Childhood neglect, the neglected trauma. A systematic review and meta-analysis of its prevalence in psychiatric disorders.

Traumatic events increase risk of mental illnesses, but childhood neglect prevalence in psychiatric disorders is understudied. This systematic review and meta-analysis assessed neglect prevalence, including emotional neglect (EN) and physical neglect (PN), among adults with psychiatric disorders. We conducted a systematic search and meta-analysis in 122 studies assessing different psychiatric disorders. Prevalence was 46.6% (95%CI[34.5-59.0]) for unspecified neglect (Ne), 43.1% (95%CI[39.0-47.4]) for EN, and 34.8% (95%CI[30.6-39.2]) for PN. Although a moderating effect of the psychiatric diagnostic category was not confirmed, some clinical diagnoses had significantly lower prevalence rates than others. Patients with bipolar disorder and major depressive disorder showed lower prevalence rates of EN and PN, whereas lower prevalence was found in psychotic disorders and eating disorders for PN only. Neglect assessment was a significant moderator for Ne and PN. No moderating effect of age and sex on neglect prevalence was found. Heterogeneity levels within and between psychiatric diagnostic categories remained high. This is the first meta-analysis examining diverse types of neglect prevalence considering different psychiatric diagnoses. Our results explore the prevalence of childhood neglect and its subtypes among adults with psychiatric disorders, contributing to understanding the nuanced interplay between neglect and specific psychiatric conditions, and guiding interventions for affected individuals.

An integrated precision medicine approach in major depressive disorder: a study protocol to create a new algorithm for the prediction of treatment response.

Major depressive disorder (MDD) is the most common psychiatric disease worldwide with a huge socio-economic impact. Pharmacotherapy represents the most common option among the first-line treatment choice; however, only about one third of patients respond to the first trial and about 30% are classified as treatment-resistant depression (TRD). TRD is associated with specific clinical features and genetic/gene expression signatures. To date, single sets of markers have shown limited power in response prediction. Here we describe the methodology of the PROMPT project that aims at the development of a precision medicine algorithm that would help early detection of non-responder patients, who might be more prone to later develop TRD. To address this, the project will be organized in 2 phases. Phase 1 will involve 300 patients with MDD already recruited, comprising 150 TRD and 150 responders, considered as extremes phenotypes of response. A deep clinical stratification will be performed for all patients; moreover, a genomic, transcriptomic and miRNomic profiling will be conducted. The data generated will be exploited to develop an innovative algorithm integrating clinical, omics and sex-related data, in order to predict treatment response and TRD development. In phase 2, a new naturalistic cohort of 300 MDD patients will be recruited to assess, under real-world conditions, the capability of the algorithm to correctly predict the treatment outcomes. Moreover, in this phase we will investigate shared decision making (SDM) in the context of pharmacogenetic testing and evaluate various needs and perspectives of different stakeholders toward the use of predictive tools for MDD treatment to foster active participation and patients' empowerment. This project represents a proof-of-concept study. The obtained results will provide information about the feasibility and usefulness of the proposed approach, with the perspective of designing future clinical trials in which algorithms could be tested as a predictive tool to drive decision making by clinicians, enabling a better prevention and management of MDD resistance.

The Elephant in the Room: A Cross-Sectional Study on the Stressful Psychological Effects of the COVID-19 Pandemic in Mental Healthcare Workers.

Despite extensive research on COVID-19's impact on healthcare workers, few studies have targeted mental health workers (MHWs) and none have investigated previous traumatic events. We investigated psychological distress in MHWs after the first lockdown in Italy to understand which COVID-19, sociodemographic, and professional variables represented greater effects, and the role of previous trauma. The survey included sociodemographic and professional questions, COVID-19 variables, and the questionnaires Life Events Checklist for DSM-5 (LEC-5), Impact of Event Scale-Revised (IES-R), and Depression Anxiety Stress Scales 21 (DASS-21). On the 271 MHWs who completed the survey (73.1% female; mean age 45.37), we obtained significant effects for contagion fear, experience of patients' death, increased workload, and worse team relationship during the first wave. Nurses were more affected and showed more post-traumatic stress symptoms, assessed by IES-R, and more depressive, anxiety, and stress symptoms, assessed by DASS-21. The strongest risk factors for distress were greater age, professional role, increased workload, worse team relationship, and separation from family members. Previous experience of severe human suffering and unwanted sexual experiences negatively impacted IES-R and DASS-21 scores. Being a psychiatrist or psychologist/psychotherapist and good team relationships were protective factors. Recent but also previous severe stressful events might represent relevant risk factors for distress, reducing resilience skills. Identifying vulnerable factors and professional categories may help in the development of dedicated measures to prevent emotional burden and support psychological health. Highlights: Psychological distress in mental health workers in the COVID-19 pandemic is more frequent in nurses, who experience more depression, anxiety, and post-traumatic stress symptoms. Previous and recent stressful events are risk factors for distress and should guide intervention strategies.

Clinical validation of a combinatorial PharmAcogeNomic approach in major Depressive disorder: an Observational prospective RAndomized, participant and rater-blinded, controlled trial (PANDORA trial).

BACKGROUND: Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder that causes serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment option; however, only approximately one third of patients respond to the first treatment because of the ineffectiveness or side effects of antidepressants. Precision medicine in psychiatry might offer clinicians the possibility to tailor treatment according to the best possible evidence of efficacy and tolerability for each subject. In this context, our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with advocacy license independence. METHODS: Our study is a prospective participant- and rater-blinded, randomized, controlled clinical observational trial enrolling 300 MDD patients who are referred to psychiatric services to receive a new antidepressant due to the failure of their current treatment and/or the onset of adverse effects. Eligible participants are randomized to the TGTG group (Treated with Genetic Test Guide) or TAU group (Treated as Usual). For all subjects, DNA is collected with a buccal brush. The primary outcome is the reduction in depressive symptomatology. The secondary outcomes involve a range of scales that assess MDD symptoms and social functioning outcomes. The assessment is performed at four timepoints: baseline and 4, 8, and 12 weeks. DISCUSSION: This project represents the first randomized controlled clinical trial to investigate whether a non-commercial PGx test improves outcomes in an MDD naturalistic cohort. Moreover, the identification of new genetic variants associated with non-response or side effects will improve the efficacy of the test, leading to further cost-saving. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04615234. Registered on November 4, 2020.

Inflammation-related microRNAs are involved in stressful life events exposure and in trauma-focused psychotherapy in treatment-resistant depressed patients.

Background: About 30% of major depressive disorder (MDD) patients are classified as resistant to treatment (treatment-resistant depression, TRD). Among the factors associated with unfavourable treatment outcomes, stressful life events play a relevant role, and trauma-focused psychotherapy has been successfully proposed for the treatment of patients with a history of such events. Stressful experiences are related to enhanced inflammation and, recently, microRNAs (miRNAs) have emerged as potential mediators of the association between these experiences and psychiatric disorders. To date, no study has explored the effects of stressful life events on miRNAs in MDD patients. Objective: The objective of the present study was to assess possible miRNA blood expression alterations in TRD patients induced by the exposure to stressful life events and to investigate the effects of trauma-focused psychotherapy on the expression profiles of the same miRNAs, as well as their possible predictivity in relation to therapy outcome. Method: The basal levels (T0) of seven candidate miRNAs (miR-15a/miR-29a/miR-125b/miR-126/miR-146a/miR-195/let-7f) were measured in the whole blood of 41 TRD patients. A subgroup of patients (n = 21) underwent trauma-focused psychotherapy; for all of them, miRNA levels were also longitudinally assessed (T4: after 4 weeks of treatment; T8: end of treatment; T12: follow-up visit), contextually to clinical evaluations. Results: miR-146a levels negatively correlated with recent stressful life event scores (p = .001), whereas the levels of miR-15a, miR-29a, miR-126, miR-195, and let-7f changed during the psychotherapy (best p = 1.98*10-9). miR-29a was also identified as a response predictor, with lower baseline levels predicting non-response (p = .019) or worse improvement in mood symptoms (p = .032). Conclusions: The study results could contribute to clarify the underlying molecular mechanisms and to identify novel biomarkers of stressful experiences and response to targeted treatments.

Antecedentes: Alrededor del 30% de los pacientes con un Trastorno Depresivo Mayor (TDM) son clasificados como resistentes a tratamiento (Depresión Resistente a Tratamiento, TRD por su sigla en inglés). Entre los factores asociados a resultados de tratamiento desfavorables, los eventos vitales estresantes juegan un rol relevante, y la psicoterapia con foco en el trauma ha sido propuesta con éxito para el tratamiento de los pacientes con historia de tales eventos. Las experiencias estresantes están relacionadas a un aumento de la inflamación y, recientemente, microARNs (miARNs), han surgido como potenciales mediadores de la asociación entre estas experiencias y trastornos psiquiátricos. A la fecha, ningún estudio ha explorado los efectos de los eventos vitales estresantes sobre los miARNs en pacientes con TDM.Objetivo: El objetivo del presente estudio fue evaluar posibles alteraciones en la expresión de miARN en sangre en pacientes con TRD inducidas por la exposición a eventos vitales estresantes e investigar los efectos de la psicoterapia con foco en el trauma sobre los perfiles de expresión de los mismos miARNs, así como su posible predictividad en relación al resultado de la terapia.Método: Los niveles basales (T0) de 7 miARN candidatos (miR-15a/miR-29a/miR-125b/miR-126/miR-146a/miR-195/let-7f) fueron medidos en la sangre completa de 41 pacientes con TRD. Un subgrupo de pacientes (n = 21) se sometió a psicoterapia con foco en el trauma; para todos ellos, los niveles de miARN fueron también evaluados longitudinalmente (T4: después de 4 semanas de tratamiento; T8: fin del tratamiento; T12: visita de seguimiento), contextualmente a evaluaciones clínicas.Resultados: Los niveles de miR-146a se correlacionaron negativamente con los puntajes de eventos vitales estresantes recientes (p = .001), mientras que los niveles de miR-15a, miR-29a, miR-126, miR-195, y let-7f cambiaron durante la psicoterapia (mejor p = p = 1.98*10−9). miR-29a también fue identificado como un predictor de respuesta, con menores niveles basales prediciendo falta de respuesta (p = .019) o menor mejoría en los síntomas anímicos (p = .032).Conclusiones: Los resultados del estudio contribuyen a clarificar los mecanismos moleculares subyacentes y a identificar nuevos biomarcadores de experiencias estresantes y respuesta a tratamientos dirigidos.