASs among AAS users or the differences between adolescent- and adult-onset users. This study provides a test of the effects of acute naturalistic AAS use and age of onset (adolescent vs. adult) on measures of inhibitory control, planning and attention, and decision making. Seventy-one active adult male AAS users completed self-report measures of impulsivity and aggression, and a subsample (11 adolescent onset vs. 11 adult onset) matched on current age were administered 4 computerized tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) (Cambridge Cognition, 2002) and the Iowa Gambling Task (Stanton, Liening, & Schultheiss, 2011). Multiple regression analyses and a series of 2 (adolescent vs. adult) × 2 (on-cycle vs. off-cycle) analyses of variance (ANOVAs) were used to examine the differential effects of age of onset and acute drug use on cognition and behavior. Regression analyses revealed larger on-cycle effects for adolescent users than adult users. Subsample analyses indicated that on-cycle users performed less well on cognitive measures of inhibitory control and attention, but not on tests of planning or decision making. Adolescent onset was associated with greater impulsivity and more acute sensitivity to AAS effects on attention. These preliminary findings suggest the possibility that acute AAS use is associated with some differences in inhibitory control and impulsivity and to a lesser degree, aggression. These effects may be more potent for those initiating AAS use in adolescence. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
In spite of the high prevalence of performance-enhancing drug (PED) use, media attention has focused almost entirely on PED use by elite athletes in order to illicitly gain a competitive advantage in sports, and not on the health risks of PEDs. There is a widespread misperception that PED use is safe or that adverse effects are manageable. In reality, the vast majority of PED users are not athletes but rather non-athlete weightlifters, and the adverse health effects of PED use are greatly underappreciated. This scientific statement synthesizes available information on the medical consequences of PED use, identifies gaps in knowledge, and aims to focus the attention of the medical community and policymakers on PED use as an important public health problem. PED users frequently consume highly supraphysiologic doses of PEDs, combine them with other PEDs and/or other classical drugs of abuse, and display additional associated risk factors. PED use has been linked to an increased risk of death and a wide variety of cardiovascular, psychiatric, metabolic, endocrine, neurologic, infectious, hepatic, renal, and musculoskeletal disorders. As randomized trials cannot ethically duplicate the large doses of PEDs and the many factors associated with PED use, we need observational studies to collect valid outcome data on the health risks associated with PEDs. In addition, we need studies regarding the prevalence of PED use, the mechanisms by which PEDs exert their adverse health effects, and the interactive effects of PEDs with sports injuries and other high-risk behaviors. We also need randomized trials to assess therapeutic interventions for treating the adverse effects of PEDs-such as the anabolic-androgen steroid withdrawal syndrome. Finally, we need to raise public awareness of the serious health consequences of PEDs.
Huntington disease is characterized by neuronal aggregates and inclusions containing polyglutamine-expanded huntingtin protein
and peptide fragments (polyQ-Htt). We have used an established cell-based assay employing a PC12 cell line overexpressing
truncated exon 1 of Htt with a 103-residue polyQ expansion that yields polyQ-Htt aggregates to investigate the fate of polyQ-Htt-drug
complexes. scyllo-Inositol is an endogenous inositol stereoisomer known to inhibit accumulation and toxicity of the amyloid-β peptide and α-synuclein.
In light of these properties, we investigated the effect of scyllo-inositol on polyQ-Htt accumulation. We show that scyllo-inositol lowered the number of visible polyQ-Htt aggregates and robustly decreased polyQ-Htt protein abundance without concomitant
cellular toxicity. We found that scyllo-inositol-induced polyQ-Htt reduction was by rescue of degradation pathways mediated by the lysosome and by the proteasome
but not autophagosomes. The rescue of degradation pathways was not a direct result of scyllo-inositol on the lysosome or proteasome but due to scyllo-inositol-induced reduction in mutant polyQ-Htt protein levels.
Smaller hippocampal volume is reported in Major Depressive Disorder (MDD). We hypothesize it may be related to fewer granule neurons (GN) in the dentate gyrus (DG), a defect possibly reversible with antidepressants. We studied age-, sex-, and postmortem interval-matched groups: no major psychopathology (controls); unmedicated-MDD; and MDD treated with serotonin reuptake inhibitors (MDD*SSRI) or tricyclics (MDD*TCA). Frozen right hippocampi were fixed, sectioned (50 μm), immunostained with neuronal nuclear marker (NeuN), and counterstained with hematoxylin. GN and glial number, and DG and granule cell layer (GCL) volumes were stereologically estimated. Fewer GNs in the anterior DG were present in unmedicated-MDDs compared with controls (p=0.013). Younger age of MDD onset correlated with fewer GNs (p=0.021). Unmedicated-MDDs had fewer mid-DG GNs than MDD*SSRIs (p=0.028) and controls (p=0.032). Anterior GCL glial number did not differ between groups. Anterior/mid GCL volume was smaller in unmedicated-MDDs vs controls (p=0.008) and larger in MDD*SSRIs vs unmedicated-MDDs (p<0.001), MDD*TCAs (p<0.001), and controls (p<0.001). Anterior GCL volume and GN number (r=0.594, p=0.001), and mid DG volume and GN number (r=0.398, p=0.044) were correlated. Anterior DG capillary density correlated with GN number (p=0.027), and with GCL (p=0.024) and DG (r=0.400, p=0.047) volumes. Posterior DG volume and GN number did not differ between groups. Fewer GNs in unmedicated-MDD without fewer neuronal progenitor cells, as previously reported, suggests a cell maturation or survival defect, perhaps related to MDD duration. This may contribute to a smaller hippocampus and is potentially reversed by SSRIs. Postmortem studies are correlative and animal studies are needed to test implied causal relationships.Neuropsychopharmacology accepted article preview online, 7 January 2013; doi:10.1038/npp.2013.5.
Studies aimed at identifying structural brain alterations associated with persistent violent behavior or psychopathy have not adequately accounted for a lifetime history of substance misuse. Thus, alterations in gray matter (GM) volume that have been reported to be correlates of violent behavior and/or psychopathy may instead be related to lifelong substance use disorders (SUDs).
To identify alterations in GM volume associated with violent behavior and those associated with lifelong SUDs.
Cross-sectional study.
Participants were recruited from penitentiaries, forensic hospitals, psychiatric outpatient services, and communities in Germany. Structural magnetic resonance imaging was performed at a university hospital.
Four groups of men were compared: 12 men with SUDs who exhibited violent behavior (hereafter referred to as violent offenders), 12 violent offenders without SUDs, 13 men with SUDs who did not exhibit violent behavior (hereafter referred to as nonoffenders), and 14 nonoffenders without SUDs.
Voxel-based morphometry was used to analyze high-resolution magnetic resonance imaging scans. Assessments of mental disorders, psychopathy (using the Psychopathy Checklist-Screening Version), aggressive behavior, and impulsivity were conducted by trained clinicians.
Compared with nonoffenders, violent offenders presented with a larger GM volume in the amygdala bilaterally, the left nucleus accumbens, and the right caudate head and with less GM volume in the left insula. Men with SUDs exhibited a smaller GM volume in the orbitofrontal cortex, ventromedial prefrontal cortex, and premotor cortex than did men without SUDs. Regression analyses indicated that the alterations in GM volume that distinguished the violent offenders from nonoffenders were associated with psychopathy scores and scores for lifelong aggressive behavior. The GM volumes of the orbitofrontal cortex and prefrontal cortex that distinguished the men with SUDs from the men without SUDs were correlated with scores for response inhibition.
These findings suggest that a greater GM volume in the mesolimbic reward system may be associated with violent behavior and that reduced GM volumes in the prefrontal cortex, orbitofrontal cortex, and premotor area characterize men with SUDs.
Sex steroids are essential for reproduction and development in animals and humans, and sex steroids also play an important role in neuroprotection following brain injury. New data indicate that sex-specific responses to brain injury occur at the cellular and molecular levels. This review summarizes the current understanding of neuroprotection by sex steroids, particularly estrogen, androgen, and progesterone, based on both in vitro and in vivo studies. Better understanding of the role of sex steroids under physiological and pathological conditions will help us to develop novel effective therapeutic strategies for brain injury.
A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n=10); from a larger study on prescription opioid dependent patients (n=133)] and matched healthy individuals (n=10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure and function.
Although illicit anabolic-androgenic steroid (AAS) use is widespread, the cardiac effects of long-term AAS use remain inadequately characterized. We compared cardiac parameters in weightlifters reporting long-term AAS use to those in otherwise similar weightlifters without prior AAS exposure.
We performed 2D tissue-Doppler and speckle-tracking echocardiography to assess left ventricular (LV) ejection fraction, LV systolic strain, and conventional indices of diastolic function in long-term AAS users (n=12) and otherwise similar AAS nonusers (n=7). AAS users (median [quartile 1, quartile 3] cumulative lifetime AAS exposure, 468 [169, 520] weeks) closely resembled nonusers in age, prior duration of weightlifting, and current intensity of weight training. LV structural parameters were similar between the two groups; however, AAS users had significantly lower LV ejection fraction (50.6% [48.4, 53.6] versus 59.1% [58.0%, 61.7%]; P=0.003 by two-tailed Wilcoxon rank sum test), longitudinal strain (16.9% [14.0%, 19.0%] versus 21.0% [20.2%, 22.9%]; P=0.004), and radial strain (38.3% [28.5%, 43.7%] versus 50.1% [44.3%, 61.8%]; P=0.02). Ten of the 12 AAS users showed LV ejection fractions below the accepted limit of normal (>or=55%). AAS users also demonstrated decreased diastolic function compared to nonusers as evidenced by a markedly lower early peak tissue velocity (7.4 [6.8, 7.9] cm/s versus 9.9 [8.3, 10.5] cm/s; P=0.005) and early-to-late diastolic filling ratio (0.93 [0.88, 1.39] versus 1.80 [1.48, 2.00]; P=0.003).
Cardiac dysfunction in long-term AAS users appears to be more severe than previously reported and may be sufficient to increase the risk of heart failure.
Glutamatergic abnormalities may underlie bipolar disorder (BD). The glutamate-modulating drug riluzole may be efficacious in bipolar depression, but few in vivo studies have examined its effect on glutamatergic neurotransmission. We conducted an exploratory study of the effect of riluzole on brain glutamine/glutamate (Gln/Glu) ratios and levels of N-acetylaspartate (NAA). We administered open-label riluzole 100-200 mg daily for 6 weeks to 14 patients with bipolar depression and obtained imaging data from 8-cm(3) voxels in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) at baseline, day 2, and week 6 of treatment, using two-dimensional J-resolved proton magnetic resonance spectroscopy at 4 T. Imaging data were analyzed using the spectral-fitting package, LCModel; statistical analysis used random effects mixed models. Riluzole significantly reduced Hamilton Depression Rating Scale (HAM-D) scores (d=3.4; p<0.001). Gln/Glu ratios increased significantly by day 2 of riluzole treatment (Cohen's d=1.2; p=0.023). NAA levels increased significantly from baseline to week 6 (d=1.2; p=0.035). Reduction in HAM-D scores was positively associated with increases in NAA from baseline to week 6 in the ACC (d=1.4; p=0.053), but was negatively associated in the POC (d=9.6; p<0.001). Riluzole seems to rapidly increase Gln/Glu ratios-suggesting increased glutamate-glutamine cycling, which may subsequently enhance neuronal plasticity and reduce depressive symptoms. Further investigation of the Gln/Glu ratio as a possible early biomarker of response to glutamate-modulating therapies is warranted.
Some, although not all, studies report small hippocampal volume in patients with major depressive disorder (MDD) relative to healthy controls. Here, we explore the contribution of key demographic and clinical variables to this difference.
We used meta-analytic techniques to provide an updated analysis of data from 32 magnetic resonance imaging studies of hippocampal volume in patients with MDD.
Our analysis confirmed the difference in hippocampal volume, but only among patients with MDD whose duration of illness was longer than 2 years or who had more than 1 disease episode. We found no such effect in studies that included patients who did not fit these criteria. The effect was limited to children and middle-aged or older adults. Analyzed collectively, studies including young adult patients showed equivalent hippocampal volumes across MDD patients and controls, a result that may be attributable to a reduced burden of illness in this population. Age at onset of disease, severity of depression at the time of scanning, sex and slice thickness did not contribute to differences in hippocampal volume between patients with MDD and controls.
The small size of many of the clinical and demographic subgroups may have limited statistical power to detect between-group differences.
Although all studies were cross-sectional, our results suggest that hippocampal volume reductions generally occur after disease onset in patients with MDD. These findings have implications for the timing of clinical interventions aimed at reducing the impact of MDD on neuronal structure and function.
The development of novel treatments for Alzheimer's disease (AD), aimed at ameliorating symptoms and modifying disease processes, increases the need for early diagnosis. Neuropsychological deficits such as poor episodic memory are a consistent feature of early-in-the-course AD, but they overlap with the cognitive impairments in other disorders such as depression, making differential diagnosis difficult. Computerised and traditional tests of memory, attention and executive function were given to four subject groups: mild AD (n = 26); questionable dementia (QD; n = 43); major depression (n = 37) and healthy controls (n = 39). A visuo-spatial associative learning test accurately distinguished AD from de-pressed/control subjects and revealed an apparent subgroup of QD patients who performed like AD patients. QD patients' performance correlated with the degree of subsequent global cognitive decline. Elements of con-textual and cued recall may account for the task's sensitivity and specificity for AD.
Background
Many patients with Parkinson disease (PD) suffer from nonmotor symptoms including depression, anxiety, sexual dysfunction, decreased energy level, and an overall decline in quality of life. Comorbid depression, hypothyroidism, and sleep disorders may account for some, but not all, of these problems. Testosterone deficiency affects 20% to 25% of males over the age of 60 years in the general population and may cause signs and symptoms of the nonmotor symptoms seen in PD. We observed numerous patients with PD whose nonmotor symptoms were refractory to treatment.
Objective
To determine whether treatment of comorbid testosterone deficiency in male patients with PD can lead to improvements in refractory nonmotor symptoms.
Methods
Case studies were reviewed of the first 5 male patients who had PD with symptoms of testosterone deficiency who were treated in our clinic. All patients had low serum testosterone levels. Screening for testosterone deficiency symptoms using the St Louis Testosterone Deficiency Questionnaire was performed for 4 of the 5 patients. Additionally, to assess the prevalence of PD, total testosterone levels in 68 patients in our PD registry were sent for evaluation.
Results
Following testosterone replacement therapy, all 5 patients experienced significant improvements in their refractory nonmotor symptoms. Of 68 male patients with PD enrolled in our PD registry, 24 (35%) had plasma evidence of testosterone deficiency. We also noted that the risk of testosterone deficiency per decade was found to increase 2.8-fold per decade (P<.001), paralleling that which is found in the general elderly male population.
Conclusions
The findings from this study reveal the heretofore unrecognized high prevalence of testosterone deficiency in elderly male patients with PD similar to that found in the general population. These symptoms, which may be refractory to antidepressants, anxiolytics, and antiparkinsonian medications, may respond to treatment with testosterone. More rigorous controlled studies will need to be undertaken to examine the treatment of this common comorbidity in male patients with PD.
Objective.
—To evaluate the acute effects of anabolic steroids on mood and behavior in male normal volunteers.Design.
—A 2-week, double-blind (subject and rater), fixed-order, placebo-controlled crossover trial of methyltestosterone.Setting.
—An inpatient research unit at the National Institutes of Health.Subjects.
—A volunteer sample of 20 men who were medication free, free of medical and psychiatric illness, not involved in athletic training, and had no prior history of anabolic steroid use.Intervention.
—A sequential trial for 3 days each of the following four drug conditions: placebo baseline, low-dose methyltestosterone (40 mg/d), high-dose methyltestosterone (240 mg/d), and placebo withdrawal.Main Outcome Measures.
—Mood and behavioral ratings were completed during each drug condition and included both subjective and objective measures.Results.
—Significant (P<.05) albeit subtle increases in symptom scores were observed during high-dose methyltestosterone administration compared with baseline in positive mood (euphoria, energy, and sexual arousal), negative mood (irritability, mood swings, violent feelings, and hostility), and cognitive impairment (distractibility, forgetfulness, and confusion). An acute manic episode was observed in one of the 20 subjects, representing a 5% incidence, even under these conservative conditions. An additional subject became hypomanic. Baseline characteristics including family psychiatric history or previous drug abuse did not predict symptom changes.Conclusion.
—This is the first placebo-controlled prospective study demonstrating the adverse and activating mood and behavioral effects of anabolic steroids.(JAMA. 1993;269:2760-2764)
Background:
We sought to expand on preliminary findings suggesting that anabolic-androgenic steroids produce psychiatric effects in some athletes who use them.Methods:
We compared 88 athletes who were using steroids with 68 nonusers, using the Structured Clinical Interview for DSM-III-R to diagnose psychiatric syndromes occurring in association with steroid use (if applicable) and in the absence of steroid use. Demographic, medical, and laboratory measures were also performed.Results:
Steroid users displayed more frequent gynecomastia, decreased mean testicular length, and higher cholesterol—high-density lipoprotein ratios than nonusers. Most strikingly, 23% of steroid users reported major mood syndromes—mania, hypomania, or major depression—in association with steroid use. Steroid users displayed mood disorders during steroid exposure significantly more frequently than in the absence of steroid exposure (P<.001) and significantly more frequently than nonusers (P<.01). Users rarely abused other drugs simultaneously with steroids.Conclusion:
Major mood disturbances associated with anabolic-androgenic steroids may represent an important public health problem for athletes using steroids and sometimes for the victims of their irritability and aggression.
Both genetic and environmental factors contribute to neurodegenerative disorders. In a large number of neurodegenerative diseases (for example, Alzheimer's disease (AD)), patients do not carry the mutant genes. Other risk factors, for example the environmental factors, should be evaluated. 17β-trenbolone is a kind of environmental hormone as well as an anabolic-androgenic steroid. 17β-trenbolone is used as a growth promoter for livestock in the USA. Also, a large portion of recreational exercisers inject 17β-trenbolone in large doses and for very long time to increase muscle and strength. 17β-trenbolone is stable in the environment after being excreted. In the present study, 17β-trenbolone was administered to adult and pregnant rats and the primary hippocampal neurons. 17β-trenbolone's distribution and its effects on serum hormone levels and Aβ42 accumulation in vivo and its effects on AD related parameters in vitro were assessed. 17β-trenbolone accumulated in adult rat brain, especially in hippocampus, and in the fetus brain. It altered Aβ42 accumulation. 17β-trenbolone induced apoptosis of primary hippocampal neurons in vitro and resisted neuroprotective function of testosterone. Presenilin-1 protein expression was down-regulated while β-amyloid peptide 42 (Aβ42) production and caspase-3 activities were increased. Both androgen and estrogen receptors mediated the processes. 17β-trenbolone played critical roles in neurodegeneration. Exercisers who inject large doses of trenbolone and common people who are exposed to 17β-trenbolone by various ways are all influenced chronically and continually. Identification of such environmental risk factors will help us take early prevention measure to slow down onset of neurodegenerative disorders.
Copyright © 2014. Published by Elsevier Inc.
Nandrolone decanoate (ND), an anabolic androgenic steroid (AAS), induces an aggressive phenotype by mechanisms involving glutamate-induced N-methyl-D-aspartate receptor (NMDAr) hyperexcitability. The astrocytic glutamate transporters remove excessive glutamate surrounding the synapse. However, the impact of supraphysiological doses of ND on glutamate transporters activity remains elusive. We investigated whether ND-induced aggressive behavior is interconnected with GLT-1 activity, glutamate levels and abnormal NMDAr responses. Two-months-old untreated male mice (CF1, n=20) were tested for baseline aggressive behavior in the resident-intruder test. Another group of mice (n=188) were injected with ND (15 mg/kg) or vehicle for 4, 11 and 19 days (short-, mid- and long-term endpoints, respectively) and were evaluated in the resident-intruder test. Each endpoint was assessed for GLT-1 expression and glutamate uptake activity in the frontoparietal cortex and hippocampal tissues. Only the long-term ND endpoint significantly decreased the latency to first attack and increased the number of attacks, which was associated with decreased GLT-1 expression and glutamate uptake activity in both brain areas. These alterations may affect extracellular glutamate levels and receptor excitability. Resident males were assessed for hippocampal glutamate levels via microdialysis both prior to, and following, the introduction of intruders. Long-term ND mice displayed significant increases in the microdialysate glutamate levels only after exposure to intruders. A single intraperitoneal dose of the NMDAr antagonists, memantine or MK-801, shortly before the intruder test decreased aggressive behavior. In summary, long-term ND-induced aggressive behavior is associated with decreased extracellular glutamate clearance and NMDAr hyperexcitability, emphasizing the role of this receptor in mediating aggression mechanisms.
Background
Previous research suggests that testosterone (T) plays a key role in shaping competitive and aggressive behavior in humans, possibly by modulating threat-related neural circuitry. However, this research has been limited by the use of T augmentation that fails to account for baseline differences and has been conducted exclusively in women. Thus, the extent to which normal physiologic concentrations of T affect threat-related brain function in men remains unknown.
Method
In the current study, we use a novel two-step pharmacologic challenge protocol to overcome these limitations and to evaluate causal modulation of threat- and aggression-related neural circuits by T in healthy young men (n =16). First, we controlled for baseline differences in T through administration of a gonadotropin releasing hormone (GnRH) antagonist. Once a common baseline was established across participants, we then administered T to within the normal physiologic range. During this second step of the protocol we acquired functional neuroimaging data to examine the impact of T augmentation on neural circuitry supporting threat and aggression.
Results
GnRH antagonism successfully reduced circulating concentrations of T and brought subjects to a common baseline. Administration of T rapidly (within 30 minutes) increased circulating T concentrations and was associated with heightened reactivity of the amygdala, hypothalamus, and periaqueductal grey to angry facial expressions.
Conclusion
These findings provide novel causal evidence that T rapidly potentiates the response of neural circuits mediating threat processing and aggressive behavior in men.
Reports an error in the original article by L. R. Squire (Psychological Review, 1992[Apr], Vol 99[2], 195–231). The caption for Figure 7 was incorrect. The corrected caption is given. (The following abstract of this article originally appeared in record 1992-26428-001.) Considers the role of the hippocampus in memory function. A central thesis involving work with rats, monkeys, and humans (which has sometimes seemed to proceed independently in 3 separate literatures) is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented that proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in the neocortex that together represent a whole memory. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Purpose:
The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered.
Materials and methods:
We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy.
Results:
Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001).
Conclusions:
Prior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men.
Background:
Millions of individuals worldwide have used anabolic-androgenic steroids (AAS) to gain muscle or improve athletic performance. Recently, in vitro investigations have suggested that supraphysiologic AAS doses cause apoptosis of neuronal cells. These findings raise the possibility, apparently still untested, that humans using high-dose AAS might eventually develop cognitive deficits.
Methods:
We administered five cognitive tests from the computerized CANTAB battery (Pattern Recognition Memory, Verbal Recognition Memory, Paired Associates Learning, Choice Reaction Time, and Rapid Visual Information Processing) to 31 male AAS users and 13 non-AAS-using weightlifters age 29-55, recruited and studied in May 2012 in Middlesbrough, UK. Testers were blinded to participants' AAS status and other historical data.
Results:
Long-term AAS users showed no significant differences from nonusers on measures of response speed, sustained attention, and verbal memory. On visuospatial memory, however, AAS users performed significantly more poorly than nonusers, and within the user group, visuospatial performance showed a significant negative correlation with total lifetime AAS dose. These were large effects: on Pattern Recognition Memory, long-term AAS users underperformed nonusers by almost one standard deviation, based on normative population scores (adjusted mean difference in z-scores=0.89; p=0.036), and performance on this test declined markedly with increasing lifetime AAS dose (adjusted change in z-score=-0.13 per 100g of lifetime AAS dose; p=0.002). These results remained stable in sensitivity analyses addressing potential confounding factors.
Conclusions:
These preliminary findings raise the ominous possibility that long-term high-dose AAS exposure may cause cognitive deficits, notably in visuospatial memory.
Chronic exposure to the anabolic androgenic steroids (AAS) nandrolone decanoate (ND) in supra-physiological doses is associated with learning and memory impairments. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we examined whether voluntary exercise would improve the cognitive deficits induced by chronic administration of ND. We also investigated the effects of ND and voluntary exercise on hippocampal BDNF levels. The rats were randomly distributed into 4 experimental groups: the vehicle-sedentary group, the ND-sedentary group, the vehicle-exercise group, and the ND-exercise group. The vehicle-exercise and the ND-exercise groups were allowed to freely exercise in a running wheel for 15days. The vehicle-sedentary and the ND-sedentary groups were kept sedentary for the same period. Vehicle or ND injections were started 14days prior to the voluntary exercise and continued throughout the 15days of voluntary exercise. After the 15-day period, the rats were trained and tested on a water maze spatial task using four trials per day for 5 consecutive days followed by a probe trial two days later. Exercise significantly improved performance during both the training and retention of the water maze task, and enhanced hippocampal BDNF. ND impaired spatial learning and memory, and this effect was not rescued by exercise. ND also potentiated the exercise-induced increase in hippocampal BDNF levels. These results seem to indicate that voluntary exercise is unable to improve the disruption of cognitive functions by chronic ND. Moreover, increased levels of BDNF may play a role in ND-induced impairments in learning and memory. The harmful effects of ND and other AAS on learning and memory should be taken into account when athletes decide to use AAS for performance or body image improvement.
Anabolic-androgenic steroids (AAS) are used in the medical treatment of many disorders. Erythropoietin (EPO) is a hematopoietic cytokine that has anti-apoptotic, anti-oxidative, and anti-inflammatory effects. The aim of the present study is to investigate the neuroprotective effects of EPO in the hippocampus, parietal cortex and prefrontal cortex, in brain damage due to nandrolone decanoate. 35 Wistar male rats were randomly divided into: (1) control group, (2) sham group, (3) nandrolone decanoate group (ND, intramuscular, 10mg/(kgweek), 8 weeks), (4) ND+low dose EPO treated group (ND+L-EPO) and (5) ND+high dose EPO treated group (ND+H-EPO). EPO was administrated by intraperitoneal injection at a dose of 100U/(kgday) for L-EPO treatment and at a dose of 500U/(kgday) for H-EPO treatment during 8 weeks. The number of neurons of CA1, CA2, CA3 and dentate gyrus of hippocampus, parietal cortex and prefrontal cortex were significantly less in the ND group compared with the control group. Treatment with H-EPO significantly preserved the number of neurons in hippocampus when compared with ND administrated. Besides, H-EPO treatment decreased the number of TUNEL-positive and active caspase-3 positive cells and MDA levels and increased GPx levels when compared to ND group. In conclusion, abuse of AAS causes reduction in the number of neurons in hippocampus, parietal cortex and prefrontal cortex regions and increases oxidative damage and therefore H-EPO may be useful as a neuroprotective agent in brain injury.
Purpose:
Anabolic androgenic steroids (AAS) are synthetic androgen-like compounds that are abused in sport communities despite their adverse effects. Nerve growth factor (NGF) influences neuronal differentiation and survival, and it also mediates higher brain functions such as learning and memory. Changes in NGF expression have been implicated in neurodegenerative disorders, including Alzheimer disease. Hence, we decided to study the effect of chronic AAS exposure on brain NGF profile, NGF-dependent cholinergic function, and related behavioral performance.
Methods:
Male Wistar rats were injected for 4 wk with either nandrolone or stanozolol at daily doses (5.0 mg·kg(-1), s.c.) that are considered equivalent to those abused by humans. NGF levels and NGF receptor (TrkA and p75NTR) expression were measured in the hippocampus and in the basal forebrain. Choline acetyltransferase expression was evaluated in basal forebrain. Spatial learning and memory were assessed using the Morris water maze.
Results:
AAS treatment caused region-specific changes in the expression of NGF and its receptors. Both nandrolone and stanozolol increased NGF levels in the hippocampus and reduced NGF levels in the basal forebrain, reduced p75NTR expression in the hippocampus, and failed to affect TrkA expression in the basal forebrain. Finally, AAS treatment reduced the expression of choline acetyltransferase in the basal forebrain and impaired the behavioral performance in the Morris water maze.
Conclusion:
The evidence that supraphysiological doses of AAS cause neurotrophic unbalance and related behavioral disturbances raises the concern that AAS abuse in humans may affect mechanisms that lie at the core of neuronal plasticity.
The LCModel method analyzes an in vivo spectrum as a Linear Combination of Model spectra of metabolite solutions in vitro. By using complete model spectra, rather than just individual resonances, maximum information and uniqueness are incorporated into the analysis. A constrained regularization method accounts for differences in phase, baseline, and lineshapes between the in vitro and in vivo spectra, and estimates the metabolite concentrations and their uncertainties. LCModel is fully automatic in that the only input is the time-domain in vivo data. The lack of subjective interaction should help the exchange and comparison of results. More than 3000 human brain STEAM spectra from patients and healthy volunteers have been analyzed with LCModel. N-acetylaspartate, cholines, creatines, myo-inositol, and glutamate can be reliably determined, and abnormal levels of these or elevated levels of lactate, alanine, scyllo-inositol, glutamine, or glucose clearly indicate numerous pathologies. A computer program will be available.
A polyclonal antibody, PA1, raised in a rabbit against fusion proteins containing fragments of the human prostatic androgen receptor (AR) was used to map the distribution of AR-like immunoreactivity in the brains of adult male and female cynomolgus monkeys. PA1 AR-immunoreactive (ARir) labeling occurred in the cell nuclei and, more weakly, in the cytoplasm of brain cells. The PA1 ARir labeling occurred primarily in brain regions previously shown on the basis of gonadal steroid autoradiography to contain androgen receptors. However, the distribution of PA1 ARir staining was substantially more restricted than that of autoradiographic labeling using 3H-androgens. The pattern of PA1 ARir labeling was closely similar between animals and occurred in the lateral septum, medial preoptic area, bed nucleus of stria terminalis, anterior, cortical, accessory basal and medial amygdala, several hypothalamic nuclei including the supraoptic, anterior, paraventricular, ventromedial and arcuate nuclei, and the premammillary nucleus. No significant sex differences were observed. With the exception of the supraoptic nucleus, reported not to be labeled by autoradiography, earlier autoradiographic findings and the current immunocytochemical results, although not congruent, have noteworthy similarities.
The posterodorsal medial amygdala (MePD) exhibits numerous sex differences including differences in volume and in the number and morphology of neurons and astroctyes. In adulthood, gonadal hormones, including both androgens and estrogens, have been shown to play a role in maintaining the masculine character of many of these sex differences, but whether adult gonadal hormones maintain the increased number and complexity of astrocytes in the male MePD was unknown. To answer this question we examined astrocytes in the MePD of male and female Long Evans rats that were gonadectomized as adults and treated for 30 days with either testosterone or a control treatment. At the end of treatment brains were collected and immunostained for glial fibrillary acidic protein. Stereological analysis revealed that adult androgen levels influenced the number and complexity of astrocytes in the MePD of both sexes, but the specific effects of androgens were different in males and females. However, sex differences in the number and complexity of adult astrocytes persisted even in the absence of gonadal hormones in adulthood, suggesting that androgens also act earlier in life to determine these adult sex differences. Using immunofluorescence and confocal microscopy, we found robust androgen receptor immunostaining in a subpopulation of MePD astrocytes, suggesting that testosterone may act directly on MePD astrocytes to influence their structure and function.
Illicit anabolic-androgenic steroid (AAS) use, for body building and body image purposes, is increasing internationally. This study describes the prevalence and symptoms of AAS use disorders obtained using a semi-structured interview among a mixed-gender sample of 100 current Australian users, that were recruited from a variety of sources. The median age of the sample was 27 years and 94% were male. The full range of DSM IV symptoms of AAS abuse and dependence were reported and over three quarters (78%) of the sample exhibited at least one symptom of abuse or dependence on AAS. A total of 23% of the participants qualified for a diagnosis of AAS dependence using DSM IV criteria and a further 25% met criteria for AAS abuse. There were no gender differences in AAS abuse or dependence diagnoses. The only variable related to an AAS substance use disorder was reporting the experience of AAS-related aggression, which may be a useful clinical indicator of the disorder.
This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD).
A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n =84) to placebo (n =82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups.
The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p =0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF Aβx-42 was decreased significantly compared to placebo (p =0.009).
Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD. Classification of evidence: Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005.
Anabolic androgenic steroid (AAS) abuse has increased among athletes in recent years. However, AAS abuse can increase hypercoagulopathy and cause cerebrovascular disease. We report a case of a 27-year-old man who had right hemiparalysis, hemianopia, dysarthria, and double vision in the middle of muscle training. He suspected acute disseminated encephalomyelitis at first, because of a preceding respiratory infection. However, extensive work-up was performed, including brain magnetic resonance imaging, transcranial Doppler and transesophageal echocardiography, confirming the final diagnosis of cardioembolic stroke. Physicians should be aware that cerebrovascular disease may be a side effect of AAS, even in younger populations.
Illicit anabolic-androgenic steroid (AAS) abuse, though an important public health problem, remains inadequately studied. Almost all AAS abusers are male and lift weights, but the risk factors for AAS use among male weightlifters remain poorly understood.
We recruited 233 experienced male weightlifters, of whom 102 (44%) reported lifetime AAS use, and assessed their childhood and adolescent attributes retrospectively, using structured clinical interviews and computerized questionnaires. This cross-sectional cohort approach-a design that we have formally presented in the recent methodological literature-utilizes a study cohort, not selected for outcomes of interest, and assesses exposures and outcomes retrospectively. We hypothesized that conduct disorder and body-image concerns would be major risk factors for subsequent AAS use among male weightlifters.
Within our study population, many attributes showed little association with AAS use, but conduct disorder and body-image concerns showed strong associations. For individuals with prior conduct disorder versus those without, the hazard ratio (95% confidence interval) for subsequent AAS use was 2.2 (1.5, 3.4). For individuals in the middle versus lowest tertile of scores on a retrospective adolescent muscle-dysmorphia scale, the hazard ratio was 1.5 (.84, 2.6); for the highest versus lowest tertile, the hazard ratio was 3.3 (2.0, 5.3); and for the linear trend of hazard ratios, p < .001.
Conduct disorder and body-image concerns represent important risk factors for AAS use among male weightlifters. Thus, assessment of these attributes may help to identify individuals most likely to require interventions to discourage this form of substance abuse.
Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High-resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. Regional changes in gray matter volume were assessed on the whole brain using tensor-based morphometry, and those significant regional changes were then independently tested for correlation with morphine dosage. Thirteen regions evidenced significant volumetric change, and degree of change in several of the regions was correlated with morphine dosage. Dosage-correlated volumetric decrease was observed primarily in the right amygdala. Dosage-correlated volumetric increase was seen in the right hypothalamus, left inferior frontal gyrus, right ventral posterior cingulate, and right caudal pons. Follow-up scans that were conducted an average of 4.7 months after cessation of opioids demonstrated many of the morphine-induced changes to be persistent. In a separate study, 9 individuals consuming blinded placebo capsules for 6 weeks evidenced no significant morphologic changes over time. The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward- and affect-processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid-induced gray matter changes.
Anabolic-androgenic steroid (AAS) abuse is associated with multiple neurobehavioral disturbances. The sites of action and the neurobiological sequels of AAS abuse are unclear at present. We investigated whether two different AASs, nandrolone and methandrostenolone, could affect neuronal survival in culture. The endogenous androgenic steroid testosterone was used for comparison. Both testosterone and nandrolone were neurotoxic at micromolar concentrations, and their effects were prevented by blockade of androgen receptors (ARs) with flutamide. Neuronal toxicity developed only over a 48-hr exposure to the steroids. The cell-impermeable analogues testosterone-BSA and nandrolone-BSA, which preferentially target membrane-associated ARs, were also neurotoxic in a time-dependent and flutamide-sensitive manner. Testosterone-BSA and nandrolone-BSA were more potent than their parent compounds, suggesting that membrane-associated ARs were the relevant sites for the neurotoxic actions of the steroids. Unlike testosterone and nandrolone, toxicity by methandrostenolone and methandrostenolone-BSA was insensitive to flutamide, but it was prevented by the glucocorticoid receptor (GR) antagonist RU-486. Methandrostenolone-BSA was more potent than the parent compound, suggesting that its toxicity relied on the preferential activation of putative membrane-associated GRs. Consistently with the evidence that membrane-associated GRs can mediate rapid effects, a brief challenge with methandrostenolone-BSA was able to promote neuronal toxicity. Activation of putative membrane steroid receptors by nontoxic (nanomolar) concentrations of either nandrolone-BSA or methandrostenolone-BSA became sufficient to increase neuronal susceptibility to the apoptotic stimulus provided by β-amyloid (the main culprit of AD). We speculate that AAS abuse might facilitate the onset or progression of neurodegenerative diseases not usually linked to drug abuse.
The aim of this study was to improve our understanding of the proposed association between anabolic-androgenic steroids (AAS) and criminality.
The study was based on interviews and criminality data involving 32 users of AAS who had sought treatment for AAS-related problems at a psychiatric addiction clinic in Sweden. A score derived from the number of crimes, their level of severity and the relevant time periods was computed to allow comparisons between subgroups sorted according to type and timing of drug use.
The criminal activity level increased for 69% of the individuals after having started to use drugs. This was particularly obvious in the group who had started its involvement with drugs by using AAS. Crimes of violence and weapon offences showed a great increase in incidence after drug use had been initiated. The study also showed a significant decrease in criminality after treatment, particularly among individuals who had started their drug use with AAS.
The results suggest that there is an association between the use of AAS and criminality, especially with regard to crimes of violence and weapon offences, and that this criminality may be enhanced when AAS are combined with other drugs of abuse.
Because many visuospatial memory tests do not reliably detect right medial temporal lobe (MTL) dysfunction, we developed a novel object recognition test using complex three-dimensional stimuli. To influence encoding strategy, half the stimuli were multicolored (color towers) and accompanied by verbally based instructions, and half were gray (gray towers) and accompanied by visuospatially based instructions. In Experiment 1, healthy subjects completed the test while performing verbal or visuospatial interference tasks or without interference. In Experiment 2, patients with unilateral amygdalohippocampectomies for intractable epilepsy completed the test without interference. Results suggest that color tower recognition was partially dependent on verbal processing and sensitive to MTL lesions in general. Recognition of gray towers was reliant on visuospatial processing, and the decay in accuracy after a delay was sensitive and specific to right MTL lesions. These findings suggest that test stimuli such as three-dimensional objects can be useful in assessing right MTL dysfunction.
Artifacts in functional magnetic resonance imaging (fMRI) data, primarily those related to motion and physiological sources, negatively impact the functional signal-to-noise ratio in fMRI studies, even after conventional fMRI preprocessing. Independent component analysis' demonstrated capacity to separate sources of neural signal, structured noise, and random noise into separate components might be utilized in improved procedures to remove artifacts from fMRI data. Such procedures require a method for labeling independent components (ICs) as representing artifacts to be removed or neural signals of interest to be spared. Visual inspection is often considered an accurate method for such labeling as well as a standard to which automated labeling methods are compared. However, detailed descriptions of methods for visual inspection of ICs are lacking in the literature. Here we describe the details of, and the rationale for, an operationalized fMRI data denoising procedure that involves visual inspection of ICs (96% inter-rater agreement). We estimate that dozens of subjects/sessions can be processed within a few hours using the described method of visual inspection. Our hope is that continued scientific discussion of and testing of visual inspection methods will lead to the development of improved, cost-effective fMRI denoising procedures.
Activation of the anterior cingulate cortex (ACC) in a spatial working memory task has been associated with risk factors for alcohol use disorders such as low alcohol effects and positive alcohol expectations in adolescents. To transfer these results into adults, we used the same task in adults.
During functional magnetic resonance imaging, 12 light social, 7 heavy social, and 11 non-abstinent-dependent alcohol drinkers performed a spatial working memory task and completed measures of automatic alcohol-related thoughts and behavior (Obsessive-Compulsive Drinking Scale-OCDS), alcohol use of the last 90 days, and general intelligence.
Behavioral performance in the spatial working memory task was not significantly different in all 3 groups. Controlling for differences in general intelligence alcohol-dependent participants showed a higher task-related activation of the dorsal ACC (dACC) in comparison with light and heavy social drinkers. Measures of the OCDS were positively correlated with the activation in the left hippocampus and right thalamus in all participants.
Our results support the findings of increased dACC activation during a spatial working memory task as a risk factor for alcohol dependence. Increased task-related activation in the dACC was only observed in alcohol-dependent participants and not in heavy social drinkers with comparable alcohol consumption. Furthermore, the absence of behavioral performance differences between groups as well as an association between dACC activation and working memory performance indicates subtle working memory deficits. Low capacity of working memory has been linked to more automatic and less self-regulated behavior in studies on natural reward processing. Therefore, additional neural activation during performance of the non-alcohol-related working memory task in participants with higher OCDS values in the left hippocampus and the right thalamus may be a consequence of decreased neural capacity because of distracting alcohol-related thoughts.
The misuse of anabolic androgenic steroids has in several reports been associated with effects resulting in altered behavior. This study used the Morris water maze task to investigate the effect of high doses of the anabolic androgenic steroid nandrolone on spatial learning and memory in male rats. During the experiment, we observed a significantly impaired Morris water maze performance in the nandrolone-treated rats compared with controls. The hippocampus, a brain region associated with cognitive function, was analyzed for mRNA expression of prodynorphin, the precursor of dynorphinergic peptides. The results indicated that the transcription levels of prodynorphin were significantly elevated in the animals treated with nandrolone compared with controls. Thus, the findings suggest that administration of nandrolone to male rats impairs memory function, possibly via dynorphinergic actions.
Alpha-synuclein (ASYN) is central in Parkinson's disease pathogenesis. Converging pieces of evidence suggest that the levels of ASYN expression play a critical role in both familial and sporadic Parkinson's disease. To elucidate the mechanism underlying wild type (WT) ASYN-mediated neurotoxicity, we have generated a novel Tet-Off SHSY-5Y cell line, conditionally expressing WT ASYN. Induction of human WT ASYN in retinoic acid-differentiated SHSY-5Y cells leads to accumulation of soluble ASYN oligomers, in the absence of inclusions, and to gradual cellular degeneration. Morphologically, the death observed is non-apoptotic. Caspases other than caspase 3, including caspase 9, are activated and caspase inhibition diminishes death by acting at a point upstream of cytochrome c release. Application of Scyllo-inositol, an oligomer-stabilizing compound, prevents neuronal death in this model. These findings are consistent with a model in which oligomeric ASYN triggers the initial activation of the apoptotic pathway, which is however blocked downstream of the mitochondrial checkpoint, thus leading to a death combining in a unique fashion both apoptotic and non-apoptotic features. This novel inducible cell model system may prove valuable in the deciphering of WT ASYN-induced pathogenic effects and in the assessment and screening of potential therapeutic strategies.
A two-dimensional, J-resolved magnetic resonance spectroscopic extraction approach was developed employing GAMMA-simulated, LCModel basis-sets. In this approach, a two-dimensional J-resolved (2D-JPRESS) dataset was resolved into a series of one-dimensional spectra where each spectrum was modeled and fitted with its theoretically customized LCModel template. Metabolite levels were derived from the total integral across the J-series of spectra for each metabolite. Phantoms containing physiologic concentrations of the major brain chemicals were used for validation. Varying concentrations of glutamate and glutamine were evaluated at and around their accepted in vivo concentrations in order to compare the accuracy and precision of our method with 30 ms PRESS. We also assessed 2D-JPRESS and 30 ms PRESS in vivo, in a single voxel within the parieto-occipital cortex by scanning ten healthy volunteers once and a single healthy volunteer over nine repeated measures. Phantom studies demonstrated that serial fitting of 2D-JPRESS spectra with simulated LCModel basis sets provided accurate concentration estimates for common metabolites including glutamate and glutamine. Our in vivo results using 2D-JPRESS suggested superior reproducibility in measuring glutamine and glutamate relative to 30 ms PRESS. These novel methods have clear implications for clinical and research studies seeking to understand neurochemical dysfunction.
Acute phencyclidine (PCP) administration mimics some aspects of schizophrenia in rats, such as behavioral alterations, increased dopaminergic activity and prefrontal cortex dysfunction. In this study, we used single-voxel (1)H-MRS to investigate neurochemical changes in rat prefrontal cortex in vivo before and after an acute injection of PCP. A short-echo time sequence (STEAM) was used to acquire spectra in a 32-microL voxel positioned in the prefrontal cortex area of 12 rats anesthetized with isoflurane. Data were acquired for 30 min before and for 140 min after a bolus of PCP (10 mg/kg, n = 6) or saline (n = 6). Metabolites were quantified with the LCModel. Time courses for 14 metabolites were obtained with a temporal resolution of 10 min. The glutamine/glutamate ratio was significantly increased after PCP injection (p < 0.0001, pre- vs. post-injection), while the total concentration of these two metabolites remained constant. Glucose was transiently increased (+70%) while lactate decreased after the injection (both p < 0.0001). Lactate, but not glucose and glutamine, returned to baseline levels after 140 min. These results show that an acute injection of PCP leads to changes in glutamate and glutamine concentrations, similar to what has been observed in schizophrenic patients, and after ketamine administration in humans. MRS studies of this pharmacological rat model may be useful for assessing the effects of potential anti-psychotic drugs in vivo.
Neuroimaging studies have documented modulation of the activity of the amygdala - a key node in the neural network underlying emotion perception and processing, and one that has also been associated with regulating aggression - by exogenous testosterone. However, results on the impact of normal range testosterone levels on explicit emotion recognition as a prerequisite for social interaction and amygdala activation in healthy young males are missing. Hence, we performed functional MRI at 3T in a group of 21 healthy males during explicit emotion recognition with a protocol specifically optimized to reliably detect amygdala activation. We observed similar amygdala activation to all emotions presented without any effect of gender of poser or laterality. Reaction times to fearful male faces were found negatively correlated to testosterone concentration, while no significant effects emerged for other emotions and neutral expressions. Correlation analyses revealed a significant positive association between testosterone levels and amygdala response to fearful and angry facial expressions, but not to other expressions. Hence, our results demonstrate that testosterone levels affect amygdala activation and also behavioral responses particularly to threat-related emotions in healthy young males. We conclude that these findings add to our understanding of emotion processing and its modulation by neuroendocrine factors.
The amygdala is composed of structurally and functionally distinct nuclei that contribute to the processing of emotion through interactions with other subcortical and cortical structures. While these circuits have been studied extensively in animals, human neuroimaging investigations of amygdala-based networks have typically considered the amygdala as a single structure, which likely masks contributions of individual amygdala subdivisions. The present study uses resting state functional magnetic resonance imaging (fMRI) to test whether distinct functional connectivity patterns, like those observed in animal studies, can be detected across three amygdala subdivisions: laterobasal, centromedial, and superficial. In a sample of 65 healthy adults, voxelwise regression analyses demonstrated positively-predicted ventral and negatively-predicted dorsal networks associated with the total amygdala, consistent with previous animal and human studies. Investigation of individual amygdala subdivisions revealed distinct differences in connectivity patterns within the amygdala and throughout the brain. Spontaneous activity in the laterobasal subdivision predicted activity in temporal and frontal regions, while activity in the centromedial nuclei predicted activity primarily in striatum. Activity in the superficial subdivision positively predicted activity throughout the limbic lobe. These findings suggest that resting state fMRI can be used to investigate human amygdala networks at a greater level of detail than previously appreciated, allowing for the further advancement of translational models.
The glutamate-glutamine cycle between neurons and glia is tightly related to excitatory glutamatergic and inhibitory GABAergic regulation in brain. The role of this neuron-astrocyte cross-talk on the neurotoxicity induced by amphetamines is not understood. Also, the impact of neurotoxic doses of amphetamines on the balance between glutamatergic and GABAergic circuits is largely unknown. The aim of this work was to assess the acute effect of a neurotoxic regimen of amphetamine (AMPH) on glutamine (GLN, an astrocytic marker) levels and on glutamine/glutamate (an index for glutamate-glutamine cycle) and GABA/glutamate ratios in rat brain. Sprague-Dawley rats were sacrificed 4 and 24 h after a single-dose regimen of AMPH (30 mg/kg, i.p.), and the caudate-putamen (CPu), frontal cortex (FC), and hippocampus (Hp) were dissected for analysis of glutamate (GLU), gamma-aminobutyric acid (GABA), and GLN. The total content of these amino acids was measured using a microbore HPLC electrochemical detector. Although AMPH did not change GLU levels, it increased both GLN content and GLN/GLU ratio (160-469%) at 4 h, but not at 24 h, in all regions after injection. Striatal GABA levels and GABA/GLU ratio were increased (46 and 100%, respectively) at 24 h. In hippocampus the GABA/GLU increase (60%) occurred as early as 4 h after treatment. To the contrary, AMPH exerted no effect in GABA/GLU balance in frontal cortex. These data strongly suggest that this neurotoxic AMPH regimen provoked an early increase in the glutamate-glutamine cycle between neurons and glia. This increase may ultimately lead to an upregulation of the inhibitory system as a compensatory response.
Rodent and monkey research has shown that ketamine can induce accelerated programmed nerve cell death (apoptosis) when administered in high doses, for prolonged periods, or both. Concern about similar neurotoxicity with human therapeutic use has prompted ongoing investigations by the Food and Drug Administration and National Institutes of Health. If the results of these inquiries are unfavorable to ketamine, such action could ultimately lead to restricted availability of this drug or even its discontinuation from the market. This article discusses the limitations of the published animal research, the challenges in extrapolating such data to humans, the need for further animal and human investigations, and the potential adverse effect on current clinical practice that might result, should the use of ketamine be restricted or the drug removed from the market.