Immune activation as a mediator of the gut-brain axis in manic episodes

To the Editor

The recent case report published in the Australian and New Zealand Journal of Psychiatry showed a 46-year-old woman admitted for a first manic episode a few days after a subtotal gastrectomy for morbid obesity (Hamdani et al., 2015). Both clinical examination and laboratory test, including serologies, were normal at admission. However, inflammatory tests showed increased levels of proinflammatory cytokines and lipopolysaccharide (LPS), an inducer of immune activation produced by Gram-negative bacteria. After the use of activated charcoal, a potent adsorbent of cytokines, the patient became asymptomatic in parallel with normalization of the inflammatory markers. This is the first evidence of the efficacy of an anti-inflammatory medication targeting the gut-brain axis for a manic episode.

It seems that this unusual manic episode in a 46-year-old woman was mediated by immune activation after severe disruption of the local commensal microbiota. The gut microbiome is a dynamic entity influenced by several factors, including genetics, diet, metabolism, age, antibiotic treatment and stress. Recent studies highlighted the ‘bottom-up’ influence of gut microbes themselves in central nervous system function. They showed that manipulation of local bacterial status (by the use of antibiotics or by changes in the permeability of intestinal walls as it happens after gastrointestinal surgeries and in heavy alcohol consumers) is associated with behavioral changes. Activation of immune system by the gut microbes was proposed as a key pathway of communication in gut-brain axis and probably partially mediates these behavioral changes (Foster and McVey Neufeld, 2013). Our group and others have reported abnormal immune activation as a pivotal pathophysiological mechanism in bipolar disorder (BD). For instance, manic and depressive episodes were associated with increased levels of inflammatory markers compared to both euthymic patients and healthy controls. Furthermore, inflammatory abnormalities during mood episodes were in the midway between controls and patients with sepsis as assessed by a systemic toxicity index (Kapczinski et al., 2010).

In conclusion, this case report added to the notion of immune activation as both a potential therapeutic target and a marker of treatment response in BD. The opportunity to treat BD based on relevant abnormalities in biological pathways as proposed in that study moves forward the field of psychiatric treatment toward a personalized medicine. Also, recent progress in molecular psychiatry and the use of multiscale biological datasets coupled with machine learning techniques may help to build biological signatures and refine predictive models of treatment selection and response.