Disconnect Between Brainstem Serotonin Neurons And Prefrontal Cortex Serotonin Receptors In Suicide

Abstract

Serotonin neurotransmission is widely reported as reduced in suicide attempt and completion. Evidence suggests reduced serotonin innervation of the prefrontal cortex and homeostatic upregulation of postsynaptic 5-HT 1A and perhaps 5-HT 2A receptors in suicide. However, in the brainstem, we have previously found more tryptophan hydroxylase serotonin biosynthetic enzyme and more serotonin in suicide decedents suggesting serotonergic hyperfunction, but also more autoreceptor binding that could result in reduced neuronal firing. We sought evidence of a disconnect between the brainstem and prefrontal cortex examining the serotonin transporter (SERT) and 5-HT 1A receptor in the dorsal and median raphe nucleus and SERT, 5-HT 1A and 5-HT 2A receptor binding in prefrontal cortex and in anterior cingulate cortex postmortem.Suicide decedents (n=11) and controls (n=18) died suddenly minimizing agonal effects and had a postmortem interval ≤ 24 hour. Autoradiography was performed in right hemisphere coronal sections at a pre-genual level and in transverse sections through the brainstem.In controls, there were correlations between DRN and MRN SERT and 5-HT 2A receptor binding throughout prefrontal cortex, and between DRN and MRN 5-HT 1A receptor binding and medial and ventral prefrontal cortex. In suicide decedents there were no such relationships.The absence of correlations between brainstem source serotonergic neuron function and receptors on target neurons in prefrontal cortex in suicides suggests a disconnect that may contribute to suicide neuropathology.

Neuropsychiatric adverse effects from CFTR modulators deserve a serious research effort

“…This receptor system is intimately related to GABA function both at the neurotransmitter and receptor level [ 26 , 27 ]. While this topic demands further study, given the central role of 5-HT2 receptor subtypes in suicidality [ 28 ] there may be a compounding effect of ETI on both GABA and serotonin (5-HT) function in vulnerable individuals.…”