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

Transl Psychiatry. 2018 Dec 14;8(1):279. doi: 10.1038/s41398-018-0309-1.

Abstract

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-HT1A, and 5-HT2A 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-HT1A binding was greater in suicides (p < 0.001), independent of MDD (p = 0.168). Alcoholism was associated with higher 5-HT1A binding (p < 0.001) but only in suicides (p < 0.001). 5-HT2A 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-HT1A binding (p = 0.004) in nonsuicides and higher 5-HT2A binding (p < 0.001). Low SERT and more 5-HT1A and 5-HT2A 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adverse Childhood Experiences*
  • Alcoholism / metabolism*
  • Autoradiography
  • Brain / metabolism*
  • Brain / physiopathology
  • Depressive Disorder, Major / metabolism*
  • Female
  • Gyrus Cinguli / metabolism
  • Gyrus Cinguli / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Suicide*

Substances

  • Receptor, Serotonin, 5-HT2A
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Receptor, Serotonin, 5-HT1A