Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology.
Dysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in mood disorders, anxiety disorders, psychosis and the action of antidepressants. A common C(-1018)G [C(-1019)G] functional polymorphism in the promoter region of the human 5-HT1A receptor gene has been reported, which may be useful in identifying psychopathology associated with altered function of the human 5-HT1A receptor. We studied the relationship of this polymorphism to psychopathology and 5-HT1A binding in prefrontal cortex. The 5-HT1A receptor genotype for the C(-1019)G polymorphism was typed in 696 unrelated psychiatric subjects, 107 unrelated healthy volunteers, and in post-mortem brain samples from 241 cases. 5-HT1A receptor binding was assayed in post-mortem prefrontal cortex using [3H]8-OH-DPAT, and specific binding determined by 1 microM 5-HT. An association of genotype distribution and allele frequency of the 5-HTR1A C(-1019)G locus was observed in schizophrenia (chi2=9.51, d.f.=2, p=0.009; chi2=9.52, d.f.=1, p=0.002; Armitage's trend test: chi2=9.07, d.f.=1, p=0.003), in substance use disorder (chi2=8.41, d.f.=2, p=0.015; chi2=8.35, d.f.=1, p=0.004; Armitage's trend test: chi2=6.27, d.f.=1, p=0.0012), and in panic attack (chi2=6.31, d.f.=2, p=0.043; chi2=6.14, d.f.=1, p=0.013; Armitage's trend test: chi2=6.27, d.f.=1, p=0.012). An association of the 5-HTR1A C(-1019)G locus with schizophrenia, substance use disorder, and panic attack was suggested by our results. In post-mortem brain samples, 5-HT1A receptor binding in prefrontal cortex and suicide were not associated with genotype. The relationship does not appear to be explained by binding differences, although we cannot rule out altered receptor affinity and transduction.
Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
Yung-Yu
YY
Huang
Cristina
C
Battistuzzi
Maria A
MA
Oquendo
Jill
J
Harkavy-Friedman
Laurence
L
Greenhill
Gil
G
Zalsman
Beth
B
Brodsky
Victoria
V
Arango
David A
DA
Brent
J John
JJ
Mann
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000328:Adult; D000483:Alleles; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism; D001345:Autoradiography; D004247:DNA / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics / Q000523:psychology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism; D017366:Serotonin Receptor Agonists; D013405:Suicide
D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D004247:DNA