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Omega-3 fatty acids improve behavioral coping to stress in multiparous rats
... This deficient diet reduced brain n-3FAs in dams [22,23] and neonates [17]. In our previous study, supplemented dams exhibited an increased ability to cope with stress when compared to deficient dams [24]. In the current study, pups from the dams used in [24] were weaned to a diet containing adequate n-3FA levels for 5 weeks prior to behavioral testing. ...
... In our previous study, supplemented dams exhibited an increased ability to cope with stress when compared to deficient dams [24]. In the current study, pups from the dams used in [24] were weaned to a diet containing adequate n-3FA levels for 5 weeks prior to behavioral testing. Because n-3FA levels were altered solely in the maternal diet but not in the pup diet after weaning, we could isolate behaviors potentially altered by maternal n-3FA ...
... Pups were housed with their dams until weaning at 21 days. Male pups from the second gestation of dams in [24] were used. Pups were from separate litters. ...
Objective:
Previously, we showed that consumption of a diet supplemented with omega-3 polyunsaturated fatty acids (n-3FAs) for two rounds of gestation and lactation increased the ability of rat dams to cope with stress when compared to dams that ingested a diet lacking n-3FAs. The objective of this study was to determine if the diets of these dams affected the behavior of their pups later in life. To isolate the neurodevelopmental effects of n-3FAs, pups from the second gestation were weaned to a diet adequate in n-3FAs. Pup testing began at 8 weeks of age and consisted of the forced swim, open field, and hole board tests to examine depression-related behavior, reaction to novelty, and learning and memory, respectively.
Results:
Given the considerable difference in the n-3FA content of the maternal diet, we expected a large effect size, however with the exception of rearing duration, maternal diet did not affect behavior in any of the tests conducted. These results suggest that maternal n-3FA supplementation during neurodevelopment likely does not affect offspring behavior when a diet adequate in n-3FA is provided post-weaning. Rather, we hypothesize that brain n-3FAs at the time of testing confer altered behavior and corroborate the need for additional research.
... Therefore, in the current study, ω-3 supplementation could also have decreased habituation time and consequent exploratory behaviour in the OFT of OM3 treatment groups, thereby presenting as decreased locomotor activity (Fig. 4A). Nevertheless, increased adaptive coping behaviour has been observed in ω-3 supplemented rodents [98], possibly due to enhanced neurogenesis and neuroplasticity [99]. However, no significant changes were observed in the hippocampal BDNF concentrations (i.e. a marker of neuroplasticity) of OM3-treated PND35 rats in the current study (Fig. 6C), so that neuroplasticity does not seem to play a key role in the observations of the current study. ...
... As such, data from the current study indicated no antidepressive-like effect of pre-pubertal OM3 treatment in either age group (PND35; Fig. 5A or PND60; Fig. 5B), after controlling for the overall reduction in general locomotor activity (implementing the two-way ANCOVAs analyses, similar to anxiety-like data described above). These results are in line with previous reports in pubertal [109] and older animals [98]. ...
Background
Major depressive disorder (MDD) affects children and adolescents, yet treatment is limited to only fluoxetine and escitalopram, with venlafaxine being a popular 'off-label' option. Based on preliminary evidence, and purported improved saftey profiles, non-pharmacological interventions, such as omega-3 essential fatty acid (n-3 EFA) supplementation and exercise have been investigated for their possible antidepressant augmentation properties. Both these interventions beneficially affect numerous MDD-associated neurobiological processes, yet the exact mechanisms remain unknown. Nevertheless, similar to antidepressant treatment, how and to which extent such early-life interventions could affect the developing brain and behaviour later in life, warrants further investigation.
Methods
Pre-pubertal male Flinders Sensitive Line (FSL) rats were treated with saline (SAL), escitalopram (ESC; 10 mg/kg/day) or venlafaxine (VEN; 10 mg/kg/day), with or without dietary intervention (standard [STD] or n-3 EFA caoted rat chow [OM3]) or exercise (sedentary [SED} or low intensity exercise [EXE]) from postnatal day 21 (PND21) to PND34. Drugs were administered subcutaneously, n-3 EFAs via diet and low intensity forced exercise by a custom-built treadmill. Following pre-pubertal treatment, animals underwent behavioural analyses in the Open field test and Forced swim test either immediately following treatments on PND35, or on PND60 (following no treatment from PND60 onwards to investigate lasting effects).
Results
None of the treatment strategies affected immobility time on PND35, however, OM3+EXE (irrespective of drug) increased PND35 swimming behaviour. Following a chronic wash-out period, immobility time on PND60 was only reduced by ESC+OM3 compared to ESC+STD (irrespective of activity). Furthermore, ESC+OM3 and VEN+OM3 increased swimming behaviour on PND60 (irrespective of activity). These behavioural alterations were observed despite significant reductions in general locomotor activity induced the Diet*Activity interaction (irrespective of drug).
Conclusion
That the long-term effects of different classes of antidepressants were beneficially augmented by pre-pubertal n-3 EFA supplementation, but not low intensity exercise, suggests neurodevelopmental processes to be positively affected, resulting in improved behaviour later in life. Overall, the current project underlines the value of early-life nutritional modifications to augment the pharmacological treatment of juvenile MDD, and in particular its potential value for long-lasting beneficial effects into adulthood.
... Both animal and human studies have shown that administration of O3FA is associated with positive neurocognitive and behavioral outcomes (McCann and Ames, 2005). In addition, animal models have shown the benefit of O3FA supplementation following traumatic and anoxic brain injury, anxiety, and cognition (Mills et al., 2011;Wu et al., 2011;Wang et al., 2013;Gonzales et al., 2015;Pusceddu et al., 2015). Animal models of O3FA deficiency during development have shown impaired neurogenesis, visual acuity, and retinal function (Anderson et al., 2005). ...
... Additionally, we found that mice treated with the DHA/ARA diet demonstrated less neophobia (increased time on the open arms of the plus maze) when compared to chow-fed controls, a finding that has been previously suggested in rat models (Pérez et al., 2013;Gonzales et al., 2015;Pusceddu et al., 2015). Pusceddu et al. (2015) demonstrated that female rats supplemented with a mixture of DHA and EPA at 2-12 days of life demonstrated a dose-dependent reduction in anxiety as measured by the elevated plus maze. ...
Polyunsaturated fatty acids serve multiple functions in neurodevelopment and neurocognitive function. Intravenous lipid emulsions are administered to children that are dependent on parenteral nutrition to provide the essential fatty acids needed to sustain growth and development. One of these emulsions, derived from fish-oil, is particularly poor in the traditional essential fatty acids, linoleic and alpha-linolenic acids. However, it does contain adequate amounts of its main derivatives, arachidonic acid (ARA) and docosahexaenoic acid (DHA), respectively. This skewed composition has raised concern about the sole use of fish-oil based lipid emulsions in children and how its administration can be detrimental to their neurodevelopment. Using a custom-made diet that contains ARA and DHA as a sole source of polyunsaturated fatty acids, we bred and fed mice for multiple generations. Compared to adult, chow-fed mice, animals maintained on this special diet showed similar outcomes in a battery of neurocognitive tests performed under controlled conditions. Chow-fed mice did perform better in the rotarod test for ataxia and balance, although both experimental groups showed a conserved motor learning capacity. Conversely, mice fed the custom diet rich in DHA and ARA showed less neophobia than the chow-fed animals. Results from these experiments suggest that providing a diet where ARA and DHA are the sole source of polyunsaturated fatty acids is sufficient to support gross visual, cognitive, motor, and social development in mice.
... Nevertheless, increased adaptive coping behaviour has been observed in ω-3 supplemented rodents [98], possibly due to enhanced neurogenesis and neuroplasticity [99]. However, no significant changes were observed in the hippocampal BDNF concentrations (i.e. a marker of neuroplasticity) of OM3-treated PND35 rats in the current study ( Figure 6C), so that neuroplasticity does not seem to play a key role in the observations of the current study. ...
... As such, data from the current study indicated no antidepressive-like effect of pre-pubertal OM3 treatment in either age group (PND35; Figure 5A or PND60; Figure 5B), after controlling for the overall reduction in general locomotor activity (implementing the two-way ANCOVAs analyses, similar to anxiety-like data described above). These results are in line with previous reports in pubertal [109] and older animals [98]. ...
Major depressive disorder (MDD) affects a significant number of children and adolescents, yet treatment options for this population remain very limited. Escitalopram (ESC) is one of only two antidepressants approved as treatment for juvenile depression. Still, delayed onset of action, and immediate plus the risk of lasting side effects contribute to low patient adherence, and places the medical prescriber in a difficult situation weighing the potential long-term effects of juvenile treatment against the known consequences of untreated MDD. Research into alternative or augmentation strategies and their long-term effects are needed to improve clinical outcome and better our understanding of the long-term consequences of early-life treatment. We investigated the early-life (postnatal day 35 (PND35)) and lasting (PND60) bio-behavioural effects of pre-pubertal (PND21 to PND34) escitalopram (ESC) administration and/or ω-3 supplementation (OM3) in stress sensitive Flinders Sensitive Line rats. Only ESC treatment showed a strong trend to decrease depressive-like behaviour via significantly increased climbing behaviour on PND35. However, OM3 treatment reduced locomotor activity and increased hippocampal neuroplasticity on PND35, suggesting improved coping behaviour and masking of possible antidepressant-like effects. Reduced locomotor activity lasted into early-adulthood on PND60, despite a treatment-free period from PND35 to PND60. Regardless, early-adulthood antidepressive-like behaviour was only observed in the combination treatment (ESC + OM3) group, despite a significant increase in serotonin turnover, suggesting strong neurodevelopmental process to be involved. Taken together, the combination of ESC and OM3 might induce lasting beneficial neurodevelopmental effects in a stress-sensitive population, suggesting a possible role in current treatment strategies.
... The EA groups received EA, and the control groups were handled without needle insertion or electrical stimulation. All animals were subjected to the open field test, 26 light-dark test 27 and forced swim test, 28 as previously described 29 The light-dark test was identical to the open field test, but included a dark-box insert that occupied half of the field. A small hole allowed the animal access to the lit part of the field. ...
... 27 Finally, a reduction of immobility in the forced-swim test was used to evaluate the antidepressant effects of the intervention. 29 Two forced swim sessions were conducted on consecutive days in each experiment; however, scoring was only performed during the second session (day 3 and 5 for experiments 1 and 2, respectively). Behavioural testing was conducted in Plexiglas chambers with infrared arrays of motion detectors mounted outside of them (Med Associates, St Albans, Vermont, USA). ...
Aim:
To evaluate the behavioural effects of head electroacupuncture (EA) using the Holtzman rat model, a genetic strain showing susceptibility to stress-evoked helplessness.
Methods:
Putative anxiolytic and antidepressant behavioural effects of head EA were investigated using the light-dark and forced swim tests, respectively. The open field test was used to investigate motor activity. A total of 28 rats were used in two experiments, each with two groups (n=7 rats each). Rats were restrained and randomised to handling only (control) or 2Hz EA on the midline head anteriorly (at Yintang) and posteriorly (at GV20) for 3 days (experiment 1) or 4 days (experiment 2).
Results:
One day of EA did not modify behaviour in any of the tests (p>0.1); however, 2 days of 2 Hz EA treatment to the head had anxiolytic-like effects, as indicated by an improvement in ambulatory time and average velocity in the light-dark test (experiment 2). Relative to the control group, the EA group demonstrated greater ambulatory time (37.0±3.7 vs 25.2±3.6 s, p<0.05) and lower average velocity (2.73±0.06 vs 3.08±0.13 cm/s, p<0.05). However, EA treatment had no significant effects on the open field and forced swim tests in either experiment.
Conclusions:
Two days of EA treatment using 2 Hz pulsating electrical current at midline anterior and posterior acupuncture points on the head induces behavioural effects suggestive of anxiolysis.
... Dietary intake of ω-3 fatty acids is reported in depression scores improvement (Banikazemi et al., 2015), as well as increased adaptive coping in stressful events (Gonzales et al., 2015). The eicosapentaenoic acid form of ω-3 fatty acid is also reported with clinical benefits on depressive symptoms (Liao et al., 2019). ...
Depression is a serious mental and mood disorder with global health and economic burden. This burden may be overwhelming in low income countries, although there are insufficient data. Most antidepressant formulations are predicated on the monoamine, neuroendocrine and neuro-inflammation hypotheses, with little or no cognizance to other neurochemicals altered in depression. A nutritional strategy with or without conventional antidepressants is recommended, as nutrition plays vital roles in the onset, severity and duration of depression, with poor nutrition contributing to its pathogenesis. This review discusses nutritional potentials of utilizing omega-3 fatty acids, proteins, vitamins, minerals and herbs or their phytochemicals in the management of depression with the aim of reducing depression burden. Literature search of empirical data in books and journals in data bases including but not limited to PubMed, Scopus, Science Direct, Web of Science and Google Scholar that might contain discussions of sampling were sought, their full text obtained, and searched for relevant content to determine eligibility. Omega-3 fatty and amino acids had significant positive anti-depression outcomes, while vitamins and minerals although essential, enhanced omega-3 fatty and amino acids activities. Some herbs either as whole extracts or their phytochemicals/metabolites had significant positive anti-depression efficacy. Nutrition through the application of necessary food classes or herbs as well as their phytochemicals, may go a long way to effectively manage depression. This therefore will provide inexpensive, natural, and non-invasive therapeutic means with reduced adverse effects that can also be applied alongside clinical management. This nutritional strategy should be given more attention in research, assessment and treatment for those with depression and other mental illness in low income countries, especially in Africa.
... On the other hand, their supplementation can contribute to the prevention of the onset of cognitive disorders by the reduction of the neurotoxicity typical of neurodegenerative disorders [7,8]. Moreover, there is some evidence that higher levels of LC n-3 PUFAs are associated with the improvement of stress coping in animal models [9]. ...
: It is the focus of increasing interest to investigate the effects of long-chain n-3 and long-chain n-6 polyunsaturated fatty acids (LC n-3 PUFAs; LC n-6 PUFAs) on psychiatric symptoms in a transdiagnostic perspective. There is some evidence that low levels of LC n-3 PUFAs and a higher ratio of LC n-6 to LC n-3 PUFAs in plasma and blood cells are associated with aggressive and impulsive behaviours. Therefore, implementation of LC n-3 PUFAs may produce positive effects on hostility, aggression, and impulsivity in both psychiatric and non-psychiatric samples across different stages of life. A possible mechanism of action of LC n-3 PUFAs in conditions characterized by a high level of impulsivity and aggression is due to the effect of these compounds on the serotonin system and membrane stability. Studies that evaluated the effects of LC n-3 PUFAs on impulsivity and aggressiveness indicated that addition of rather low doses of these agents to antipsychotic treatment might reduce agitation and violent behaviours in psychosis, attention deficit hyperactivity disorder, personality disorders, and impulsive control and conduct disorders. The present review is aimed at examining and discussing available data from recent trials on this topic.
... The shuttle box escape test was used to measure escape learning. The procedure was modified from Gonzales [21]. The shuttle box (60×20×20 cm) consisted of two equally-sized compartments separated by an open door. ...
... Here, for the first time, the hyperactivity in OFT was evident for up to 8 weeks after OBX. OFT is a relevant tool for assessing behavioral disturbances in rodents (Gonzales et al., 2015;Padilla et al., 2010), and there is a wide diversity of symptoms present in mood disorders (Belmaker and Agam, 2008;Mann, 2005). However, there is lack of studies on the time-course of OBX-induced OFT behavioral changes (Mucignat-Caretta et al., 2006). ...
Major depressive disorder (MDD) is a neuropsychiatric disease that is associated with profound disturbances in affected individuals. Elucidating the pathophysiology of MDD has been frustratingly slow, especially concerning the neurochemical events and brain regions associated with disease progression. Thus, we evaluated the time-course (up to 8 weeks) behavioral and biochemical effects in mice that underwent to a bilateral olfactory bulbectomy (OBX), which is used to modeling depressive-like behavior in rodents. Similar to the symptoms in patients with MDD, OBX induced long-lasting (e.g., impairment of habituation to novelty, hyperactivity and an anxiety-like phenotype) and transient (e.g., loss of self-care and motivational behavior) behavioral effects. Moreover, OBX temporarily impaired hippocampal synaptosomal mitochondria, in a manner that would be associated with hippocampal-related synaptotoxicity. Finally, long-lasting pro-oxidative (i.e., increased levels of reactive oxygen species and nitric oxide and decreased glutathione levels) and pro-inflammatory (i.e., increased levels of pro-inflammatory cytokines IL-1, IL-6, TNF-α and decreased anti-inflammatory cytokine IL-10 levels) effects were induced in the hippocampus by OBX. Additionally, these parameters were transiently affected in the posterior and frontal cortices. This study is the first to suggest that the transient and long-lasting behavioral effects from OBX strongly correlate with mitochondrial, oxidative and inflammatory parameters in the hippocampus; furthermore, these effects show a weak correlation with these parameters in the cortex. Our findings highlight the underlying mechanisms involved in the biochemical time course of events related to depressive behavior.
... 44 A recent study examined the effect of diet enriched with omega-3 fatty acid in rats has shown that it helps promote behavioral escape changes, which is consistent with enhanced adaptive management of stressful events suggesting that omega-3 fatty acids can help in preventing the onset of stress-related depressive disorders. 45 A study was undertaken to address the question of how maternal diet influences development and puberty. The researchers examined the effect of DHA sufficient and deficient diets on rat gestation, lactation and weaning periods; the findings suggest that increased resilience to emotional stressors and decreased propensity to mood disorders, which are common occurrences during adolescence, can be controlled by maintaining sufficient DHA levels in the diet throughout development. ...
Depression is a condition in which an individual feels lethargic, irritable, and guilty, has difficulty and trouble, no enjoyment in life, mood swings, sometimes suicidal ideation and thoughts, and loss of pleasure in activities. There are hundreds of millions of individuals suffering from major depression disorder all over the world. This leads to a considerable portion of the economy going for treatment as large amounts of money are spent on drugs every year. Pharmaceutical drugs are not very effective and they also have side effects that compound the problem. There are number of studies which shows that omega-3 fatty acids are proving to be very effective against the treatment of major depression disorder and other psychiatric disorders. However, the data regarding the efficacy of omega-3 fatty acids in depression treatment are conflicted. This article reviews the recent research showing the relation between omega-3 fatty acids and depression. The roles of the omega-3 fatty acids in the treatment of depression are being studied with increased pace in the last decade due to heightened prevalence of depression. It is emphasized that omega-3 fatty acids have no record of associated side effects, which deserves greater attention for further research.
O objetivo deste trabalho foi investigar o potencial ansiolítico do L-triptofano, ômega 3, magnésio e das vitaminas do complexo B em estudantes universitárias com ansiedade. O estudo teve caráter experimental clínico, randomizado, de abordagem quali-quantitativa e foi composto por 16 estudantes que foram divididas em dois grupos, o grupo controle (GC) que recebeu o tratamento e o grupo placebo (GP) que recebeu apenas ômega 3. Para avaliar o nível de ansiedade aplicou-se a escala Hospitalar de Ansiedade e Depressão (HAD) antes e dias antes do término do tratamento de 35 dias com os nutrientes já citados. Os resultados mostraram que antes do tratamento 100% das acadêmicas do GC apresentaram provável quadro de ansiedade e após o tratamento 57% (p< 0,05) foram classificadas com improvável ansiedade e 43% com possível ansiedade. Em relação ao GP observou-se que antes do tratamento nenhuma das estudantes foi classificada com improvável ansiedade e após o tratamento 57% (p<0,05) foram classificadas nessa categoria. A suplementação com L- triptofano, ômega 3, magnésio e vitaminas do complexo B se mostrou eficaz contra os sintomas da ansiedade, assim como o uso do ômega 3 no GP.
As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA) exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations) found in n-3 PUFA supplemented mice also pointed toward an effective neuroprotection. On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.
Postpartum depression (PPD) is a psychiatric disorder that occurs in 10-15% of childbearing women. It is hypothesized that omega-3 fatty acids, which are components of fish oil, may attenuate depression symptoms. In order to examine this hypothesis, the animal model of postpartum depression was established in the present study. Ovariectomized female rats underwent hormone-simulated pregnancy (HSP) regimen and received progesterone and estradiol benzoate or vehicle for 23 days, mimicking the actual rat's pregnancy. The days after hormone termination were considered as the postpartum period. Forced feeding of menhaden fish oil, as a source of omega-3, with three doses of 1, 3, and 9g/kg/d, fluoxetine 15mg/kg/d, and distilled water 2ml/d per rat started in five postpartum-induced and one vehicle group on postpartum day 1 and continued for 15 consecutive days. On postpartum day 15, all groups were tested in the forced swimming test (FST) and open field test (OFT), followed by a biochemical assay. Results showed that the postpartum-induced rats not treated with menhaden fish oil, exhibited an increase in immobility time seen in FST, hippocampal concentration of corticosterone and plasmatic level of corticosterone, and pro-inflammatory cytokines. These depression-related effects were attenuated by supplementation of menhaden fish oil with doses of 3 and 9g/kg. Moreover, results of rats supplemented with menhaden fish oil were comparable to rats treated with the clinically effective antidepressant, fluoxetine. Taken together, these results suggest that menhaden fish oil, rich in omega-3, exerts beneficial effect on postpartum depression and decreases the biomarkers related to depression such as corticosterone and pro-inflammatory cytokines.
Omega-3 (n-3) fatty acids are important for adequate brain function and cognition. The aim of the present study was to evaluate how n-3 fatty acids influence the persistence of long-term memory (LTM) in an aversive memory task and to explore the putative mechanism involved. Female rats received isocaloric diets that included n-3 (n-3 group) or not (D group). The adult litters were subjected to an inhibitory avoidance task (0.7 mA, 1.0 seconds foot shock) to elicit persistent LTM. Twelve hours after the training session, the fatty acid profile and the brain derived neurotrophic factor (BDNF) content of the dorsal hippocampus were assessed. In addition, we measured the activation of the NR2B subunit of the N-methyl-d-aspartate (NMDA) receptor and the SRC family protein Fyn. Despite pronounced learning in both groups, the persistence of LTM was abolished in the D group 7 days after the training session. We also observed that the D group presented reductions in hippocampal DHA (22:6 n-3) and BDNF content. Twelve hours after the training session, the D group showed decreased NR2B and Fyn phosphorylation in the dorsal hippocampus, with no change in the total content of these proteins. Further, there was a decrease in the interaction of Fyn with NR2B in the D group, as observed by co-immunoprecipitation. Taken together, these data suggest that n-3 fatty acids influence the persistence of LTM by maintaining adequate levels of DHA and BDNF as well as by influencing the activation of NR2B and Fyn during the period of memory formation.
Although several studies have reported an association between mental disorders and serum levels of brain-derived neurotrophic factor (BDNF), this association is still poorly understood. The study of factors associated with both BDNF levels and mental disorders, such as n-3 polyunsaturated fatty acids (n-3 PUFAs), may help to elucidate the mechanisms mediating the relationship between the two variables. Therefore, the present study aimed to evaluate whether the intake n-3 PUFAs correlates with serum levels of BDNF.
This study involved 137 adolescents drawn from a community sample, including a group with high levels of anxiety, assessed using the Screen for Children and Anxiety Related Emotional Disorders. Blood samples were collected and serum BDNF levels were measured. n-3 PUFAs were estimated using a food frequency questionnaire for adolescents. Correlations were performed to assess the association between n-3 PUFAs intake and BDNF levels. Effects of potential confounders (total fat consumption, age, gender and anxiety) were examined using linear regression models. There was a direct correlation between n-3 PUFAs consumption and serum BDNF levels, which remained significant even after accounting for potential confounders.
We were able to detect a correlation between n-3 PUFAs intake and peripheral BDNF levels. Our study was limited by its small sample size, and our external validity may be restricted by the oversampling of anxious adolescents. Our findings may help determine the nature of the association between mental disorders and serum levels of BDNF. However, more studies are needed to elucidate the possible mechanisms by which n-3 PUFAs intake affects BDNF levels, and how this may lead to an increased vulnerability to psychiatric disorders.
Background:
Population-based estimates of prevalence of anxiety and comorbid depression are lacking. Therefore, we estimated the prevalence and risk factors for postpartum anxiety and comorbid depressive symptoms in a population-based sample of women.
Methods:
Using multinomial logistic regression, we examined the prevalence and risk factors for postpartum anxiety and depressive symptoms using 2009-2010 data from the Illinois and Maryland Pregnancy Risk Assessment Monitoring System, a population-based survey of mothers who gave birth to live infants. Survey participants are asked validated screening questions on anxiety and depressive symptoms.
Results:
Among 4451 postpartum women, 18.0% reported postpartum anxiety symptoms, of whom 35% reported postpartum depressive symptoms (6.3% overall). In the multivariable model, higher numbers of stressors during pregnancy (adjusted odds ratio [aOR] range: 1.3-9.7) and delivering an infant at ≤27 weeks gestation (aOR range: 2.0-5.7) were associated with postpartum anxiety and postpartum depressive symptoms, experienced individually or together. Smoking throughout pregnancy was associated with postpartum anxiety symptoms only (aOR=2.3) and comorbid anxiety and depressive symptoms (aOR=2.9).
Conclusions:
Given the possible adverse effects of postpartum anxiety and comorbid depression on maternal health and infant development, clinicians should be aware of the substantial prevalence, comorbidity, and risk factors for both conditions and facilitate identification, referral, and/or treatment.
Evidence that depressive symptoms are inversely related to n-3 (ω3) fatty acids is growing among United States adults. We assessed whether self-reported depressive symptoms were inversely associated with n-3 fatty acid intakes by using a cross-sectional study in 1746 adults (aged 30-65 y) in Baltimore City, MD (2004-2009). The 20-item Center for Epidemiologic Studies-Depression Scale (CES-D) was used, with a CES-D score ≥16 suggestive of elevated depressive symptoms (EDS). By using the mean of two 24-h dietary recalls, n-3 highly unsaturated fatty acids (HUFAs; ≥20 carbons), n-3 polyunsaturated fatty acids (PUFAs; ≥18 carbons), and plausible ratios with n-6 (ω6) fatty acids were estimated. EDS prevalence was 18.1% among men and 25.6% among women. In women, the uppermost tertile (tertile 3) of n-3 PUFAs (compared with tertile 1) was associated with reduced odds of EDS by 49%, with a substantial sex differential. The n-3 PUFA:n-6:PUFA ratio was inversely related to EDS among women (tertile 2 vs. tertile 1, OR: 0.74; 95% CI: 0.41, 1.32; tertile 3 vs. tertile 1, OR: 0.47; 95% CI: 0.27, 0.83). A similar pattern was noted for n-3 HUFA:n-6 HUFA among women. For CES-D subscales, n-3 PUFA (% of energy) was inversely related to somatic complaints, whereas positive affect was directly related to n-3 HUFA (% of energy; total population and among women), n-3 HUFA:n-6 HUFA (women), and n-3 HUFA:n-6 PUFA (total population and among women). In sum, among United States women, higher intakes of n-3 fatty acids [absolute (n-3) and relative to n-6 fatty acids (n-3:n-6)] were associated with lower risk of elevated depressive symptoms, specifically in domains of somatic complaints (mainly n-3 PUFAs) and positive affect (mainly n-3 HUFAs).
Little is known about relationships between dietary patterns, n-3 polyunsaturated fatty acids (PUFA) intake and excessive anxiety during pregnancy.
To examine whether dietary patterns and n-3 PUFA intake from seafood are associated with high levels of anxiety during pregnancy.
Pregnant women enrolled from 1991-1992 in ALSPAC (n 9,530). Dietary patterns were established from a food frequency questionnaire using principal component analysis. Total intake of n-3 PUFA (grams/week) from seafood was also examined. Symptoms of anxiety were measured at 32 weeks of gestation with the Crown-Crisp Experiential Index; scores ≥9 corresponding to the 85(th) percentile was defined as high anxiety symptoms. Multivariate logistic regression models were used to estimate the OR and 95% CI, adjusted by socioeconomic and lifestyle variables.
Multivariate results showed that women in the highest tertile of the health-conscious (OR 0.77; 0.65-0.93) and the traditional (OR 0.84; 0.73-0.97) pattern scores were less likely to report high levels of anxiety symptoms. Women in the highest tertile of the vegetarian pattern score (OR 1.25; 1.08-1.44) were more likely to have high levels of anxiety, as well as those with no n-3 PUFA intake from seafood (OR 1.53; 1.25-1.87) when compared with those with intake of >1.5 grams/week.
The present study provides evidence of a relationship between dietary patterns, fish intake or n-3 PUFA intake from seafood and symptoms of anxiety in pregnancy, and suggests that dietary interventions could be used to reduce high anxiety symptoms during pregnancy.
Depression is a common disorder affecting 10-15% women in the postpartum period. Postpartum depression can disrupt early mother-infant interaction, and constitutes a risk factor for early child development. Recently, attention has been drawn to the hypothesis that a low intake of seafood in pregnancy can be a risk factor for postpartum depression. Seafood is a unique dietary source of the marine omega-3 fatty acids and is a natural part of a healthy balanced diet that is especially important during pregnancy.
In a community based prospective cohort in a municipality in Western Norway, we investigated both nutritional and psychological risk factors for postpartum depression. The source population was all women who were pregnant within the period November 2009 - June 2011. The fatty acid status in red blood cells was assessed in the 28(th) gestation week and participants were screened for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS) three months after delivery. The aim of the present study was to investigate if a low omega-3 index in pregnancy is a possible risk factor for postpartum depression.
In a simple regression model, the omega-3 index was associated with the EPDS score in a nonlinear inverse manner with an R square of 19. Thus, the low omega-3 index explained 19% of the variance in the EPDS score. The DPA content, DHA content, omega-3 index, omega-3/omega-6 ratio, total HUFA score, and the omega-3 HUFA score were all inversely correlated with the EPDS score. The EPDS scores of participants in the lowest omega-3 index quartile were significantly different to the three other omega-3 index quartiles.
In this study population, a low omega-3 index in late pregnancy was associated with higher depression score three months postpartum.
Chronic stress leads to secretion of the adrenal steroid hormone corticosterone, inducing hippocampal atrophy and dendritic hypertrophy in the rat amygdala. Both alterations have been correlated with memory impairment and increased anxiety. Supplementation with omega-3 fatty acids improves memory and learning in rats. The aim of this study was to evaluate the effects of omega-3 supplementation on learning and major biological and behavioral stress markers. Male Sprague--Dawley rats were randomly assigned to three experimental groups: 1) Control, 2) Vehicle, animals supplemented with water, and 3) omega-3, rats supplemented with omega-3 (100 mg of DHA+25 mg of EPA). Each experimental group was divided into two subgroups: one of which was not subjected to stress while the other was subjected to a restraint stress paradigm. Afterwards, learning was analyzed by avoidance conditioning. As well, plasma corticosterone levels and anxiety were evaluated as stress markers, respectively by ELISA and the plus-maze test. Restraint stress impaired learning and increased both corticosterone levels and the number of entries into the open-arm (elevated plus-maze). These alterations were prevented by omega-3 supplementation. Thus, our results demonstrate that omega-3 supplementation had two beneficial effects on the stressed rats, a strong anti-stress effect and improved learning.
Long chain n-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may slow cognitive decline. DHA plays an important role in neural function and decreased plasma DHA are associated with cognitive decline in healthy elderly adults and in patients with Alzheimer's disease. In this study we tested a hypothesis that DHA protects cognitive functions of male Wistar rats against negative impact of prolonged restraint stress. Specifically, we attempted to characterize the preventive action of prolonged treatment with DHA enriched preparation (daily dose of DHA: 300mg/kg, p.o. for 21days) in comparison with positive control (fluoxetine: 10mg/kg daily, p.o. for 21days) against an impairment caused by chronic restraint stress (2h daily for 21days) on recognition memory tested in a object recognition task and on the spatial working memory tested in Morris water maze. We found that administration of DHA enriched preparation prevented deleterious effects of chronic restraint stress both on recognition (p<0.01) and on the working spatial memory (p<0.001).
Background:
Our aim was to assess whether an early introduced n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation affects depression symptoms, anxiety and emotional state in patients with acute myocardial infarction (AMI) and no history of mental disorders.
Methods:
Fifty two patients with AMI were enrolled into the study and randomized to the study group (group P; n=26; standard therapy+n-3 PUFA 1 g daily) or the control group (group C; n=26; standard therapy). The following psychological tests were used at the baseline (3rd day of AMI) and after one month (30±1 days): Beck Depression Inventory (BDI), State-Trait Anxiety Inventory in a specific situation (STAI-S) and as a general trait (STAI-T), Emotional State Questionnaire (ESQ).
Results:
The baseline characteristics, pharmacotherapy and BDI, STAI-S/T and ESQ were similar between both groups. The mean test scores assessed for all patients (group P and C) during the one-month observation were significantly lower for BDI (p=0.04), STAI-T (p=0.03), STAI-S (p=0.01) and harm/loss emotions (p=0.005). After adjusting for age, sex, body mass index, coronary artery disease severity, ejection fraction, serum troponin level and the baseline tests results, n-3 PUFA intervention revealed additional significant decrease in BDI (p=0.046), STAI-S (p=0.03) and harm/loss emotions (p=0.04).
Conclusions:
Our study provides novel and preliminary observations--n-3 PUFA supplementation reveals additional decreasing effects on depressive and anxiety symptoms in early post-MI patients.
Abstract Recent studies indicate that an oil extract from Salvia sclarea may provide clinical benefits in various pathological conditions. In comparison to extracts from other Salvia species, S. sclarea oil contains twice as much omega-3 fatty acids, which are involved in eicosanoid synthesis pathways, and has been found to contain significant levels of the psychoactive monoterpane linalool. In the present study, we examined the mood stabilizing and anxiolytic-like effects of chronic food administration of S. sclarea oil extract on behavioral and physiological parameters of mice with prominent dominant and submissive features in behavioral assays used to test mood stabilizing and antidepressant drugs. Experimental animals received oil supplemented food from the age of 4 weeks or from conception via their pregnant dams. Each age group received either S. sclarea oil- or sunflower oil-enriched feed. Dominant animals, whose pregnant mothers received S. sclarea oil-enriched feed from the date of conception, showed a significant reduction of dominant and anxiety-like behavior, in comparison to their sunflower oil-treated counterparts. S. sclarea oil-treated submissive animals exhibited a similar tendency, and showed a significant reduction in blood corticosterone levels. These findings enforce the hypothesis that S. sclarea oil possesses anxiolytic properties.
Background
The purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats.
Methods
Cognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance.
Results
After 7 weeks of KO intake, both males and females treated with KO were significantly better in discriminating between the active and the inactive levers in the ALSAT from day 1 of training (p<0.01). Both KO and IMIP prevented resignation/depression on the third day in the UALST. Similarly, a shorter immobility time was observed for the KO and IMIP groups compared to the control in the FST (p<0.001). These data support a robust antidepressant-like potential and beneficial cognitive effect of KO. Changes in expression of synaptic plasticity-related genes in the prefrontal cortex and hippocampus were also investigated. mRNA for brain-derived neurotrophic factor (Bdnf) was specifically upregulated in the hippocampus of female rats receiving 7 weeks of KO supplementation (p=0.04) and a similar trend was observed in males (p=0.08). Males also exhibited an increase in prefrontal cortex expression of Arc mRNA, a key protein in long-term synaptic plasticity (p=0.05). IMIP induced clear effects on several plasticity related genes including Bdnf and Arc.
Conclusions
These results indicate that active components (eicosapentaenoic acid, docosahexaenoic acid and astaxanthin) in KO facilitate learning processes and provide antidepressant-like effects. Our findings also suggest that KO might work through different physiological mechanisms than IMIP.
Aim of this study was to identify whether docosahexaenoic acid (DHA) has a vital antidepressant by hypothalamic-pituitary-adrenal axis (HPA axis) or not.
Mice were divided into 2 groups: control group and DHA dietary group. DHA dietary group was treated with DHA dietary everyday for consecutive 50 days. The forced swimming test and tail suspension test were conducted. Hypothalamic and erythrocyte fatty acids and monoamine neurotransmitters levels in hypothalamus were assayed; corticosterone, adrenocorticotropic hormone and corticotropin-releasing factor in serum, hypothalamus and pituitary were assayed, respectively.
(1) In the forced swimming test, DHA dietary significantly decreased immobility time, whereas swimming time and climbing time were increased. In tail suspension test，DHA dietary significantly shortened immobility time. (2) DHA dietary increased the ration of n-3/n-6 (polyunsaturated fatty acids) and DHA level in hypothalamic and erythrocyte fatty acids; (3) DHA dietary significantly increased 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and dopamine levels in hypothalamus; (4) DHA dietary significantly decreased serum corticosterone level by 20.23% and serum adrenocorticotropic hormone level by 25.13%; significantly increased serum corticotropin releasing factor level by 21.92%. Besides, DHA dietary decreased arginine vasopressin level by 20.11% in hypothalamus, by 23.76% in pituitary tissues, respectively; (5) DHA dietary decreased corticotropin-releasing factor levels by 30.83% in hypothalamus, by 29.75% in pituitary tissues, respectively. In hypothalamus, DHA dietary decreased significantly adrenocorticotropic hormone level by 19.14%, but insignificantly decreased adrenocorticotropic hormone level in pituitary.
DHA shows an antidepressant property. Moreover, DHA has multiple effects on depression including the monoamine neurotransmitter systems, red blood cell membranes and HPA axis.
Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days) on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF) activity, anxiety in the elevated-plus maze (EPM), the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test) and entries into the open arms (EPM). Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stress-induced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress.
Depressive symptoms may increase the risk of progressing from mild cognitive impairment (MCI) to dementia. Consumption of n-3 PUFA may alleviate both cognitive decline and depression. The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA, DHA and EPA, for depressive symptoms, quality of life (QOL) and cognition in elderly people with MCI. We conducted a 6-month double-blind, randomised controlled trial. A total of fifty people aged >65 years with MCI were allocated to receive a supplement rich in EPA (1·67 g EPA + 0·16 g DHA/d; n 17), DHA (1·55 g DHA + 0·40 g EPA/d; n 18) or the n-6 PUFA linoleic acid (LA; 2·2 g/d; n 15). Treatment allocation was by minimisation based on age, sex and depressive symptoms (Geriatric Depression Scale, GDS). Physiological and cognitive assessments, questionnaires and fatty acid composition of erythrocytes were obtained at baseline and 6 months (completers: n 40; EPA n 13, DHA n 16, LA n 11). Compared with the LA group, GDS scores improved in the EPA (P=0·04) and DHA (P=0·01) groups and verbal fluency (Initial Letter Fluency) in the DHA group (P=0·04). Improved GDS scores were correlated with increased DHA plus EPA (r 0·39, P=0·02). Improved self-reported physical health was associated with increased DHA. There were no treatment effects on other cognitive or QOL parameters. Increased intakes of DHA and EPA benefited mental health in older people with MCI. Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia. This needs to be investigated in larger, depressed samples with MCI.
Mental illnesses account for a larger proportion of disability in developed countries than any other group of illnesses, including cancer and heart disease. In 2004, an estimated 25% of adults in the United States reported having a mental illness in the previous year. The economic cost of mental illness in the United States is substantial, approximately $300 billion in 2002. Population surveys and surveys of health-care use measure the occurrence of mental illness, associated risk behaviors (e.g., alcohol and drug abuse) and chronic conditions, and use of mental health-related care and clinical services. Population-based surveys and surveillance systems provide much of the evidence needed to guide effective mental health promotion, mental illness prevention, and treatment programs. This report summarizes data from selected CDC surveillance systems that measure the prevalence and impact of mental illness in the U.S. adult population. CDC surveillance systems provide several types of mental health information: estimates of the prevalence of diagnosed mental illness from self-report or recorded diagnosis, estimates of the prevalence of symptoms associated with mental illness, and estimates of the impact of mental illness on health and well-being. Data from the CDC 2005-2008 National Health and Nutrition Examination Survey indicate that 6.8% of adults had moderate to severe depression in the 2 weeks before completing the survey. State-specific data from the CDC 2006 Behavioral Risk Factor Surveillance System (BRFSS), the most recent BRFSS data available, indicate that the prevalence of moderate to severe depression was generally higher in southeastern states compared with other states. Two other CDC surveys on ambulatory care services, the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, indicate that during 2007-2008, approximately 5% of ambulatory care visits involved patients with a diagnosis of a mental health disorder, and most of these were classified as depression, psychoses, or anxiety disorders. Future surveillance should pay particular attention to changes in the prevalence of depression both nationwide and at the state and county levels. In addition, national and state-level mental illness surveillance should measure a wider range of psychiatric conditions and should include anxiety disorders. Many mental illnesses can be managed successfully, and increasing access to and use of mental health treatment services could substantially reduce the associated morbidity.
Essential polyunsaturated fatty acids (PUFAs) are critical nutritional lipids that must be obtained from the diet to sustain homeostasis. Omega-3 and -6 PUFAs are key components of biomembranes and play important roles in cell integrity, development, maintenance, and function. The essential omega-3 fatty acid family member docosahexaenoic acid (DHA) is avidly retained and uniquely concentrated in the nervous system, particularly in photoreceptors and synaptic membranes. DHA plays a key role in vision, neuroprotection, successful aging, memory, and other functions. In addition, DHA displays anti-inflammatory and inflammatory resolving properties in contrast to the proinflammatory actions of several members of the omega-6 PUFAs family. This review discusses DHA signalolipidomics, comprising the cellular/tissue organization of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains rich in DHA-containing phospholipids, and the cellular and molecular events revealed by the uncovering of signaling pathways regulated by DHA and docosanoids, the DHA-derived bioactive lipids, which include neuroprotectin D1 (NPD1), a novel DHA-derived stereoselective mediator. NPD1 synthesis agonists include neurotrophins and oxidative stress; NPD1 elicits potent anti-inflammatory actions and prohomeostatic bioactivity, is anti-angiogenic, promotes corneal nerve regeneration, and induces cell survival. In the context of DHA signalolipidomics, this review highlights aging and the evolving studies on the significance of DHA in Alzheimer's disease, macular degeneration, Parkinson's disease, and other brain disorders. DHA signalolipidomics in the nervous system offers emerging targets for pharmaceutical intervention and clinical translation.
Recent evidence suggests a role for diet quality in the common mental disorders depression and anxiety. We aimed to investigate the association between diet quality, dietary patterns, and the common mental disorders in Norwegian adults.
This cross-sectional study included 5731 population-based men and women aged 46 to 49 and 70 to 74 years. Habitual diet was assessed using a validated food frequency questionnaire, and mental health was measured using the Hospital Anxiety and Depression Scale.
After adjustments for variables including age, education, income, physical activity, smoking, and alcohol consumption, an a priori healthy diet quality score was inversely related to depression (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.59-0.84) and anxiety (OR = 0.77, 95% CI = 0.68-0.87) in women and to depression (OR = 0.83, 95% CI = 0.70-0.99) in men. Women scoring higher on a healthy dietary pattern were less likely to be depressed (OR = 0.68, 95% CI = 0.57-0.82) or anxious (OR = 0.87, 95% CI = 0.77-0.98), whereas men were more likely to be anxious (OR = 1.19, 95% CI = 1.03-1.38). A traditional Norwegian dietary pattern was also associated with reduced depression in women (OR = 0.77, 95% CI = 0.64-0.92) and anxiety in men (OR = 0.77, 95% CI = 0.61-0.96). A western-type diet was associated with increased anxiety in men (OR = 1.27, 95% CI = 1.14-1.42) and women (OR = 1.29, 95% CI = 1.17-1.43) before final adjustment for energy intake.
In this study, those with better quality diets were less likely to be depressed, whereas a higher intake of processed and unhealthy foods was associated with increased anxiety.
In the United States, intake of n-3 fatty acids is approximately 1.6 g/d ( approximately 0.7% of energy), of which 1.4 g is alpha-linolenic acid (ALA; 18:3) and 0.1-0.2 g is eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6). The primary sources of ALA are vegetable oils, principally soybean and canola. The predominant sources of EPA and DHA are fish and fish oils. Intake data indicate that the ratio of n-6 to n-3 fatty acids is approximately 9.8:1. Food disappearance data between 1985 and 1994 indicate that the ratio of n-6 to n-3 fatty acids has decreased from 12.4:1 to 10.6:1. This reflects a change in the profile of vegetable oils consumed and, in particular, an approximate 5.5-fold increase in canola oil use. The ratio of n-6 to n-3 fatty acids is still much higher than that recommended (ie, 2.3:1). Lower ratios increase endogenous conversion of ALA to EPA and DHA. Attaining the proposed recommended combined EPA and DHA intake of 0.65 g/d will require an approximately 4-fold increase in fish consumption in the United States. Alternative strategies, such as food enrichment and the use of biotechnology to manipulate the EPA and DHA as well as ALA contents of the food supply, will become increasingly important in increasing n-3 fatty acid intake in the US population.
To identify and describe dietary patterns in a cohort of pregnant women, and investigate whether dietary patterns during pregnancy are related to postpartum depression (PPD).
The study uses data from the prospective mother-child cohort 'Rhea' study. Pregnant women completed an FFQ in mid-pregnancy and the Edinburg Postpartum Depression Scale (EPDS) at 8-10 weeks postpartum. Dietary patterns during pregnancy ('health conscious', 'Western') were identified using principal component analysis. Associations between dietary patterns categorized in tertiles and PPD symptoms were investigated by multivariable regression models after adjusting for confounders.
Heraklion, Crete, Greece, 2007-2010.
A total of 529 women, participating in the 'Rhea' cohort.
High adherence to a 'health conscious' diet, characterized by vegetables, fruit, pulses, nuts, dairy products, fish and olive oil, was associated with lower EPDS scores (highest v. lowest tertile: β-coefficient = -1·75, P = 0·02). Women in the second (relative risk (RR) = 0·52, 95 % CI 0·30, 0·92) or third tertile (RR = 0·51, 95 % CI 0·25, 1·05) of the 'health conscious' dietary pattern were about 50 % less likely to have high levels of PPD symptoms (EPDS ≥ 13) compared with those in the lowest tertile.
This is the first prospective study showing that a healthy diet during pregnancy is associated with reduced risk for PPD. Additional longitudinal studies and trials are needed to confirm these findings.
The associations between different sources of dietary n-3 (omega-3) and n-6 (omega-6) fatty acids and the risk of depression have not been prospectively studied.
The objective was to examine the relation between different n-3 and n-6 types with clinical depression incidence.
We prospectively studied 54,632 US women from the Nurses' Health Study who were 50-77 y of age and free from depressive symptoms at baseline. Information on diet was obtained from validated food-frequency questionnaires. Clinical depression was defined as reporting both physician-diagnosed depression and regular antidepressant medication use.
During 10 y of follow-up (1996-2006), 2823 incident cases of depression were documented. Intake of long-chain n-3 fatty acids from fish was not associated with depression risk [relative risk (RR) for 0.3-g/d increment: 0.99; 95% CI: 0.88, 1.10], whereas α-linolenic acid (ALA) intake was inversely associated with depression risk (multivariate RR for 0.5-g/d increment: 0.82; 95% CI: 0.71, 0.94). The inverse association between ALA and depression was stronger in women with low linoleic acid (LA) intake (P for interaction = 0.02): a 0.5-g/d increment in ALA was inversely associated with depression in the first, second, and third LA quintiles [RR (95% CI): 0.57 (0.37, 0.87), 0.62 (0.41, 0.93), and 0.68 (0.47, 0.96), respectively] but not in the fourth and fifth quintiles.
The results of this large longitudinal study do not support a protective effect of long-chain n-3 from fish on depression risk. Although these data support the hypothesis that higher ALA and lower LA intakes reduce depression risk, this relation warrants further investigation.
Uncertainty about the benefits of dietary docosahexaenoic acid (DHA) for pregnant women and their children exists, despite international recommendations that pregnant women increase their DHA intakes.
To determine whether increasing DHA during the last half of pregnancy will result in fewer women with high levels of depressive symptoms and enhance the neurodevelopmental outcome of their children.
A double-blind, multicenter, randomized controlled trial (DHA to Optimize Mother Infant Outcome [DOMInO] trial) in 5 Australian maternity hospitals of 2399 women who were less than 21 weeks' gestation with singleton pregnancies and who were recruited between October 31, 2005, and January 11, 2008. Follow-up of children (n = 726) was completed December 16, 2009.
Docosahexaenoic acid-rich fish oil capsules (providing 800 mg/d of DHA) or matched vegetable oil capsules without DHA from study entry to birth.
High levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale at 6 weeks or 6 months postpartum. Cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition, at 18 months.
Of 2399 women enrolled, 96.7% completed the trial. The percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups (9.67% vs 11.19%; adjusted relative risk, 0.85; 95% confidence interval [CI], 0.70-1.02; P = .09). Mean cognitive composite scores (adjusted mean difference, 0.01; 95% CI, -1.36 to 1.37; P = .99) and mean language composite scores (adjusted mean difference, -1.42; 95% CI, -3.07 to 0.22; P = .09) of children in the DHA group did not differ from children in the control group.
The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood.
anzctr.org.au Identifier: ACTRN12605000569606.
Decreased tissue levels of n-3 (omega-3) fatty acids, particularly docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and postpartum depression. This study examined the effects of a diet-induced loss of brain DHA content and concurrent reproductive status on dopaminergic parameters in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 20-22% lower than those fed a control diet containing adequate alpha-linolenic acid. Decreased brain DHA produced a significant main effect of decreased density of ventral striatal D(2)-like receptors. Virgin females with decreased DHA also exhibited higher density of D(1)-like receptors in the caudate nucleus than virgin females with normal DHA. These receptor alterations are similar to those found in several rodent models of depression, and are consistent with the proposed hypodopaminergic basis for anhedonia and motivational deficits in depression.
Anthropometry or human body measurements provide important indicators of nutritional status in children and adults (1). In children, measurements reflect general health status, dietary adequacy, and growth and development over time. In adults, body measurements are used to evaluate health and dietary status, disease risk, and body composition. This report presents anthropometric reference data for 2011-2014 for U.S. children and adults. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.
This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations.
A simple system is described to analyze the possibility that increased exploratory behavior is an index for the anxiolytic effects of benzodiazepines in laboratory rodents. Mice were allowed free run in a two-chambered arena, where two-thirds of the area was illuminated and one-third was darkened. The two chambers were separated by a black partition equipped with photocells across the opening, and the entire cage rested on an Animex activity monitor. Transitions across the partition between the light and dark chambers, and total Animex locomotor activity, were increased by clonazepam and chlordiazepoxide, in dose-dependent ranges consistent with previously reported behavior models. The increased exploratory activity with benzodiazepines does not appear to be a non-specific increase in general motor activity, as locomotion in clonazepam and chlordiazepoxide treated mice placed in a bare, undifferentiated cage was not significantly different from vehicle treated mice.
Although several epidemiological studies have reported that higher intake of n-3 long-chain polyunsaturated fatty acids during pregnancy is associated with both a reduced risk of postpartum depression and improved neurodevelopmental outcomes in offspring, the results of other intervention trials have been inconsistent. Despite the uncertainty of benefit, there are now international recommendations for pregnant women to increase their intake of docosahexaenoic acid (DHA), the n-3 long-chain polyunsaturated fatty acids believed to be responsible for the improved outcomes. The DHA to Optimize Mother Infant Outcome (DOMINO) study was a double-blind, multicenter, randomized controlled trial designed primarily to determine whether DHA supplementation during the last half of pregnancy would reduce the risk of maternal postpartum depression and improve early neurodevelopmental outcome of offspring. The study subjects were 2399 women with singleton pregnancies <21 weeks' gestation who were enrolled in 5 Australian maternity hospitals between 2005 and 2008, and 726 offspring who were followed up until 18 months of age. The women were randomly assigned to receive fish oil capsules providing 800 mg/d of DHA (n = 1197) or identical capsules without DHA (n = 1202). The level of postpartum depression was evaluated using a self-reported Edinburgh Postnatal Depression Scale (EPDS). A score >12 on the EPDS at 6 weeks or 6 months postpartum indicated a high level of depression. In the offspring, neurodevelopmental outcomes were compared at 18 months of age in the DHA group (n = 351) and the control group (n = 375) using the Cognitive and Language Composite Scales of the Bayley Scales of Infant and Toddler Development, Third Edition. More than 96% of the 2399 enrolled women completed the trial. There was no significant difference between the DHA and control groups in the percentage of women reporting high levels of depressive symptoms (EPDS score >12) at 6 weeks (DHA group: 9.6% vs. control group: 10.9%) or 6 months postpartum (9.7% vs. 11.5%); the adjusted relative risks were 0.87 (95% confidence interval [CI], 0.68–1.10; P = 0.24) and 0.83 (95% CI, 0.66–1.05; P = 0.11). Similarly, there was no significant difference between children in the DHA group and those in the control group with respect to mean cognitive scores (adjusted mean difference, 0.01; 95% CI, −1.36 to 1.37; P = 0.99) and mean language composite scores (adjusted mean difference, −1.42; 95% CI, −3.07 to 0.22; P = 0.09). These findings provide no support for routine supplementation with DHA in pregnant women, either to reduce symptoms of postpartum depression or to improve neurodevelopmental cognitive or language outcomes in early childhood.
Inflammation is a condition which contributes to a range of human diseases. It involves a multitude of cell types, chemical mediators, and interactions. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids found in oily fish and fish oil supplements. These fatty acids are able to partly inhibit a number of aspects of inflammation including leukocyte chemotaxis, adhesion molecule expression and leukocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines, and T-helper 1 lymphocyte reactivity. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of marine n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor peroxisome proliferator activated receptor γ and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked, although the full extent of this is not yet elucidated. Animal experiments demonstrate benefit from marine n-3 fatty acids in models of rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in RA demonstrate benefit, but clinical trials of fish oil in IBD and asthma are inconsistent with no overall clear evidence of efficacy. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance."
Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized.
Although lower levels of omega-3 polyunsaturated fatty acids (PUFAs) are found in major depressive disorder, less is known about PUFA status and anxiety disorders.
Medication-free participants with DSM-IV-defined major depressive disorder (MDD), with (n = 18) and without (n = 41) comorbid DSM-IV anxiety disorders, and healthy volunteers (n = 62) were recruited from October 2006 to May 2010 for mood disorder studies at the New York State Psychiatric Institute. Participants were 18-73 years of age (mean age, 35.8 ± 12.6 years). Depression and anxiety severity was assessed using depression and anxiety subscales from the 17-item Hamilton Depression Rating Scale. Plasma PUFAs eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) and the ratio of arachidonic acid (AA; 22:4n-6) to EPA (AA:EPA) were quantified. This secondary analysis employed analysis of variance with a priori planned contrasts to test for diagnostic group differences in log-transformed PUFA levels (logDHA, logEPA, and logAA:EPA).
Plasma levels of logDHA (F2,118 = 4.923, P = .009), logEPA (F2,118 = 6.442, P = .002), and logAA:EPA (F2,118 = 3.806, P = .025) differed across groups. Participants with MDD had lower logDHA (t118 = 2.324, P = .022) and logEPA (t118 = 3.175, P = .002) levels and higher logAA:EPA levels (t118 = -2.099, P = .038) compared with healthy volunteers. Lower logDHA (t118 = 2.692, P = .008) and logEPA (t118 = 2.524, P = .013) levels and higher logAA:EPA levels (t118 = -2.322, P = .022) distinguished anxious from nonanxious MDD. Depression severity was not associated with PUFA plasma levels; however, anxiety severity across the entire sample correlated negatively with logDHA (rp = -0.22, P = .015) and logEPA (rp = -0.25, P = .005) levels and positively with logAA:EPA levels (rp = 0.18, P = .043).
The presence and severity of comorbid anxiety were associated with the lowest EPA and DHA levels. Further studies are needed to elucidate whether omega-3 PUFA supplementation may preferentially alleviate MDD with more severe anxiety.
Depression during pregnancy has adverse consequences for both mother and child. Although common in western countries, depression appears to be virtually absent in countries with high seafood intake. We test the hypothesis that low seafood intake during pregnancy is associated with increased prevalence of depressive symptoms.
This study used data prospectively collected from women participating in the Avon Longitudinal Study of Parents and Children in the period 1991-1992. At 32 weeks' gestation, the mother completed a questionnaire that included symptoms of depression and a food frequency questionnaire from which the amount of omega-3 fatty acids from fish was calculated. Statistical analysis took social and lifestyle factors into account.
Unadjusted and adjusted analyses showed lower maternal intake of omega-3 from seafood was associated with high levels of depressive symptoms. Compared with women consuming more than 1.5 g omega-3 from seafood per week, those consuming none were more likely to have high levels of depressive symptoms at 32 weeks' gestation (adjusted odds ratios = 1.54; 95% confidence interval = 1.25-1.89).
These observational data support an association between low omega-3 intake from seafood and increased risk of high levels of depressive symptoms during pregnancy. Eating seafood during pregnancy may have beneficial effects on mental well-being.
Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid (DHA), has been associated with perinatal depression, but there is evidence that supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA in treating depressive symptoms. This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression.
We enrolled 126 pregnant women at risk for depression (Edinburgh Postnatal Depression Scale score 9-19 or a history of depression) in early pregnancy and randomly assigned them to receive EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA), or soy oil placebo. Subjects completed the Beck Depression Inventory (BDI) and Mini-International Neuropsychiatric Interview at enrollment, 26-28 weeks, 34-36 weeks, and at 6-8 weeks' postpartum. Serum fatty acids were analyzed at entry and at 34-36 weeks' gestation.
One hundred eighteen women completed the trial. There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation. The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively. Serum DHA- concentrations at 34-36 weeks were inversely related to BDI scores in late pregnancy.
EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum.
Brain docosahexaenoic acid (DHA, 22:6n-3) accumulates rapidly during brain development and is essential for normal neurological function. The aim of this study was to evaluate whether brain development was the critical period in which DHA deficiency leads to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress later in life. Rats were exposed to an n-3 fatty acid-deficient diet or the same diet supplemented with fish oil as an n-3 fatty acid-adequate diet either throughout the preweaning period from embryo to weaning at 3 weeks old or during the postweaning period from 3 to 10 weeks old. Exposure to the n-3 fatty acid-deficient diet during the preweaning period resulted, at weaning, in a significant decrease in hypothalamic DHA levels and a reduced male offspring body weight. DHA deficiency during the preweaning period significantly increased and prolonged restraint stress-induced changes in colonic temperature and serum corticosterone levels, caused a significant increase in GABA(A) antagonist-induced heart rate changes and enhanced depressive-like behavior in the forced swimming test and anxiety-like behavior in the plus-maze test in later life. These effects were not seen in male rats fed the n-3 fatty acid-deficient diet during the postweaning period. These results suggest that brain development is the critical period in which DHA deficiency leads to excessive HPA responses to stress and elevated behavioral indices of depression and anxiety in adulthood. We propose that these effects of hypothalamic DHA deficiency during brain development may involve a GABA(A) receptor-mediated mechanism.
This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST). A behavior sampling technique was developed to score the active behaviors swimming, climbing and diving, as well as immobility. The rat's behavior was recorded at the end of each 5-s period during the test session. The sampling technique was both reliable, as demonstrated by test-retest reliability and inter-rater reliability, and valid, as shown by comparison to the timing of behavior durations. Five different antidepressant drugs which block monoamine uptake and two 5-HT1A receptor agonists were shown to decrease immobility in the FST; however, they produced distinct patterns of active behaviors. The selective NE uptake inhibitors desipramine and maprotiline selectively increased climbing, whereas the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline and paroxetine selectively increased swimming. The 5-HT1A receptor agonists 8-OH-DPAT and gepirone also selectively increased swimming. These results show that:1) SSRIs are not false negatives in the FST; 2) at least two behaviorally distinct processes occur in the FST; and 3) enhancement of NE neurotransmission may mediate climbing in the FST, whereas enhancement of 5-HT neurotransmission may mediate swimming.
A simple system is described to analyze the possibility that increased exploratory behavior is an index for the anxiolytic effects of benzodiazepines in laboratory rodents. Mice were allowed free run in a two-chambered arena, where two-thirds of the area was illuminated and one-third was darkened. The two chambers were separated by a black partition equipped with photocells across the opening, and the entire cage rested on an Animex activity monitor. Transitions across the partition between the light and dark chambers, and total Animex locomotor activity, were increased by clonazepam and chlordiazepoxide, in dose-dependent ranges consistent with previously reported behavior models. The increased exploratory activity with benzodiazepines does not appear to be a non-specific increase in general motor activity, as locomotion in clonazepam and chlordiazepoxide treated mice placed in a bare, undifferentiated cage was not significantly different from vehicle treated mice.
Observational studies suggest association between low concentrations of omega-3 family fatty acids and greater risk for post-partum depression (PPD). The objective was to investigate the effect of unbalanced dietary intake of omega-6/omega-3 ratio >9:1 in the prevalence for PPD. The study comprises a prospective cohort with four waves of follow-up during pregnancy and one following delivery. PPD was evaluated according to the Edinburgh Post-partum Depression Scale (PPD ≥ 11) in 106 puerperae between 2005 and 2007, in Rio de Janeiro, Brazil. Independent variables included socio-demographic, obstetric, pre-pregnancy body mass index (BMI) and dietary intake data, which were obtained by means of a food frequency questionnaire in the first trimester of pregnancy. Statistical analysis involved calculation of PPD prevalence and multivariate Poisson regression with robust variance. PPD prevalence amounted to 26.4% [n = 28; confidence interval (CI) 95%: 18.0-34.8], and higher prevalences of PPD were observed in women who consumed an omega-6/omega-3 ratio >9:1 (60.0%) and in those with pre-pregnancy BMI <18.5 kg/m(2) (66.7%). These variables held as factors associated to PPD in the multivariate model, elevating the chances of occurrence of the outcome in 2.50 (CI 95%: 1.21-5.14) and 4.01 times (CI 95%: 1.96-8.20), respectively. Analyses were adjusted for age, schooling, pre-pregnancy BMI, lipids consumption and time elapsed since delivery. It verified an association between omega-6/omega-3 ratio above 9:1, the levels recommended by the Institute of Medicine, and the prevalence of PPD. These results add to the evidence regarding the importance of omega-6 and omega-3 fatty acids in the regulation of mental health mechanisms.
Epidemiological data and clinical trials suggest that n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have preventive and therapeutic effects on depression; however, the underlying mechanism remains elusive. The present study aimed to examine the behavioral effects and antidepressant mechanism of n-3 PUFA using a forced swimming test. Eleven-week-old male Sprague-Dawley rats were fed an American Institute of Nutrition-93M diet containing 0%, 0.5% or 1% EPA and DHA relative to the total energy intake in their diet for 12 weeks (n=8 per group). Total dietary intake, body weight and hippocampus weights were not significantly different among groups. The groups administered 0.5% and 1% EPA+DHA diets had significantly higher levels of n-3 PUFA in their brain phospholipids compared to those in the control group. The immobility time was significantly decreased and the climbing time was significantly increased in the 0.5% and 1% EPA+DHA groups compared with those in the 0% EPA+DHA group. Plasma serotonin concentration and hippocampus c-AMP response element binding protein (CREB) expression were significantly increased in the 0.5% and 1% EPA+DHA groups compared with those in the 0% EPA+DHA group. Conversely, interleukin (IL)-6 expression was significantly reduced in the 0.5% and 1% EPA+DHA groups compared with that in the 0% EPA+DHA group. However, there were no dose-dependent effects of n-3 PUFA and no significant differences in expressions of IL-1β, tumor necrosis factor-α, brain-derived neurotrophic factor or phosphorylated CREB. In conclusion, long-term intake of EPA+DHA induced antidepressant-like effects in rats and overexpression of CREB via decreased IL-6 expression.
Docosahexaenoic acid (DHA) and arachidonic acid (AA) are the major polyunsaturated fatty acids (PUFA) in the neuronal membrane. Most DHA and AA accumulation in the brain occurs during the perinatal period via placenta and milk. This study examined whether maternal brain levels of DHA and AA are depleted during pregnancy and lactation due to meeting the high demand of the developing nervous system in the offspring and evaluated the effects of the reproductive cycle on serotonin metabolism and of fish oil (FO) on postpartum anxiety. Pregnant rats were fed during pregnancy and lactation with a sunflower oil-based n-3 PUFA-deficient diet without or with FO supplementation, which provided 0.37% of the energy source as n-3 PUFA, and the age-matched virgin rats were fed the same diets for 41 days. In both sets of postpartum rats, decreased DHA levels compared to those in virgin females were seen in the hypothalamus, hippocampus, frontal cortex, cerebellum, olfactory bulb and retina, while AA depletion was seen only in the hypothalamus, hippocampus and frontal cortex. Serotonin levels were decreased and turnover increased in the brainstem and frontal cortex in postpartum rats compared to virgin rats. FO supplementation during pregnancy and lactation prevented the decrease in maternal brain regional DHA levels, inhibited monoamine oxidase-A activity in the brainstem and decreased anxiety-like behavior. We propose that the reproductive cycle depletes maternal brain DHA levels and modulates maternal brain serotonin metabolism to cause postpartum anxiety and suggest that FO supplementation may be beneficial for postpartum anxiety in women on an n-3 PUFA-deficient diet.
Recent evidence has demonstrated dietary influence on the manifestation of different types of behaviors induced by stressor tasks. The present study examined the impact of ω-3 polyunsaturated fatty acids (PUFAs) supplementation in an early phase of the brain development with the goal of preventing or even attenuating the occurrence of stress-related behaviors such as depressive-like behaviors, anxiety and cognitive dysfunctions in male rats subjected to restraint stress. Our results indicated that the supplementation regimen successfully counteracted the anxiogenic effects of stress as evidenced by the rats' increased exploration time in the aversive arms of the elevated plus maze. The forced swimming test indicated that immobility and swimming were more deeply influenced by PUFAs supplementation, thereby demonstrating an antidepressant effect. Furthermore, cognitive function was shown to be intensely affected by restraint stress, but the effects were surprisingly counteracted by the PUFAs supplementation. Lastly, plasmatic corticosterone levels were demonstrated to be drastically increased by the restraint stress; however, PUFAs supplementation promoted a reduction of this stress-related hormone to levels that were comparable to those observed in the control group. Our results suggested that the mechanisms underlying these effects are possibly associated with the reduction of corticosterone levels promoted by the PUFAs supplementation in the stress-induced animals. Further studies to examine the participation of PUFAs in mediating different behaviors in rats subjected to restraint stress are warranted.
Despite the advances in psychopharmacology, the treatment of depressive disorders is still not satisfactory. Side effects and resistance to antidepressant drugs are the greatest complications during treatment. Based on recent evidence, omega-3 fatty acids may influence vulnerability and outcome in depressive disorders. The aim of this study was to further characterize the omega-3 antidepressant-like effect in rats in terms of its behavioral features in the depression model forced swimming test either alone or in combination with antidepressants fluoxetine or mirtazapine. Ultimately, we prompted to determine the lowest dose at which omega-3 fatty acids and antidepressant drugs may still represent a pharmacological advantage when employed in combined treatments. Chronic diet supplementation with omega-3 fatty acids produced concentration-dependent antidepressant-like effects in the forced swimming test displaying a behavioral profile similar to fluoxetine but different from mirtazapine. Fluoxetine or mirtazapine at antidepressant doses (10 and 20 mg/kg/day, respectively) rendered additive effects in combination with omega-3 fatty acid supplementation (720 mg/kg/day). Beneficial effects of combined treatment were also observed at sub-effective doses (1 mg/kg/day) of fluoxetine or mirtazapine, since in combination with omega-3 fatty acids (720 mg/kg/day), antidepressants potentiated omega-3 antidepressant-like effects. The antidepressant-like effects occurred in the absence of changes in brain phospholipid classes. The therapeutic approach of combining omega-3 fatty acids with low ineffective doses of antidepressants might represent benefits in the treatment of depression, especially in patients with depression resistant to conventional treatments and even may contribute to patient compliance by decreasing the magnitude of some antidepressant dose-dependent side effects.
Learned helplessness in animals has been used to model disorders such as depression and post-traumatic stress disorder (PTSD), but there is a lack of knowledge concerning which individual behavioral characteristics at baseline can predict helpless behavior after exposure to inescapable stress. The first aim of this study was to determine behavioral predictors of helplessness using the novel and familiar open-field tests, sucrose consumption, and passive harm-avoidance tasks before learned helplessness training and testing. Individual differences in physiologic responses to restraint stress were also assessed. A cluster analysis of escape latencies from helplessness testing supported the division of the sample population of Holtzman rats into approximately 50% helpless and 50% non-helpless. Linear regression analyses further revealed that increased reactivity to the novel environment, but not general activity or habituation, predicted susceptibility to learned helplessness. During restraint stress there were no mean differences in heart rate, heart rate variability, and plasma corticosterone between helpless and non-helpless rats; however, a lower heart rate during stress was associated with higher activity levels during exploration. Our most important finding was that by using an innocuous screening tool such as the novel and familiar open-field tests, it was possible to identify subjects that were susceptible to learned helplessness.
Antidepressants require adaptive brain changes before efficacy is achieved, and they may impact the affectively disordered brain differently than the normal brain. We previously demonstrated metabolic disturbances in limbic and cortical regions of the congenitally helpless rat, a model of susceptibility to affective disorder, and we wished to test whether administration of fluoxetine would normalize these metabolic differences. Fluoxetine was chosen because it has become a first-line drug for the treatment of affective disorders. We hypothesized that fluoxetine antidepressant effects may be mediated by decreasing metabolism in the habenula and increasing metabolism in the ventral tegmental area. We measured the effects of fluoxetine on forced swim behavior and regional brain cytochrome oxidase activity in congenitally helpless rats treated for 2 weeks with fluoxetine (5mg/kg, i.p., daily). Fluoxetine reduced immobility in the forced swim test as anticipated, but congenitally helpless rats responded in an atypical manner, i.e., increasing climbing without affecting swimming. As hypothesized, fluoxetine reduced metabolism in the habenula and increased metabolism in the ventral tegmental area. In addition, fluoxetine reduced the metabolism of the hippocampal dentate gyrus and dorsomedial prefrontal cortex. This study provided the first detailed mapping of the regional brain effects of an antidepressant drug in congenitally helpless rats. All of the effects were consistent with previous studies that have metabolically mapped the effects of serotonergic antidepressants in the normal rat brain, and were in the predicted direction of metabolic normalization of the congenitally helpless rat for all affected brain regions except the prefrontal cortex.
Insufficient availability of n-3 polyunsaturated fatty acids (PUFA) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain. Low tissue levels of DHA are associated with neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD). In this study, 1st- and 2nd-litter male Long-Evans rats were raised from conception on a Control diet containing alpha-linolenic acid (4.20 g/kg diet), the dietarily essential fatty acid precursor of DHA, or a diet Deficient in alpha-linolenic acid (0.38 g/kg diet). The Deficient diet resulted in a decrease in brain phospholipid DHA of 48% in 1st-litter pups and 65% in 2nd-litter pups. Activity, habituation, and response to spatial change in a familiar environment were assessed in a single-session behavioral paradigm at postnatal days 28 and 70, inclusive. Activity and habituation varied by age with younger rats exhibiting higher activity, less habituation, and less stimulation of activity induced by spatial novelty. During the first and second exposures to the test chamber, 2nd-litter Deficient pups exhibited higher levels of activity than Control rats or 1st-litter Deficient pups, and less habituation during the first exposure, but were not more active after introduction of a novel spatial stimulus. The higher level of activity in a familiar environment, but not after introduction of a novel stimulus is consistent with clinical observations in ADHD. The observation of this effect only in 2nd-litter rats fed the Deficient diet suggests that brain DHA content, rather than dietary n-3 PUFA content, likely underlies these effects.