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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: INTRODUCTION:Severe 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 ANALYSIS:A 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 DISSEMINATION:The 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.

SUBMITTER: Manchia M

PROVIDER: S-EPMC7045141 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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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.

Manchia Mirko M Paribello Pasquale P Arzedi Carlo C Bocchetta Alberto A Caria Paola P Cocco Cristina C Congiu Donatella D Cossu Eleonora E Dettori Tinuccia T Frau Daniela V DV Garzilli Mario M Manca Elias E Meloni Anna A Montis Maria A MA Mura Andrea A Nieddu Mariella M Noli Barbara B Pinna Federica F Pisanu Claudia C Robledo Renato R Severino Giovanni G Sogos Valeria V Chillotti Caterina C Carpiniello Bernardo B Del Zompo Maria M Ferri Gian Luca GL Ferri Gian Luca GL Vanni Roberta R Squassina Alessio A

BMJ open 20200126 1

<h4>Introduction</h4>Severe 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 inte ...[more]

PMID: 31988227

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Project description:BackgroundThe vast majority of older people with mental illness prefer to live independently in their own homes. Barriers caused by the health care system often prevent adequate, adapted treatments. With regard to the increasing ageing of the population, the determination of effective, age-appropriate service models for elderly patients with mental illness is clearly required. The aim of this review is to examine and to evaluate multidisciplinary psychogeriatric treatment models that include home visits, particularly with regard to the effects on psychiatric symptoms, social and mental health rehabilitation and quality of life.MethodsA systematic review was carried out of empirical studies with participants who were diagnosed with a mental illness according to ICD-10, aged 60?years or older, and who were living at home. The inclusion criteria comprised a duration of intervention of at least 12?weeks and a minimum of two interventions and domiciliary visits delivered by a multidisciplinary team. The online databases Medline, PsychInfo, Web of Science, Cochrane Register of Controlled Trials, and Google Scholar, as well as hand search, were used to search for relevant studies published between 1996 and 2016. An additional search was performed for studies published between 2016 and 2019. After removing duplicates, abstracts were screened and the remaining articles were included for full-text review.ResultsOf the 3536 records discovered in total, 260 abstracts appeared to be potentially eligible. Of these, 30 full-text articles were assessed for eligibility. For the additional search 415 records and abstracts were screened and 11 articles were read full text. Finally, only three studies fully met the inclusion criteria for this review. The results indicate that psychogeriatric home treatment is associated with significant improvements of psychiatric symptoms and psychosocial problems, fewer admissions to hospital and nursing homes, as well as lower costs of care.ConclusionsPsychogeriatric home treatment has positive effects on older people with mental illness. However, these findings are based upon a small number of studies. The need for further research, especially to specify the effective factors in psychogeriatric home treatment, is clearly indicated.

Project description:Background: Previous studies have revealed associations between psychiatric disorder diagnosis and shorter telomere length. Here, we attempt to discern whether genetic risk for psychiatric disorders, or use of pharmacological treatments (i.e., antidepressants), predict shorter telomere length and risk for aging-related disease in a United Kingdom population sample. Methods: DNA samples from blood were available from 351 participants who were recruited as part of the South East London Community Health (SELCoH) Study, and for which whole-genome genotype data was available. Leukocyte telomere length was characterized using quantitative polymerase chain reactions. Individualized polygenic risk scores for major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) were calculated using Psychiatric Genomics Consortium summary statistics. We subsequently performed linear models, to discern the impact polygenic risk for psychiatric disorders (an etiological risk factor) and antidepressant use (common pharmacological treatment) have on telomere length, whilst accounting for other lifestyle/health factors (e.g., BMI, smoking). Results: There were no significant associations between polygenic risk for any of the psychiatric disorders tested and telomere length (p > 0.05). Antidepressant use was significantly associated with shorter telomere length and this was independent from a depression diagnosis or current depression severity (p ? 0.01). Antidepressant use was also associated with a significantly higher risk of aging-related disease, which was independent from depression diagnosis (p ? 0.05). Conclusion: Genetic risk for psychiatric disorders is not associated with shorter telomere length. Further studies are now needed to prospectively characterize if antidepressant use increases risk for aging-related disease and telomere shortening, or whether people who age faster and have aging-related diseases are just more likely to be prescribed antidepressants.

Project description:OBJECTIVE:evaluation of telomere length change in acutely ill adult patients. DESIGN:Blood samples were drawn on the first and seventh day of intensive care unit (ICU) stay to assess telomere length using a polymerase chain reaction (PCR)-based technique. Demographic data collected included age, weight, admission diagnosis, baseline laboratory values (pH, C- reactive protein (CRP), serum albumin level, white blood cell count (WBC) count, platelet count), and baseline SOFA and APACHE II scores. Additional data collected during the ICU stay included a repeated WBC count, the presence of positive blood cultures and outcome data, including death in the ICU or following discharge, whether ventilated or not at ICU discharge, and destination following discharge, i.e., medical ward or rehabilitation. SETTING:General ICU in tertiary hospital. PATIENTS:Forty patients admitted to the ICU within 72 h of hospital admission suffering from an acute illness were included in this prospective, observational study. MAIN RESULTS:Of the 40 patients studied, telomere shortening was noted in 21, telomere lengthening in 11, and no significant change in the other eight. The age of patients demonstrating telomere shortening was statistically significantly younger (45.4 vs. 61.5 years, p < 0.023) compared to those showing increased telomere length. In addition, a significant correlation was observed between the difference in telomere length and the corresponding difference in WBC count (telomere shortening was associated with a decreased WBC count and vice versa). A trend toward shortening was seen in patients with sepsis (p = 0.07). No significant correlations were found for any other demographic or outcome parameter and changes in telomere length. CONCLUSION:Changes in telomere length, both shortening and lengthening, were evident in the acute setting, but no associations between such changes with outcome were noted. Further studies in more homogeneous groups of patients appear to be warranted.

Project description:BACKGROUND:Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consumption and/or unhealthy nutrition. We investigated whether critically ill children admitted to the PICU have shorter-than-normal telomeres, and whether early parenteral nutrition (PN) independently affects telomere length when adjusting for known determinants of telomere length. METHODS:Telomere length was quantified in leukocyte DNA from 342 healthy children and from 1148 patients who had been enrolled in the multicenter, randomised controlled trial (RCT), PEPaNIC. These patients were randomly allocated to initiation of PN within 24 h (early PN) or to withholding PN for one week in PICU (late PN). The impact of early PN versus late PN on the change in telomere length from the first to last PICU-day was investigated with multivariable linear regression analyses. RESULTS:Leukocyte telomeres were 6% shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825) telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in healthy children (P <?0.0001)). Adjusted for potential baseline determinants and leukocyte composition, early PN was associated with telomere shortening during PICU stay as compared with late PN (estimate early versus late PN -0.021 T/S-units, 95% CI -0.038; 0.004, P = 0.01). Other independent determinants of telomere length identified in this model were age, gender, baseline telomere length and fraction of neutrophils in the sample from which the DNA was extracted. Telomere shortening with early PN was independent of post-randomisation factors affected by early PN, including longer length of PICU stay, larger amounts of insulin and higher risk of infection. CONCLUSIONS:Shorter than normal leukocyte telomeres are present in critically ill children admitted to the PICU. Early initiation of PN further shortened telomeres, an effect that was independent of other determinants. Whether such telomere-shortening predisposes to long-term consequences of paediatric critical illness should be further investigated in a prospective follow-up study. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01536275 . Registered on 16 February 2012.

Dataset Information

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.

Publications

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.

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