A meta-study on transcription factor networks in the suicidal brain

Abstract

There is evidence supporting the presence of brain gene expression differences between suicides and non-suicides. Such differences have been implicated in suicide pathophysiology. However, regulatory factors underlying these gene expression differences have not been fully understood. Therefore, the identification of differences in regulatory mechanisms, i.e., transcriptional factors between suicides and non-suicides is crucial for the understanding of suicide neurobiology. In this study, we conducted a transcription factor network meta-study with freely available data from the prefrontal cortex of suicides and non-suicides with different mental disorders, including major depression disorder, bipolar disorder and schizophrenia, as well as healthy controls. Disorder-specific characteristics of suicides and non-suicides transcription factor networks were detected, i.e., the presence of immune response genes in both suicides and non-suicides with major depression disorder networks. Also, we found the presence of ESR1, which has been implicated to give resilience to social stress, in the non-suicides network but not in the suicides with major depression network. Suicides and non-suicides with bipolar disorder shared only three genes in common: FOS, CRY1 and PER2. In addition, we found a higher number of genes involved in immune response in the non-suicides with bipolar disorder compared to the suicides with bipolar disorder network. The suicides and non-suicides with schizophrenia networks exhibited clear differences, including the presence of circadian cycle genes in the suicides with schizophrenia network and their absence in the non-suicides with schizophrenia network. The results of this study provide insight on the regulatory mechanisms underpinning transcriptional changes in the suicidal brain.

Keywords: Bipolar disorder; Major depression disorder; Prefrontal cortex; Schizophrenia; Suicidal behavior.