5HTTLPR Polymorphism, stressful events, neuropsychological performance and brain connectivity in eating disorders

Abstract Introduction. Low functioning variants of 5HTTLPR have been associated to an increased risk of depression in subjects who experienced stressful events, to altered cognitive functioning and decisional processes, and functional and structural neural patterns. Contrasting evidence is available up to now in Eating Disorders (ED), and no study has evaluated the polymorphism effect on brain connectivity according to graph theory in Anorexia Nervosa (AN). Methods. We recruited up to 735 patients with life-time history of AN or bulimia nervosa (BN) according to DSM-IV criteria and up to 241 healthy controls (HC) for the assessment of the association between 5HTTLPR polymorphism and ED. We merged our Biobank data from BIO.Ve.D.A. and meta-analyzed 22 former studies. Patients underwent a structured diagnostic interview for present or life-time ED, an interview for presence and severity of stressful events, Edinburgh Handedness Inventory, Wisconsin Card Sorting Test, Trail A making test, Trail B making test, Iowa Gambling Task, Cognitive Bias Task, psychopathology rating scales for ED and general symptoms. Finally patients with AN and HCs underwent a Magnetic Resonance; their brains’ connectivity integration and segregation measures were then measured with Graph Analysis Toolbox, according to 5HTTLPR polymorpshim. Results. Our results from a meta-analysis including data from BIO.Ve.D.A. and 22 previous studies, suggest that 5HTTLPR polymorphism does not have a role per se in determing ED onset. However it may moderate the effect of SEs in increasing the risk of ED onset, and the influence of SEs on ED severity, anxious, depressive and obsessive symptoms. When we tested both a multiplicative and an additive model, which is considered to be more representative of a real-world gene by environment interaction, such a 5HTTLPR by SE interaction was not confirmed instead. S allele was associated with worse performance at Cognitive Bias Task and Trail Making B, and with increased ED psychopathology, general psychopathology, anxious, depressive, and obsessive symptoms. Finally S allele was associated with decreased segregation measures at brain connectivity analysis according to graph theory compared with L allele in AN; this was an opposite association compared with healthy controls who had higher modularity associated with S allele instead. Conclusions. 5HTTLPR polymorphism does not seem to be a causal factor of ED per se, but it seems to play a role in moderating the role of stressful events in increasing ED risk. Such a moderation however did not reflect a gene by environment interaction according to either a multiplicative or additive model. S allele was associated with higher psychopathology scores, and worse neuropsychological functions in AN, and with a disrupted segregation measures of brain signal connectivity compared to HCs

Osteoarthritis increases the risk of cardiovascular disease: Data from the osteoarthritis initiative

Objective: Although osteoarthritis (OA) is a common condition in older adults, the role of OA in increasing cardiovascular disease (CVD) incidence is still debated. The aim of this study was to investigate the association between OA and the onset of CVD in a large database of American adults. Design: Longitudinal. Setting: Community-dwelling. Participants: People with OA or at high risk of OA. Measurements:. Osteoarthritis was defined as the presence of OA of the hand, knee, hip, back/neck or of other sites. CVD was defined as self-reported presence of heart attack, heart failure, stroke and other cerebral atherosclerotic conditions, and peripheral artery disease. Results: A total 4,265 persons without CVD (mean age=60.8 years, females=59.2%) at baseline were analyzed (1,775 with OA versus 2,490 without). Over a mean of 8.2 years, according to an adjusted Cox’s regression analysis for 11 potential baseline confounders, study participants with OA of any joint had a significantly higher risk of developing CVD compared to those without OA (Hazard ratio (HR): =1.27; 95% CI: 1.03-1.56). The presence of hand OA was associated with a higher risk of developing CVD (HR=1.31; 95%CI: 1.01-1.68) with respect to those who had no OA. Knee, hip and back/neck OA did not, instead, increase the risk of developing CVD. The association between OA and CVD was significant in the women, but not in the men. Conclusions: OA, in particular, when it affects the hand and is found in women, was associated with a higher risk of developing CVD

Lurasidone in the Treatment of Bipolar Depression: : Systematic Review of Systematic Reviews

Copyright © 2017 Michele Fornaro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction. A burgeoning number of systematic reviews considering lurasidone in the treatment of bipolar depression have occurred since its Food and Drug Administration extended approval in 2013. While a paucity of available quantitative evidence still precludes preliminary meta-analysis on the matter, the present quality assessment of systematic review of systematic reviews, nonetheless, aims at highlighting current essential information on the topic. Methods. Both published and unpublished systematic reviews about lurasidone mono- or adjunctive therapy in the treatment of bipolar depression were searched by two independent authors inquiring PubMed/Cochrane/Embase/Scopus from inception until October 2016. Results. Twelve included systematic reviews were of moderate-to-high quality and consistent in covering the handful of RCTs available to date, suggesting the promising efficacy, safety, and tolerability profile of lurasidone. Concordance on the drug profile seems to be corroborated by a steadily increasing number of convergent qualitative reports on the matter. Limitations. Publication, sponsorship, language, citation, and measurement biases. Conclusions. Despite being preliminary in nature, this overview stipulates the effectiveness of lurasidone in the acute treatment of Type I bipolar depression overall. As outlined by most of the reviewed evidence, recommendations for future research should include further controlled trials of extended duration.Peer reviewe

Harmonizing early intervention strategies: scoping review of clinical high risk for psychosis and borderline personality disorder

AimsTo map studies assessing both clinical high risk for psychosis (CHR-P) and borderline personality disorder (BPD) in clinical samples, focusing on clinical/research/preventive paradigms and proposing informed research recommendations.MethodsWe conducted a PRISMA-ScR/JBI-compliant scoping review (protocol: https://osf.io/8mz7a) of primary research studies (cross-sectional/longitudinal designs) using valid measures/criteria to assess CHR-P and BPD (threshold/subthreshold) in clinical samples, reporting on CHR-P/psychotic symptoms and personality disorder(s) in the title/abstract/keywords, identified in Web of Science/PubMed/(EBSCO)PsycINFO until 23/08/2023.Results33 studies were included and categorized into four themes reflecting their respective clinical/research/preventive paradigm: (i) BPD as a comorbidity in CHR-P youth (k = 20), emphasizing early detection and intervention in psychosis; (ii) attenuated psychosis syndrome (APS) as a comorbidity among BPD inpatients (k = 2), with a focus on hospitalized adolescents/young adults admitted for non-psychotic mental disorders; (iii) mixed samples (k = 7), including descriptions of early intervention services and referral pathways; (iv) transdiagnostic approaches (k = 4) highlighting “clinical high at risk mental state” (CHARMS) criteria to identify a pluripotent risk state for severe mental disorders.ConclusionThe scoping review reveals diverse approaches to clinical care for CHR-P and BPD, with no unified treatment strategies. Recommendations for future research should focus on: (i) exploring referral pathways across early intervention clinics to promote timely intervention; (ii) enhancing early detection strategies in innovative settings such as emergency departments; (iii) improving mental health literacy to facilitate help-seeking behaviors; (iv) analysing comorbid disorders as complex systems to better understand and target early psychopathology; (v) investigating prospective risk for BPD; (vi) developing transdiagnostic interventions; (vii) engaging youth with lived experience of comorbidity to gain insight on their subjective experience; (viii) understanding caregiver burden to craft family-focused interventions; (ix) expanding research in underrepresented regions such as Africa and Asia, and; (x) evaluating the cost-effectiveness of early interventions to determine scalability across different countries.Systematic Review Registrationhttps://osf.io/8mz7a

Physical activity, suicidal ideation, suicide attempt and death among individuals with mental or other medical disorders:a systematic review of observational studies

A growing body of research has demonstrated the potential role for physical activity as an intervention across mental and other medical disorders. However, the association between physical activity and suicidal ideation, attempts, and deaths has not been systematically appraised in clinical samples. We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, EMBASE, and PsycINFO for observational studies investigating the influence of physical activity on suicidal behaviour up to December 6, 2023. Of 116 eligible full-text studies, seven (n=141691) were included. Depression was the most frequently studied c mental condition (43%, k=3), followed by chronic pain as the most common other medical condition (29%, k=2). Two case-control studies examined suicide attempts and found an association between physical activity and a reduced frequency of such attempts. However, in studies examining suicidal ideation (k=3) or suicide deaths (k=2), no consistent associations with physical activity were observed. Overall, our systematic review found that physical activity may be linked to a lower frequency of suicide attempts in non-prospective studies involving individuals with mental disorders

Psychological, psychiatric, and behavioral sciences measurement scales: best practice guidelines for their development and validation

Psychiatric, psychological, and behavioral sciences scales provide quantitative representations of phenomena such as emotions, beliefs, functioning, and social role perceptions. Methodologists and researchers have criticized current scale development practices, emphasizing that inaccurate measurements can derail theory development and clinical decisions, thereby impeding progress in mental health research and practice. These shortcomings often stem from a lack of understanding of appropriate scale development techniques. This article presents a guide to scope, organize, and clarify the process of scale development and validation for psychological and psychiatric use by integrating current methodological literature with the authors’ real-world experience. The process is divided into five phases comprising 18 steps. In the Preliminary Phase, the need for a new scale is assessed, including a review of existing measures. In the Item Development Phase, the construct is defined, and an initial pool of items is generated, incorporating literature reviews, expert feedback, and target population evaluation to ensure item relevance and clarity. During the Scale Construction Phase, the scale is finalized through the administration of surveys to a large sample, followed by parallel analysis, exploratory factor, and item descriptive statistics to identify functional items. In the Scale Evaluation Phase, the dimensionality, reliability, and validity of the scale are rigorously tested using both classical and modern psychometric techniques. Finally, in the Finalization Phase, the optimal item sequence is decided, and a comprehensive inventory manual is prepared. In sum, this structured approach provides researchers and clinicians with a comprehensive methodology for developing reliable, valid, and user-friendly psychological, psychiatric, and behavioral sciences measurement scales

A narrative review of digital biomarkers in the management of major depressive disorder and treatment-resistant forms

IntroductionDepression is the leading cause of worldwide disability, until now only 3% of patients with major depressive disorder (MDD) experiences full recovery or remission. Different studies have tried to better understand MDD pathophysiology and its resistant forms (TRD), focusing on the identification of candidate biomarkers that would be able to reflect the patients’ state and the effects of therapy. Development of digital technologies can generate useful digital biomarkers in a real-world setting. This review aims to focus on the use of digital technologies measuring symptom severity and predicting treatment outcomes for individuals with mood disorders.MethodsTwo databases (PubMed and APA PsycINFO) were searched to retrieve papers published from January 1, 2013, to July 30, 2023, on the use of digital devices in persons with MDD. All papers had to meet specific inclusion criteria, which resulted in the inclusion of 12 articles.ResultsResearch on digital biomarkers confronts four core aspects: (I) predicting diagnostic status, (II) assessing symptom severity and progression, (III) identifying treatment response and (IV) monitoring real-word and ecological validity. Different wearable technologies have been applied to collect physiological, activity/sleep, or subjective data to explore their relationships with depression.DiscussionDepression’s stable rates and high relapse risk necessitate innovative approaches. Wearable devices hold promise for continuous monitoring and data collection in real world setting.ConclusionMore studies are needed to translate these digital biomarkers into actionable interventions to improve depression diagnosis, monitoring and management. Future challenges will be the applications of wearable devices routinely in personalized medicine

Validation of the collaborative outcomes study on health and functioning during infection times (COH-FIT) questionnaire for adults

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health. Keywords: COH-FIT; Covid-19; Pandemic; Survey: P-factor: well-being: mental health: psychiatry: psychometri

Risk factors of postpartum depression and depressive symptoms: umbrella review of current evidence from systematic reviews and meta-analyses of observational studies

Background: Evidence on risk factors for postpartum depression (PPD) are fragmented and inconsistent. Aims: To assess the strength and credibility of evidence on risk factors of PPD, ranking them based on the umbrella review methodology. Method: Databases were searched until 1 December 2020, for systematic reviews and meta-analyses of observational studies. Two reviewers assessed quality, credibility of associations according to umbrella review criteria (URC) and evidence certainty according to Grading of Recommendations-Assessment-Development-Evaluations criteria. Results: Including 185 observational studies (n = 3 272 093) from 11 systematic reviews, the association between premenstrual syndrome and PPD was the strongest (highly suggestive: odds ratio 2.20, 95%CI 1.81-2.68), followed by violent experiences (highly suggestive: odds ratio (OR) = 2.07, 95%CI 1.70-2.50) and unintended pregnancy (highly suggestive: OR=1.53, 95%CI 1.35-1.75). Following URC, the association was suggestive for Caesarean section (OR = 1.29, 95%CI 1.17-1.43), gestational diabetes (OR = 1.60, 95%CI 1.25-2.06) and 5-HTTPRL polymorphism (OR = 0.70, 95%CI 0.57-0.86); and weak for preterm delivery (OR = 2.12, 95%CI 1.43-3.14), anaemia during pregnancy (OR = 1.47, 95%CI 1.17-1.84), vitamin D deficiency (OR = 3.67, 95%CI 1.72-7.85) and postpartum anaemia (OR = 1.75, 95%CI 1.18-2.60). No significant associations were found for medically assisted conception and intra-labour epidural analgesia. No association was rated as 'convincing evidence'. According to GRADE, the certainty of the evidence was low for Caesarean section, preterm delivery, 5-HTTLPR polymorphism and anaemia during pregnancy, and 'very low' for remaining factors. Conclusions: The most robust risk factors of PDD were premenstrual syndrome, violent experiences and unintended pregnancy. These results should be integrated in clinical algorithms to assess the risk of PPD

Risk factors of postpartum depression and depressive symptoms: umbrella review of current evidence from systematic reviews and meta-analyses of observational studies

BackgroundEvidence on risk factors for postpartum depression (PPD) are fragmented and inconsistent.AimsTo assess the strength and credibility of evidence on risk factors of PPD, ranking them based on the umbrella review methodology.MethodDatabases were searched until 1 December 2020, for systematic reviews and meta-analyses of observational studies. Two reviewers assessed quality, credibility of associations according to umbrella review criteria (URC) and evidence certainty according to Grading of Recommendations-Assessment-Development-Evaluations criteria.ResultsIncluding 185 observational studies (n = 3 272 093) from 11 systematic reviews, the association between premenstrual syndrome and PPD was the strongest (highly suggestive: odds ratio 2.20, 95%CI 1.81–2.68), followed by violent experiences (highly suggestive: odds ratio (OR) = 2.07, 95%CI 1.70–2.50) and unintended pregnancy (highly suggestive: OR=1.53, 95%CI 1.35–1.75). Following URC, the association was suggestive for Caesarean section (OR = 1.29, 95%CI 1.17–1.43), gestational diabetes (OR = 1.60, 95%CI 1.25–2.06) and 5-HTTPRL polymorphism (OR = 0.70, 95%CI 0.57–0.86); and weak for preterm delivery (OR = 2.12, 95%CI 1.43–3.14), anaemia during pregnancy (OR = 1.47, 95%CI 1.17–1.84), vitamin D deficiency (OR = 3.67, 95%CI 1.72–7.85) and postpartum anaemia (OR = 1.75, 95%CI 1.18–2.60). No significant associations were found for medically assisted conception and intra-labour epidural analgesia. No association was rated as ‘convincing evidence’. According to GRADE, the certainty of the evidence was low for Caesarean section, preterm delivery, 5-HTTLPR polymorphism and anaemia during pregnancy, and ‘very low’ for remaining factors.ConclusionsThe most robust risk factors of PDD were premenstrual syndrome, violent experiences and unintended pregnancy. These results should be integrated in clinical algorithms to assess the risk of PPD