title: Abnormal fatty acid composition in the frontopolar cortex of patients with affective disorders.
abstract: Bipolar and major depressive disorders are essentially relapsing and remitting disorders of affect with nearly full recovery between episodes. Although the underlying molecular mechanisms remain unclear, myelin-related abnormalities have long been suspected. Here, using novel statistical analysis, we show that subtle but significant abnormalities exist in the composition of fatty acids (FAs), including docosapentaenoic acid (22:5n-3), one of the omega-3 polyunsaturated FAs, found in the post-mortem frontopolar cortex (FPC) of subjects with bipolar or major depressive disorders, although not in those with schizophrenia. These abnormalities were all aggravated in a myelin level-dependent manner, suggesting their close relationship with myelination. Animal studies have further revealed that chronic antidepressant treatment induces robust changes in brain FA metabolism, but contributes only part of the abnormalities found in the affective disorder brains. These findings indicate that the pathophysiology of affective disorders involves an unknown type of perturbed myelination in the FPC that may serve as a novel diagnostic and therapeutic target.
authors.affiliation: Affective Disorders Research Team, Schizophrenia and Affective Disorders Research Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan. tatebayashi-ys@igakuken.or.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tatebayashi
authors.forename: N
authors.initials: N
authors.lastname: Nihonmatsu-Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: M
authors.initials: M
authors.lastname: Soma
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis*; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012559:Schizophrenia / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; C026219:docosapentaenoic acid