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Sensorimotor gating of schizophrenia patients is influenced by 5-HT2A receptor polymorphisms


Quednow, B B; Kühn, K U; Mössner, R; Schwab, S G; Schuhmacher, A; Maier, W; Wagner, M (2008). Sensorimotor gating of schizophrenia patients is influenced by 5-HT2A receptor polymorphisms. Biological Psychiatry, 64(5):434-437.

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-HT2AR) 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. Thus, we investigated the impact of three 5-HT2AR polymorphisms (A-1438G, T102C, H452Y) on PPI in schizophrenia patients.
Methods: We analyzed the 5-HT2AR 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-HT2AR 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 to all other variants. 5-HT2AR A-1438G and T102C genotype explained about 11% of the PPI and early habituation variance. In contrast, the 5-HT2AR H452Y polymorphism did not affect startle parameter.
Conclusions: Our findings suggest that PPI and habituation are modulated by 5-HT2AR A-1438G and T102C genotype in schizophrenia. Consequently, alterations within brain 5-HT2ARs may contribute to the PPI deficits in schizophrenia.

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-HT2AR) 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. Thus, we investigated the impact of three 5-HT2AR polymorphisms (A-1438G, T102C, H452Y) on PPI in schizophrenia patients.
Methods: We analyzed the 5-HT2AR 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-HT2AR 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 to all other variants. 5-HT2AR A-1438G and T102C genotype explained about 11% of the PPI and early habituation variance. In contrast, the 5-HT2AR H452Y polymorphism did not affect startle parameter.
Conclusions: Our findings suggest that PPI and habituation are modulated by 5-HT2AR A-1438G and T102C genotype in schizophrenia. Consequently, alterations within brain 5-HT2ARs may contribute to the PPI deficits in schizophrenia.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 September 2008
Deposited On:25 Aug 2008 10:58
Last Modified:05 Apr 2016 12:26
Publisher:Elsevier
ISSN:0006-3223
Publisher DOI:10.1016/j.biopsych.2008.02.019
PubMed ID:18420180
Permanent URL: http://doi.org/10.5167/uzh-3302

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