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Evidence that the COMTVal158Met Polymorphism Moderates Subclinical Psychotic and Affective Symptoms in Unaffected First-Degree Relatives of Patients With Schizophrenia

Published online by Cambridge University Press:  06 March 2008

Ruud van Winkel
Affiliation:
University Psychiatric Center, Katholieke Universiteit Leuven, Leuvensesteenweg 517, 3070Kortenberg, Belgium Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University, P.O. Box 616, 6200MD Maastricht, The Netherlands
Pilar Isusi
Affiliation:
Centro de Salud Mental de LLodio, Llodio, Spain
Paloma Galdos
Affiliation:
Centro de Salud Mental de LLodio, Llodio, Spain
Elena Echevarria
Affiliation:
Centro de Salud Mental de LLodio, Llodio, Spain
José Ramón Bilbao
Affiliation:
Unidad de Investigación, Universidad del País Vasco/Hospital de Cruces, Barakaldo, Bizkaia, Spain
Ainhoa Martin-Pagola
Affiliation:
Unidad de Investigación, Universidad del País Vasco/Hospital de Cruces, Barakaldo, Bizkaia, Spain
Luis Castaño
Affiliation:
Unidad de Investigación, Universidad del País Vasco/Hospital de Cruces, Barakaldo, Bizkaia, Spain
Sergi Papiol
Affiliation:
Unitat d'Antropologia, Departament Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028Barcelona, Spain
Ron Mengelers
Affiliation:
Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University, P.O. Box 616, 6200MD Maastricht, The Netherlands
Lydia Krabbendam
Affiliation:
Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University, P.O. Box 616, 6200MD Maastricht, The Netherlands
Jim van Os
Affiliation:
Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University, P.O. Box 616, 6200MD Maastricht, The Netherlands Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, LondonSE5 8AF, UK
Inez Myin-Germeys*
Affiliation:
Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University, P.O. Box 616, 6200MD Maastricht, The Netherlands School of Psychological Sciences, University of Manchester, UK
*
Corresponding author. Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience, Maastricht University, P.O. Box 616 (VIJV), 6200 MD Maastricht, The Netherlands. Tel.: +31 43 3688683; fax: +31 43 3688689. E-mail addresses: [email protected] (R. van Winkel), j. [email protected] (J. van Os), [email protected] (I. Myin-Germeys).
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Abstract

Objectives.

Psychotic patients with COMTVal158Met Met alleles were recently found to display more intense psychotic and affective responses to daily life stressors. We aimed to test the hypothesis that the Met allele is implicated in the development of affective and psychotic symptomatology in subjects genetically at risk for schizophrenia, by testing if unaffected first-degree relatives of patients with schizophrenia who share a Met allele have greater concordance of symptomatology than relatives not sharing a Met allele.

Methods.

Unaffected relatives (n = 38) were arranged in as many genetically related pairs as possible (n = 26), and Met-sharing between Index Unaffected Subject (IUS) and Related Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) total score.

Results.

Multilevel regression revealed an interaction between RUS BPRS score and Met-sharing in the model of IUS BPRS score (interaction χ2 = 3.78, p = 0.05). Stratified analyses revealed that IUS–RUS total BPRS scores were significantly associated in the case of Met-sharing (B = 0.57, 95% CI: 0.22–0.93, p = 0.002), but were not when there was no Met-sharing.

Conclusion.

These findings support the hypothesis that the Met allele may be involved in the causation of psychopathology, at least in populations with a genetic predisposition to psychosis.

Type
Original article
Copyright
Copyright © European Psychiatric Association 2008

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Footnotes

1

Contributed equally.

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