The Immunology of Bipolar Disorder

Barbosa, Izabela Guimarães; Machado‐Vieira, Rodrigo; Soares, Jair C.; Teixeira, Antônio Lúcio

doi:10.1159/000356539

Cited by 125 publications

(64 citation statements)

References 44 publications

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“…A possible explanation for these observations centers on the role of the cytokine IFN-γ, which is required for neopterin release from monocytes/macrophages (Murr et al, 2002). IFN-γ release has been reported to be lower in BD (Barbosa et al, 2014). In this way, perhaps neopterin is not being stimulated for release in our BD group.…”

Section: Discussionmentioning

confidence: 99%

Peripheral zinc and neopterin concentrations are associated with mood severity in bipolar disorder in a gender-specific manner

Millett

Mukherjee

Reider

et al. 2017

Psychiatry Research

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Bipolar disorder (BD) is a recurrent, episodic mood disorder for which there are no current diagnostic, prognostic or theranostic biomarkers. Two peripheral markers of the acute phase immune response, zinc and neopterin, are consistently associated with severity of depression in literature. Given gender differences in clinical presentation of BD and in inflammatory processes, we aimed to explore the interaction between gender and immune biomarkers to predict mood severity in BD. Participants with DSM IV BD I and II were recruited through the Pennsylvania Psychiatric Institute during an acute mood episode. Healthy controls (HC) were recruited through advertisements. Participants fasted for at least 6 hours when blood was drawn for biomarkers. We found that zinc concentrations were significantly lower in the BD group at baseline (p<.05), and there was also a significant interaction between gender and zinc (p<.05), associated with depression severity. Also, we found a significant interaction between gender and neopterin, associated with mania severity (p<.05). We found that mania severity was associated with neopterin in men, while depression severity was positively associated with zinc in women. Our report bears replication in larger samples and highlights the potential for differences in the underlying pathophysiology between men and women with BD.

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Section: Discussionmentioning

confidence: 99%

Peripheral zinc and neopterin concentrations are associated with mood severity in bipolar disorder in a gender-specific manner

Millett

Mukherjee

Reider

et al. 2017

Psychiatry Research

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“…The pathophysiology of bipolar disorder has yet to be well understood, while recent studies have indicated abnormal immunological functions may be a contributing factor (1, 2). Microglia, immune cells in the brain, play important roles in the process of brain inflammation, and recent positron emission tomography (PET) studies have shown microglial overactivation in the brain of patients with various psychiatric disorders including bipolar disorder (3–8).…”

Section: Bipolar Disorder and Microgliamentioning

confidence: 99%

Microglial CD206 Gene Has Potential as a State Marker of Bipolar Disorder

et al. 2017

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The pathophysiology of bipolar disorder, especially the underlying mechanisms of the bipolarity between manic and depressive states, has yet to be clarified. Microglia, immune cells in the brain, play important roles in the process of brain inflammation, and recent positron emission tomography studies have indicated microglial overactivation in the brain of patients with bipolar disorder. We have recently developed a technique to induced microglia-like (iMG) cells from peripheral blood (monocytes). We introduce a novel translational approach focusing on bipolar disorder using this iMG technique. We hypothesize that immunological conditional changes in microglia may contribute to the shift between manic and depressive states, and thus we herein analyzed gene profiling patterns of iMG cells from three patients with rapid cycling bipolar disorder during both manic and depressive states, respectively. We revealed that the gene profiling patterns are different between manic and depressive states. The profiling pattern of case 1 showed that M1 microglia is dominant in the manic state compared to the depressive state. However, the patterns of cases 2 and 3 were not consistent with the pattern of case 1. CD206, a mannose receptor known as a typical M2 marker, was significantly downregulated in the manic state among all three patients. This is the first report to indicate the importance of shifting microglial M1/M2 characteristics, especially the CD206 gene expression pattern between depressive and manic states. Further translational studies are needed to dig up the microglial roles in the underlying biological mechanisms of bipolar disorder.

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“…These effects lead to the destruction or atrophy of neurons and loss of glial elements [96]. CNS-derived cytokines produce similar responses [97]. …”

Section: Inflammation Pathwaymentioning

confidence: 99%

Mood Therapeutics: Novel Pharmacological Approaches for Treating Depression

Henter

Sousa

Gold

et al. 2017

Expert Review of Clinical Pharmacology

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Introduction Real-world effectiveness trials suggest that antidepressant efficacy is limited in many patients with mood disorders, underscoring the urgent need for novel therapeutics to treat these disorders. Areas Covered Here, we review the clinical evidence supporting the use of novel modulators for the treatment of mood disorders, including specific glutamate modulators such as: 1) high-trapping glutamatergic modulators; 2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists; 3) NMDA receptor glycine-site partial agonists; and 4) metabotropic glutamate receptor (mGluR) modulators. We also discuss other promising, non-glutamatergic targets for potential rapid antidepressant effects in mood disorders, including the cholinergic system, the glucocorticoid system, and the inflammation pathway, as well as several additional targets of interest. Clinical evidence is emphasized, and non-pharmacological somatic treatments are not reviewed. In general, this paper only explores agents available in the United States. Expert Commentary Of these novel targets, the most promising—and the ones for whom the most evidence exists—appear to be the ionotropic glutamate receptors. However, moving forward will require us to fully embrace the goal of personalized medicine and will require health professionals to pre-emptively identify potential responders.

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The Immunology of Bipolar Disorder

Cited by 125 publications

References 44 publications

Peripheral zinc and neopterin concentrations are associated with mood severity in bipolar disorder in a gender-specific manner

Peripheral zinc and neopterin concentrations are associated with mood severity in bipolar disorder in a gender-specific manner

Microglial CD206 Gene Has Potential as a State Marker of Bipolar Disorder

Mood Therapeutics: Novel Pharmacological Approaches for Treating Depression

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