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Genes signaling inflammatory stress reactions shared between schizophrenia, bipolar disorder

Study findings from the Schizophrenia Research Institute in Sydney, Australia show that patients diagnosed with schizophrenia and bipolar disorder share biological markers common to stress and immune reactions.

Researchers examined eight inflammatory transcripts present in cortical gray matter tissue samples from patients with a schizophrenic or bipolar diagnosis and noted a similar expression pattern found in previous research in a separate post mortem cohort of individuals with schizophrenia.

Stu G. Fillman, PhD, and colleagues analyzed data gathered from tissue samples taken from the Stanley Medical Research Institute Array Cohort, which included 35 mentally healthy individuals, 35 patients with schizophrenia and 34 patients with bipolar disorder.

“Our data suggest an interrelationship between stress signaling and immune function in the frontal cortex of a portion of individuals, primarily those with bipolar disorder and schizophrenia,” Fillman and colleagues wrote. “Although data on cortisol levels of individuals in this cohort are not currently available, it is plausible that elevated cortisol levels in individuals with schizophrenia and bipolar disorder may drive the observed changes in both stress and inflammatory gene messenger RNAs.”

RNA was extracted from tissue samples taken from the middle frontal gyrus, and complementary DNA was synthesized from these samples. Previous research provided messenger RNA expression data from the same cohort, which the researchers used for statistical comparison.

Samples were divided into a high inflammation/stress group (n=32) and a low inflammation/stress group (n=68) using levels of inflammatory-related transcripts (n=8) and glucocorticoid receptor signaling pathway transcripts (n=12). Patients with a schizophrenic diagnosis showed the highest levels of the inflammatory-related gene SERPINA3 (P<0.05), compared with patients with a bipolar diagnosis and control patients with no DSM-5 diagnosis. These individuals also showed shared gene expression changes involving immunity factors, cell growth, inhibitory signaling and cell death.

The data showed that the high inflammation/stress level group was composed of a significantly greater amount of patients with a schizophrenic diagnosis (n=15) or a bipolar diagnosis (n=11), vs. controls (n=6).

“It is noteworthy that we observed a significant number of controls (18% of the group) that also displayed the elevated markers of both inflammation and stress in the brain,” the researchers wrote. “This may suggest that some individuals have a biological resiliency to the negative effects of chronic inflammation, the mechanisms of which have not yet been identified, or that we are observing a mix of individuals in both chronic and acute inflammatory states.”

Disclosure: The researchers report no relevant financial disclosures.