AUTHOR=Yang Mi , Cui Ying , Xue Mei , Forster Mattew T. , Lang Xiaoe , Xiu Meihong , Li Zezhi , Zhang Xiangyang 

TITLE=Sexual dimorphism in the relationship between Forkhead-Box P2 and BMI with cognitive deficits in schizophrenia

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.920352

DOI=10.3389/fnagi.2022.920352

ISSN=1663-4365

ABSTRACT=<p><italic>FOXP2</italic>, cognitive deficits, and schizophrenia are associated with neurodegenerative pathophyisiology. Mounting evidence suggests that body mass index (BMI) and <italic>FOXP2</italic> may contribute to cognitive deficits in schizophrenia. However, the sex difference in the contribution of <italic>FOXP2</italic> and BMI, as well as their potential interaction with cognitive deficits in schizophrenia, have not been investigated. A total of 867 schizophrenia patients and 402 controls were recruited. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The polymorphism rs10447760 of the <italic>FOXP2</italic> gene was genotyped. Male schizophrenia patients had superior language performance compared to female patients (<italic>F</italic> = 17.83; <italic>p</italic><sub>Bonferroni</sub> &lt; 0.0001). BMI was positively associated with language scores in male patients with schizophrenia (<italic>ß</italic> = 0.60, <italic>t</italic> = 3.30, <italic>p</italic> = 0.001), as well as in patients with schizophrenia who carried the <italic>FOXP2</italic> rs10447760 CC genotype (<italic>ß</italic> = 0.53, <italic>t</italic> = 3.16, <italic>p</italic> = 0.002). Interestingly, this association was only found in male patients with schizophrenia who also carried the <italic>FOXP2</italic> rs10447760 CC genotype (<italic>ß</italic> = 0.63, <italic>t</italic> = 3.44, <italic>p</italic> = 0.001). Our study reveals a sex difference in the language deficits of schizophrenia patients and shows sexual dimorphism in the contribution of <italic>FOXP2</italic>, BMI, and their interaction to cognitive deficits in patients with schizophrenia.</p>