We studied a large sample of rigorously diagnosed, generally unmedicated patients with major depressive disorder (n = 179), bipolar affective disorder (n = 102), or schizophrenia (n = 125) to determine if increased cerebrospinal fluid (CSF) protein is associated with a particular diagnosis or gender. Men had a higher mean CSF protein level than women across all diagnoses (p < 0.001). There were no differences across diagnosis among the female patients. Men with unipolar depression had a higher mean CSF protein content than other male patients (n = 0.029), but depressed bipolar males had an equivalently elevated mean level. Considered apart from unipolar or bipolar diagnosis, the depressive syndrome was strongly associated with increased CSF protein in men (p = 0.004); again, there was no difference across type of illness (depression versus mania) among women. Elevated CSF protein content seems to be associated with illness syndrome rather than diagnosis, and may represent an important finding among men with depression.
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