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Schizophrenia Bulletin Advance Access published online on November 27, 2009
Schizophrenia Bulletin, doi:10.1093/schbul/sbp134
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© The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

The Early Auditory Gamma-Band Response Is Heritable and a Putative Endophenotype of Schizophrenia

Mei-Hua Hall1,2, Grantley Taylor2, Pak Sham5, Katja Schulze3, Fruhling Rijsdijk4, Marco Picchioni3, Timothea Toulopoulou3, Ulrich Ettinger6, Elvira Bramon3, Robin M. Murray3 and Dean F. Salisbury2
2 Cognitive Neuroscience Laboratory, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478
3 Division of Psychological Medicine
4 Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK
5 Department of Psychiatry, University of Hong Kong, Hong Kong
6 Department of Psychiatry, University of Munich, Germany

1 To whom correspondence should be addressed; tel: 617-855-3632, fax: 617-855-2778, e-mail: mhall{at}mclean.harvard.edu

Background: Reduced power and phase locking of the early auditory gamma-band response (EAGBR) have been reported in schizophrenia, but findings are equivocal. Further, little is known about genetic (heritability) and environmental influences on the EAGBR or its potential as an endophenotype of schizophrenia. The present study used a twin design to examine whether EAGBR power and phase locking are heritable and reduced in schizophrenic patients and their unaffected co-twins and thus putative endophenotypes of schizophrenia. Methods: The study sample included a total of 194 individuals, consisting of 15 monozygotic [MZ] twin pairs concordant for schizophrenia, 9 MZ twin pairs discordant for schizophrenia, and 42 MZ and 31 dizygotic (DZ) control pairs. Evoked power and phase-locking factor of the EAGBR were computed on Morlet wavelet–transformed electroencephalogram responses to standard tones during an auditory oddball target detection task. Structural equation modeling was applied to estimate heritability and genetic and environmental correlations with schizophrenia for the EAGBR measures. Results: Both evoked power and phase-locking phenotypes were heritable traits (power: h2 = 0.65; phase locking: h2 = 0.63). Impaired EAGBR measures were significantly associated with schizophrenia. Patients with schizophrenia and their unaffected identical co-twins exhibited significantly reduced EAGBR power compared with control subjects. In each phenotype, shared genetic factors were likely the source of the observed associations with schizophrenia. Conclusions: Our results support EAGBR measures as putative endophenotypes of schizophrenia, likely reflecting an ubiquitous local cortical circuit deficit.

Keywords: gamma oscillation / endophenotype / schizophrenia / twin / heritability


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