Relationship between omega-3 fatty acids and plasma neuroactive steroids in alcoholism, depression and controls

Deficiency in the long-chain ω-3 fatty acid, docosahexaenoic acid (DHA) has been associated with increased corticotropin releasing hormone and may contribute to hypothalamic pituitary axis (HPA) hyperactivity. Elevated levels of the neuroactive steroids, allopregnanolone (3α,5α-THP) and 3α,5α-tetrahydrodeoxycorticosterone (THDOC) appear to counter-regulate HPA hyperactivity. Plasma essential fatty acids and neurosteroids were assessed among 18 male healthy controls and among 34 male psychiatric patients with DSM-III alcoholism, depression, or both. Among all subjects, lower plasma DHA was correlated with higher plasma THDOC (r=−0.3, P<0.05) and dihydroprogesterone (DHP) (r=−0.52, P<0.05). Among psychiatric patients lower DHA was correlated with higher DHP (r=−0.60, P<0.01), and among healthy controls lower plasma DHA was correlated with higher THDOC (r=−0.83, P<0.01) and higher isopregnanolone (3β,5α-THP) (r=−0.55, P<0.05). In this pilot observational study, lower long-chain ω-3 essential fatty acid status was associated with higher neuroactive steroid concentrations, possibly indicating increased feedback inhibition of the HPA axis.