Cognitive Impairments Related to COMT and Neuregulin 1 Phenotypes as Transdiagnostic Markers in Schizophrenia Spectrum Patients

<b>Background:</b> Research on the interaction between antipsychotic treatment and cognitive dysfunction in schizophrenia spectrum disorders (SSDs) is extensive, yet the role of genetic polymorphisms in catechol-O-methyltransferase (COMT) and neuregulin 1 (NRG1) remains underexplored. <b>Methods</b>: This study evaluates the impact of COMT (rs4680) and NRG1 (rs3924999 and rs35753505) polymorphisms on cognitive functions in SSD patients. A cross-sectional study was conducted with fifty-four patients, assessed using the Positive and Negative Syndrome Scale (PANSS) and the CNS Vital Signs battery. <b>Results</b>: Significant cognitive function differences were observed across SSD diagnostic categories (<i>p</i> < 0.001). The NRG1 rs35753505 TT genotype was significantly associated with better verbal memory performance compared to the CC genotype (<i>p</i> = 0.03), while no significant differences were observed for other genotypes. The NRG1 rs3924999 AA genotype showed superior reasoning performance compared to AG and GG genotypes (<i>p</i> = 0.01), with AG and GG associated with lower scores (<i>p</i> = 0.01 and <i>p</i> = 0.02, respectively). Additionally, the COMT Val158Met genotype significantly influenced processing speed, with patients at the first episode of psychosis showing higher scores than chronic patients (<i>p</i> = 0.01). <b>Conclusions</b>: These findings suggest that NRG1 and COMT polymorphisms may influence cognitive domains in schizophrenia spectrum disorders, potentially informing personalized treatment and cognitive rehabilitation strategies.