Systematic review and meta-analysis of transcriptomic studies on different brain regions reveals different sex-based profiles in schizophrenic patients

Schizophrenia is a severe neuropsychiatric disorder characterised by altered perception, mood and behaviour that, despite its relatively low prevalence, causes a profound impact in patients and society. Regarding genetic factors, previous studies have related dopamine receptor D2, different genes involved in glutamatergic neurotransmission, synaptic plasticity, and several immune functions. Sex differences have been clearly established in the epidemiology, symptomatology and outcome of schizophrenia. Nevertheless, the effects of schizophrenia in the transcriptome considering sex and the cerebral regions are barely explored. In this study, we performed a systematic review and sex-based meta-analysis using RNAseq studies of postmortem brain samples. Here we show that genes related to immune response functions are overexpressed in cortical regions of males and hippocampus of females, whereas cortical regions of females overexpressed genes related to neurotransmission and synapses. Regarding the meta-analysis of all brain regions available, we found again that genes related to synaptic plasticity and transmission were enriched in females, while those involved in the organisation of genetic information and protein folding were more expressed in males. Our results suggest multiple sex-based transcriptomic profiles as a consequence of schizophrenia on the brain. These results provide new insights into the role of sex in the effects of schizophrenia and facilitates the exploration of sex-specific markers of the disease. ### Competing Interest Statement The authors have declared no competing interest.