Involvement of gut microbiota in schizophrenia and treatment resistance to antipsychotics

The gut microbiota is constituted by more than 40, 000 bacterial species involved in key processes including high order brain functions. Altered composition of gut microbiota has been implicated in psychiatric disorders and in modulating the efficacy and safety of psychotropic medications. In this work we characterized the composition of the gut microbiota in 38 patients with schizophrenia (SCZ) and 20 healthy controls (HC), and tested if SCZ patients with different response to antipsychotics (18 patients with treatment resistant schizophrenia (TRS), and 20 responders (R)) had specific patterns of gut microbiota composition associated with different response to antipsychotics. Moreover, we also tested if patients treated with typical antipsychotics (n=20) presented significant differences when compared to patients treated with atypical antipsychotics (n=31). Our findings showed the presence of distinct composition of gut microbiota in SCZ versus HC, with several bacteria at the different taxonomic levels only present in either one group or the other. Similar findings were observed also depending on treatment response and exposure to diverse classes of antipsychotics. Our results suggest that composition of gut microbiota could constitute a biosignatures of SCZ and TRS

Exploring the role of gut microbiota in major depressive disorder and in treatment resistance to antidepressants

Major depressive disorder (MDD) is a common severe psychiatric illness, exhibiting suboptimal response to existing pharmacological treatments. Although its etiopathogenesis is still not completely understood, recent findings suggest that an altered composition of the gut microbiota might play a role. Here we aimed to explore potential differences in the composition of the gut microbiota between patients with MDD and healthy controls (HC) and to identify possible signatures of treatment response by analyzing two groups of MDD patients characterized as treatment-resistant (TR) or responders (R) to antidepressants. Stool samples were collected from 34 MDD patients (8 TR, 19 R and 7 untreated) and 20 HC. Microbiota was characterized using the 16S metagenomic approach. A penalized logistic regression analysis algorithm was applied to identify bacterial populations that best discriminate the diagnostic groups. Statistically significant differences were identified for the families of Paenibacillaceae and Flavobacteriaceaea, for the genus Fenollaria, and the species Flintibacter butyricus, Christensenella timonensis, and Eisenbergiella massiliensis among others. The phyla Proteobacteria, Tenericutes and the family Peptostreptococcaceae were more abundant in TR, whereas the phylum Actinobacteria was enriched in R patients. Moreover, a number of bacteria only characterized the microbiota of TR patients, and many others were only detected in R. Our results confirm that dysbiosis is a hallmark of MDD and suggest that microbiota of TR patients significantly differs from responders to antidepressants. This finding further supports the relevance of an altered composition of the gut microbiota in the etiopathogenesis of MDD, suggesting a role in response to antidepressants

Endovascular Abdominal Aortic Aneurysm Repair With Ovation Alto Stent Graft: Protocol for the ALTAIR (ALTo endogrAft Italian Registry) Study

Background: Since 2010, the Ovation Abdominal Stent Graft System has offered an innovative sealing option for abdominal aortic aneurysm (AAA) by including a sealing ring filled with polymer 13 mm from the renal arteries. In August 2020, the redesigned Ovation Alto, with a sealing ring 6 mm closer to the top of the fabric, received CE Mark approval. Objective: This registry study aims to evaluate intraoperative, perioperative, and postoperative results in patients treated by the Alto stent graft (Endologix Inc.) for elective AAA repair in a multicentric consecutive experience. Methods: All consecutive eligible patients submitted to endovascular aneurysm repair (EVAR) by Alto Endovascular AAA implantation will be included in this analysis. Patients will be submitted to EVAR procedures based on their own preferences, anatomical features, and operators experience. An estimated number of 300 patients submitted to EVAR with Alto stent graft should be enrolled. It is estimated that the inclusion period will be 24 months. The follow-up period is set to be 5 years. Full data sets and cross-sectional images of contrast-enhanced computed tomography scan performed before EVAR, at the first postoperative month, at 24 or 36 months, and at 5-year follow-up interval will be reported in the central database for a centralized core laboratory review of morphological changes. The primary endpoint of the study is to evaluate the technical and clinical success of EVAR with the Alto stent graft in short- (90-day), mid- (1-year), and long-term (5-year) follow-up periods. The following secondary endpoints will be also addressed: operative time; intraoperative radiation exposure; contrast medium usage; AAA sac shrinkage at 12-month and 5-year follow-up; any potential role of patients' baseline characteristics, valuated on preoperative computed tomography angiographic study, and of device configuration (number of component) in the primary endpoint. Results: The study is currently in the recruitment phase and the final patient is expected to be treated by the end of 2023 and then followed up for 5 years. A total of 300 patients will be recruited. Analyses will focus on primary and secondary endpoints. Updated results will be shared at 1- and 3-5-year follow-ups. Conclusions: The results from this registry study could validate the safety and effectiveness of the new design of the Ovation Alto Stent Graft. The technical modifications to the endograft could allow for accommodation of a more comprehensive range of anatomies on-label

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

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

Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications

Individuals with severe psychiatric disorders have a reduced life expectancy compared to the general population. At the biological level, patients with these disorders present features that suggest the involvement of accelerated aging, such as increased circulating inflammatory markers and shorter telomere length (TL). To date, the role of the interplay between inflammation and telomere dynamics in the pathophysiology of severe psychiatric disorders has been scarcely investigated. In this study we measured T-lymphocytes TL with quantitative fluorescent in situ hybridization (Q-FISH) and plasma levels of inflammatory markers in a cohort comprised of 40 patients with bipolar disorder (BD), 41 with schizophrenia (SZ), 37 with major depressive disorder (MDD), and 36 non-psychiatric controls (NPC). TL was shorter in SZ and in MDD compared to NPC, while it was longer in BD (modelF(6, 137) = 20.128,p = 8.73 x 10(-17), effect of diagnosis,F-3 = 31.870;p = 1.08 x 10(-15)). There was no effect of the different classes of psychotropic medications, while duration of treatment with mood stabilizers was associated with longer TL (Partial correlation controlled for age and BMI: correlation coefficient = 0.451;p = 0.001). Levels of high-sensitivity C-Reactive Protein (hsCRP) were higher in SZ compared to NPC (adjusted p = 0.027), and inversely correlated with TL in the whole sample (r = -0.180;p = 0.042). Compared to NPC, patients with treatment resistant (TR) SZ had shorter TL (p = 0.001), while patients with TR MDD had higher levels of tumor necrosis factor-alpha (TNF alpha) compared to NPC (p = 0.028) and to non-TR (p = 0.039). Comorbidity with cardio-metabolic disorders did not influence the observed differences in TL, hsCRP, and TNF alpha among the diagnostic groups. Our study suggests that patients with severe psychiatric disorders present reduced TL and increased inflammation