Neuron density and serotonin receptor binding in prefrontal cortex in suicide

Abstract

Although serotonin receptor and cytoarchitectonic alterations are reported in prefrontal cortex (PFC) in suicide and depression, no study has considered binding relative to neuron density. Therefore, we measured neuron density and SERT, 5-HT1A and 5-HT2A binding in matched suicides and controls. Suicides and normal controls (N=15 matched pairs) were psychiatrically characterized. Neuron density and binding were determined in dorsal (BA9) and ventral (BA47) PFC by stereology and quantitative autoradiography in near-adjacent sections. Binding index was defined as the ratio of receptor binding to neuron density. Suicides had lower neuron density in the gyrus of both areas. The binding index was lower for the serotonin transporter in BA47 but not in BA9; the 5-HT1A binding index was higher in BA9 but not in BA47, while the 5-HT2A binding index was not different between groups. SERT binding was lower in suicides in BA47 but not BA9, while 5-HT1A binding was higher in BA9 but not BA47. SERT binding negatively correlated with 5-HT1A binding in BA47 in suicides. Neuron density decreased with age. 5-HT1A binding index was higher in females than males. We found lower neuron density and lower SERT binding index in both PFC regions in suicides. More 5-HT1A binding with less SERT binding and the negative correlation in depressed suicides suggests post-synaptic receptor upregulation, and it is independent of the difference in neuron density. Thus, abnormalities in both cortical neurons and in their serotonergic innervation are present in suicides and future studies need to determine whether cortical changes reflect the trophic effect of altered serotonin innervation.

Correlation between Bipolar Affective Disorder and Suicide reviewing by the risk factors: a systematic review

“…The reduction in 5-HT2A levels is also in concordance with another study comparing suicide versus non-suicide schizophrenia subjects using also Affymetrix microarrays, suggesting that this reduction in 5-HT2A levels might be involved in suicide irrespective of the diagnosis. We also observed decreased expression in suicide group of the brain specific ADCY1, a brain specific form of adenylate cyclase, suggesting altered neurotransmission and cyclic AMP signaling in suicide and confirms previous observations pointing to cAMP signaling alterations in suicide and mood disorders and in animal models of depression [136][137][138][139][140][141][142][143][144][145]. Both serotonergic alterations and second messenger systems underline global neurotransmission alterations in the DLPFC that seem to play a role in the predisposition to commit suicide [128].…”

Transcriptional regulation of the 5-HT1Areceptor: implications for mental illness

“…Consistent with this, 5-HT 1A autoreceptor levels negatively correlate with levels of the plasmalemmal 5-HT transporter (SERT) in PET studies [137,138], and in post-mortem studies [108,139]. Interestingly, increased 5-HT 1A autoreceptor binding is associated with reduced response to antidepressants [102,140], which could reflect greater autoreceptor-mediated inhibition of 5-HT.…”

Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals

“…34 Moreover, postmortem studies have consis tently shown neurochemical evidence of serotonergic hypo function in victims of suicide. [35][36][37] We hypothesized that de pressed individuals would display an inflammatory profile characterized by increased cytokine expression that would correlate with increased KP activity. Results of the present study did not confirm our assumptions.…”