Meta-analysis of sex differences in gene expression in schizophrenia

Schizophrenia is a severe psychiatric disorder which influences around 1% of the worldwide population. Differences between male and female patients with schizophrenia have been noted. There is an earlier age of onset in males compared with females with this diagnosis, and in addition, there are differences in symptom profiles between the sexes. The underlying molecular mechanism of sex difference remains unclear. Here we present a comprehensive analysis to reveal the sex differences in gene expression in schizophrenia with stringent statistics criteria. We compiled a data set consisting of 89 male controls, 90 male schizophrenia patients, 35 female controls and 32 female schizophrenia patients from six independent studies of the prefrontal cortex (PFC) in postmortem brain. When we tested for a sex by diagnosis interaction on gene expression, 23 genes were up-regulated and 23 genes were down-regulated in the male group (q-value < 0.05), several genes are related to energy metabolism, while 4 genes are located on sex chromosome. No genes were statistically significant in the female group when multiple testing correction were conducted (q-value <0.05), most likely due to the small sample size. Our protocol and results from the male group provide a starting point for identifying the underlying different mechanism between male and female schizophrenia patients.