No abstract

Molecular components of the dopaminergic system may play an important role in the pathophysiology of schizophrenia. In this study, we investigated the relationship of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) with therapeutic response to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) and cognitive functions. No associations were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S genotype and the S allele were more frequent in the non-responder patients (n = 28) than in the group of responders (n = 47) (cut-off: >20-point improvement in Global Assessment of Functioning (GAF) scale). The patients with S/S genotype completed fewer categories and had more perseverative errors in the Wisconsin Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients did not differ in positive and negative symptoms, GAF scores, WCST failure to maintain set, and verbal learning. No differences in symptoms or WCST measures were observed in the patients with different DAT genotypes. These results suggest that the S/S genotype of the DRD3 is associated with worse therapeutic response and more severe executive dysfunctions in patients with schizophrenia.

In this study, the authors investigated the relationship between the Ser9Gly (SG) polymorphism of the dopamine D3 receptor (DRD3) and striatal habit learning in healthy controls and patients with schizophrenia. Participants were given the weather prediction task, during which probabilistic cue-response associations were learned for tarot cards and weather outcomes (rain or sunshine). In both healthy controls and patients with schizophrenia, participants with Ser9Ser (SS) genotype did not learn during the early phase of the task (1-50 trials), whereas participants with SG genotype did so. During the late phase of the task (51-100 trials), both participants with SS and SG genotype exhibited significant learning. Learning rate was normal in patients with schizophrenia. These results suggest that the DRD3 variant containing glycine is associated with more efficient striatal habit learning in healthy controls and patients with schizophrenia.

A functional polymorphism of the brain-derived neurotrophic factor (BDNF Val66Met) has been reported to affect memory-related hippocampal activity. Apolipoprotein E (ApoE) gene polymorphism is known to be associated with Alzheimer disease (AD), dementia with Lewy bodies (DLB), and Pick disease (PiD). We tested the hypothesis that BDNF Val and ApoE epsilon4 alleles confer susceptibility to AD, DLB, and PiD. The study included 160 AD, 34 DLB patients, 38 autopsy-confirmed PiD, and 164 age-matched healthy control (HC) probands. The frequency of the BDNF Val allele was significantly higher in AD, but there were no statistical differences in the allele distribution in PiD or in DLB as compared with HC. The Val/Met genotype occurred with statistically significantly higher frequency in PiD than in HC. The ApoE epsilon4 allele was significantly overrepresented in all dementias as compared with HC. Genotypes containing both ApoE epsilon4 and BDNF Val alleles occurred more frequently in all investigated dementias than in HC. We suggest that the presence of the BDNF Val allele in itself and in combination with the ApoE epsilon4 allele can be risk factors for AD, and the results indicate a synergistic effect of the 2 polymorphisms on DLB and PiD risk.