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ObjectiveImmunologic abnormalities have been found in bipolar disorder and acute mania. However, there have been fewer studies of patients with acute bipolar depression. MethodBlood samples were obtained from individuals with acute bipolar depression, acute mania, and controls. These samples were evaluated for antibodies to human herpesviruses, gliadin, Toxoplasma gondii, and endogenous retroviruses as well as for C-reactive protein (CRP) and pentraxin-3 using immunoassay methods. Linear regression models were used to compare the levels of the markers controlling for demographic and clinical variables. A subset of the bipolar depressed group was evaluated at a 6-month follow-up. ResultsThe sample consisted of 82 individuals with acute bipolar depression, 147 with acute mania, and 280 controls. The levels of CRP and IgG antibodies to an endogenous retrovirus, Mason-Pfizer monkey virus (MPMV), were significantly elevated in the bipolar depressed group. Levels of pentraxin-3 were reduced in both psychiatric groups. An evaluation of 32 individuals 6months after hospitalization for bipolar depression showed a significant decrease in the levels of MPMV antibodies, but not a change in the other markers. ConclusionIndividuals with acute bipolar depression show immune alterations. Some of the alterations are similar to those found in acute mania.