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Schematic representation of oxytocinergic (OT; solid black) and mesocorticolimbic dopaminergic (DA; dashed blue) pathways. DA is synthesized in ventral tegmental area (VTA) and projects to nucleus accumbens (NAcc) and amygdala (Amyg) as well as prefrontal cortex (PFC). OT, which is synthesized in paraventricular nucleus (PVN), projects to key limbic sites on the DA pathway (VTA, NAcc, and Amyg), thus potentially allowing it to modulate DA activity. We note that while only neurotransmitter effects of OT are illustrated here, neuromodulatory effects via OT diffusion through extracellular space may also play a role in these processes. Via PFC, which is densely interconnected with many other regions of the brain (dark red solid lines), motivational factors may be able to influence attention and perception (see for review 79 ). Brain art adapted from illustrations created by Patrick Lynch, medical illustrator, and C. Carl Jaffe, MD, cardiologist (available at https://commons.wikimedia.org/wiki/File:Brain_human_lateral_view.svg and https://commons. wikimedia.org/wiki/File:Brain_human_sagittal_section.svg) and licensed under a Creative Commons Attribution 2.5 Generic License, 2006 (CC BY 2.5).
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Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social p...
Citations
... A recent randomized controlled trial (RCT) however did not show any significant effects between the OXT and placebo group in aberrant behavior, social communication, or cognition [86]. At the neural networks level, it has been shown that intranasal OXT leads to increased activation in the brain regions known to be involved in perceiving and thinking about social-emotional information and enhances effective connectivity between nodes of the brain's reward and socioemotional processing systems [87,88]. There were no noted side effects in these studies on children with ASD, thus far, although animal studies have raised the possibility of increased basal OXT levels with long-term OXT administration; the clinical effects of this being unclear. ...
... ABA is the gold standard for treating social deficits in ASD, but it can require upwards of 40 h per week to be effective (Eldevik et al., 2010;Linstead et al., 2017). Administering oxytocin immediately prior to ABA might improve the efficacy and efficiency of therapy by enhancing the salience of the therapeutic social information (Gordon et al., 2013(Gordon et al., , 2016Shamay-Tsoory and Abu-Akel, 2016;Xue et al., 2020), increasing the signal-to-noise ratio of that information as it is processed in the brain (Oettl et al., 2016;Froemke and Young, 2021), and accelerating learning by promoting synaptic plasticity at a molecular level (Dölen et al., 2013;Rajamani et al., 2018;Nardou et al., 2019;Froemke and Young, 2021). Notably, the goal of oxytocin-enhanced ABA therapy would not be to improve social behavior transiently through direct and immediate pharmacological activity, but rather to improve behavior more permanently by using oxytocin to enhance the learning and neural rewiring that occurs during behavioral therapy . ...
... Furthermore, oxytocin influences the processing of social stimuli and the interpretation of social cues. It enhances social information's salience and reward value, making social stimuli more rewarding and reinforcing social bonding [21-25, [67][68][69][70][71][72]. Oxytocin also modulates the activity of brain regions involved in empathy and social cognition, promoting the understanding of others' emotions and intentions [73][74][75][76][77]. ...
Epilepsy is a neurological disorder characterised by recurrent seizures, which can significantly impact patients' quality of life. While current management strategies for epilepsy, such as antiepileptic drugs and surgery, are effective for many patients, there is a need for novel therapies that can provide better seizure control and improve patients' outcomes. Oxytocin, a neuropeptide known for its role in social bonding and trust, has emerged as a promising therapy for epilepsy. Preclinical studies have shown that oxytocin can reduce seizure activity and improve seizure outcomes in animal models of epilepsy. In contrast, clinical studies have suggested that oxytocin may reduce seizure frequency and severity in some epilepsy patients. This chapter reviews the current knowledge of oxytocin and epilepsy, including the potential mechanisms of oxytocin's antiepileptic effects, the limitations and challenges of clinical studies, and future research directions and implications. The chapter also discusses the broader impact of oxytocin research on understanding social behaviour and neurological disorders. Overall, the chapter highlights the potential of oxytocin as a novel therapy for epilepsy management and underscores the need for further research.
... Furthermore, cortical activity was greater in brain regions surrounding the right posterior superior temporal sulcus, and functional connectivity between prefrontal lobes (e.g., ventral prefrontal and orbitofrontal) and the limbic reward system was enhanced in these individuals. These changes appear to enhance a patient's interest in social information and pleasure rewards [28,29], which may explain why oxytocin is effective in treating core symptoms of ASD children. ...
Purpose
The purpose of this article is to examine the efficacy of oxytocin in treating core symptoms of autism spectrum disorder (ASD) with children.
Methods
A systematic literature search was conducted to identify randomized controlled trials (RCTs) of oxytocin for the treatment of core symptoms in children with ASD. The search included studies published between January 1, 1999 and March 15, 2023, that were randomized, single or double-blinded, and included a placebo control group. Standard screening rules were applied to select relevant studies, resulting in the inclusion of five RCTs involving 486 children with ASD.
Results
Ultimately, a total of five RCTs, involving 486 children with ASD, were included in the review using standard screening rules.One of the included studies demonstrated a statistically significant improvement in Social Responsiveness Scale (SRS) and Repetitive Behavior Scale-Revised (RBS) scores when children with ASD were treated with oxytocin (24 IU/2 days for 6 weeks). The improvement in core symptoms persisted at the 6-month follow-up. The meta-analysis findings suggested that oxytocin might have a moderate effect in improving the core symptom of narrow interests and repetitive stereotyped behaviors in children with ASD.
Conclusion
While the therapeutic value of oxytocin in treating core symptoms of ASD in children is not fully established, the results of this meta-analysis indicate a potential moderate effect. However, further studies with larger sample sizes and more robust RCTs are needed to directly demonstrate the efficacy of oxytocin. Future research should also focus on effect size and outcome evaluation accuracy while minimizing bias in RCT experiments.
... 139,140 These effects on eye gaze have led to the study of intranasal oxytocin in the treatment of autism. [141][142][143] Oxytocin is one of the few drugs that have been tested to improve social motivation in schizophrenia. Intranasal oxytocin has been assessed in relation to several symptoms of schizophrenia, including deficits in social cognition and social motivation. ...
Background and hypothesis:
Diminished social motivation is a negative symptom of schizophrenia and leads to severe functional consequences for many patients suffering from the illness. However, there are no effective medications available to treat this symptom. Despite the lack of approved treatments for patients, there is a growing body of literature on the effects of several classes of drugs on social motivation in healthy volunteers that may be relevant to patients. The aim of this review is to synthesize these results in an effort to identify novel directions for the development of medications to treat reduced social motivation in schizophrenia.
Study design:
In this article, we review pharmacologic challenge studies addressing the acute effects of psychoactive drugs on social motivation in healthy volunteers and consider how these findings may be applied to deficits in social motivation in schizophrenia. We include studies testing amphetamines and 3,4-methylenedioxymethamphetamine (MDMA), opioids, cannabis, serotonergic psychedelics, antidepressants, benzodiazepines, and neuropeptides.
Study results:
We report that amphetamines, MDMA, and some opioid medications enhance social motivation in healthy adults and may represent promising avenues of investigation in schizophrenia.
Conclusions:
Given the acute effects of these drugs on behavioral and performance-based measures of social motivation in healthy volunteers, they may be particularly beneficial as an adjunct to psychosocial training programs in patient populations. It remains to be determined how these medications affect patients with deficits in social motivation, and in which contexts they may be most effectively administered.
... Over the years, technological progress has made it possible to measure the cerebral effects of psychotropic substances. fMRI has already been used in people with ASD, to study the brain effects of riluzole, propranolol and oxytocin during cognitive tasks [23, 83,84]. MRS has been already used to determine alteration in E/I dynamics in BG and dorsomedial prefrontal cortex (DMPFC) [24]. ...
... The present work advances our understanding of the social neuroscience of music, which is an emerging area of research that examines the social processes related to music and the human brain (Greenberg et al., 2021). When we consider the extensive overlap between the dopamine and oxytocin circuitry and the bidirectional interactions between the two systems, as both influence each other during social processes and have projections to the mPFC (Baskerville et al., 2009;Baskerville & Douglas, 2010;Buijs et al., 1984;Gordon et al., 2016), we can begin to expand our understanding of the network underlying social interactions involving improvisation. The potential interactions between oxytocin and dopamine during improvised drumming may likely enhance the feel-good aspects of connecting to others and contribute to socially motivated functioning and a shared sense of groupishness (Baskerville & Douglas, 2010;Gordon et al., 2011). ...
Improvisation is a natural occurring phenomenon that is central to social interaction. Yet, improvisation is an understudied area in group processes and intergroup relations. Here we build on theory and research about human herding to study the contributions of improvisation on group efficacy and its biobehavioral underpinnings. We employed a novel multimodal approach and integrative method when observing face-to-face interactions-51 triads (total N = 153) drummed together in spontaneous-free improvisations as a group, while their electrodermal activity was monitored simultaneously with their second-by-second rhythmic coordination on a shared electronic drum machine. Our results show that three hypothesized factors of human herding-physiological synchrony, behavioral coordination, and emotional contagion-predict a sense of group efficacy in its group members. These findings are some of the first to show herding at three levels (physiological, behavioral, and mental) in a single study and lay a basis for understanding the role of improvisation in social interaction.
... see refs. [20,28,39,40]). Therefore, to better understand the neurobiological correlates of adaptive behaviour and outcome, here we examined them both cross-sectionally and longitudinally, i.e. across time and age, and in relation to neurotypicals. Our results suggest that a change in adaptive behaviour is paralleled by not only cross-sectional but also longitudinal neuroanatomical variation. ...
Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6–30 years), with two assessment time points separated by ~12–24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.
... Wskazuje na to szereg badań przedklinicznych [54,55] oraz klinicznych [56,57]. Donosowa administracja OT poprawia umiejętności związane z poznaniem społecznym [58], a kontakty społeczne są jednym z czynników warunkujących uwalnianie OT [59]. Interneuronalny poziom OT jest ponadto ściśle powiązany z nastawieniem na poszukiwanie wsparcia oraz z umiejętnością korzystania z oferowanej pomocy [60]. ...
Introduction:
Fragile X syndrome is rare genetic aberration, causing intelectual disability
and, in some cases, autism manifestations. Children, especially males, with genetic
aberration have problems with eye fixation, psychomotor hyperactivity and inadequate stress
response. Therapy including pharmacotherapy of autism is still controversial and it is a very
hard task, requiring interdisciplinary approach. One of promising substances, involved in the
social functions in mammals is the neuropeptide — oxytocin. This peptide is responsible for
creation of social relation, bonding, regulation of neurohormonal axes and anxiety. Aim of the
study was analysis and display of literature data focusing on oxytocin administration in the
therapy of autism in individuals with fragile X syndrome.
Presentation of data: Innovative pharmacotherapy with oxytocin relies on intransal
application and provides promising therapeutic outcome, allevating autism symptoms. So far,
one successful clinical trial was performed with this method in patients with fragile X
syndrome.
Summary: Series of clinical studies focusing on effectivity of oxytocin in various
manifestations of autism indicate, that this direction of pharmacotherapy is valid and it
should be still developed, also in individuals with genetic syndromes.
... In patients with marked social impairments pharmacological modulation of the coupling between VS and MFG has been associated with improved computation of future positive social outcomes (I. Gordon et al., 2016;Greene et al., 2018), and effects on this circuit may thus reflect a potential mechanism via which losartan can increase social motivation. ...
Social deficits and dysregulations in dopaminergic midbrain-striato-frontal circuits represent transdiagnostic symptoms across psychiatric disorders. Animal models suggest that interactions between the dopamine (DA) and renin-angiotensin system (RAS) may modulate learning and reward-related processes. The present study therefore examined the behavioral and neural effects of the Angiotensin II type 1 receptor (AT1R) antagonist losartan on social reward and punishment processing in humans. A preregistered randomized double-blind placebo-controlled between-subject pharmacological design was combined with a social incentive delay (SID) functional MRI (fMRI) paradigm during which subjects could avoid social punishment or gain social reward. Healthy volunteers received a single-dose of losartan (50 mg, n = 43, female = 17) or placebo (n = 44, female = 20). We evaluated reaction times (RTs) and emotional ratings as behavioral and activation and functional connectivity as neural outcomes. Relative to placebo, losartan modulated the reaction time and arousal differences between social punishment and social reward. On the neural level the losartan-enhanced motivational salience of social rewards was accompanied by stronger ventral striatum-prefrontal connectivity during reward anticipation. Losartan increased the reward-neutral difference in the ventral tegmental area (VTA) and attenuated VTA associated connectivity with the bilateral insula in response to punishment during the outcome phase. Thus, losartan modulated approach-avoidance motivation and emotional salience during social punishment versus social reward via modulating distinct core nodes of the midbrain-striato-frontal circuits. The findings document a modulatory role of the renin-angiotensin system in these circuits and associated social processes, suggesting a promising treatment target to alleviate social dysregulations.
