title: Sensorimotor gating of schizophrenia patients is influenced by 5-HT2A receptor polymorphisms.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Bonn, Germany. quednow@bli.uzh.ch
authors.forename: Boris B
authors.initials: BB
authors.lastname: Quednow
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Kühn
authors.forename: Rainald
authors.initials: R
authors.lastname: Mössner
authors.forename: Sibylle G
authors.initials: SG
authors.lastname: Schwab
authors.forename: Anna
authors.initials: A
authors.lastname: Schuhmacher
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
mesh_terms: 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
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D014443:Tyrosine; D006639:Histidine