title: Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder.
abstract: Levels of norepinephrine (NE), serotonin (5-HT), dopamine (DA), and their major metabolites were determined in postmortem brain obtained from nine subjects with antemortem histories meeting DSM-III-R criteria for bipolar affective disorder. Compared with controls, no statistically significant differences were found in mean levels of NE, 5-HT, or DA in any brain area of bipolar subjects. NE turnover as estimated by the ratio of the major NE metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) to NE was increased in frontal (+107%), temporal (+103%), and occipital (+64%) cortex and thalamus (+83%). Significant decreases were found in the major 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA), in frontal (-54%) and parietal cortex (-64%), and in 5-HIAA/5-HT ratio in temporal cortex (-55%), with a trend for decreases in both measures in caudate nucleus. In addition, levels of the major DA metabolite, homovanillic acid (HVA) were significantly decreased (-46%) in parietal cortex and HVA/DA ratios were significantly reduced (-66%) in occipital cortex obtained from bipolar compared to control subjects. Our data, taken together with previous findings regarding monoamines in postmortem brain of depressed and suicide subjects, suggest that decreased 5-HT metabolite levels and turnover may be common to all mood disorders. Increased cortical NE turnover, however, may be a more important component in the pathophysiology of bipolar disorder.
authors.affiliation: Department of Psychiatry, Institute of Medical Science, University of Toronto, Canada.
authors.forename: L T
authors.initials: LT
authors.lastname: Young
authors.forename: J J
authors.initials: JJ
authors.lastname: Warsh
authors.forename: S J
authors.initials: SJ
authors.lastname: Kish
authors.forename: K
authors.initials: K
authors.lastname: Shannak
authors.forename: O
authors.initials: O
authors.lastname: Hornykeiwicz
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D001923:Brain Chemistry; D001931:Brain Mapping; D004298:Dopamine / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000032:analysis / Q000378:metabolism; D008875:Middle Aged; D009638:Norepinephrine / Q000032:analysis* / Q000378:metabolism; D012016:Reference Values; D012701:Serotonin / Q000032:analysis* / Q000378:metabolism; D013405:Suicide / Q000523:psychology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D008094:Lithium; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid