Current knowledge on psychiatric illness following periods of social distancing during the COVID-19 pandemic is mostly limited to smaller studies in selected populations. This nationwide study of all 4.6 million Danish adults examined if periods of social distancing were associated with changes in surrogate measures of mental health.

All Danish adults (≥18 years) were included and rates of collection of antidepressant prescriptions, psychiatric hospital admissions, and suicide or suicide attempts for the periods March 12, 2020–May 20, 2020 (lockdown period 1), and December 21, 2020–March 1, 2021 (lockdown period 2), were compared to corresponding periods 1 year prior. Individuals were censored due to death or SARS-CoV-2 infection.

Antidepressant consumption increased for both period 1 and period 2, with an incidence rate ratio (IRR) of 1.02 (95% CI: 1.01–1.02, p < 0.001) and IRR 1.08 (95% CI: 1.08–1.09, p < 0.001) respectively, compared to the control periods. Psychiatric hospitalization rates decreased significantly, with an IRR of 0.65 (95% CI: 0.63–0.66, p < 0.001) for period 1, and IRR 0.86 (95% CI: 0.84–0.88, p < 0.001) for period 2. The risk of suicide did not increase in period 1, IRR 0.96 (95% CI: 0.82–1.13, p = 0.64), but seemed increased during period 2, IRR 1.19 (95% CI: 1.02–1.38, p = 0.03).

Periods of social distancing during the COVID-19 pandemic were associated with an increase of antidepressant consumption, but decreased rates of psychiatric hospitalization. Suicide risk seemed increased during the second lockdown period.

Despite uncertain benefits, antidepressants are used in the management of personality disorders (PDs). We investigated the association between antidepressants and two adverse outcomes - suicidal behaviour and violent crimes - in individuals with PDs.

We used nationwide Danish healthcare registries to identify all individuals with a diagnosed PD aged 18–64 years from 2007 to 2016. Antidepressant use was identified using dispensed prescriptions. Individuals were followed up for healthcare presentations of suicidal behaviour and separately for police-recorded charges of violent crimes. We applied a within-individual design comparing rates of suicidal behaviour and violent crimes during time periods of antidepressant treatment with periods without treatment. Subgroup analyses were performed according to PD clusters, individual antidepressants, specific PDs, psychiatric comorbidities, and history of suicidal behaviour and violent crime.

The cohort included 167,319 individuals with a diagnosed PD, 19,519 (12%) of whom were prescribed antidepressants and presented at least one outcome event during follow-up, making them eligible for within-individual analyses. Overall, we found an association with lower rates of suicidal behavior during periods of antidepressant treatment, compared with periods when individuals were not on antidepressants (incidence rate ratio 0.86, 95% CI 0.84–0.89). However, this association was modified by specific PDs, individual antidepressants, comorbidities, and past history. For violent crimes, we did not observe consistent associations in any direction.

Antidepressants were associated with lower rates of suicidal behaviour, but less clearly in violent crimes. Types of PDs, individual antidepressants, and comorbidities modified these associations.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

The development of guidelines is time-consuming and cost-intensive. The heterogeneity of clinical practice, evidence, and patients’ needs is an issue across Europe. An European core guidance for a specific psychiatric disorder may help to overcome this issue. Here, we present a progress report on the European Psychiatric Association (EPA) proof-of-concept approach to develop a European consensus guidance on the pharmacological treatment of schizophrenia.

All national psychiatric associations in Europe were contacted to provide their schizophrenia guidelines. Six guidelines were rated by three experts, experienced in the development of national and international guidelines, from three different countries (Italy, Hungary, and Germany), and the German schizophrenia guideline published in 2019 was found to have the highest quality. For this proof-of-concept approach, 45 recommendations on the pharmacological treatment of schizophrenia from the German guideline were evaluated in a two-step Delphi process to determine their acceptability throughout the European continent.

44 experts participated in the first round and 40 experts in the second round of the Delphi process. Agreement among the involved experts was reached for 75% of the presented recommendations from the German schizophrenia guidelines. 11 out of 45 recommendations (24.4%) did not reach this level of agreement.

This progress report highlights the possibility of developing a pan-European core guidance on the pharmacological treatment of schizophrenia by adapting national guidelines and reconciling their recommendations. However, several barriers in this adaptation process, such as non-agreement in recommendations with strong scientific evidence in the reconciling process, were identified and must be considered when developing the final guidance.

Childhood maltreatment (CM) significantly increases the risk of developing post-traumatic stress disorder (PTSD) for which the prevalence in Europe is higher than initially assumed. While the high economic burden of PTSD is well-documented, little is known about the health care cost differences between individuals with PTSD-CM and those without PTSD in Germany. This study aimed to determine the excess health care and absenteeism costs associated with PTSD-CM in Germany.

Baseline data from a multi-center randomized controlled trial on individuals with PTSD-CM (n = 361) were combined with data from individuals without PTSD (n = 4760). Entropy balancing was used to balance the data sets with regard to sociodemographic characteristics. Six-month excess health care costs from a societal perspective were calculated for 2022, using two-part models with logit specification for the first part and a generalized linear model for the second part.

The total six-month excess costs associated with PTSD-CM were €8864 (95% CI: €6855 to €10,873) per person. Of this, the excess health care costs accounted for €4647 (95% CI €3296 to €5997) and the excess costs of absenteeism for €4217 (95% CI: €3121 to €5314). Individuals with mild to moderate PTSD symptoms incurred total excess costs of €6038 (95% CI: €3879 to €8197), while those with severe to extreme symptoms faced €11,433 (95% CI: €8220 to €14,646).

Excess health care and absenteeism costs associated with PTSD-CM were substantial, with absenteeism accounting for roughly half of the total excess costs.

Many psychiatric and somatic comorbidities increase the risk of suicidal behavior, but the effect of co-existing comorbidities is sparsely elucidated. We described co-existence of psychiatric and somatic comorbidities and the influence of the combined comorbidity burden on the risk of suicidal behavior.

We defined two case populations above 10 years in the Danish health registries: those who 1) died by suicide (2010–2020) and 2) had an incident suicide attempt (2010–2021). Co-existing somatic and psychiatric comorbidities and relative odds of suicidal behavior at increasing comorbidity burden were assessed.

Among 5.9 million Danish citizens (2021), 6,257 individuals died by suicide whereas 30,570 had an incident suicide attempt. More than half had ≥2 co-existing psychiatric and/or somatic comorbidities. Of those who died by suicide, 18% had co-existing mood disorders and stress disorders, while 5% had both mood disorders and cancer. An 88-fold increase of odds for attempting suicide and a 35-fold increase of odds for suicide were observed among those with the highest combined burden of somatic and psychiatric comorbidities relative to those without. The presence of somatic comorbidities seemed to protect against suicide in older individuals.

Psychiatric and somatic comorbidities commonly co-exist in individuals with suicidal behavior. Higher combined burden of psychiatric and somatic comorbidities increased the odds of suicidal behavior, though the presence of somatic diseases had a potential protective effect on the risk of suicide in older individuals. This warrants collaboration and enhanced awareness of suicidal behavior risks across somatic and psychiatric departments.

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.

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.

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.