Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims.
Suicide and depression are associated with reduced serotonergic neurotransmission. In suicides, there is a reduction in serotonin transporter (SERT) sites and an increase in postsynaptic 5-HT(1A) receptors in localized regions of the prefrontal cortex. In depression, there is a diffuse decrease in SERT binding throughout the dorsoventral extent of the prefrontal cortex. Serotonergic innervation of the prefrontal cortex arises predominantly from neurons in the brainstem dorsal raphe nucleus (DRN). We, therefore, examined postmortem SERT binding and mRNA expression, as well as 5-HT(1A) autoreceptor binding in the DRN of 10 matched pairs of controls and depressed suicide victims. The concentration of SERT sites, SERT mRNA, and 5-HT(1A) binding was not different between controls and suicides (p >.05). In the DRN of suicides, the volume of tissue defined by 5-HT(1A) binding was 40% smaller than controls. An index of the total number of 5-HT(1A) receptors (receptor binding x volume of receptor distribution) was 43.3% lower in the DRN of suicides, compared with controls. The suicide group had 54% fewer DRN neurons expressing SERT mRNA compared with controls. In the serotonin neurons that expressed the SERT gene, expression per neuron was greater in suicides. Less total 5-HT(1A) and SERT binding is consistent with results of in vivo studies in depression. Less feedback inhibition of serotonin DRN firing via 5-HT(1A) autoreceptors and enhancement of serotonin action due to less uptake of serotonin, is consistent with compensatory changes in response to hypofunction in depressed suicides.
Arango
V
V
Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
Underwood
M D
MD
Boldrini
M
M
Tamir
H
H
Kassir
S A
SA
Hsiung
S
S
Chen
J J
JJ
Mann
J J
JJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D001933:Brain Stem / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D003866:Depressive Disorder / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007099:Imipramine / Q000031:analogs & derivatives; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000096:biosynthesis*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012727:Sex Characteristics; D013405:Suicide
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C024316:cianopramine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007099:Imipramine