While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse.

Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction.

After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects (p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak.

We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.

The COVID-19 pandemic introduced unique stressors that posed significant threats to adolescent mental health. However, limited research has examined the impact of trauma exposure on vulnerability to subsequent stressor-related mental health outcomes in adolescents. Furthermore, it is unclear whether there are protective factors that promote resilience against the negative impacts of COVID-19 stressors in adolescents with prior trauma exposure. This preregistered study aimed to investigate the impact of trauma on COVID-19 stressor-related mental health difficulties in adolescents, in addition to the role of protective factors.

Aims were investigated in a sample of 9696 adolescents (mean age 12.85 ± 0.88 years) from the Adolescent Brain Cognitive Development Study. Linear mixed-effects models were employed to examine (a) the associations of early trauma exposure (exposed v. non-exposed), COVID-19 stressors, and perceived stress, sadness, and positive affect levels during the pandemic period in the US, and (b) the role of protective factors (physical activity, parental support, and improvements in family and peer relationships) in these associations.

There was a positive association between COVID-19 stressors and sadness, which was enhanced in trauma-exposed adolescents. Improvements in family and peer relationships mitigated the association between COVID-19 stressors and poor mental health outcomes, regardless of prior traumatic experience.

These findings support the hypothesis that prior trauma elevates risk of mental health difficulties in the face of future stressors. Results underscore the protective role of enhanced social relationships as targets for early prevention and intervention in those experiencing acute stressors, regardless of prior traumatic experiences.

The association between negative wealth shocks and depression among middle-aged and older individuals remains unclear. Our study aimed to assess the association between negative wealth shocks and depression and its trajectories, and to explore cross-national differences in these associations

Our sample included 21 999 participants, of which 9519 were from the Health and Retirement Study (2012–2020), 4936 from the English Longitudinal Study of Ageing (2012–2020), 2520 from the China Health and Retirement Longitudinal Study (2011–2020), and 5024 from the Mexican Health and Aging Study (2012–2021). We used latent class trajectory models to identify depressive trajectories, alongside mixed-model logistic regression and multinomial logistic regression to evaluate associations.

In the USA (OR 1.73, 95% CI 1.40–2.16), England (OR 1.71, 95% CI 1.09–2.70), and China (OR 1.38, 95% CI 1.09–1.75), negative wealth shocks were associated with subsequent depressive symptoms, but not in Mexico (OR 1.06, 95% CI 0.86–1.29). Additionally, negative wealth shocks were associated with several depressive trajectories in the USA and China. This association occurred only in increasing–decreasing trajectory in England, while no significant association was found across any trajectory in Mexico.

Negative wealth shocks were associated with subsequent depressive symptoms, with significant associations observed in some specific depressive trajectories. These associations exhibited cross-national differences, underscoring the importance of considering country-specific contexts when addressing the mental health impacts of wealth shocks.

Studies suggest severe mental disorders (SMDs), such as schizophrenia, major depressive disorder and bipolar disorder, are associated with common alterations in brain activity, albeit with a graded level of impairment. However, discrepancies between study findings likely to results from both small sample sizes and the use of different functional magnetic resonance imaging (fMRI) tasks. To address these issues, data-driven meta-analytic approach designed to identify homogeneous brain co-activity patterns across tasks was conducted to better characterize the common and distinct alterations between these disorders.

A hierarchical clustering analysis was conducted to identify groups of studies reporting similar neuroimaging results, independent of task type and psychiatric diagnosis. A traditional meta-analysis (activation likelihood estimation) was then performed within each of these groups of studies to extract their aberrant activation maps.

A total of 762 fMRI study contrasts were targeted, comprising 13 991 patients with SMDs. Hierarchical clustering analysis identified 5 groups of studies (meta-analytic groupings; MAGs) being characterized by distinct aberrant activation patterns across SMDs: (1) emotion processing; (2) cognitive processing; (3) motor processes, (4) reward processing, and (5) visual processing. While MAG1 was mostly commonly impaired, MAG2 was more impaired in schizophrenia, while MAG3 and MAG5 revealed no differences between disorder. MAG4 showed the strongest between-diagnoses differences, particularly in the striatum, posterior cingulate cortex, and ventromedial prefrontal cortex.

SMDs are characterized mostly by common deficits in brain networks, although differences between disorders are also present. This study highlights the importance of studying SMDs simultaneously rather than independently.

The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 (N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21).

We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

Should COVID-19 have a direct impact on the risk of depression, it would suggest specific pathways for prevention and treatment. In this retrospective population-based study, we aimed to examine the association of prior SARS-CoV-2 infection with depressive symptoms, distinguishing self-reported v. biologically confirmed COVID-19.

32 007 participants from the SAPRIS survey nested in the French CONSTANCES cohort were included. COVID-19 was measured as followed: ad hoc serologic testing, self-reported PCR or serology positive test results, and self-reported COVID-19. Depressive symptoms were measured with the Center of Epidemiologic Studies-Depression Scale (CES-D). Outcomes were depressive symptoms (total CES-D score, its four dimensions, and clinically significant depressive symptoms) and exposure was prior COVID-19 (no COVID-19/self-reported unconfirmed COVID-19/biologically confirmed COVID-19).

In comparison to participants without COVID-19, participants with self-reported unconfirmed COVID-19 and biologically confirmed COVID-19 had higher CES-D scores (β for one interquartile range increase [95% CI]: 0.15 [0.08–0.22] and 0.09 [0.05–0.13], respectively) and somatic complaints dimension scores (0.15 [0.09–0.21] and 0.10 [0.07–0.13]). Only those with self-reported but unconfirmed COVID-19 had higher depressed affect dimension scores (0.08 [0.01–0.14]). Accounting for ad hoc serologic testing only, the CES-D score and the somatic complaints dimension were only associated with the combination of self-reported COVID-19 and negative serology test results.

The association between COVID-19 and depressive symptoms was merely driven by somatic symptoms of depression and did not follow a gradient consistent with the hypothesis of a direct impact of SARS-CoV-2 infection on the risk of depression.

It remains uncertain whether long-term use of benzodiazepines is associated with age-related cognitive decline, and if cognitive ability in early life is the driver of any association. This study examines the association of cognitive ability in young adulthood with later use of benzodiazepines and explores whether the use of benzodiazepines during adult life is associated with cognitive decline in late midlife.

The study samples include cognitive tests on the Børge Priens Prøve (BPP) from the conscription board examination (age 19 years) from 335 513 men born 1949–1961 and data from re-examinations of 5183 men 44 years later. Cognitive decline was defined as the difference between scores at the conscription board and the re-examination. Information on purchases of benzodiazepines was obtained from the Danish National Prescription Registry, 1995–2022. Associations were analysed using Cox proportional hazards and linear regression.

In total, 120 911 (36%) men purchased benzodiazepines during a follow-up of 20 years. Lower cognitive scores in young adulthood were associated with a higher risk of initiating benzodiazepines (hazard ratio [95% CI] = 0.71[0.68–0.75]). Men with the highest cumulative use of benzodiazepines had larger cognitive decline (β-coefficient [95% CI] = −1.66 [−2.09 to −1.23] BPP scores) compared with never users. Current benzodiazepine users showed a larger cognitive decline than never users (β-coefficient [95% CI] = −2.42[−3.18 to −1.66] BPP scores) and this partially explained the above association. These estimates for cognitive decline were relatively small and may lack clinical relevance.

Low cognitive ability increases the risk of benzodiazepine use in adulthood and cognitive decline is more pronounced in those with the highest benzodiazepine use compared with never-use, but the difference lacks clinical significance.

The neural correlates underlying late-life depressive symptoms and cognitive deterioration are largely unclear, and little is known about the role of chronic physical conditions in such association. This research explores both concurrent and longitudinal associations between late-life depressive symptoms and cognitive functions, with examining the neural substrate and chronic vascular diseases (CVDs) in these associations.

A total of 4109 participants (mean age = 65.4, 63.0% females) were evaluated for cognitive functions through various neuropsychological assessments. Depressive symptoms were assessed by the Geriatric Depression Scale and CVDs were self-reported. T1-weighted magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) data were acquired in a subsample (n = 791).

Cognitively, higher depressive symptoms were correlated with poor performance across all cognitive domains, with the strongest association with episodic memory (r = ‒0.138, p < 0.001). Regarding brain structure, depressive symptoms were negatively correlated with thalamic volume and white matter integrity. Further, white matter integrity was found to mediate the longitudinal association between depressive symptoms and episodic memory (indirect effect = −0.017, 95% CI −0.045 to −0.002) and this mediation was only significant for those with severe CVDs (β = −0.177, p = 0.008).

This study is one of the first to provide neural evidence elucidating the longitudinal associations between late-life depressive symptoms and cognitive dysfunction. Additionally, the severity of CVDs strengthened these associations, which enlightens the potential of managing CVDs as an intervention target for preventing depressive symptoms-related cognitive decline.

Affective responses to the menstrual cycle vary widely. Some individuals experience severe symptoms like those with premenstrual dysphoric disorder, while others have minimal changes. The reasons for these differences are unclear, but prior studies suggest stressor exposure may play a role. However, research in at-risk psychiatric samples is lacking.

In a large clinical sample, we conducted a prospective study of how lifetime stressors relate to degree of affective change across the cycle. 114 outpatients with past-month suicidal ideation (SI) provided daily ratings (n = 6187) of negative affect and SI across 1–3 menstrual cycles. Participants completed the Stress and Adversity Inventory (STRAIN), which measures different stressor exposures (i.e. interpersonal loss, physical danger) throughout the life course, including before and after menarche. Multilevel polynomial growth models tested the relationship between menstrual cycle time and symptoms, moderated by stressor exposure.

Greater lifetime stressor exposure predicted a more pronounced perimenstrual increase in active SI, along with marginally significant similar patterns for negative affect and passive SI. Additionally, pre-menarche stressors significantly increased the cyclicity of active SI compared to post-menarche stressors. Exposure to more interpersonal loss stressors predicted greater perimenstrual symptom change of negative affect, passive SI and active SI. Exploratory item-level analyses showed that lifetime stressors moderated a more severe perimenstrual symptom trajectory for mood swings, anger/irritability, rejection sensitivity, and interpersonal conflict.

These findings suggest that greater lifetime stressor exposure may lead to heightened emotional reactivity to ovarian hormone fluctuations, elevating the risk of psychopathology.

Previous observational epidemiological studies have suggested that coffee consumption during pregnancy may affect fetal neurodevelopment. However, results are inconsistent and may represent correlational rather than causal relationships. The present study investigated whether maternal coffee consumption was observationally associated and causally related to offspring childhood neurodevelopmental difficulties (NDs) in the Norwegian Mother, Father and Child Cohort Study.

The observational relationships between maternal/paternal coffee consumption (before and during pregnancy) and offspring NDs were assessed using linear regression analyses (N = 58694 mother-child duos; N = 22 576 father-child duos). To investigate potential causal relationships, individual-level (N = 46 245 mother-child duos) and two-sample Mendelian randomization (MR) analyses were conducted using genetic variants previously associated with coffee consumption as instrumental variables.

We observed positive associations between maternal coffee consumption and offspring difficulties with social-communication/behavioral flexibility, and inattention/hyperactive-impulsive behavior (multiple testing corrected p < 0.005). Paternal coffee consumption (negative control) was not observationally associated with the outcomes. After adjusting for potential confounders (smoking, alcohol, education and income), the maternal associations attenuated to the null. MR analyses suggested that increased maternal coffee consumption was causally associated with social-communication difficulties (individual-level: beta = 0.128, se = 0.043, p = 0.003; two-sample: beta = 0.348, se = 0.141, p = 0.010). However, individual-level MR analyses that modelled potential pleiotropic pathways found the effect diminished (beta = 0.088, se = 0.049, p = 0.071). Individual-level MR analyses yielded similar estimates (heterogeneity p = 0.619) for the causal effect of coffee consumption on social communication difficulties in maternal coffee consumers (beta = 0.153, se = 0.071, p = 0.032) and non-consumers (beta = 0.107, se = 0.134, p = 0.424).

Together, our results provide little evidence for a causal effect of maternal coffee consumption on offspring NDs.

This study examined the power of theory-derived models to account for the development of PTSD, Complex PTSD (CPTSD), depression, and anxiety in children and adolescents who had experienced a single-event trauma.

Children (n = 234, aged 8–17 years) recruited from local Emergency Departments were assessed at two and nine weeks post-trauma. Data obtained from self-report questionnaires completed by the child, telephone interviews with parents, and hospital data were used to develop four predictive models of risk factors for PTSD, CPTSD, depression, and Generalized Anxiety Disorder (GAD). ICD-11 proposed diagnostic criteria were used to generate measures for CPTSD and PTSD to assess for risk factors and identify the sample prevalence of these disorders.

At nine weeks post-trauma, 64% did not meet criteria for any disorder, 23.5% met criteria for PTSD, and 5.2% met criteria for CPTSD. 23.9% and 10.7% had developed clinically significant symptoms of depression and GAD, respectively. A cognitive model was the most powerful predictive model, a psychosocial model was weak, and subjective markers of event severity were more powerful than objective measures.

Youth exposed to single-incident trauma may develop different forms of psychopathology, and PTSD and CPTSD are frequently experienced alongside other conditions. The cognitive model of PTSD shows utility in identifying predictors of PTSD, CPTSD, depression, and GAD, particularly the role of trauma-related negative appraisals. This supports the application of cognitive interventions which focus upon re-appraising trauma-related beliefs in youth.

Whether the recent rise in adolescent self-reported depressive symptoms is influenced by changing reporting behavior is much debated. Most studies use observed sum scores to document trends but fail to assess whether their measures are invariant across time, a prerequisite for meaningful inferences about change. We examined whether measurement noninvariance, indicative of changing perceptions and reporting of symptoms, may influence the assessment of time trends in adolescent depressive symptoms.

Data stem from the nationwide repeated cross-sectional Ungdata-surveys (2010–2019) of 560 712 responses from adolescents aged 13 to 19 years. Depressive symptoms were measured with the Kandel and Davies' six-item Depressive Mood Inventory. Using structural equation modeling, we examined measurement invariance across time, gender and age, and estimated the consequences of noninvariance on cross-cohort time trends.

Across most conditions, the instrument was found measurement invariant across time. The few noninvariant parameters detected had negligible impact on trend estimates. From 2014, latent mean depressive symptom scores increased among girls. For boys, a U shaped pattern was detected, whereby an initial decrease in symptoms was followed by an increase from 2016. Larger issues of noninvariance were found across age in girls and between genders.

From a measurement perspective, the notion that changed reporting of symptoms has been an important driver of secular trends in depressive symptoms was not supported. Thus, other causes of these trends should be considered. However, noninvariance across age (in girls) and gender highlights that depressive symptoms are not necessarily perceived equivalently from early to late adolescence and across gender.

Cross-sectional studies have identified health risks associated with epigenetic aging. However, it is unclear whether these risks make epigenetic clocks ‘tick faster’ (i.e. accelerate biological aging). The current study examines concurrent and lagged within-person changes of a variety of health risks associated with epigenetic aging.

Individuals from the Great Smoky Mountains Study were followed from age 9 to 35 years. DNA methylation profiles were assessed from blood, at multiple timepoints (i.e. waves) for each individual. Health risks were psychiatric, lifestyle, and adversity factors. Concurrent (N = 539 individuals; 1029 assessments) and lagged (N = 380 individuals; 760 assessments) analyses were used to determine the link between health risks and epigenetic aging.

Concurrent models showed that BMI (r = 0.15, PFDR < 0.01) was significantly correlated to epigenetic aging at the subject-level but not wave-level. Lagged models demonstrated that depressive symptoms (b = 1.67 months per symptom, PFDR = 0.02) in adolescence accelerated epigenetic aging in adulthood, also when models were fully adjusted for BMI, smoking, and cannabis and alcohol use.

Within-persons, changes in health risks were unaccompanied by concurrent changes in epigenetic aging, suggesting that it is unlikely for risks to immediately ‘accelerate’ epigenetic aging. However, time lagged analyses indicated that depressive symptoms in childhood/adolescence predicted epigenetic aging in adulthood. Together, findings suggest that age-related biological embedding of depressive symptoms is not instant but provides prognostic opportunities. Repeated measurements and longer follow-up times are needed to examine stable and dynamic contributions of childhood experiences to epigenetic aging across the lifespan.

Little is known about socioeconomic equity in access to healthcare among people with eating disorders in Australia. This study aims to measure the extent of inequity in eating disorder-related healthcare utilization, analyze trends, and explore the sources of inequalities using New South Wales (NSW) administrative linked health data for 2005 to 2020.

Socioeconomic inequities were measured using concentration index approach, and decomposition analysis was conducted to explain the factors accounting for inequality. Healthcare utilization included: public inpatient admissions, private inpatient admissions, visits to public mental health outpatient clinics and emergency department visits, with three different measures (probability of visit, total and conditional number of visits) for each outcome.

Private hospital admissions due to eating disorders were concentrated among individuals from higher socioeconomic status (SES) from 2005 to 2020. There was no significant inequity in the probability of public hospital admissions for the same period. Public outpatient visits were utilized more by people from lower SES from 2008 to 2020. Emergency department visits were equitable, but more utilized by those from lower SES in 2020.

Public hospital and emergency department services were equitably used by people with eating disorders in NSW, but individuals from high SES were more likely to be admitted to private hospitals for eating disorder care. Use of public hospital outpatient services was higher for those from lower SES. These findings can assist policymakers in understanding the equity of the healthcare system and developing programs to improve fairness in eating disorder-related healthcare in NSW.

The ways in which perceived harm due to substance use affects relationships between psychotic and suicidal experiences are poorly understood. The goal of the current study was to redress this gap by investigating the moderating effects of harm due to substance use on pathways involving positive psychotic symptoms, the perceived cognitive-emotional sequelae of those symptoms, and suicidal ideation.

The design was cross-sectional. Mediation and moderated mediation pathways were tested. The predictor was severity of positive psychotic symptoms. Cognitive interpretative and emotional characteristics of both auditory hallucinations and delusions were mediators. Suicidal ideation was the outcome variable. General symptoms associated with severe mental health problems were statistically controlled for.

There was evidence of an indirect pathway between positive psychotic symptom severity and suicidal ideation via cognitive interpretation and emotional characteristics of both auditory hallucinations and delusions. Harm due to drug use, but not alcohol use, moderated the indirect pathway involving delusions such that it was most prominent when harm due to drug use was at medium-to-high levels. The components of suicidal ideation that were most strongly affected by this moderated indirect pathway were active intent, passive desire, and lack of deterrents.

From both scientific and therapy development perspectives, it is important to understand the complex interplay between, not only the presence of auditory hallucinations and delusions, but the ensuing cognitive and emotional consequences of those experiences which, when combined with harm associated with substance use, in particular drug use, can escalate suicidal thoughts and acts.

Around the world, people living in objectively difficult circumstances who experience symptoms of generalized anxiety disorder (GAD) do not qualify for a diagnosis because their worry is not ‘excessive’ relative to the context. We carried out the first large-scale, cross-national study to explore the implications of removing this excessiveness requirement.

Data come from the World Health Organization World Mental Health Survey Initiative. A total of 133 614 adults from 12 surveys in Low- or Middle-Income Countries (LMICs) and 16 surveys in High-Income Countries (HICs) were assessed with the Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-5 criteria for GAD were compared to respondents meeting all criteria for GAD, and to respondents without GAD, on clinically-relevant correlates.

Removing the excessiveness requirement increases the global lifetime prevalence of GAD from 2.6% to 4.0%, with larger increases in LMICs than HICs. Non-excessive and excessive GAD cases worry about many of the same things, although non-excessive cases worry more about health/welfare of loved ones, and less about personal or non-specific concerns, than excessive cases. Non-excessive cases closely resemble excessive cases in socio-demographic characteristics, family history of GAD, and risk of temporally secondary comorbidity and suicidality. Although non-excessive cases are less severe on average, they report impairment comparable to excessive cases and often seek treatment for GAD symptoms.

Individuals with non-excessive worry who meet all other DSM-5 criteria for GAD are clinically significant cases. Eliminating the excessiveness requirement would lead to a more defensible GAD diagnosis.

Although numerous neuroimaging studies have depicted neural alterations in individuals with obsessive–compulsive disorder (OCD), a psychiatric disorder characterized by intrusive cognitions and repetitive behaviors, the molecular mechanisms connecting brain structural changes and gene expression remain poorly understood.

This study combined the Allen Human Brain Atlas dataset with neuroimaging data from the Meta-Analysis (ENIGMA) consortium and independent cohorts. Later, partial least squares regression and enrichment analysis were performed to probe the correlation between transcription and cortical thickness variation among adults with OCD.

The cortical map of case-control differences in cortical thickness was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms preferentially expressed across different cell types and cortical layers. These genes were specifically expressed in brain tissue, spanning all cortical developmental stages. Protein–protein interaction analysis revealed that these genes coded a network of proteins encompassing various highly interactive hubs.

The study findings bridge the gap between neural structure and transcriptome data in OCD, fostering an integrative understanding of the potential biological mechanisms.