Research suggests that most mental health conditions have their onset in the critically social period of adolescence. Yet, we lack understanding of the potential social processes underlying early psychopathological development. We propose a conceptual model where daily-life social interactions and social skills form an intermediate link between known risk and protective factors (adverse childhood experiences, bullying, social support, maladaptive parenting) and psychopathology in adolescents – that is explored using cross-sectional data.

N = 1913 Flemish adolescent participants (Mean age = 13.8; 63% girls) were assessed as part of the SIGMA study, a large-scale, accelerated longitudinal study of adolescent mental health and development. Self-report questionnaires (on risk/protective factors, social skills, and psychopathology) were completed during class time; daily-life social interactions were measured during a subsequent six-day experience-sampling period.

Registered uncorrected multilevel linear regression results revealed significant associations between all risk/protective factors and psychopathology, between all risk/protective factors and social processes, and between all social processes and psychopathology. Social processes (social skills, quantity/quality of daily social interactions) were uniquely predicted by each risk/protective factor and were uniquely associated with both general and specific types of psychopathology. For older participants, some relationships between social processes and psychopathology were stronger.

Unique associations between risk/protective factors and psychopathology signify the distinct relevance of these factors for youth mental health, whereas the broad associations with social processes support these processes as broad correlates. Results align with the idea of a social pathway toward early psychopathology, although follow-up longitudinal research is required to verify any mediation effect.

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.

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.

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.

Pain resilience and regional gray matter volume (rGMV) are established correlates of adaptation to chronic pain within cross-sectional studies. Extending such work, this prospective cohort study tested the status of baseline pain resilience dimension scores and rGMV as risk factors for subsequent exacerbations in chronic pain disability and intensity.

142 adults with chronic musculoskeletal pain completed an initial assessment comprising a structural magnetic resonance imaging scan and self-report measures of cognitive/affective positivity and behavioral perseverance pain resilience dimensions, disability, pain intensity, and demographics. Disability and pain intensity were outcomes re-assessed at a 6-month follow-up. The impact of pain resilience dimension scores and identified rGMV sites on follow-up outcomes was examined after controlling for other baseline correlates of outcomes. Mediating effects of identified rGMV sites on pain resilience dimension-follow-up outcome relations were also evaluated.

Aside from the significant multivariate effect of lower behavioral perseverance and cognitive/affective positivity scores, augmented left precuneus, temporal pole, superior temporal gyrus (STG), and precentral gyrus rGMV combined to predict higher follow-up disability levels, independent of covariates. Higher left fusiform gyrus rGMV levels predicted follow-up exacerbations in pain intensity, but pain resilience dimension scores did not. Finally, left precuneus and left temporal pole STG rGMV partially mediated cognitive/affective positivity-follow-up disability relations.

Findings underscore deficits in pain resilience and increased rGMV as potential risk factors for poorer subsequent outcomes of chronic musculoskeletal pain and provide foundations for further prospective extensions as well as targeted intervention research.

It is well established that there is a substantial genetic component to eating disorders (EDs). Polygenic risk scores (PRSs) can be used to quantify cumulative genetic risk for a trait at an individual level. Recent studies suggest PRSs for anorexia nervosa (AN) may also predict risk for other disordered eating behaviors, but no study has examined if PRS for AN can predict disordered eating as a global continuous measure. This study aimed to investigate whether PRS for AN predicted overall levels of disordered eating, or specific lifetime disordered eating behaviors, in an Australian adolescent female population.

PRSs were calculated based on summary statistics from the largest Psychiatric Genomics Consortium AN genome-wide association study to date. Analyses were performed using genome-wide complex trait analysis to test the associations between AN PRS and disordered eating global scores, avoidance of eating, objective bulimic episodes, self-induced vomiting, and driven exercise in a sample of Australian adolescent female twins recruited from the Australian Twin Registry (N = 383).

After applying the false-discovery rate correction, the AN PRS was significantly associated with all disordered eating outcomes.

Findings suggest shared genetic etiology across disordered eating presentations and provide insight into the utility of AN PRS for predicting disordered eating behaviors in the general population. In the future, PRSs for EDs may have clinical utility in early disordered eating risk identification, prevention, and intervention.

Treatment resistance is a major challenge in psychiatric disorders. Early detection of potential future resistance would improve prognosis by reducing the delay to appropriate treatment adjustment and recovery. Here, we sought to determine whether neurodevelopmental markers can predict therapeutic response.

Healthy controls (N = 236), patients with schizophrenia (N = 280) or bipolar disorder (N = 78) with a known therapeutic outcome, were retrospectively included. Age, sex, education, early developmental abnormalities (obstetric complications, height, weight, and head circumference at birth, hyperactivity, dyslexia, epilepsy, enuresis, encopresis), neurological soft signs (NSS), and ages at first subjective impairment, clinical symptoms, treatment, and hospitalization, were recorded. A supervised algorithm leveraged NSS and age at first clinical signs to classify between resistance and response in schizophrenia.

Developmental abnormalities were more frequent in schizophrenia and bipolar disorder than in controls. NSS significantly differed between controls, responsive, and resistant participants with schizophrenia (5.5 ± 3.0, 7.0 ± 4.0, 15.0 ± 6.0 respectively, p = 3 × 10−10) and bipolar disorder (5.5 ± 3.0, 8.3 ± 3.0, 12.5 ± 6.0 respectively, p < 1 × 10−10). In schizophrenia, but not in bipolar disorder, age at first subjective impairment was three years lower, and age at first clinical signs two years lower, in resistant than responsive subjects (p = 2 × 10−4 and p = 9 × 10−3, respectively). Age at first clinical signs and NSS accurately predicted treatment response in schizophrenia (area-under-curve: 77 ± 8%, p = 1 × 10−14).

Neurodevelopmental features such as NSS and age of clinical onset provide a means to identify patients who may require rapid treatment adaptation.

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.

People with schizophrenia-spectrum and bipolar disorders (severe mental illnesses; ‘SMI’) experience excess mortality. Our aim was to explore longer-term trends in mortality, including the COVID-19 pandemic period, with a focus on additional vulnerabilities (psychiatric comorbidities and race/ ethnicity) in SMI.

Retrospective cohort study using electronic health records from secondary mental healthcare, covering a UK region of 1.3 million people. Mortality trends spanning fourteen years, including the COVID-19 pandemic, were assessed in adults with clinician-ascribed ICD-10 diagnoses for schizophrenia-spectrum and bipolar disorders.

The sample comprised 22 361 people with SMI with median follow-up of 10.6 years. Standardized mortality ratios were more than double the population average pre-pandemic, increasing further during the pandemic, particularly in those with SMI and psychiatric comorbidities. Mortality risk increased steadily among people with SMI and comorbid depression, dementia, substance use disorders and anxiety over 13-years, increasing further during the pandemic. COVID-19 mortality was elevated in people with SMI and comorbid depression (sub-Hazard Ratio: 1.48 [95% CI 1.03–2.13]), dementia (sHR:1.96, 1.26–3.04) and learning disabilities (sHR:2.30, 1.30–4.06), compared to people with only SMI. COVID-19 mortality risk was similar for minority ethnic groups and White British people with SMI. Elevated all-cause mortality was evident in Black Caribbean (adjusted Rate Ratio: 1.40, 1.11–1.77) and Black African people with SMI (aRR: 1.59, 1.07–2.37) during the pandemic relative to earlier years.

Mortality has increased over time in people with SMI. The pandemic exacerbated pre-existing trends. Actionable solutions are needed which address wider social determinants and address disease silos.

This article presents the results of two studies investigating increased intra-individual variability (IIV) in the performance of individuals with attention deficit hyperactivity disorder (ADHD), in two cognitive domains: numerosity judgments and quantitative and verbal reasoning.

Study 1, a pre-registered experiment, involved approximately 200 participants (42.66% female; mean age: 36.86; standard deviation of age: 10.70) making numerical judgments at two time-points. ADHD-symptom severity was assessed on a continuous scale. In Study 2, we collected the data of approximately 3000 examinees who had taken a high-stakes admissions test for higher education (assessing quantitative and verbal reasoning). The sample comprised only people formally diagnosed with ADHD. The control group consisted of approximately 200 000 examinees, none of whom presented with ADHD.

The results of Study 1 revealed a positive correlation between IIV (distance between judgments at the two time-points) and ADHD symptom severity. The results of Study 2 demonstrated that IIV (distance between the scores on two test chapters assessing the same type of reasoning) was greater among examinees diagnosed with ADHD. In both studies, the findings persisted even after controlling for performance level.

The results indicate that individuals with ADHD, v. those without, exhibit less consistent numerosity judgments and greater fluctuation in performance on verbal and quantitative reasoning. The measurement of the same psychological constructs appears to be less precise among individuals with ADHD compared to those without. We discuss the theoretical contributions and practical implications of our results for two fields: judgment and decision-making, and assessment.

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 Hierarchical Taxonomy of Psychopathology (HiTOP) offers a promising framework to identify the neurobiological mechanisms of psychopathology. Many forms of psychopathology are characterized by dysfunctional emotional reactivity. The late positive potential (LPP) is an event-related potential component that provides an index of neurobiological emotional reactivity. Several categorical disorders have demonstrated a similar association with the emotion-modulated LPP. It is possible that higher-order dimensional representations of psychopathology might explain the comparable results. The present study examined the association between HiTOP-consistent pathological personality dimensions across multiple levels of the hierarchy and neurobiological emotional reactivity.

The sample included 215 18–35-year-old adults (86% female) who were oversampled for psychopathology. Participants completed the emotional interrupt task while electroencephalography was recorded to examine the LPP. Participants also completed the Comprehensive Assessment of Traits relevant to Personality Disorders to assess pathological personality.

At the spectra level, higher negative emotionality was associated with a larger emotion-modulated LPP, while higher detachment was associated with a smaller emotion-modulated LPP. There were no associations between higher-order psychopathology levels and the emotion-modulated LPP. Compared to categorical diagnoses, spectra-level personality pathology dimensions significantly improved the prediction of the emotion-modulated LPP.

The present study indicates that HiTOP spectra levels of negative emotionality and detachment demonstrate unique associations with neurobiological emotional reactivity. The study highlights the utility of examining dimensional and hierarchical, rather than categorical, representations of psychopathology in the attempt to identify the neurobiological origins of psychopathology.

Theory and research indicated that executive functioning (EF) correlated with, preceded, and stemmed from worry in generalized anxiety disorder (GAD). The present secondary analysis (Zainal & Newman, 2023b) thus determined whether EF domains mediated the effect of a 14-day (5 prompts/day) mindfulness ecological momentary intervention (MEMI) against a self-monitoring control (SM) for GAD.

Participants (N = 110) diagnosed with GAD completed self-reported (Attentional Control Scale, GAD Questionnaire, Perseverative Cognitions Questionnaire) and performance-based tests (Letter-Number Sequencing, Stroop, Trail Making Test-B, Verbal Fluency) at baseline, post-treatment, and one-month follow-up (1MFU). Causal mediation analyses determined if pre-post changes in EF domains preceded and mediated the effect of MEMI against SM on pre-1MFU changes in GAD severity and trait repetitive negative thinking (RNT).

MEMI was more efficacious than SM in improving pre–post inhibition (β = −2.075, 95% [−3.388, −0.762], p = .002), working memory (β = 0.512, 95% [0.012, 1.011], p = .045), and set-shifting (β = −2.916, 95% [−5.142, −0.691], p = .010) but not verbal fluency and attentional control. Within groups, MEMI but not SM produced improvements in all examined pre–post EF outcomes except attentional control. Only pre–post improvements in inhibition mediated the effect of MEMI against SM on pre-1MFU reductions in GAD severity (β = −0.605, 95% [−1.357, −0.044], p = .030; proportion mediated = 7.1%) and trait RNT (β = −0.024, 95% [−0.054, −0.001], p = .040; proportion mediated = 7.4%). These patterns remained after conducting sensitivity analyses with non-linear mediator-outcome relations.

Optimizing MEMI for GAD might entail specifically boosting inhibition plausibly by augmenting it with dialectical behavioral therapy, encouraging high-intensity physical exercises, and targeting negative emotional contrast avoidance.

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.

Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.

Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.

Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.

While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.