COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects

Neuroimaging Intermediate Phenotypes of Executive Control Dysfunction in Schizophrenia

“…A key concept here is the failure to deactivate or decouple non-task-related areas of the brain during task performance, particularly areas of the 'default mode network' (DMN), a group of mainly midline and temporal cortical areas which are suppressed during the performance of tasks which require external attention, and activated during self-referential mental activities (104). Reduced WM-induced deactivation of the medial prefrontal cortex, a key DMN area, has been found in patients (52,(105)(106)(107)(108)(109)(110)(111), first-degree relatives (52,110,112), and carriers of the Val/Val COMT genotype (111).…”

COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation

“…Three studies resported a significant or trendlevel association between the Val/Val genotype and a worse performance (accuracy and reaction time) on the n-back task in patients with schizophrenia, schizophreniform disorder and schizoaffective disorder 26,40,64 and in their relatives, 40,64 whereas 1 study found no association. 27 Interestingly, the 3 studies that detected a significant association used a version of the n-back task that requires a higher cognitive load, suggesting that the association between the COMT Val 158 Met polymorphism and performance on the n-back task in patients with schizophrenia-spectrum disorders may become apparent when a more challenging performance is required (for details about the different versions of the tasks used, see Appendix 1, Table S1, available at cma.ca/jpn). In healthy individuals, 3 studies found a significant association between the COMT Val 158 Met polymorphism and performance on the n-back task.…”

“…30 Eight studies did not find a COMT Val 158 Met genotype effect on n-back task performance in healthy individuals. 18,21,26,27,41,44,47,58 …”

“…This finding has also been reported in patients with schizophrenia and in their relatives. 27,67 Step 2a: Can the neuropsychological tasks identified (n-back and CPT) be considered endophenotypes?…”

COMT val158met polymorphism and molecular alterations in the human dorsolateral prefrontal cortex: Differences in controls and in schizophrenia

“…the val allele encodes a more active isoform than the met allele (Chen et al, 2004). The val158met polymorphism (hereafter referred to as COMT val/met) has been extensively studied with evidence that this polymorphism influences DLPFC activity (Ceaser et al, 2013; Egan et al, 2001; Eisenberg et al, 2010; Pomarol-Clotet et al, 2010; Takizawa et al, 2009) and executive function, particularly working memory (Barnett et al, 2007; Tsuchimine et al, 2013). COMT inhibition improves cognitive performance on specific tasks in rats (Tunbridge et al, 2004) and humans (Apud and Weinberger, 2007; Farrell et al, 2012).…”