Complex psychiatry最新文献

Introduction: The current study embarked on an Arabic translation of the BNSS and an examination of its psychometric properties in a Tunisian sample of inpatients and outpatients with schizophrenia.

Methods: Care recipients with schizophrenia (N = 178) completed administrations of the A-BNSS, the Scale for the Assessment of Negative Symptoms (SANS), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), and the St. Hans Rating Scale (SHRS).

Results: The A-BNSS produced strong evidence for the reliability of the scale with Cronbach's alpha and interrater ICC estimates for the full measure and its subscales falling in the good to excellent range. The A-BNSS showed excellent convergent validity with large correlations of its full scale and subscale scores with the SANS and PANSS-negative symptom scores. The A-BNSS showed minimal correlations with PANSS-positive and emotional distress scores, CDSS depression, and SHRS extrapyramidal symptoms, suggesting strong discriminant validity. CFA favored a five-factor model consistent with the NIMH consensus domains.

Conclusion: The study supports the robust psychometric properties of the Arabic translation of the BNSS rendering it promising for the assessment of negative symptoms in Arabic-speaking individuals with schizophrenia. Along with preexisting translations, this extension of the language repertoire of the BNSS would support cross-cultural deconstruction of the phenomenology of negative symptoms and outcome evaluation in global clinical trials.

Introduction: The 22q11.2 deletion syndrome is a genetic disorder characterized by pronounced age-dependent emergence of learning and cognitive deficits, including working memory and anxiety-related symptoms. The deletion confers a 20-fold increased risk of a schizophrenia diagnosis, but there are currently no approved pharmacological therapies for this condition. We have previously shown that treatment with a glycogen synthase kinase 3 (GSK3) paralog-nonselective inhibitor during early postnatal development rescues working memory task acquisition in the Df(16)A ^+/- mouse model of the 22q11.2 deletion. However, GSK3 paralog-nonselective inhibitors are associated with significant toxicological side effects, limiting their therapeutic potential. Here, we build upon this work by testing a newly developed GSK3α paralog-selective inhibitor with less potential for toxicological challenges.

Methods: Using the Df(16)A ^+/- mouse model, we evaluated the effects of GSK3α inhibition on spatial working memory and approach-avoidance behavior.

Results: We found that early postnatal GSK3α inhibition from postnatal day 7 (P7) to P28 restored spatial working memory performance in adult Df(16)A ^+/- mice under conditions of increased working memory demand. Additionally, we observed heightened exploratory behavior in Df(16)A ^+/- mice that was reverted to baseline levels by GSK3α inhibition in a genotype-independent manner.

Conclusion: Overall, we provide evidence supporting the feasibility and effectiveness of paralog-selective GSK3α inhibition-mediated rescue of cognitive function in a model of altered neurodevelopment.

Introduction: We have made tremendous advances in understanding the etiology of substance use disorders (SUDs). Despite these advances, screening for SUDs has remained largely unchanged. In this paper, we describe an effort to build a program that integrates advances across genomics, developmental psychology, and epidemiology to provide individuals with personalized information about their addiction risk profile.

Methods: The program was developed based on foundational work from a NIDA-funded project that conducted multivariate analyses of externalizing phenotypes to advance gene identification for SUDs and then characterized how polygenic scores (PGS) and early life behavioral and environmental factors predicted SUDs in diverse longitudinal samples. Based on this work, we created PGS and a behavioral and environmental risk index to generate personalized risk profiles. We carefully considered ethical concerns when developing the program.

Results: We created a user-friendly, self-directed online platform that provides personalized risk information, including overall risk for developing an SUD based on an individual's combination of genetic, behavioral, and environmental risk, and specific information about genetic risk, based on PGS, and behavioral/environmental risk. Data from the first 188 participants enrolled in an ongoing study to evaluate the platform indicate high satisfaction and low distress at receiving genetic information.

Conclusion: Provision of personalized feedback about addiction risk factors, including genetic information along with behavioral and environmental feedback, may be a viable way to promote earlier screening and intervention with the goal of preventing substance use problems before they start.

Introduction: The aim of this study was to evaluate the association between blepharoptosis (ptosis) and the prevalence of mental health disorders in adults, including anxiety, depression, bipolar disorder, schizophrenia spectrum disorders, and substance use/addictive disorders.

Methods: Cross-sectional study using data from the National Institutes of Health's All of Us Research Program. The study included 4,411 adults diagnosed with ptosis and 4,411 propensity score-matched controls, matched by age, sex, race, education, and income. A 1:1 propensity score-matched analysis was performed, comparing adults with ptosis to matched controls. Logistic regression was used to adjust for potential confounders, including body mass index, elevated blood pressure, and blood glucose levels. Prevalence rates of anxiety, depression, bipolar disorder, schizophrenia spectrum disorders, and substance use/addictive disorders. The primary outcome was the association between ptosis and any mental health disorder.

Results: Adults with ptosis exhibited significantly higher rates of mental health disorders compared to controls, including anxiety (46.8% vs. 28.9%), depression (44.9% vs. 27.8%), bipolar disorder (5.8% vs. 3.6%), schizophrenia spectrum disorders (1.8% vs. 1.1%), and substance use/addictive disorders (23.4% vs. 17.0%). The prevalence of any mental health disorder was significantly higher in the ptosis group (63.4% vs. 44.8%, p < 0.001). After adjustment, ptosis was associated with increased odds of any mental health disorder (aOR: 1.92, 95% CI, 1.76-2.10) and each specific mental health disorder.

Conclusion: Ptosis is associated with a significantly higher prevalence of mental health disorders, suggesting it may be an independent risk factor. Mental health screenings and psychosocial support should be considered for patients with ptosis. Further research is needed to explore causal mechanisms and stratify risk based on ptosis etiology and severity. This study may be subject to Berkson's bias, wherein individuals with ptosis may have more frequent health care encounters, increasing the likelihood of being diagnosed with psychiatric conditions.

Introduction: Clinical notes in electronic health records offer valuable insight into the symptom profiles and trajectories of patients with severe mental illness (SMI). However, systematically extracting symptoms at scale remains a challenge, especially in languages other than English. We developed a light, accurate, and interpretable natural language processing (NLP) algorithm to extract psychiatric phenotypes from Spanish clinical notes.

Methods: We selected a set of 136 core psychiatric phenotypes and annotated 4,000 clinical note sections (e.g., Chief Complaint, Plan; called "documents") and 240 complete visit notes (called "entries") from two psychiatric hospitals in Colombia: Hospital Mental de Antioquia (HOMO) and Clínica San Juan de Dios Manizales (CSJDM). For phenotypes meeting frequency and inter-annotator reliability thresholds, we developed three NLP algorithms (HOMO, CSJDM, and COMBINED) for phenotype extraction and context labeling (e.g., negation, family history, uncertainty). We evaluated performance at the document and entry levels, as well as across hospitals.

Results: Document-level performance at both hospitals was high (average F1 scores of 0.84 and 0.85). Moreover, on phenotypes meeting our document-level performance threshold of F1 ≥0.7, entry-level performance was high as well (average F1 of 0.75 and 0.78), as was the cross-hospital transportability of the algorithms (F1 of 0.75 HOMO-to-CSJDM and 0.77 CSJDM-to-HOMO). The COMBINED algorithm improved overall recall, without significantly decreasing precision (F1 of 0.78 and 0.77 on HOMO and CSJDM, respectively). The application of our algorithm for 50 high-performing phenotypes to the notes of 9,737 SMI patients highlighted the transdiagnostic nature of many core SMI phenotypes; 44/50 phenotypes were recorded in over 10% of patients across diagnoses. Multiple correspondence analysis further revealed variation in symptom space across diagnoses; while major depressive disorder and schizophrenia form distinct clusters, patients with bipolar disorder span the entire phenotypic spectrum.

Conclusion: Our tool enables the systematic investigation of psychiatric symptoms from psychiatric notes, facilitating large-scale investigations in Spanish-speaking populations.

Introduction: We are in the midst of an opioid epidemic. In the USA, more than a third of the country knows someone who has died from an opioid overdose. Prescription opioids (e.g., oxycodone, hydrocodone, and fentanyl) are commonly used and misused, and it has been estimated that approximately 8-12% of individuals who misuse opioids will subsequently develop an opioid use disorder (OUD). While emphasis has been placed on understanding OUD and the associated adverse effects, there remains a critical gap in systematically characterizing the multifactorial pathways (e.g., behavioral, clinical, genetic, and socio-demographic characteristics) that contribute to the transition from initial use to misuse to OUD.

Methods: To address this gap, we introduce the Prescription Opioid Medication Survey (POMS), an online 120-item assessment that compiles multiple validated and standardized instruments. POMS is intended for individuals with any lifetime prescription opioid use. POMS captures various aspects of prescription opioid use including data on opioid use patterns, subjective effects (e.g., euphoria, nausea), problematic use, withdrawal, OUD, overdose, treatment history, and remission. It also addresses comorbid risk factors such as surgical history, chronic pain, other substance use disorders (SUD; e.g., nicotine, alcohol, cannabis, stimulants), other addictive behaviors (i.e., gambling, sexual behaviors, and gaming), and family history of SUD and other addictive behaviors. Mental health assessments, including screening for depression and anxiety, self-reports of eight psychiatric disorders (anxiety, depression, bipolar, schizophrenia, attention-deficit/hyperactivity disorder, post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders), and related mental health conditions (e.g., loneliness, suicide, trauma) are included, along with data on personality traits (e.g., risk-taking, delay discounting, wisdom) and socio-demographic factors. POMS is intended to be administered in clinical settings and large population-based cohorts, facilitating data collection that can enable discoveries to inform better prevention and intervention strategies for OUD.

Conclusion: POMS offers a comprehensive tool for systematically capturing the multifactorial risk factors associated with opioid misuse and OUD, providing insights that can inform prevention and intervention strategies.

Introduction: Caffeine is a widely consumed psychoactive compound that can cause anxiety and sleep difficulties, in part due to genetic variation. We investigated the association between caffeine consumption, psychological distress, and sleep difficulties in a genetically informative cohort of individuals with a history of depression.

Methods: Survey data and genetic information were sourced from the Australian Genetics of Depression Study (AGDS [n = 20,689, %_female = 75%, mean age = 43 ± 15 years]). Associations between caffeine consumption and symptoms of distress and sleep disturbance, as well as 9 genetic variants associated with caffeine consumption behaviour, were assessed using linear regression.

Results: The highest consumers of caffeine reported higher psychological distress measured by the Kessler 10 scale (β = 1.21, SE = 0.25, p = 1.4 × 10^-6) compared to the lowest consumers. Consumption was associated with 2 genetic variants with effect sizes ∼0.35 additional caffeinated drinks/day between opposite homozygotes (p < 0.005). A deletion near MMS22L/POU3F2 was associated with 10% increased odds of reporting caffeine susceptibility (OR = 1.1 per deletion [95% CI: 1.04-1.17], p = 0.002).

Conclusions: Higher rates of caffeine consumption were associated with higher levels of psychological distress, but not insomnia, in individuals with a history of depression. While the direction of causality is unclear, caffeine consumption may be a modifiable factor to reduce distress in individuals susceptible to mental health problems. Some of the previous findings of common variant associations with caffeine consumption and susceptibility were replicated.

Introduction: Sleep deprivation affects cognitive performance and immune function, yet its mechanisms and biomarkers remain unclear. This study explored the relationships among gene expression, brain metabolism, sleep deprivation, and sex differences.

Methods: Fluorodeoxyglucose-18 positron emission tomography measured brain metabolism in regions of interest, and RNA analysis of blood samples assessed gene expression pre- and post-sleep deprivation. Mixed model regression and principal component analysis identified significant genes and regional metabolic changes.

Results: There were 23 and 28 differentially expressed probe sets for the main effects of sex and sleep deprivation, respectively, and 55 probe sets for their interaction (FDR-corrected p < 0.05). Functional analysis of genes affected by sleep deprivation revealed pathway enrichment in nucleoplasm- and UBL conjugation-related genes. Genes with significant sex effects mapped to chromosomes Y and 19 (Benjamini-Hochberg FDR p < 0.05), with 11 genes (4%) and 29 genes (10.5%) involved, respectively. Differential gene expression highlighted sex-based differences in innate and adaptive immunity. For brain metabolism, sleep deprivation resulted in significant decreases in the left insula, left medial prefrontal cortex (BA32), left somatosensory cortex (BA1/2), and left motor premotor cortex (BA6) and increases in the right inferior longitudinal fasciculus, right primary visual cortex (BA17), right amygdala, left cerebellum, and bilateral pons.

Conclusion: Sleep deprivation broadly impacts brain metabolism, gene expression, and immune function, revealing cellular stress responses and hemispheric vulnerability. These findings enhance our understanding of the molecular and functional effects of sleep deprivation.

Background: Substance use disorder (SUD) is closely associated with epigenetic modifications that significantly impact mental health outcomes. Alcohol and drug misuse induce widespread changes in the epigenome and transcriptome of the central nervous system, disrupting critical processes such as reward signaling and emotional regulation. These alterations in epigenetic regulation and gene expression often persist even after substance cessation, potentially contributing to the onset or worsening of psychiatric conditions, including schizophrenia, depression, stress, and anxiety.

Summary: This review delves into key epigenetic mechanisms underlying SUD and its comorbid psychiatric disorders, with a focus on DNA methylation, histone modifications, and noncoding RNA regulation. Additionally, it examines the influence of environmental and biological factors on the epigenome and evaluates emerging epigenetic-based therapeutic strategies aimed at treating SUD and related psychiatric conditions.

Key messages: Gaining a deeper understanding of the epigenetic mechanisms driving SUD and its associated psychiatric disorders is crucial for the development of effective therapeutic interventions. This review highlights the potential of epigenetic-based pharmacological strategies to mitigate the societal and personal burdens linked to SUD and its mental health complications.

Introduction: Research has identified multiple risk factors associated with suicide attempt (SA) among individuals with psychiatric illness. However, there is limited research among those with an alcohol use disorder (AUD), despite their disproportionately higher rates of SA.

Methods: We examined lifetime SA in 4,068 individuals with an AUD from the Collaborative Study on the Genetics of Alcoholism (23% lifetime SA; 53% female; mean age: 38). We explored risk for lifetime SA across other clinical conditions ascertained from a clinical interview, polygenic scores for comorbid psychiatric problems, and neurocognitive functioning.

Results: Participants with an AUD who attempted suicide had greater rates of trauma exposure, major depressive disorder, post-traumatic stress disorder, other substance use disorders (SUDs), and suicidal ideation. Polygenic scores for SA, depression, and PTSD were associated with increased odds of reporting an SA (ORs = 1.22-1.44). Participants who reported an SA also had decreased right hemispheric frontal-parietal theta and decreased interhemispheric temporal-parietal alpha electroencephalogram resting-state coherences relative to those who did not, but differences were small.

Conclusions: Overall, individuals with an AUD who report lifetime SA experience greater levels of trauma, have more severe comorbidities, and carry increased polygenic risk for other psychiatric problems. Our results demonstrate the need to further investigate SAs in the presence of SUDs.