A multidisciplinary approach to mental illness: do inflammation, telomere length and microbiota form a loop? A protocol for a cross-sectional study on the complex relationship between inflammation, telomere length, gut microbiota and psychiatric disorders

Abstract

IntroductionSevere psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders.Methods and analysisA cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychiatric controls. Each group includes individuals suffering, or not, from age-related comorbidities, to account for the impact of these medical conditions on the biological make-up of recruited patients. The inflammatory state, microbiota composition and telomere length (TL) are assessed.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the University Hospital Agency of Cagliari (PG/2018/11693, 5 September 2018). The study is conducted in accordance with the principles of good clinical practice and the Declaration of Helsinki, and in compliance with the relevant Italian national legislation. Written, informed consent is obtained from all participants. Participation in the study is on a voluntary basis only. Patients will be part of the dissemination phase of the study results, during which a local conference will be organised and families of patients will also be involved. Moreover, findings will be published in one or more research papers and presented at national and international conferences, in posters or oral communications.

Involvement of Gut Microbiota in Schizophrenia and Treatment Resistance to Antipsychotics

“…The recruitment process of our cohorts of 38 patients affected by SCZ and 20 HC took place at the community mental health center of the Section of Psychiatry of the Department of Medical Science and Public Health, University of Cagliari and University Hospital Agency of Cagliari and was previously detailed [ 35 ]. The study was conducted according to the guidelines of the Declaration of Helsinki, in compliance with the Italian national legislation, and approved by the Ethics Committee of the University Hospital Agency of Cagliari (PG/2018/11693, 5th of September 2018).…”

Exploring the Role of Gut Microbiota in Major Depressive Disorder and in Treatment Resistance to Antidepressants

“…In addition, twenty healthy control (HC) subjects were recruited through word of mouth among hospital staff, their families, and university students. Assessment procedures have been detailed in Manchia et al [21]. Briefly, patients were included in the study if: (1) they had a diagnosis of MDD according to Diagnostic and statistical manual of mental disorders DSM-IV-TR (DSM IV-TR) [22] criteria; (2) were able to express a consent to participate formulated by signing the consent form; (3) were of age between 18 and 70 years old; (4) were in euthymic phases.…”

Linking the Triad of Telomere Length, Inflammation, and Gut Dysbiosis in the Manifestation of Depression

“…Accelerated TL shortening has been noted in chronic inflammation and patients with depression. − Depressive patients also display detrimental changes in gut microbiota, which subsequently modify the gut–brain communication and inflammatory responses. In this context, Manchia et al recently suggested the importance of the TL, inflammation, and gut microbiota triad in the development of mental disorders . Thus, considering a strong interlink between telomere biology and neuropsychiatric illnesses, a literature review on this subject is valuable for an early diagnosis, timely interventions, and developing new therapeutics.…”

“…In this context, Manchia et al recently suggested the importance of the TL, inflammation, and gut microbiota triad in the development of mental disorders. 13 Thus, considering a strong interlink between telomere biology and neuropsychiatric illnesses, a literature review on this subject is valuable for an early diagnosis, timely interventions, and developing new therapeutics. Herein, we comprehensively discuss three key features: (i) involvement of inflammation in depression; (ii) role of gut dysbiosis and increased intestinal permeability in depression; and (iii) telomere attrition in depression (Figure 1).…”