X Chromosome Marker Could Diagnose Serious Mental Disorders

Expression of a gene responsible for inactivation of one of the two copies of the X chromosome in women may serve as a biological marker for diagnosing serious mental health conditions, according to a study published online June 16 in EBioMedicine. Over-expression of XIST, the master gene for X chromosome inactivation, and the related X-linked KDM5C gene may improve diagnosis of bipolar disorder or recurrent major depression in females.

"Our results indicate that a large subpopulation of female psychiatric patients from the general population may have abnormal function of the inactive X chromosome," lead author Xianjin Zhou, Ph.D., from University of California, San Diego, said in a statement. "These results are powerful in that early diagnosis of mental illness could possibly happen with a simple blood test, leading to better interventions, therapy, and treatment options."

Zhou and colleagues previously analyzed protein translation in lymphoblastoid cells and found significantly larger variation of activity in female psychiatric patients, compared to healthy controls. In the present study, XIST and related genes were studied in 36 lymphoblastoid cell lines from healthy females and 60 similar cell lines from female patients with bipolar disorder or recurrent major depression. Real-time polymerase chain reaction was used to quantify relative expression of all genes.

The researchers found that XIST is significantly over-expressed in female patients with either bipolar disorder or major depression. Significant upregulation was also seen in the X-linked escapee gene KDM5C in both sets of patients. Expression of the two genes was highly correlated.

"About 30 percent to 60 percent of the patients can be diagnosed by these markers using different stringency," the authors explain in the paper. They do caution, however, that most of the patients in the study have a family history of mental disorders and display severe psychiatric symptoms, which may cause an over-estimation the prevalence of abnormal XIST and KDM5C expression in the general population of female psychiatric patients without family history and/or with milder psychiatric symptoms.

Takeaway: Though needing further validation, use of gene expression markers could vastly improve diagnosis of major mental illness, where a lack of biological markers has hampered definitive diagnosis and treatment of psychiatric disorders, which rely on clinicians' subjective assessment and patients' self-reported symptoms.