Sensorimotor gating of schizophrenia patients is influenced by 5-HT2A receptor polymorphisms.
BACKGROUND
Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), suggesting a sensorimotor gating deficit. The serotonin-2A receptor (5-HT(2A)R) has been implicated in both the pathogenesis of schizophrenia and the PPI deficits of schizophrenia patients. Moreover, both schizophrenia and PPI are thought to be inheritable. We investigated the impact of three 5-HT(2A)R polymorphisms (A-1438G, T102C, H452Y) on PPI in schizophrenia patients.


METHODS
We analyzed the 5-HT(2A)R A-1438G, T102C, and H452Y polymorphisms and assessed startle reactivity, habituation, and PPI of ASR in 68 Caucasian schizophrenia inpatients. Patients were also examined with the Positive and Negative Syndrome Scale.


RESULTS
The 5-HT(2A)R A-1438G and T102C polymorphisms were in complete linkage disequilibrium. Patients carrying the T102C TT and the A-1438G AA allele show significantly higher PPI levels and a faster early habituation compared with all other variants. 5-HT(2A)R A-1438G and T102C genotype explained approximately 11% of the PPI and early habituation variance. In contrast, the 5-HT(2A)R H452Y polymorphism did not affect startle parameters.


CONCLUSIONS
Our findings suggest that PPI and habituation are modulated by 5-HT(2A)R A-1438G and T102C genotype in schizophrenia. Consequently, alterations within brain 5-HT(2A)Rs may contribute to the PPI deficits in schizophrenia.
Quednow
Boris B
BB
Department of Psychiatry, University of Bonn, Germany. quednow@bli.uzh.ch
Kühn
Kai-Uwe
KU
Mössner
Rainald
R
Schwab
Sibylle G
SG
Schuhmacher
Anna
A
Maier
Wolfgang
W
Wagner
Michael
M
D000161:Acoustic Stimulation / Q000379:methods; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006185:Habituation, Psychophysiologic / Q000502:physiology; D006639:Histidine / Q000235:genetics; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia / Q000150:complications / Q000235:genetics*; D014443:Tyrosine / Q000235:genetics
D044402:Receptor, Serotonin, 5-HT2A; D014443:Tyrosine; D006639:Histidine