No abstract

A body of evidence has implicated dietary deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of recurrent mood disorders including major depressive disorder (MDD) and bipolar disorder. Cross-national and cross-sectional evidence suggests that greater habitual intake of n-3 PUFA is associated with reduced risk for developing mood symptoms. Meta-analyses provide strong evidence that patients with mood disorders exhibit low blood n-3 PUFA levels which are associated with increased risk for the initial development of mood symptoms in response to inflammation. While the etiology of this n-3 PUFA deficit may be multifactorial, n-3 PUFA supplementation is sufficient to correct this deficit and may also have antidepressant effects. Rodent studies suggest that n-3 PUFA deficiency during perinatal development can recapitulate key neuropathological, neurochemical, and behavioral features associated with mood disorders. Clinical neuroimaging studies suggest that low n-3 PUFA biostatus is associated with abnormalities in cortical structure and function also observed in mood disorders. Collectively, these findings implicate dietary n-3 PUFA insufficiency, particularly during development, in the pathophysiology of mood dysregulation, and support implementation of routine screening for and treatment of n-3 PUFA deficiency in patients with mood disorders.

The skin flush response to niacin is abnormally blunted among a subset of patients with schizophrenia (SZ), preferentially associates with SZ compared to other mental illnesses, occurs frequently in nonpsychotic members of SZ-affected families, appears heritable, and shows evidence of genetic association. The niacin response abnormality (NRA) may prove to be a useful SZ endophenotype. Using a laser Doppler flowmeter, we undertook this study to estimate the prevalence of NRA in SZ (n = 70), bipolar disorder (BP, n = 59), and healthy control (HC, n = 87) groups, and to estimate its specificity for the illness. From the dose-response curves, we calculated the concentration of methylnicotinate required to elicit a half-maximal blood flow (MBF) response (EC50 value) and MBF value for each subject. The median log10EC50 of the SZ was above the third quartile of log10EC50 of either the HC or BP groups, whereas the MBF was significantly lower in the SZ than in the HC or BP groups. With a definition of NRA of having both EC50 above the ninetieth percentile of the control samples and MBF response below the sixtieth percentile for the control range, the NRA predicted SZ with 31% sensitivity and 97% specificity. Moreover, the NRA was not influenced by age, gender, race, and cigarette smoking. In summary, the NRA may define a SZ subtype with a clinically significant phospholipid signaling defect. Understanding its molecular origins may shed light on the pathophysiology of SZ and suggest new tools for its early diagnosis and treatment.

A body of translational evidence has implicated dietary deficiency in long-chain omega-3 (LCn-3) fatty acids, including eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and potentially etiology of different psychiatric disorders. Case–control studies have consistently observed low erythrocyte (red blood cell) EPA and/or DHA levels in patients with major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Low erythrocyte EPA + DHA biostatus can be treated with fish oil-based formulations containing preformed EPA + DHA, and extant evidence suggests that fish oil supplementation is safe and well-tolerated and may have therapeutic benefits. These and other data provide a rationale for screening for and treating LCn-3 fatty acid deficiency in patients with psychiatric illness. To this end, we have implemented a pilot program that routinely measures blood fatty acid levels in psychiatric patients entering a residential inpatient clinic. To date over 130 blood samples, primarily from patients with treatment-refractory mood or anxiety disorders, have been collected and analyzed. Our initial results indicate that the majority (75 %) of patients exhibit whole blood EPA + DHA levels at ≤4 percent of total fatty acid composition, a rate that is significantly higher than general population norms (25 %). In a sub-set of cases, corrective treatment with fish oil-based products has resulted in improvements in psychiatric symptoms without notable side effects. In view of the urgent need for improvements in conventional treatment algorithms, these preliminary findings provide important support for expanding this approach in routine psychiatric practice.