Treatment-resistant depression (TRD) affects 10–30% of patients with major depressive disorder, leading to increased comorbidities, higher mortality, and significant economic and social burdens. This study aimed to compare the efficacy and safety of bupropion and aripiprazole as augmentation therapies for TRD.

This population-based, retrospective cohort study included adults aged ≥18 years with a diagnosis of depressive disorder who met the criteria for TRD. Data were collected from a nationwide claims database in South Korea. Patients prescribed bupropion were matched 1:1 with those prescribed aripiprazole. Subgroup analyses were performed according to age. An as-treated analysis was performed as the primary analysis, and an intention-to-treat analysis was performed to identify different risk windows. The primary outcome was depression-related hospitalization, and the secondary outcomes were first-time diagnoses of movement disorder and seizure.

A total of 5,619 patients (bupropion: n = 1,568; aripiprazole: n = 4,051) were included in this study. Bupropion was associated with lower risks of hospitalization (hazard ratio [HR]: 0.51; 95% confidence interval [CI] 0.29–0.86) and movement disorders (HR: 0.56; 95% CI 0.36–0.85) than aripiprazole. No significant difference in seizure risk (HR: 0.65; 95% CI 0.30–1.31) was observed between the two treatments. The subgroup analysis of participants aged ≥60 years revealed no significant differences in the three outcomes between the two medications.

Bupropion augmentation is associated with a significantly lower risk of depression-related re-hospitalization and movement disorders in patients with TRD. Therefore, bupropion augmentation can be a comprehensive treatment strategy for TRD.

A variety of treatment options for people with alcohol use disorder (AUD) exist. Surveys estimate that 1 in 10 people with AUD utilise treatment, but real-world treatment pathways remain covert. This data-linkage study seeks to characterise treatment utilisation patterns to identify gaps in treatment access and delivery in Germany.

Linking individual-level data from three sources (statutory health insurance, pension funds, outpatient addiction care services) identified seven alcohol-related treatment types delivered in outpatient (brief psychiatric consultation; formal psychotherapy; pharmacotherapy; low-threshold counselling), inpatient (standard, somatic inpatient treatment; intensive inpatient treatment with somatic and psychosocial care), or either of the two settings (long-term rehabilitation treatment) during 2016–2021. For patients with a new AUD diagnosis (ICD-10: F10.1–9), treatment utilisation over 24 months was recorded and patterns were identified using latent class analyses.

Of n = 9,491 patients with a new AUD diagnosis, 30% utilised at least one alcohol-related treatment type. Treatment utilisation was associated with younger age, female sex, unemployment, German nationality, and lower physical comorbidity. Among treatment entrants, nearly half received only brief psychiatric consultation. A similar share of patients utilised standard or intensive inpatient treatment; the latter occasionally followed by rehabilitation treatment. Formal psychotherapy, low-threshold counselling, and pharmacotherapy were rarely utilised and were mostly used in conjunction with other treatments.

The real-world utilisation of alcohol-related treatments contrasts with existing guidelines, as most patients with diagnosed AUD do not receive adequate care. Structural and social barriers should be minimised to ensure healthcare provision for those affected.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used due to their profound efficacy in glycemic control and weight management. Real-world observations have revealed potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs. This study aimed to comprehensively investigate and characterize these neuropsychiatric AEs with GLP-1RAs.

We analyzed GLP-1RA adverse reaction reports using the FDA Adverse Event Reporting System database. Disproportionality analysis using reporting odds ratio (ROR) identified eight categories of neuropsychiatric AEs associated with GLP-1RAs. We conducted descriptive and time-to-onset (TTO) analyses and explored neuropsychiatric AE signals among individual GLP-1RAs for weight loss and diabetes mellitus (DM) indications.

We identified 25,110 cases of GLP-1RA-related neuropsychiatric AEs. GLP-1RAs showed an association with headache (ROR 1.74, 95% confidence interval [CI] 1.65–1.84), migraine (ROR 1.28, 95%CI 1.06–1.55), and olfactory and sensory nerve abnormalities (ROR 2.44, 95%CI 1.83–3.25; ROR 1.69, 95%CI 1.54–1.85). Semaglutide showed a moderate suicide-related AEs signal in the weight loss population (ROR 2.55, 95%CI 1.97–3.31). The median TTO was 16 days (interquartile range: 3–66 days).

In this study, we identified eight potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs and, for the first time, detected positive signals for migraine, olfactory abnormalities, and sensory abnormalities. We also observed positive suicide-related signals of semaglutide, in weight loss population. This study provides a reliable basis for further investigation of GLP-1RA-related neuropsychiatric AEs. However, as an exploratory study, our findings require confirmation through large-scale prospective studies.

Acute health and social services for children and adolescents often struggle with youth aggression and violence. Early identification of violence risk during institutional stay can help prevent violent incidents. As such, this study assessed the predictive accuracy of the Violence Risk Assessment Checklist for Youth (V-RISK-Y) aged 12–18 in two different juvenile settings providing 24-hour services for youth. Institutions were included from child and adolescent inpatient psychiatry and residential youth care under child protective services.

A prospective, naturalistic observational study design was employed. V-RISK-Y was administered for youth admitted to four acute inpatient psychiatric units and four acute residential youth care institutions. Incidents of violence and threats during the youth’s stay were registered by institutional staff. In total, 517 youth were included in analyses, 59 of whom were registered with at least one incident of violence or threats during their stay. Area under curve (AUC) and logistic regression analyses were used to assess predictive accuracy and validity of V-RISK-Y.

For the overall sample, V-RISK-Y had good predictive accuracy, and the sum score of V-RISK-Y significantly predicted registered violent incidents. Stratified analyses indicated good predictive accuracy of V-RISK-Y for the inpatient units, but not for the residential youth care institutions.

Findings imply that V-RISK-Y is accurate in identifying violence risk for youth admitted to inpatient psychiatric units but has limited predictive accuracy in residential youth care institutions. Future research should explore approaches to correctly identify violence risk in residential care settings.

Recent stressful life events (SLEs) are an established risk factor for a range of psychiatric disorders. Animal studies have shown evidence of gray matter (GM) reductions associated with stress, and previous work has found similar associations in humans. However longitudinal studies investigating the association between stress and changes in brain structure are limited.

The current study uses longitudinal data from the UK Biobank and comprises 4,543 participants with structural neuroimaging and recent SLE data (mean age = 61.5 years). We analyzed the association between recent SLEs and changes in brain structure, determined using the longitudinal FreeSurfer pipeline, focusing on total GM volume and five a priori brain regions: the hippocampus, amygdala, anterior cingulate cortex, orbitofrontal cortex, and insula. We also examined if depression and childhood adversity moderated the relationship between SLEs and brain structure.

Individuals who had experienced recent SLEs exhibited a slower rate of hippocampal decrease over time compared to individuals who did not report any SLEs. Individuals with depression exhibited smaller GM volumes when exposed to recent SLEs. There was no effect of childhood adversity on the relationship between SLEs and brain structure.

Our findings suggest recent SLEs are not directly associated with an accelerated decline in brain volumes in a population sample of older adults, but instead may alter brain structure via affective disorder psychopathology. Further work is needed to investigate the effects of stress in younger populations who may be more vulnerable to stress-induced changes, and may yet pinpoint brain regions linked to stress-related disorders.

Estimating the risk of developing bipolar disorder (BD) in children and adolescents (C&A) with depressive disorders is important to optimize prevention and early intervention efforts. We aimed to quantitatively examine the risk of developing BD from depressive disorders and identify factors which moderate this development.

In this systematic review and meta-analysis (PROSPERO:CRD42023431301), PubMed and Web-of-Science databases were searched for longitudinal studies reporting the percentage of C&A with ICD/DSM-defined depressive disorders who developed BD during follow-up. Data extraction, random-effects meta-analysis, between-study heterogeneity analysis, quality assessment, sub-group analyses, and meta-regressions were conducted.

Thirty-nine studies were included, including 72,371 individuals (mean age=13.9 years, 57.1% females); 14.7% of C&A with a depressive disorder developed BD after 20.4–288 months: 9.5% developed BD-I (95% CI=4.7 to 18.1); 7.7% developed BD-II (95% CI=3.2% to 17.3%); 19.8% (95% CI=9.9% to 35.6%) of C&A admitted into the hospital with a depressive disorder developed BD. Studies using the DSM (21.6%, 95% CI=20.2% to 23.1%) and studies evaluating C&A with a major depressive disorder only (19.8%, 95% CI=16.8% to 23.1%) found higher rates of development of BD. Younger age at baseline, a history of hospitalization and recruitment from specialized clinics were associated with an increased risk of developing BD at follow-up. Quality of included studies was good in 76.9% of studies.

There is a substantial risk of developing BD in C&A with depressive disorders. This is particularly the case for C&A with MDD, DSM-diagnosed depressive disorders, and C&A admitted into the hospital. Research exploring additional predictors and preventive interventions is crucial.

Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.

This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).

In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.

Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.

Beyond psychosis prediction, clinical high-risk (CHR-P) symptoms show clinical relevance by their association with functional impairments and psychopathology, including personality pathology. Impaired personality functioning is prioritized in recent dimensional personality disorder models (DSM-5, ICD-11), yet underexplored in CHR-P, as are associations with cognitive biases, which early studies indicate as possibly linking CHR-P-symptoms and personality pathology.

A community sample (N = 444, 17–60 years, 61.8% female) was assessed via clinical telephone interview and online questionnaires. Using zero-inflated Poisson models, we explored associations of personality functioning, cognitive biases, current psychopathology, and psychosocial functioning with likelihood and severity of overall CHR-P, as well as perceptive (per-) and non-perceptive (nonper-)CHR-P-symptoms distinctly.

Higher nonper-CHR-P-symptom likelihood was associated with more impaired personality functioning and psychosocial functioning, while more severe cognitive biases were associated with higher CHR-P- and per-CHR-P-symptom likelihood, alongside higher CHR-P- and nonper-CHR-P-symptom severity. Further, more axis-I diagnoses were linked to higher CHR-P-, per-CHR-P-, and nonper-CHR-P-symptom likelihood, and younger age to higher CHR-P- and per-CHR-P-symptom severity, with CHR-P-symptom severity appearing higher in females. In an exploratory analysis, personality functioning elements identity and self-direction, and cognitive biases dichotomous thinking, emotional reasoning, and catastrophizing, respectively, showed multifaceted associations with nonper-CHR-P-symptom likelihood and overall CHR-P-symptom expression.

Our study supports the association of CHR-P-symptoms with multiple mental health factors. Findings suggest intricate associations between personality functioning impairments and cognitive biases with CHR-P-symptom expression in non-help-seeking populations, possibly contributing to different per-CHR-P- and nonper-CHR-P-symptom expression patterns. Therefore, they should be targeted in future longitudinal studies, aiming at better understanding CHR-P-manifestations to inform preventive intervention.

Cardiovascular disease (CVD) is twice as prevalent among individuals with mental illness compared to the general population. Prevention strategies exist but require accurate risk prediction. This study aimed to develop and validate a machine learning model for predicting incident CVD among patients with mental illness using routine clinical data from electronic health records.

A cohort study was conducted using data from 74,880 patients with 1.6 million psychiatric service contacts in the Central Denmark Region from 2013 to 2021. Two machine learning models (XGBoost and regularised logistic regression) were trained on 85% of the data from six hospitals using 234 potential predictors. The best-performing model was externally validated on the remaining 15% of patients from another three hospitals. CVD was defined as myocardial infarction, stroke, or peripheral arterial disease.

The best-performing model (hyperparameter-tuned XGBoost) demonstrated acceptable discrimination, with an area under the receiver operating characteristic curve of 0.84 on the training set and 0.74 on the validation set. It identified high-risk individuals 2.5 years before CVD events. For the psychiatric service contacts in the top 5% of predicted risk, the positive predictive value was 5%, and the negative predictive value was 99%. The model issued at least one positive prediction for 39% of patients who developed CVD.

A machine learning model can accurately predict CVD risk among patients with mental illness using routinely collected electronic health record data. A decision support system building on this approach may aid primary CVD prevention in this high-risk population.

This systematic review and meta-analysis evaluates the prevalence of disruptive mood dysregulation disorders (DMDD) in community-based and clinical populations.

PubMed and PsychINFO databases were searched, using terms specific to DMDD, for studies of prevalence and comorbidity rates conducted in youths below 18.

Fourteen studies reporting data from 2013 to 2023 were included. The prevalence of DMDD in the community-based samples was 3.3% (95% confidence interval [CI], 1.4–6.0) and 21.9% (95% CI, 15.5–29.0) in the clinical population. The differences in the identification strategy of DMDD were associated with significant heterogeneity between studies in the community-based samples, with a prevalence of 0.82% (95% CI, 0.11–2.13) when all diagnosis criteria were considered. Anxiety, depressive disorders, and ADHD were the most frequent comorbidity present with DMDD. The association with other neurodevelopmental disorders remained poorly investigated.

Caution is required when interpreting these findings, considering the quality of the reviewed data and the level of unexplained heterogeneity among studies. This review stresses the importance of considering a strict adhesion to DMDD criteria when exploring its clinical correlates.

The lifetime prevalence of PTSD ranges from 6 to 20% and is often associated with comorbid disorders. Despite the significant impact of PTSD, specific data on healthcare utilization related to PTSD remain limited. This study aims to characterize PTSD-related hospitalizations in France over the past decade.

This nationwide longitudinal retrospective study analyzed PTSD-related hospitalizations in France from 2013 to 2022 using the French National Hospitals Database. Data included discharge records from general and psychiatric hospitals, detailing demographics, admission/discharge dates, ICD-10 diagnoses, and hospitalization specifics.

Between 2013 and 2022, 69,108 patients underwent 125,349 hospitalizations with a PTSD diagnosis (0.4% of all inpatient cases) in France. Psychiatric facilities accounted for 74,988 hospitalizations (1% of all psychiatric inpatient cases in France), while general hospitals recorded 50,361 hospitalizations (0.02% of all non-psychiatric inpatient cases). The percentage of inpatients diagnosed with PTSD increased from 0.68 to 2.22% in psychiatric facilities and from 0.02 to 0.04% in general hospitals over the study period. Females were younger in both settings and had longer stays compared to males in psychiatric facilities. Over time, there was a decrease in median age and an increase in part-time hospitalizations in psychiatric facilities. Mood disorders, stress-related disorders, and substance use disorders were prevalent comorbidities in both settings.

This study highlights a rise in PTSD-related hospitalizations in France, particularly in psychiatric facilities and after 2019, with high rates among women and an increase in hospitalization of younger individuals. These findings highlight the necessity for improved care strategies tailored to the increasing number of younger patients with PTSD.

Recent advances in natural language processing (NLP), particularly in language processing methods, have opened new avenues in semantic data analysis. A promising application of NLP is data harmonization in questionnaire-based cohort studies, where it can be used as an additional method, specifically when only different instruments are available for one construct as well as for the evaluation of potentially new construct-constellations. The present article therefore explores embedding models’ potential to detect opportunities for semantic harmonization.

Using models like SBERT and OpenAI’s ADA, we developed a prototype application (“Semantic Search Helper”) to facilitate the harmonization process of detecting semantically similar items within extensive health-related datasets. The approach’s feasibility and applicability were evaluated through a use case analysis involving data from four large cohort studies with heterogeneous data obtained with a different set of instruments for common constructs.

With the prototype, we effectively identified potential harmonization pairs, which significantly reduced manual evaluation efforts. Expert ratings of semantic similarity candidates showed high agreement with model-generated pairs, confirming the validity of our approach.

This study demonstrates the potential of embeddings in matching semantic similarity as a promising add-on tool to assist harmonization processes of multiplex data sets and instruments but with similar content, within and across studies.

Polygenic risk scores for educational attainment (PRSEA), cognitive reserve (CR), and clinical symptoms are associated with functioning in first-episode psychosis (FEP). Nevertheless, the mechanisms underlying their complex interaction are yet to be explored. This study assessed the mediating role of CR and clinical symptoms, both negative (NS) and positive (PS), on the interrelationship between PRSEA and functionality, one year after a FEP.

A total of 162 FEP patients underwent clinical, functional, and genetic assessments. Using genome-wide association study summary results, PRSEA were constructed for each individual. Two mediation models were performed. The parallel mediation model explored the relationship of PRSEA with functionality through CR and clinical symptoms. The serial mediation model tested a causal chain of the three mediators: CR, NS, and PS. Mediation analysis was performed using the PROCESS function V.4.1 in SPSS V.22.

A serial mediation model revealed a causal chain for PRSEA > CR > NS > Functionality (β = −0.35, 95%CI [−0.85, −0.04], p < 0.05). The model fit the data satisfactorily (CFI = 1.00; RMSEA = 0.00; SRMR = 7.2 × 10−7). Conversely, no parallel mediation was found between the three mediators, PRSEA and functionality and the model poorly fit the data (CFI = 0.30; RMSEA = 0.25; SRMR = 0.11).

Both CR and NS mediate the relationship between PRSEA and functionality at one-year follow-up, using serial mediation analysis. This may be relevant for prevention and personalized early intervention to reduce illness impact and improve functional outcomes in FEP patients.

Racial and ethnic experiences of discrimination (EODs) are associated with numerous psychiatric symptoms, including outcomes along the psychosis spectrum; however, less is known about mechanisms by which EODs confer risk for psychotic-like experiences (PLEs; common subthreshold psychotic symptoms). Furthermore, work on gendered racism asserts that the intersection of race and gender impacts the nature of EODs experienced and, in turn, may impact the relationship between EODs and PLEs.

To utilize an intersectional lens (race and gender) to examine whether psychological correlates of EODs (post-traumatic stress, anxiety, depression, and dissociation) mediate the EOD–PLE relationship.

Undergraduates at a diverse, semipublic university (N = 1,759) completed self-report questionnaires (Experiences of Discrimination Scale, Prodromal Questionnaire, Center for Epidemiologic Studies Depression Scale, State–Trait Anxiety Inventory, Dissociative Experiences Scale, and Post-Traumatic Stress Disorder Checklist – Civilian Version). Analyses stratified the sample by race (non-Hispanic White, Black, and Asian) and examined three multiple mediation models, moderated by gender, examining the pathway from EODs to PLEs, through other psychiatric symptoms.

In the full sample, all psychiatric symptoms significantly mediated the relationship between EODs and PLEs. Only depression varied by gender, such that the indirect effect was only significant in female participants (β = 0.09; 95% CI [0.02, 0.16]). Across race-stratified groups, significant mediators varied by both race and gender.

These findings underscore the importance of accounting for intersectionality and multiple psychological symptoms in understanding the EOD–PLE associations, which differ by race and ethnicity as well as gender, and should be considered in clinical treatment of individuals with PLEs and history of EODs.

Hippocampal disruptions represent potential neuropathological biomarkers in depressed adolescents with cognitive dysfunctions. Given heterogeneous outcomes of whole-hippocampus analyses, we investigated subregional abnormalities in depressed adolescents and their associations with symptom severity and cognitive dysfunctions.

MethodsSeventy-nine first-episode depressive patients (ag = 15.54 ± 1.83) and 71 healthy controls (age = 16.18 ± 2.85) were included. All participants underwent T1 and T2 imaging, completed depressive severity assessments, and performed cognitive assessments on memory, emotional recognition, cognitive control, and attention. Freesurfer was used to segment each hippocampus into 12 subfields. Multivariable analyses of variance were performed to identify overall and disease severity-related abnormalities in patients. LASSO regression was also conducted to explore the associations between hippocampal subfields and patients’ cognitive abilities.

Depressed adolescents showed decreases in dentate gyrus, CA1, CA2/3, CA4, fimbria, tail, and molecular layer. Analyses of overall symptom severity, duration, self-harm behavior, and suicidality suggested that severity-related decreases mainly manifested in CA regions and involved surrounding subfields with disease severity increases. LASSO regression indicated that hippocampal subfield abnormalities had the strongest associations with memory impairments, with CA regions and dentate gyrus showing the highest weights.

Hippocampal abnormalities are widespread in depressed adolescents and such abnormalities may spread from CA regions to surrounding areas as the disease progresses. Abnormalities in CA regions and dentate gyrus among these subfields primarily link with memory impairments in patients. These results demonstrate that hippocampal subsections may serve as useful biomarkers of depression progression in adolescents, offering new directions for early clinical intervention.

One of the most relevant risk factors for suicide is the presence of previous attempts. The symptomatic profile of people who reattempt suicide deserves attention. Network analysis is a promising tool to study this field.

To analyze the symptomatic network of patients who have attempted suicide recently and compare networks of people with several attempts and people with just one at baseline.

1043 adult participants from the Spanish cohort “SURVIVE” were part of this study. Participants were classified into two groups: single attempt group (n = 390) and reattempt group (n = 653). Different network analyses were carried out to study the relationships between suicidal ideation, behavior, psychiatric symptoms, diagnoses, childhood trauma, and impulsivity. A general network and one for each subgroup were estimated.

People with several suicide attempts at baseline scored significantly higher across all clinical scales. The symptomatic networks were equivalent in both groups of patients (p > .05). Although there were no overall differences between the networks, some nodes were more relevant according to group belonging.

People with a history of previous attempts have greater psychiatric symptom severity but the relationships between risk factors show the same structure when compared with the single attempt group. All risk factors deserve attention regardless of the number of attempts, but assessments can be adjusted to better monitor the occurrence of reattempts.

Recent years show an exponential increased interest (“renaissance”) in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit.

In this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments.

In addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation.

Four recommendations are formulated for further research and clinical implementation.