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.

Everything changes but nothing changes: gender stereotypes in the Italian population.

PURPOSE: Gender stereotypes refer to consensual or cultural shared beliefs about the attributes of men and women, influencing society behaviors, interpersonal relationships, education, and workplace. The literature has shown the existence of gender stereotypes on career choices, internalization of roles, and school and social experiences and demonstrates the impact of demographic factors on stereotypes. However, all the studies conducted in Italy available in scientific literature analyzed small sample sizes within specific schools of university settings, with a limited age range. METHODS: To assess the current state of gender stereotypes in Italy, we conducted an online survey from October 2022 to January 2023 on the general population residing in Italy. The questionnaire comprised sociodemographic factors and questions about gender stereotypes, investigating six fields: games, jobs, personality traits, home and family activities, sports, and moral judgments. RESULTS: The study involved 1854 participants, mostly women (70.1%) with an undergraduate or postgraduate degree (57.5%). The statistical and descriptive analyses revealed that gender stereotypes influenced respondents' beliefs, with statistically significant effects observed in most questions when stratifying by age, gender, and degree. Principal component analysis was performed to assess latent variables in different fields, revealing significant main stereotypes in each category. No statistically significant differences between men and women were found for the fields home and family activities, games, and moral judgments, confirming that stereotypes affect both men and women in the same way. CONCLUSIONS: Our results show the persistence of gender stereotypes in any fields investigated, although our cohort is predominantly composed of high educational level women living in the North of Italy. This demonstrates that the long-standing gender stereotypes are prevalent, pernicious, and, unfortunately, internalized at times even by successful women pushbacking and sabotaging them unconsciously.

DNA methylation changes in association with trauma-focused psychotherapy efficacy in treatment-resistant depression patients: a prospective longitudinal study.

Background: Stressful events increase the risk for treatment-resistant depression (TRD), and trauma-focused psychotherapy can be useful for TRD patients exposed to early life stress (ELS). Epigenetic processes are known to be related to depression and ELS, but there is no evidence of the effects of trauma-focused psychotherapy on methylation alterations.Objective: We performed the first epigenome-wide association study to investigate methylation changes related to trauma-focused psychotherapies effects in TRD patients.Method: Thirty TRD patients assessed for ELS underwent trauma-focused psychotherapy, of those, 12 received trauma-focused cognitive behavioural therapy, and 18 Eye Movement Desensitization and Reprocessing (EMDR). DNA methylation was profiled with Illumina Infinium EPIC array at T0 (baseline), after 8 weeks (T8, end of psychotherapy) and after 12 weeks (T12 - follow-up). We examined differentially methylated CpG sites and regions, as well as pathways analysis in association with the treatment.Results: Main results obtained have shown 110 differentially methylated regions (DMRs) with a significant adjusted p-value area associated with the effects of trauma-focused psychotherapies in the entire cohort. Several annotated genes are related to inflammatory processes and psychiatric disorders, such as LTA, GFI1, ARID5B, TNFSF13, and LST1. Gene enrichment analyses revealed statistically significant processes related to tumour necrosis factor (TNF) receptor and TNF signalling pathway. Stratified analyses by type of trauma-focused psychotherapy showed statistically significant adjusted p-value area in 141 DMRs only for the group of patients receiving EMDR, with annotated genes related to inflammation and psychiatric disorders, including LTA, GFI1, and S100A8. Gene set enrichment analyses in the EMDR group indicated biological processes related to inflammatory response, particularly the TNF signalling pathway.Conclusion: We provide preliminary valuable insights into global DNA methylation changes associated with trauma-focused psychotherapies effects, in particular with EMDR treatment.

Stressful events increase treatment-resistant depression, and trauma-focused psychotherapy can be useful for these patients.Epigenome-wide data shows changes associated with trauma-focused psychotherapies, especially eye movement desensitization and reprocessing therapy, in treatment-resistant depression patients.Genes and biological pathways related to inflammatory and immune systems are among the most statistically significant results.

Biological markers of sex-based differences in major depressive disorder and in antidepressant response.

Major depressive disorder (MDD) presents different clinical features in women and men, with women being more affected and responding differently to antidepressant treatment. Specific molecular mechanisms underlying these differences are not well studied and this narrative review aims at providing an overview of the neurobiological features underlying sex-differences in biological systems involved in MDD pathophysiology and response to antidepressant treatment, focusing on human studies. The majority of the reviewed studies were performed through candidate gene approaches, focusing on biological systems involved in MDD pathophysiology, including the stress response, inflammatory and immune, monoaminergic, neurotrophic, gamma-aminobutyric acid and glutamatergic, and oxytocin systems. The influence of the endocrine system and sex-specific hormone effects are also discussed. Genome, epigenome and transcriptome-wide approaches are less frequently performed and most of these studies do not focus on sex-specific alterations, revealing a paucity of omics studies directed to unravel sex-based differences in MDD. Few studies about sex-related differences in antidepressant treatment response have been conducted, mostly involving the inflammatory system, with less evidence on the monoaminergic system and sparse evidence in omics approaches. Our review covers the importance of accounting for sex-differences in research, optimizing patient stratification for a more precise diagnostic and individualized treatment for women and men.

Molecular Biomarkers of Electroconvulsive Therapy Effects and Clinical Response: Understanding the Present to Shape the Future.

Electroconvulsive therapy (ECT) represents an effective intervention for treatment-resistant depression (TRD). One priority of this research field is the clarification of ECT response mechanisms and the identification of biomarkers predicting its outcomes. We propose an overview of the molecular studies on ECT, concerning its course and outcome prediction, including also animal studies on electroconvulsive seizures (ECS), an experimental analogue of ECT. Most of these investigations underlie biological systems related to major depressive disorder (MDD), such as the neurotrophic and inflammatory/immune ones, indicating effects of ECT on these processes. Studies about neurotrophins, like the brain-derived neurotrophic factor (BDNF) and the vascular endothelial growth factor (VEGF), have shown evidence concerning ECT neurotrophic effects. The inflammatory/immune system has also been studied, suggesting an acute stress reaction following an ECT session. However, at the end of the treatment, ECT produces a reduction in inflammatory-associated biomarkers such as cortisol, TNF-alpha and interleukin 6. Other biological systems, including the monoaminergic and the endocrine, have been sparsely investigated. Despite some promising results, limitations exist. Most of the studies are concentrated on one or few markers and many studies are relatively old, with small sample sizes and methodological biases. Expression studies on gene transcripts and microRNAs are rare and genetic studies are sparse. To date, no conclusive evidence regarding ECT molecular markers has been reached; however, the future may be just around the corner.

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.

Social Cognition in a Research Domain Criteria Perspective: A Bridge Between Schizophrenia and Autism Spectra Disorders.

Schizophrenia and autism spectra disorders are currently conceptualized as distinct clinical categories. However, the relationship between these two nosological entities has been revisited in recent years due to the evidence that they share some important clinical and neurobiological features, putting into question the nature and the extent of their commonalities and differences. In this respect, some core symptoms that are present in both disorders, such as social cognitive deficits, could be a primary target of investigation. This review briefly summarizes the commonalities and overlapping features between schizophrenia and autism spectra disorders in social cognitive functions, considering this construct in a Research Domain Criteria perspective. The clinical manifestation of deficits in social cognition are similar in schizophrenia spectrum disorders and autism spectrum disorders, and brain areas that appear to be altered in relation to these impairments are largely shared; however, the results of various studies suggest that, in some cases, the qualitative nature of these alterations may be different in the two spectra. Moreover, relevant differences could be present at the level of brain networks and connections. More research is required in this field, regarding molecular and genetic aspects of both spectra, to better define the neurobiological mechanisms involved in social cognition deficits, with the objective of developing specific and targeted treatments.

Genomic changes in progression of low-grade gliomas.

Using a one-megabase BAC-based array comparative genomic hybridization technique (aCGH), we have investigated a series of 16 low-grade gliomas (LGGs) and their subsequent progression to higher-grade malignancies. The most frequent chromosome imbalances in primary tumors were gains of chromosomes 7q, 8q, and 22q, and losses of chromosomes 1p, 13q, and 19q. In tumor progression, gains of chromosomes 11q, 7q, 20q, and 21q, and losses of chromosomes 9p, including CDKN2A locus, 19q, 14q, 1p, and 6q were the most frequent genomic disequilibria. Progressive tumors were more imbalanced than primary tumors in terms of altered chromosomal arms (3.8 vs. 6.6 in mean abnormal chromosomal arm) and altered BACs (17 vs. 21%). Interestingly, putative novel candidate genes associated with glioma progression were identified, in particular DOCK8, PTPRD, CER1, TPHO, DHFR, MSH3, ETS1, ACACA, and CSE1L.