title: Relationship between the hypothalamic-pituitary-adrenal-axis and fatty acid metabolism in recurrent depression.
abstract: Alterations in hypothalamic-pituitary-adrenal (HPA)-axis activity and fatty acid (FA)-metabolism have been observed in (recurrent) major depressive disorder (MDD). Through the pathophysiological roles of FAs in the brain and cardiovascular system, a hypothesized relationship between HPA-axis activity and FA-metabolism could form a possible missing link accounting for the association of HPA-axis hyperactivity with recurrence and cardiovascular disease in MDD. In 137 recurrent MDD-patients and 73 age- and sex-matched controls, we therefore investigated associations between salivary cortisol (morning and evening) and the following indicators of FA-metabolism measured in the red blood cell membrane: (I) three main FAs [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)], and (II) structural FA indices (unsaturation, chain length, peroxidation) calculated from concentrations of 29 FAs to delineate overall FA-characteristics. In addition, we compared these associations in patients with those in controls. In patients, evening cortisol concentrations were significantly negatively associated with DHA (B=-1.358; SE=0.499; t=-2.72; p=.006), the unsaturation index (B=-0.021; SE=0.009; t=-2.42; p=.018), chain length index (B=-0.060; SE=0.025; t=-2.41; p=.019), and peroxidation index (B=-0.029; SE=0.012; t=-2.48; p=.015). The relations between cortisol and the latter three variables were significantly negative in patients relative to controls. Significance remained after correction for confounders. Our results suggest a relationship between HPA-axis activity and FA-metabolism in recurrent MDD. Future randomized experimental intervention studies using clinical outcome measures could help to further elucidate the suggested effects of hypercortisolemia in the brain and cardiovascular system in recurrent MDD.
authors: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: R.J.Mocking@amc.uva.nl.
authors: Roel J T
authors: RJ
authors: Mocking
authors: Henricus G
authors: HG
authors: Ruhé
authors: Johanna
authors: J
authors: Assies
authors: Anja
authors: A
authors: Lok
authors: Maarten W J
authors: MW
authors: Koeter
authors: Ieke
authors: I
authors: Visser
authors: Claudi L H
authors: CL
authors: Bockting
authors: Aart H
authors: AH
authors: Schene
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000097:blood; D002940:Circadian Rhythm; D003866:Depressive Disorder / Q000097:blood / Q000503:physiopathology*; D004281:Docosahexaenoic Acids / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000097:blood; D004910:Erythrocyte Membrane / Q000737:chemistry; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008297:Male; D008563:Membrane Lipids / Q000097:blood*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012008:Recurrence; D012636:Secretory Rate; D012959:Socioeconomic Factors
chemical_list: D005227:Fatty Acids; D008563:Membrane Lipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid
keywords: Cortisol; Depressive disorder; Docosahexaenoic acids; Eicosapentaenoic acid; Fatty acids; Glucocorticoids; Major; Metabolic networks and pathways; Psychiatry; Recurrence; n-3 PUFA