TY  - JOUR
PY  - 2018//
TI  - Serotonin receptors and suicide, major depression, alcohol use disorder and reported early life adversity
JO  - Translational psychiatry
A1  - Underwood, Mark D.
A1  - Kassir, Suham A.
A1  - Bakalian, Mihran J.
A1  - Galfalvy, Hanga
A1  - Dwork, Andrew J.
A1  - Mann, J. John
A1  - Arango, Victoria
SP  - 279
EP  - 279
VL  - 8
IS  - 1
N2  - 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<sub>1A</sub>, and 5-HT<sub>2A</sub> 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<sub>1A</sub> binding was greater in suicides (p < 0.001), independent of MDD (p = 0.168). Alcoholism was associated with higher 5-HT<sub>1A</sub> binding (p < 0.001) but only in suicides (p < 0.001). 5-HT<sub>2A</sub> 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<sub>1A</sub> binding (p = 0.004) in nonsuicides and higher 5-HT<sub>2A</sub> binding (p < 0.001). Low SERT and more 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> binding in the neocortex in depressed suicides is dependent on Axis I diagnosis and reported childhood adversity. <br><br>FINDINGS in alcoholism differed from those in depression and suicide indicating a distinct serotonin system pathophysiology.<p />  <p>Language: en</p>
LA  - en
SN  - 2158-3188
UR  - http://dx.doi.org/10.1038/s41398-018-0309-1
ID  - ref1
ER  -