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Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder
- Ole Köhler-Forsberg, Louisa Sylvia, Thilo Deckersbach, Michael Joshua Ostacher, Melvin McInnis, Dan Iosifescu, Charles Bowden, Susan McElroy, Joseph Calabrese, Michael Thase, Richard Charles Shelton, Mauricio Tohen, James Kocsis, Edward Friedman, Terence Ketter, Andrew Alan Nierenberg
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- Journal:
- Acta Neuropsychiatrica / Volume 30 / Issue 5 / October 2018
- Published online by Cambridge University Press:
- 07 December 2017, pp. 297-305
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Objective
Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences.
MethodsWe included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases.
ResultsThe overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32–1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=−0.19–1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms.
ConclusionImmune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.
Guidelines for the recognition and management of mixed depression
- Stephen M. Stahl, Debbi A. Morrissette, Gianni Faedda, Maurizio Fava, Joseph F. Goldberg, Paul E. Keck, Yena Lee, Gin Malhi, Ciro Marangoni, Susan L. McElroy, Michael Ostacher, Joshua D. Rosenblat, Eva Solé, Trisha Suppes, Minoru Takeshima, Michael E. Thase, Eduard Vieta, Allan Young, Mark Zimmerman, Roger S. McIntyre
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- Journal:
- CNS Spectrums / Volume 22 / Issue 2 / April 2017
- Published online by Cambridge University Press:
- 28 February 2017, pp. 203-219
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- Article
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A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM–IV definition of “mixed states” wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.