Abstract
The nicotinic system is involved in the pathophysiology of schizophrenia. However, very little is known about its genetic basis and how it relates to clinical symptoms and potentially pharmacological intervention. Here, we investigated five single nucleotide polymorphisms (SNPs) [rs3826029] [rs2337506] [rs982574] [rs904952] [rs2337980] of the cholinergic nicotinic receptor gene, alpha 7 subunit (CHRNA7) and their association to schizophrenia. We found an association with rs904952 (p = 0.009) in a German sample of 224 schizophrenic patients and 224 healthy control subjects. The same trend was shown in an independent Georgian sample of 50 schizophrenic patients, 57 first order unaffected relatives, and 51 healthy controls. In addition, visual backward masking (VBM), a sensitive test for early visual information processing, was assessed in the Georgian sample. In line with prior studies, VBM performance deficits were much more pronounced in schizophrenic patients and their unaffected relatives compared to healthy controls (schizophrenic patients: 156 ms; unaffected relatives: 60 ms; healthy controls: 33 ms). VBM was strongly correlated with SNP rs904952 (H[2] = 7.3, p = 0.026). Our results further support the notion that changes in the nicotinic system are involved in schizophrenia and open the avenue for pharmacological intervention.
Highlights
Schizophrenia is a severe disease affecting patients’ professional and social life
cholinergic nicotinic receptor alpha 7 subunit (CHRNA7) AND THE DIAGNOSIS OF SCHIZOPHRENIA In the German sample, we found an association of CHRNA7 with the diagnosis of schizophrenia
The p-value remained significant after Bonferroni correction for five single nucleotide polymorphisms (SNPs) (0.05/5 = 0.01)
Summary
Schizophrenia is a severe disease affecting patients’ professional and social life. Schizophrenia is strongly influenced by genetic factors. A major reason for the contradicting findings is the large number of genetic and environmental factors contributing to the pathophysiology of schizophrenia [5]. Evidence for a relationship between the cholinergic nicotinic receptor alpha 7 subunit (CHRNA7) and schizophrenia was shown by both association [9,10,11] and linkage studies [12,13,14], with mixed results [5, 15]. A deletion of 15q13.3, the chromosomal location of CHRNA7, was identified in schizophrenic patients [16,17,18] together with deficiencies in cholinergic transcription in the corpus callosum [7] and reductions of the receptor protein in the hippocampus, cortex, and thalamus [6, 19, 20]. Several lines of evidence point to the nicotinic system, current drugs applied in schizophrenic patients largely neglected this system
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