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.
BACKGROUND:Schizophreniapatients 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 schizophreniapatients. 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 schizophreniapatients. 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: Wendy Hasenkamp; Michael P Epstein; Amanda Green; Lisette Wilcox; William Boshoven; Barbara Lewison; Erica Duncan Journal: Psychiatry Res Date: 2010-05-16 Impact factor: 3.222
Authors: Nadine Petrovsky; Boris B Quednow; Ulrich Ettinger; Anne Schmechtig; Rainald Mössner; David A Collier; Kai-Uwe Kühn; Wolfgang Maier; Michael Wagner; Veena Kumari Journal: Neuropsychopharmacology Date: 2010-03-10 Impact factor: 7.853
Authors: Philipp A Csomor; Katrin H Preller; Mark A Geyer; Erich Studerus; Theodor Huber; Franz X Vollenweider Journal: Neuropsychopharmacology Date: 2014-05-07 Impact factor: 7.853
Authors: Wolfgang Maier; Rainald Mössner; Boris B Quednow; Michael Wagner; René Hurlemann Journal: Eur Arch Psychiatry Clin Neurosci Date: 2008-11 Impact factor: 5.270