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 pathophysiological of bipolar disorder.