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Omega-3s, neural networks and mental health

Omega-3s and mental health.jpg
Research indicates that EPA and DHA omega-3s may affect the brain’s corticolimbic circuit maturation.

Mood disorders, including major depressive disorder, bipolar disorder and anxiety disorders are among the most common psychiatric disorders and are a major cause of disability globally.1 These disorders are associated with psychosocial impairment and excess premature mortality attributable to suicide and cardiovascular-related disorders.2,3,4 Once established, these disorders are typically treated with medications that often have undesirable side-effects and limited long-term efficacy.5,6,7 Medication discontinuation frequently leads to symptomatic relapse suggesting that a secondary prevention approach is sub-optimal and does not correct underlying pathophysiology mechanisms. Therefore, developing a clearer understanding of modifiable risk factors associated with the initial development of mood/anxiety dysregulation may offer new opportunities to intervene prior to illness onset, i.e., primary prevention.

Consistent with a neurodevelopmental etiology, mood and anxiety disorders frequently initially emerge in childhood and adolescence. Importantly, this development period is associated with robust changes in the functional and structural maturation of corticolimbic circuitry known to play a key role in regulating mood and anxiety.8,9 Indeed, compelling neuroimaging evidence indicates that mood and anxiety disorders are associated with abnormal corticolimbic circuit connectivity.10,11,12 Therefore, identifying safe and effective interventions to optimize corticolimbic circuit maturation may represent a plausible strategy to mitigate emotional dysregulation in youth.

A growing body of evidence has identified a deficiency in omega-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), as a candidate for a modifiable neurodevelopmental risk for mood and anxiety disorders. This is supported in part by cross-sectional evidence that patients with mood and anxiety disorders exhibit significantly lower blood omega-3 PUFA levels compared with healthy subjects.13,14,15 Importantly, lower blood omega-3 PUFA levels are also observed in first-episode adolescent patients indicating that omega-3 PUFA insufficiency coincides with, and likely precedes, the initial onset of illness.16 Although controversial, controlled intervention trials further suggest that increasing omega-3 PUFA biostatus reduce mood and anxiety symptoms after the disorder has become established.17,18 These and other findings support a potential role of omega-3 PUFA insufficiency in the etiology of mood and anxiety disorders. However, the role of omega-3 PUFAs in corticolimbic circuit maturation is currently poorly understood.

Evidence from animal studies demonstrate that brain DHA levels progressively increase over the course of perinatal development and accumulate in synaptic membranes.19,20 Recent evidence suggests that deficits in perinatal DHA accrual impairs synaptogenesis and synaptic plasticity, as well as synaptic pruning, indicating a potential role in circuit maturation.21,22,23 Like humans, rodent corticolimbic circuitry undergoes substantial maturational changes during adolescent development,24 and deficits in perinatal DHA accrual are associated with elevated behavioral indices of anxiety and depression.25,26 A non-human primate study found that developmental omega-3 PUFA insufficiency reduced resting-state functional connectivity in corticolimbic networks in adulthood.27 Human preterm birth, which reduces fetal DHA accrual, is associated with enduring functional connectivity abnormalities in corticolimbic networks as well as increased risk for mood and anxiety disorders in childhood and adolescence.28,29 While these associations support a potential link between developmental omega-3 PUFA insufficiency, corticolimbic circuit maturation abnormalities, and mood and anxiety disorders, additional research is needed to formally evaluate this mechanism.

Ongoing translational research using different neuroimaging techniques is investigating the relationship between omega-3 PUFA biostatus and corticolimbic circuit connectivity in youth with or at high-risk for mood and anxiety disorders and in rat developmental models. It is anticipated that this research will clarify the role of omega-3 PUFAs in the structural and functional maturation of corticolimbic circuitry, and thereby provide an empirical foundation in support of omega-3 PUFA intervention as a primary prevention strategy to mitigate emotional dysregulation in youth.

Robert K. McNamara, Ph.D., is a professor of psychiatry and neuroscience at the University of Cincinnati College of Medicine.

Register for GOED Exchange 2020, hosted by GOED (the Global Organization of EPA and DHA Omega-3s) to learn more from McNamara during an expert session on omega-3s and brain health. 



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