Abstract
Working memory deficits are found in different psychiatric populations and are most pronounced in schizophrenia. There is preliminary evidence from pharmacological studies that the verbal and visuospatial subcomponents of working memory are subject to differential neurotransmitter modulation. Here, we investigated the impact of well-known polymorphisms of the dopamine transporter gene (SLC6A3, DAT) and the catechol-O-methyl-transferase gene (COMT) as well as the serotonin transporter gene (SLC6A4, 5-HTT) on these specific working memory subcomponents in a mixed sample of patients and healthy individuals. Twenty healthy subjects and 80 patients diagnosed with schizophrenia, bipolar I disorder, or obsessive-compulsive disorder underwent genotyping for the DAT variable number of tandem repeats (VNTR), the COMT val/met-, and the 5-HTT promoter length polymorphism (5-HTTLPR) and neuropsychological testing using a battery of well-characterized, brain circuit–specific working memory tasks. DAT genotype revealed a significant and selective effect on visuospatial working memory, while there was no effect on verbal working memory functioning. 5-HTT genotype, by contrast, exerted a significant and selective effect on verbal working memory task performance. COMT genotype did not show any influence on either working memory domain. The results of the present study provide evidence for a differential impact of genetic polymorphisms of the dopaminergic and serotonergic systems on verbal and visuospatial working memory functioning. Together with prior evidence suggesting the existence of subgroups of schizophrenia patients exhibiting isolated deficits in only one working memory domain, this finding further supports the idea of endophenotypically and pathophysiologically distinct subgroups of schizophrenia with implications for personalized therapeutic approaches.
Highlights
Working memory (WM) deficits have been described in different psychiatric populations and are most prominently found in schizophrenia [21]
We investigated the impact of well-known polymorphisms of the dopamine transporter gene (SLC6A3, DAT) and the catechol-Omethyl-transferase gene (COMT) as well as the serotonin transporter gene (SLC6A4, 5-HTT) on these specific working memory subcomponents in a mixed sample of patients and healthy individuals
Twenty healthy subjects and 80 patients diagnosed with schizophrenia, bipolar I disorder, or obsessive-compulsive disorder underwent genotyping for the DAT variable number of tandem repeats (VNTR), the COMT val/met, and the 5-HTT promoter length polymorphism (5-HTTLPR) and neuropsychological testing using a battery of well-characterized, brain circuit– specific working memory tasks
Summary
Working memory (WM) deficits have been described in different psychiatric populations and are most prominently found in schizophrenia [21]. According to the endophenotype concept [24], neurocognitive functions are thought to mediate between the genetic basis of psychiatric disorders and their complex and often phase-dependent clinical phenotype. Eur Arch Psychiatry Clin Neurosci (2012) 262:667–676 pathophysiological processes with an impact on both endophenotype and disease. In this context, genes that directly affect the neurotransmitter systems that are presumably involved in the pathophysiology of psychiatric disorders are especially interesting. Genes that directly affect the neurotransmitter systems that are presumably involved in the pathophysiology of psychiatric disorders are especially interesting Knowledge about their pathophysiological effects could help to generate new therapeutic approaches for treating both cognitive dysfunction and clinical symptomatology
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