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

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

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

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

The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic

Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations: . Cross-sectional survey, preponderance of non-representative participants. Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics. Keywords: COH-FIT; COVID-19; adolescents; adults; anxiety; children; depression; functioning; international; mental health; physical health; post-traumatic; psychiatry; representative; resilience; survey; well-being

Evidence-based umbrella review of cognitive effects of prefrontal tDCS

Abstract Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique, which has been increasingly used as an investigational tool in neuroscience. In social and affective neuroscience research, the prefrontal cortex has been primarily targeted, since this brain region is critically involved in complex psychobiological processes subserving both 'hot' and 'cold' domains. Although several studies have suggested that prefrontal tDCS can enhance neuropsychological outcomes, meta-analyses have reported conflicting results. Therefore, we aimed to assess the available evidence by performing an umbrella review of meta-analyses. We evaluated the effects of prefrontal active vs sham tDCS on different domains of cognition among healthy and neuropsychiatric individuals. A MeaSurement Tool to Assess Systematic Reviews 2 was employed to evaluate the quality of meta-analyses, and the GRADE system was employed to grade the quality of evidence of every comparison from each meta-analysis. PubMed/MEDLINE, PsycINFO and the Cochrane Database of Systematic Reviews were searched, and 11 meta-analyses were included resulting in 55 comparisons. Only 16 comparisons reported significant effects favoring tDCS, but 13 of them had either very low or low quality of evidence. Of the remaining 39 comparisons which reported non-significant effects, 38 had either very low or low quality of evidence. Meta-analyses were rated as having critically low and low quality. Among several reasons to explain these findings, the lack of consensus and reproducibility in tDCS research is discussed

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

Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A)

Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth. Keywords: Adolescents; Children; Covid-19; Mental health; Pandemic; Physical health; Resilience

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