But what is the extent to which the disturbances in the inflammatory system proceed, cause, are associated with, and/or are consequences of mood disorders? Each of these possibilities could be of relevance in any patient. Results from longitudinal studies show that a proinflammatory balance is associated with an increased risk for incident mood disorders. For some individuals with mood disorders, perturbations in the inflammatory-homeostatic network are more pronounced during a state of depression compared with periods of remission. Mechanistically, this may be related to proinflammatory effects of sleep disruption, chaotic eating patterns, as well as dysphoric cognitive emotional processing. For other individuals, the magnitude of disturbance in the inflammatory system may be greater later in the illness trajectory after multiple episodes, suggesting a communicative and/or consequential effect.
Additional confounding factors relevant to mood disorders are the effect of comorbidity on the inflammatory system and iatrogenic effects. For example, overweight/obesity, as well as diabetes mellitus, are associated with abnormalities in the inflammatory system, while some medications (and other treatment modalities), may exert either salutary and/or amplifying effects on the proinflammatory balance (eg, lithium and weight-promoting drugs respectively).
Advances in neuroscience have enabled the identification of disturbances in the inflammatory system across multimodal and multilevel units of analysis. Disturbances in the inflammatory system have been identified in genetic variance, peripheral and central cytokine alterations, brain nodal structure, and circuit alteration in response to inflammatory challenge. Moreover, findings indicate associations between inflammation and motivation, reward, cognitive emotional processing, and cognition.
Can anti-inflammatory treatments ameliorate depressive symptoms?
Conventional treatments for mood disorders can exert clinically mediated effects on the human inflammatory system. It is largely a consequence of the “streetlight” effect that relatively little attention has been given to it, with most of the emphasis over the past several decades on the monoamine system. It is not without historical interest that the first Nobel prize in medicine and physiology awarded to a psychiatrist was for the therapeutic effects of malaria fever for individuals institutionalized in insane asylums.4
Conventional pharmacotherapy (eg, SSRIs), as well as other classes of psychiatric medication (eg, lithium) exert effects across disparate levels of the inflammatory system. Perhaps the most compelling proof-of-concept that SSRI therapy indirectly engages inflammatory systems is replicated evidence that the prophylactic use of SSRI reduces the hazard for incident depressive episodes in persons receiving interferon-α therapy for hepatitis C or cancer. Conventional pharmacotherapies, small to moderate-sized study trials, as well as systematic reviews and meta-analyses, give reason to believe that clinically significant benefits within dimensional measures of depression, anxiety, anhedonia, and cognitive functions may be realized with these treatments.
Dr. McIntyre reports that he is on the Speakers Bureau for AstraZeneca, Bristol-Myers Squibb, Janssen-Ortho, Eli Lilly, Lundbeck, Pfizer, Shire, Otsuka, Purdue, Takeda, and Allergan; he has received research support/grants from Stanley Medical Research Institute, National Alliance for Research on Schizophrenia and Depression (NARSAD), and National Institutes of Mental Health. Dr. Rong reports no conflicts of interest concerning the subject matter of this article.
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