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GENETIC VARIATION OF AND WORKING MEMORY IN SCHIZOPHRENIA

 

Working memory is responsible for keeping pertinent information “online” in the human brain, enabling decision making, reasoning, comprehension, learning, and memory storage. 

Working memory is responsible for keeping pertinent information “online” in the human brain, enabling decision making, reasoning, comprehension, learning, and memory storage. This critical function involves manipulation and/or maintenance of data and does so by engaging a network of brain circuitry (notably in the prefrontal, parietal and subcortical brain regions). Malfunctioning working memory, especially with regard to the manipulation of available information, is common in schizophrenia.

Researchers at the Lieber Institute for Brain Development (LIBD) have been exploring the genetic underpinning of working memory sub-processes in order to identify causes of schizophrenia-related cognitive dysfunction and how it might be effectively treated. Previous studies have shown that working memory is controlled genetically and glitches in working memory have been linked to genetic variability in the signaling of an important brain chemical called dopamine. In a paper published online in the journal Brain on April 23, 2012, scientists at LIBD, with colleagues at the National Institute of Mental Health, reported new findings about the impact of variability in the structure of the dopamine signaling genes COMT, DRD2 and AKT1 on the brain circuitry involved in working memory processes.

Malfunctioning working memory, especially with regard to the manipulation of available information, is common in schizophrenia.

The research team, used functional magnetic resonance imaging (fMRI) in non-psychiatric control subjects to identify which aspects of working memory—maintenance and manipulation—were influenced by variability in the structure of these three genes. The researchers found that variations in dopamine-related gene structures corresponded to the modified functioning of both working memory maintenance and manipulation processes.

Variability in the COMT gene affected both working memory maintenance (in the prefrontal and parietal brain regions) and working memory manipulation (in the prefrontal and subcortical regions). Variability in DRD2 and AKT1, on the other hand, influenced only working memory manipulation in the subcortical brain region.

Differences in the structure of DRD2 and AKT1 were also observed to alter the effects of anti-psychotic medications on cognition in individuals with schizophrenia. In a subset of patients with schizophrenia who had specific forms of these genes, increased use of anti-psychotic medication was significantly correlated with decreased IQ. This additional finding suggests these gene effects may relate to the broader cognitive effects of DRD2-inhibiting medications (anti-psychotics) in patients who receive them and may offer direction for the future development of better treatments.