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Serotonin neurotransmitter deficits are reported in suicide, major depressive disorder (MDD) and alcohol use disorder (AUD). To compare pathophysiology in these disorders, we mapped brain serotonin transporter (SERT), 5-HT 1A , and 5-HT 2A  receptor binding throughout prefrontal cortex and in anterior cingulate cortex postmortem. Cases and controls died suddenly minimizing agonal effects and had a postmortem interval ≤24 h to avoid compromised brain integrity. Neuropathology and toxicology confirmed absence of neuropathology and psychotropic medications. For most subjects (167 of 232), a DSM-IV Axis I diagnosis was made by psychological autopsy. Autoradiography was performed in right hemisphere coronal sections at a pre-genual level. Linear model analyses included sex and age with group and Brodmann area as interaction terms. SERT binding was lower in suicides ( p  = 0.004) independent of sex (females < males,  p  < 0.0001), however, the lower SERT binding was dependent on MDD diagnosis ( p  = 0.014). Higher SERT binding was associated with diagnosis of alcoholism ( p  = 0.012). 5-HT 1A  binding was greater in suicides ( p  < 0.001), independent of MDD ( p  = 0.168). Alcoholism was associated with higher 5-HT 1A  binding ( p  < 0.001) but only in suicides ( p  < 0.001). 5-HT 2A  binding was greater in suicides ( p  < 0.001) only when including MDD ( p  = 0.117) and alcoholism ( p  = 0.148) in the model. Reported childhood adversity was associated with higher SERT and 5-HT 1A  binding ( p  = 0.004) in nonsuicides and higher 5-HT 2A  binding ( p  < 0.001). Low SERT and more 5-HT 1A  and 5-HT 2A  binding in the neocortex in depressed suicides is dependent on Axis I diagnosis and reported childhood adversity. Findings in alcoholism differed from those in depression and suicide indicating a distinct serotonin system pathophysiology.

Serotonin receptors and suicide, major depression, alcohol use disorder and reported early life adversity