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Genetic variation of serotonin receptor function affects prepulse inhibition of the startle

  • Biological Psychiatry - Original Article
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Abstract

Prepulse inhibition (PPI) is the attenuation of the startle response towards an instantaneous and intense stimulus when preceded by a weaker non-startling stimulus. Deficits in this sensorimotor gating process have been associated with the pathophysiology of schizophrenia and other psychiatric disorders. Among the neurotransmitters involved in PPI modulation, serotonin (5-HT) has so far received comparably little attention. While a recent pharmacological study suggests an important role of different 5-HT receptor (5-HTR) subtypes in PPI modulation, the mechanisms by which 5-HTR impact on PPI remain to be further elucidated. Therefore, we employed a molecular genetic approach in order to examine whether PPI is associated with two functional 5-HTR gene polymorphisms, 5-HTR1A C−1019G and 5-HTR2A T102C. In a sample of 81 healthy volunteers, we found no significant main effects of the polymorphisms, but a significant interaction effect on PPI at short (50 ms) and mid-long (150 ms) pulse–prepulse intervals. The presence of the 5-HTR2A T allele (reported to result in higher 5-HTR2A expression) led to attenuated PPI only in the absence of the 5-HTR1A G allele (reported to result in reduced 5-HTR1A autoreceptor expression). Our results may indicate that a higher 5-HTR2A expression together with a reduced 5-HTR1A autoreceptor expression and consequently, elevated firing rates of serotonergic neurons results in elevated 5-HTR2A activation by serotonin which could potently attenuate PPI. While further research into the molecular mechanisms underlying this interaction is needed, our results underscore the role of 5-HTR in PPI modulation and further implicate the 5-HTR1A G−1019C and the 5-HTR2A T102C polymorphisms in the pathophysiology of schizophrenia.

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Acknowledgements

The authors like to thank Nicole Steigerwald for technical assistance in DNA processing and genotyping and Ulrich Buhss for excellent work in processing and analysing the EMG data.

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Authors and Affiliations

  1. Personality and Individual Differences, Institute of Psychology II, Dresden University of Technology, 01062, Dresden, Germany

    David Bräuer, Alexander Strobel, Tilman Hensch, Kersten Diers & Burkhard Brocke

  2. Institute of Psychology, J. W. Goethe University Frankfurt/Main, Frankfurt/Main, Germany

    Alexander Strobel

  3. Molecular and Clinical Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

    Klaus-Peter Lesch

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  1. David Bräuer
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  2. Alexander Strobel
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  3. Tilman Hensch
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  4. Kersten Diers
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  5. Klaus-Peter Lesch
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  6. Burkhard Brocke
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Correspondence to David Bräuer.

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Bräuer, D., Strobel, A., Hensch, T. et al. Genetic variation of serotonin receptor function affects prepulse inhibition of the startle. J Neural Transm 116, 607–613 (2009). https://doi.org/10.1007/s00702-009-0222-0

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  • DOI: https://doi.org/10.1007/s00702-009-0222-0

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