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Affective symptoms are associated with markers of inflammation and immune activation in bipolar disorders but not in schizophrenia
Authors:Hope Sigrun  Dieset Ingrid  Agartz Ingrid  Steen Nils E  Ueland Thor  Melle Ingrid  Aukrust Pål  Andreassen Ole A
Affiliation:aDepartment of Psychiatry, Østfold Hospital, Fredrikstad, Norway;bInstitute of Clinical Medicine, Section of Psychiatry, University of Oslo, Oslo, Norway;cDivision of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway;dDepartment of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway;eResearch Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway;fDepartment of Endocrinology, Oslo University Hospital, Oslo, Norway;gSection of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Norway;hFaculty of Medicine, University of Oslo, Oslo, Norway
Abstract:

Objective

Elevated levels of inflammation are reported in bipolar disorders (BP), but how this relates to affective symptoms is unclear. We aimed to determine if immune markers that consistently have been reported elevated in BP were associated with depressive and manic symptoms, and if this was specific for BP.

Methods

From a catchment area, 112 BP patients were included together with 153 schizophrenia (SCZ) patients and 239 healthy controls. Depression and mania were assessed and the patients were grouped into depressed, neutral, and elevated mood. We measured the immune markers tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), high sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG) and von Willebrand factor (vWf) which have been found increased in severe mental disorders.

Results

In BP all inflammatory markers were lowest in depressed state, with significant group differences after control for confounders with respect to TNF-R1 (p = 0.04), IL-1Ra (p = 0.02), OPG (p = 0.004) and IL-6 (p = 0.005). STNF-R1 was positively correlated with the item elevated mood (p = 0.02) whereas sad mood was negatively correlated with OPG (p = 0.0003), IL-1Ra (p = 0.001) and IL-6 (p = 0.006). Compared to controls the neutral mood group had significantly higher levels of OPG (p = 0.0003) and IL-6 (p = 0.005), and the elevated mood group had higher levels of TNF-R1 (p = 0.000005) and vWf (p = 0.002). There were no significant associations between affective states orsymptoms in SCZ.

Conclusions

The current associations between inflammatory markers and affective symptomatology in BP and not SCZ suggest that immune related mechanisms are associated with core psychopathology of BP.
Keywords:Severe mental disorders  Mania  Depression  Affective symptoms  Soluble tumor necrosis factor receptor 1  Interleukin-1Ra  Interleukin 6  von Willebrand factor  Osteoprotegerin  CRP
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