a1 Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany
a2 Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany
a3 Institute of Human Genetics, RWTH Aachen University, Germany
a4 Department of Genomics, Life and Brain Centre, University of Bonn, Germany
a5 Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany
Background Schizophrenia is a complex disorder with a high heritability. Family members have an increased risk not only for schizophrenia per se but also for schizophrenia spectrum disorders. Impairment of neuropsychological functions found in schizophrenia patients are also frequently observed in their relatives. The dystrobrevin-binding protein 1 (DTNBP1) gene located at chromosome 6p22.3 is one of the most often replicated vulnerability genes for schizophrenia. In addition, this gene has been shown to modulate general cognitive abilities both in healthy subjects and in patients with schizophrenia.
Method In a sample of 521 healthy subjects we investigated an association between the DTNBP1 genotype [single nucleotide polymorphism (SNP) rs1018381], personality traits [using the NEO Five-Factor Inventory (NEO-FFI) and the Schizotypal Personality Questionnaire – Brief Version (SPQ-B)] and cognitive function (estimated IQ, verbal fluency, attention, working memory and executive function).
Results Significantly lower scores on the SPQ-B (p=0.0005) and the Interpersonal Deficit subscale (p=0.0005) in carriers of the A-risk allele were detected. There were no differences in any of the cognitive variables between groups.
Conclusions The results indicate that genetic variation of the DTNBP1 genotype might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.
(Received July 11 2008)
(Revised December 14 2008)
(Accepted January 15 2009)
(Online publication April 01 2009)