Markers of inflammation and stress distinguish subsets of individuals with schizophrenia and bipolar disorder.

Schizophrenia and bipolar disorder share a number of common features,
both symptomatically and biologically. Abnormalities in the neuroimmune
and the stress-signaling pathways have been previously identified in
brains of individuals with both diseases. However, the possible
relationship between abnormalities in stress and neuroimmune signaling
within the cortex of people with psychotic illness has not been defined.
To test the hypothesis that combined alterations in brain stress
responsiveness and neuroimmune/inflammatory status are characteristic of
some individuals suffering from major mental illness, we examined gene
expression in the Stanley Array Cohort of 35 controls, 35 individuals
with schizophrenia and 34 individuals with bipolar disorder. We used
levels of 8 inflammatory-related transcripts, of which SERPINA3 was
significantly elevated in individuals with schizophrenia (F(2,88)=4.137,
P<0.05), and 12 glucocorticoid receptor signaling (stress) pathway
transcripts previously examined, to identify two clusters of
individuals: a high inflammation/stress group (n=32) and a low (n=68)
inflammation/stress group. The high inflammation/stress group has a
significantly greater number of individuals with schizophrenia (n=15),
and a trend toward having more bipolar disorder individuals (n=11), when
compared with controls (n=6). Using these subgroups, we tested which
microarray-assessed transcriptional changes may be associated with high
inflammatory/stress groups using ingenuity analysis and found that an
extended network of gene expression changes involving immune, growth
factors, inhibitory signaling and cell death factors also distinguished
these groups. Our work demonstrates that some of the heterogeneity in
schizophrenia and bipolar disorder may be partially explained by
inflammation/stress interactions, and that this biological subtype cuts
across Diagnostic and Statistical Manual of Mental Disorders
(DSM)-defined categories.

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