Effect of DISC1 on the P300 Waveform in Psychosis

Madiha Shaikh; Mei-Hua Hall; Katja Schulze; Anirban Dutt; Kuang Li; Ian Williams; Muriel Walshe; Miguel Constante; Matthew Broome; Marco Picchioni; Timothea Toulopoulou; David Collier; Daniel Stahl; Fruhling Rijsdijk; John Powell; Robin M. Murray; Maria Arranz; Elvira Bramon-Bosch

doi:10.1093/schbul/sbr101

Effect of DISC1 on the P300 Waveform in Psychosis

Madiha Shaikh, Mei-Hua Hall, Katja Schulze, Anirban Dutt, Kuang Li, Ian Williams, Muriel Walshe, Miguel Constante, Matthew Broome, Marco Picchioni, Timothea Toulopoulou, David Collier, Daniel Stahl, Fruhling Rijsdijk, John Powell, Robin M. Murray, Maria Arranz, Elvira Bramon-Bosch

Research output: Contribution to journal › Article › peer-review

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Abstract

Introduction: Abnormalities in the neurophysiological measures P300 amplitude and latency constitute endophenotypes for psychosis. Disrupted-in-Schizophrenia-1 (DISC1) has been proposed as a promising susceptibility gene for schizophrenia, and a previous study has suggested that it is associated with P300 deficits in schizophrenia.

Methods: We examined the role of variation in DISC1 polymorphisms on the P300 endophenotype in a large sample of patients with schizophrenia or psychotic bipolar disorder (n = 149), their unaffected relatives (n = 130), and unrelated healthy controls (n = 208) using linear regression and haplotype analysis.

Results: Significant associations between P300 amplitude and latency and DISC1 polymorphisms/haplotypes were found. Those homozygous for the A allele of single-nucleotide polymorphism (SNP) rs821597 displayed significantly reduced P300 amplitudes in comparison with homozygous for the G allele (P = .009) and the heterozygous group (P = .018). Haplotype analysis showed a significant association for DISC1 haplotypes (rs3738401 vertical bar rs6675281 vertical bar rs821597 vertical bar rs821616 vertical bar rs967244 vertical bar rs980989) and P300 latency. Haplotype GCGTCG and ACGTTT were associated with shorter latencies.

Discussion: The P300 waveform appears to be modulated by variation in individual SNPs and haplotypes of DISC1. Because DISC1 is involved in neurodevelopment, one hypothesis is that disruption in neural connectivity impairs cognitive processes illustrated by P300 deficits observed in this sample.

Original language	English
Pages (from-to)	161-167
Number of pages	7
Journal	Schizophrenia Bulletin
Volume	39
Issue number	1
Early online date	30 Aug 2011
DOIs	https://doi.org/10.1093/schbul/sbr101
Publication status	Published - Jan 2013

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Shaikh, M., Hall, M.-H., Schulze, K., Dutt, A., Li, K., Williams, I., Walshe, M., Constante, M., Broome, M., Picchioni, M., Toulopoulou, T., Collier, D., Stahl, D., Rijsdijk, F., Powell, J., Murray, R. M., Arranz, M., & Bramon-Bosch, E. (2013). Effect of DISC1 on the P300 Waveform in Psychosis. Schizophrenia Bulletin, 39(1), 161-167. https://doi.org/10.1093/schbul/sbr101

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abstract = "Introduction: Abnormalities in the neurophysiological measures P300 amplitude and latency constitute endophenotypes for psychosis. Disrupted-in-Schizophrenia-1 (DISC1) has been proposed as a promising susceptibility gene for schizophrenia, and a previous study has suggested that it is associated with P300 deficits in schizophrenia. Methods: We examined the role of variation in DISC1 polymorphisms on the P300 endophenotype in a large sample of patients with schizophrenia or psychotic bipolar disorder (n = 149), their unaffected relatives (n = 130), and unrelated healthy controls (n = 208) using linear regression and haplotype analysis. Results: Significant associations between P300 amplitude and latency and DISC1 polymorphisms/haplotypes were found. Those homozygous for the A allele of single-nucleotide polymorphism (SNP) rs821597 displayed significantly reduced P300 amplitudes in comparison with homozygous for the G allele (P = .009) and the heterozygous group (P = .018). Haplotype analysis showed a significant association for DISC1 haplotypes (rs3738401 vertical bar rs6675281 vertical bar rs821597 vertical bar rs821616 vertical bar rs967244 vertical bar rs980989) and P300 latency. Haplotype GCGTCG and ACGTTT were associated with shorter latencies. Discussion: The P300 waveform appears to be modulated by variation in individual SNPs and haplotypes of DISC1. Because DISC1 is involved in neurodevelopment, one hypothesis is that disruption in neural connectivity impairs cognitive processes illustrated by P300 deficits observed in this sample.",

author = "Madiha Shaikh and Mei-Hua Hall and Katja Schulze and Anirban Dutt and Kuang Li and Ian Williams and Muriel Walshe and Miguel Constante and Matthew Broome and Marco Picchioni and Timothea Toulopoulou and David Collier and Daniel Stahl and Fruhling Rijsdijk and John Powell and Murray, {Robin M.} and Maria Arranz and Elvira Bramon-Bosch",

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doi = "10.1093/schbul/sbr101",

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AU - Shaikh, Madiha

AU - Hall, Mei-Hua

AU - Schulze, Katja

AU - Dutt, Anirban

AU - Li, Kuang

AU - Williams, Ian

AU - Walshe, Muriel

AU - Constante, Miguel

AU - Broome, Matthew

AU - Picchioni, Marco

AU - Toulopoulou, Timothea

AU - Collier, David

AU - Stahl, Daniel

AU - Rijsdijk, Fruhling

AU - Powell, John

AU - Murray, Robin M.

AU - Arranz, Maria

AU - Bramon-Bosch, Elvira

PY - 2013/1

Y1 - 2013/1

N2 - Introduction: Abnormalities in the neurophysiological measures P300 amplitude and latency constitute endophenotypes for psychosis. Disrupted-in-Schizophrenia-1 (DISC1) has been proposed as a promising susceptibility gene for schizophrenia, and a previous study has suggested that it is associated with P300 deficits in schizophrenia. Methods: We examined the role of variation in DISC1 polymorphisms on the P300 endophenotype in a large sample of patients with schizophrenia or psychotic bipolar disorder (n = 149), their unaffected relatives (n = 130), and unrelated healthy controls (n = 208) using linear regression and haplotype analysis. Results: Significant associations between P300 amplitude and latency and DISC1 polymorphisms/haplotypes were found. Those homozygous for the A allele of single-nucleotide polymorphism (SNP) rs821597 displayed significantly reduced P300 amplitudes in comparison with homozygous for the G allele (P = .009) and the heterozygous group (P = .018). Haplotype analysis showed a significant association for DISC1 haplotypes (rs3738401 vertical bar rs6675281 vertical bar rs821597 vertical bar rs821616 vertical bar rs967244 vertical bar rs980989) and P300 latency. Haplotype GCGTCG and ACGTTT were associated with shorter latencies. Discussion: The P300 waveform appears to be modulated by variation in individual SNPs and haplotypes of DISC1. Because DISC1 is involved in neurodevelopment, one hypothesis is that disruption in neural connectivity impairs cognitive processes illustrated by P300 deficits observed in this sample.

AB - Introduction: Abnormalities in the neurophysiological measures P300 amplitude and latency constitute endophenotypes for psychosis. Disrupted-in-Schizophrenia-1 (DISC1) has been proposed as a promising susceptibility gene for schizophrenia, and a previous study has suggested that it is associated with P300 deficits in schizophrenia. Methods: We examined the role of variation in DISC1 polymorphisms on the P300 endophenotype in a large sample of patients with schizophrenia or psychotic bipolar disorder (n = 149), their unaffected relatives (n = 130), and unrelated healthy controls (n = 208) using linear regression and haplotype analysis. Results: Significant associations between P300 amplitude and latency and DISC1 polymorphisms/haplotypes were found. Those homozygous for the A allele of single-nucleotide polymorphism (SNP) rs821597 displayed significantly reduced P300 amplitudes in comparison with homozygous for the G allele (P = .009) and the heterozygous group (P = .018). Haplotype analysis showed a significant association for DISC1 haplotypes (rs3738401 vertical bar rs6675281 vertical bar rs821597 vertical bar rs821616 vertical bar rs967244 vertical bar rs980989) and P300 latency. Haplotype GCGTCG and ACGTTT were associated with shorter latencies. Discussion: The P300 waveform appears to be modulated by variation in individual SNPs and haplotypes of DISC1. Because DISC1 is involved in neurodevelopment, one hypothesis is that disruption in neural connectivity impairs cognitive processes illustrated by P300 deficits observed in this sample.

U2 - 10.1093/schbul/sbr101

DO - 10.1093/schbul/sbr101

M3 - Article

SN - 0586-7614

VL - 39

SP - 161

EP - 167

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

IS - 1

ER -

Effect of DISC1 on the P300 Waveform in Psychosis

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