The association between weight and depressive symptoms is well established, but the direction of effects remains unclear. Most studies rely on body mass index (BMI) as the sole weight indicator, with few examining the aetiology of the association between weight indicators and depressive symptoms.

We analysed data from the Twins Early Development Study (TEDS) and UK Adult Twin Registry (TwinsUK) (7658 and 2775 twin pairs, respectively). A phenotypic cross-lagged panel model assessed the directionality between BMI and depressive symptoms at ages 12, 16, and 21 years in TEDS. Bivariate correlations tested the phenotypic association between a range of weight indicators and depressive symptoms in TwinsUK. In both samples, structural equation modelling of twin data investigated genetic and environmental influences between weight indicators and depression. Sensitivity analyses included two-wave phenotypic cross-lagged panel models and the exclusion of those with a BMI <18.5.

Within TEDS, the relationship between BMI and depression was bidirectional between ages 12 and 16 with a stronger influence of earlier BMI on later depression. The associations were unidirectional thereafter with depression at 16 influencing BMI at 21. Small genetic correlations were found between BMI and depression at ages 16 and 21, but not at 12. Within TwinsUK, depression was weakly correlated with weight indicators; therefore, it was not possible to generate precise estimates of genetic or environmental correlations.

The directionality of the relationship between BMI and depression appears to be developmentally sensitive. Further research with larger genetically informative samples is needed to estimate the aetiological influence on these associations.

Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models.

Participants from both the NAPLS2 and NAPLS3 samples were classified as either ‘long’ or ‘short’ symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis.

The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78).

These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.

Aberrant reward functioning is implicated in depression. While attention precedes behavior and guides higher-order cognitive processes, reward learning from an attentional perspective – the effects of prior reward-learning on subsequent attention allocation – has been mainly overlooked.

The present study explored the effects of reward-based attentional learning in depression using two separate, yet complimentary, studies. In study 1, participants with high (HD) and low (LD) levels of depression symptoms were trained to divert their gaze toward one type of stimuli over another using a novel gaze-contingent music reward paradigm – music played when fixating the desired stimulus type and stopped when gazing the alternate one. Attention allocation was assessed before, during, and following training. In study 2, using negative reinforcement, the same attention allocation pattern was trained while substituting the appetitive music reward for gazing the desired stimulus type with the removal of an aversive sound (i.e. white noise).

In study 1 both groups showed the intended shift in attention allocation during training (online reward learning), while generalization of learning at post-training was only evident among LD participants. Conversely, in study 2 both groups showed post-training generalization. Results were maintained when introducing anxiety as a covariate, and when using a more powerful sensitivity analysis. Finally, HD participants showed higher learning speed than LD participants during initial online learning, but only when using negative, not positive, reinforcement.

Deficient generalization of learning characterizes the attentional system of HD individuals, but only when using reward-based positive reinforcement, not negative reinforcement.

Although common mental health problems have been widely studied with self-stigma, few studies have focused on the mediating effect of self-stigma in the relationship between mental health problems and help-seeking behaviours of refugee adolescents. Therefore, the purpose of the present study was to examine whether self-stigma mitigates the adverse effects of stress, anxiety, and depression symptoms on the help-seeking behaviours of Syrian adolescents living in Turkey.

The participants of this study included 488 Syrian refugee adolescents (boys, 63.73%; girls, 3627%) living in Turkey. Participants completed the Depression Anxiety Stress Scale and General Help-Seeking Scale and Self-Stigma of Seeking Psychology Help Scale.

The findings revealed that stress (β = 0.19, p < 0.01), anxiety (β = 0.12, p < 0.05), and depression (β = 0.17, p < 0.01) had significant and positive predictive effects on self-stigma, but not on help-seeking behaviours. Also, self-stigma (β = −0.12, p < 0.01) had a significant negative predictive effect on help-seeking behaviours. With regard to the indirect effects, the findings showed that self-stigma fully mediated the associations between stress – help-seeking [effect = −0.05, 95% confidence interval (CI) −0.11 to −0.01], anxiety – help-seeking (effect = −0.04, 95% CI −0.09 to −0.01)], and depression – help-seeking (effect = −0.05, 95% CI −0.12 to −0.01).

Our findings highlight the potential negative effects of self-stigma on the help-seeking behaviours of Syrian refugee adolescents, both directly and indirectly. These results can be used to develop and implement effective and efficient interventions to address the unmet mental health needs of refugee adolescents.

In a birth-cohort study, we followed offspring with prenatal cocaine exposure (PCE) to investigate longitudinal associations of PCE with self-reported behavioral adjustment from early adolescence to emerging adulthood (EA). Environmental pathways (family functioning, non-kinship care, maltreatment) were specified as potential mediators of PCE.

Participants were 372 (190 PCE; 47% male), primarily Black, low socioeconomic status, enrolled at birth. Internalizing and externalizing behaviors were assessed using Youth Self-Report at ages 12 and 15 and Adult Self-Report at age 21. Extended random-intercept cross-lagged panel modeling was used to account for potential bidirectional relationships between internalizing and externalizing behaviors over time, examining potential mediators.

Adjusting for covariates, significant indirect effects were found for each mediator at different ages. For family functioning, these were both internalizing (β = 0.83, p = 0.04) and externalizing behaviors (β = 1.58, p = 0.02) at age 12 and externalizing behaviors at age 15 (β = 0.51, p = 0.03); for non-kinship care, externalizing behaviors at ages 12 (β = 0.63, p = 0.02) and 15 (β = 0.20, p = 0.03); and for maltreatment, both internalizing and externalizing behaviors at ages 15 (β = 0.64, p = 0.02 for internalizing; β = 0.50, p = 0.03 for externalizing) and 21 (β = 1.39, p = 0.01 for internalizing; β = 1.11, p = 0.01 for externalizing). Direct associations of PCE with internalizing and externalizing behaviors were not observed, nor cross-lagged relationships between internalizing and externalizing behaviors.

Negative associations of PCE with behavioral adjustment persist into EA via environmental pathways, specifying intervention points to disrupt adverse pathways toward healthy development.

Preliminary evidence shows that discordance in stress experience, expression, and physiology (EEP) in adolescents is linked to depression, suicidal ideation (SI), non-suicidal self-injury (NSSI), and brain functioning. This study employs person-centered analysis to probe the relationship between stress responses, psychopathology, and neural patterns in female adolescents who are oversampled for engagement in NSSI.

Adolescent females (N = 109, ages 12–17) underwent a social stress test from which self-report measures of stress experience, observer ratings of stress expression, and physiological metrics of stress (via salivary cortisol) were obtained. Multi-trajectory modeling was employed to identify concordant and discordant stress EEP groups. Depressive symptoms, SI and attempt, NSSI engagement, frontal and limbic activation to emotional stimuli, and resting state fronto-limbic connectivity were examined in the EEP groups derived from the multi-trajectory models.

Four groups were identified, three of which demonstrated relatively concordant EEP and one which demonstrated discordant EEP (High Experience-High Expression-Low Physiology). Further, replicating past research, the High Experience-High Expression-Low Physiology discordant group exhibited higher depressive symptoms, SI, suicide attempt, and NSSI episodes (only for sensitivity analyses based on past year) relative to other EEP groups. No significant group differences in brain functioning emerged.

Results indicate that within-person, multi-level patterns in stress responding capture risk for dysfunction including depression and self-injurious thoughts and behaviors. Further interrogating of system-level stress functioning may better inform assessment and intervention efforts.

The incidence of psychotic disorders varies in different geographic areas. As there has been no report from Turkey, this study aimed to provide the treated incidence rate of first-episode psychosis (FEP) in a defined area.

All individuals, aged 15–64 years, presenting with FEP (ICD-10 F20-29, F30-33) to mental health services in a defined catchment-area in Sinop which is located in the Black Sea region of the northern Turkey were recorded over a 4-year period (2009 to 2012). Incidence rates of psychotic disorders and their 95% confidence intervals (CIs) were estimated. Poisson regression was applied to estimate the differences in incidence rate ratio (IRR) by age, sex, and urbanicity.

One hundred and fifteen FEP participants were identified during the 4 years. Crude incidence rates of all psychoses, schizophrenia, other psychotic disorders, and affective psychotic disorders were respectively 38.5 (95% CI 27.1–49.9), 10.7 (95% CI 6.6–14.8), 10.0 (95% CI 5.7–14.3) and 17.7 (95% CI 11.3–24.2) per 100 000 person-years. After age-sex standardisation the rates increased slightly. There were no gender differences in the incidence rates. IRR of any psychotic disorder was highest in the youngest age group (15–24 years) compared to the oldest age group (55–64 years), 7.9 (95% CI 2.8–30.5). In contrast with previous studies, the incidence rate of any psychotic disorder was not significantly increased in urban areas compared with rural areas.

The current study, the first of its kind from Turkey, indicates that the risk of schizophrenia and other psychotic disorders in a lowly urbanised area of Turkey is comparable to those reported in Western European cities.

Everyday affective fluctuations are more extreme and more frequent in adolescence compared to any other time in development. Successful regulation of these affective experiences is important for good mental health and has been proposed to depend on affective control. The present study examined whether improving affective control through a computerised affective control training app (AffeCT) would benefit adolescent mental health.

One-hundred and ninety-nine participants (11–19 years) were assigned to complete 2 weeks of AffeCT or placebo training on an app. Affective control (i.e. affective inhibition, affective updating and affective shifting), mental health and emotion regulation were assessed at pre- and post-training. Mental health and emotion regulation were assessed again one month and one year later.

Compared with the placebo group, the AffeCT group showed significantly greater improvements in affective control on the trained measure. AffeCT did not, relative to placebo, lead to better performance on untrained measures of affective control. Pre- to post-training change in affective control covaried with pre- to post-training change in mental health problems in the AffeCT but not the placebo group. These mental health benefits of AffeCT were only observed immediately following training and did not extend to 1 month or year post-training.

In conclusion, the study provides preliminary evidence that AffeCT may confer short-term preventative benefits for adolescent mental health.

Common mental disorders (CMDs) including depression, anxiety, and stress are very common, but it is unclear whether the last decades of social, economic, and political change have impacted incidence of CMD. This study explored temporal trends in the recorded incidence of CMD in the United Kingdom.

We used data from general practices in the United Kingdom (Clinical Practice Research Datalink) to estimate the annual recorded incidence of CMD for 2000–2020, including symptoms, diagnosis, or pharmaceutical treatment. Trends were explored by sex, age, ethnicity, region, deprivation, and comorbidity.

We included 29 480 164 individuals who were followed up for 12.5 years on average (s.d. = 6.4 years). The recorded incidence of CMD episodes was 55.9 per 1000 person-years in 2000 [95% confidence interval (CI) 55.8–56.1], increasing to 79.6 per 1000 person-years in 2019 (95% CI 79.5–79.8). Females had higher recorded incidence rates, as did those living in more deprived areas. We observed striking patterns by age over time, with rates in ages 16–24 increasing from 40.2 per 1000 in 2000 (95% CI 39.8–40.5), to 107.8 per 1000 in 2019 (95% CI 107.0–108.6). In contrast, the rates in those aged ≥55 years decreased since 2014. There were differing patterns of incidence by ethnic group, with a steeper increase in Asian, Black, and mixed groups in recent years.

Overall, the incidence of recorded CMD in the UK general practice increased between 2000 and 2019 with a small decrease in 2020. The overall trends obscured important differences across population subgroups, which may have implications for prevention.

Our confidence, a form of metacognition, guides our behavior. Confidence abnormalities have been found in obsessive–compulsive disorder (OCD). A first notion based on clinical case–control studies suggests lower confidence in OCD patients compared to healthy controls. Contrarily, studies in highly compulsive individuals from general population samples showed that obsessive–compulsive symptoms related positively or not at all to confidence. A second notion suggests that an impairment in confidence estimation and usage is related to compulsive behavior, which is more often supported by studies in general population samples. These opposite findings call into question whether findings from highly compulsive individuals from the general population are generalizable to OCD patient populations.

To test this, we investigated confidence at three hierarchical levels: local confidence in single decisions, global confidence in task performance and higher-order self-beliefs in 40 OCD patients (medication-free, no comorbid diagnoses), 40 controls, and 40 matched highly compulsive individuals from the general population (HComp).

In line with the first notion we found that OCD patients exhibited relative underconfidence at all three hierarchical levels. In contrast, HComp individuals showed local and global overconfidence and worsened metacognitive sensitivity compared with OCD patients, in line with the second notion.

Metacognitive functioning observed in a general highly compulsive population, often used as an analog for OCD, is distinct from that in a clinical OCD population, suggesting that OC symptoms in these two groups relate differently to (meta)cognitive processes. These findings call for caution in generalizing (meta)cognitive findings from general population to clinical samples.

Parent-adolescent interactions, particularly parental criticism and praise, have previously been identified as factors relevant to self-concept development and, when negative, to adolescent depression. Yet, whether adolescents with depression show aberrant emotional and neural reactivity to parental criticism and praise is understudied.

Adolescents with depression (n = 20) and healthy controls (n = 59) received feedback supposedly provided by their mother or father in the form of negative (‘untrustworthy’), neutral (‘chaotic’), and positive (‘respectful’) personality evaluations while in an MRI-scanner. After each feedback word, adolescents reported their mood. Beforehand, adolescents had rated whether these personality evaluations matched their self-views.

In both groups, mood decreased after criticism and increased after praise. Adolescents with depression reported blunted mood responses after praise, whereas there were no mood differences after criticism. Neuroimaging analyses revealed that adolescents with depression (v. healthy controls) exhibited increased activity in response to criticism in the subgenual anterior cingulate cortex, temporal pole, hippocampus, and parahippocampal gyrus. Praise consistent with adolescents' self-views improved mood independent of depression status, while criticism matching self-views resulted in smaller mood increases in adolescents with depression (v. healthy controls). Exploratory analyses indicated that adolescents with depression recalled criticism (v. praise) more.

Adolescents with depression might be especially attentive to parental criticism, as indexed by increased sgACC and hippocampus activity, and memorize this criticism more. Together with lower positive impact of praise, these findings suggest that cognitive biases in adolescent depression may affect how parental feedback is processed, and may be fed into their self-views.

There are phenomenological similarities between social anxiety disorder (SAD) and posttraumatic stress disorder, such as a provoking aversive event, posttraumatic stress symptoms (e.g. intrusions) in response to these events and deficient (context-dependent) fear conditioning processes. This study investigated the neural correlates of context-dependent extinction recall and fear renewal in SAD, specifically in patients with intrusions in response to an etiologically relevant aversive social event.

During functional magnetic resonance imaging a two-day context-dependent fear conditioning paradigm was conducted in 54 patients with SAD and 54 healthy controls (HC). This included fear acquisition (context A) and extinction learning (context B) on one day, and extinction recall (context B) as well as fear renewal (contexts C and A) one day later. The main outcome measures were blood oxygen level-dependent responses in regions of interest and skin conductance responses.

Patients with SAD showed reduced differential conditioned amygdala activation during extinction recall in the safe extinction context and during fear renewal in the acquisition context compared to HC. Patients with clinically relevant intrusions moreover exhibited hypoactivation of the ventromedial prefrontal cortex (vmPFC) during extinction learning, extinction recall, and fear renewal in a novel context, while amygdala activation more strongly decreased during extinction learning and increased during fear renewal in the acquisition context compared with patients without intrusions.

Our study provides first evidence that intrusions in SAD are associated with similar deficits in context-dependent regulation of conditioned fear via the vmPFC as previously demonstrated in posttraumatic stress disorder.

Smoking contributes to a variety of neurodegenerative diseases and neurobiological abnormalities, suggesting that smoking is associated with accelerated brain aging. However, the neurobiological mechanisms affected by smoking, and whether they are genetically influenced, remain to be investigated.

Using structural magnetic resonance imaging data from the UK Biobank (n = 33 293), a brain age predictor was trained on non-smoking healthy groups and tested on smokers to obtain the BrainAge Gap (BAG). The cumulative effect of multiple common genetic variants associated with smoking was then calculated to acquire a polygenic risk score (PRS). The relationship between PRS, BAG, total gray matter volume (tGMV), and smoking parameters was explored and further genes included in the PRS were annotated to identify potential molecular mechanisms affected by smoking.

The BrainAge in smokers was predicted with very high accuracy (r = 0.725, MAE = 4.16). Smokers had a greater BAG (Cohen's d = 0.074, p < 0.0001) and higher PRS (Cohen's d = 0.63, p < 0.0001) than non-smokers. A higher PRS was associated with increased amount of smoking, mediated by BAG and tGMV. Several neurotransmitters and ion channel pathways were enriched in the group of smoking-related genes involved in addiction, brain synaptic plasticity, and some neurological disorders.

By using a simplified single indicator of the entire brain (BAG) in combination with the PRS, this study highlights the greater BAG in smokers and its linkage with genes and smoking behavior, providing insight into the neurobiological underpinnings and potential features of smoking-related aging.

Anorexia nervosa (AN) is characterized by sizable, widespread gray matter (GM) reductions in the acutely underweight state. However, evidence for persistent alterations after weight-restoration has been surprisingly scarce despite high relapse rates, frequent transitions to other psychiatric disorders, and generally unfavorable outcome. While most studies investigated brain regions separately (univariate analysis), psychiatric disorders can be conceptualized as brain network disorders characterized by multivariate alterations with only subtle local effects. We tested for persistent multivariate structural brain alterations in weight-restored individuals with a history of AN, investigated their putative biological substrate and relation with 1-year treatment outcome.

We trained machine learning models on regional GM measures to classify healthy controls (HC) (N = 289) from individuals at three stages of AN: underweight patients starting intensive treatment (N = 165, used as baseline), patients after partial weight-restoration (N = 115), and former patients after stable and full weight-restoration (N = 89). Alterations after weight-restoration were related to treatment outcome and characterized both anatomically and functionally.

Patients could be classified from HC when underweight (ROC-AUC = 0.90) but also after partial weight-restoration (ROC-AUC = 0.64). Alterations after partial weight-restoration were more pronounced in patients with worse outcome and were not detected in long-term weight-recovered individuals, i.e. those with favorable outcome. These alterations were more pronounced in regions with greater functional connectivity, not merely explained by body mass index, and even increases in cortical thickness were observed (insula, lateral orbitofrontal, temporal pole).

Analyzing persistent multivariate brain structural alterations after weight-restoration might help to develop personalized interventions after discharge from inpatient treatment.

The stressful minority position of transgender persons may result in a high risk of psychosis. Conflicting data suggest that the observed risk depends on setting of recruitment. We assessed the relative risk of non-affective psychotic disorder (NAPD) in a large, representative cohort of transgender persons.

This cohort was composed using: data on legal sex change from the Dutch population registry and data on dispensing of cross-sex hormones (route 1), and a registry of insurance claims from mental health care including persons with a diagnosis of gender identity disorder (DSM-IV) or gender dysphoria (DSM-5) (route 2). They were matched by sex at birth, calendar year and country of birth to controls from the general population. Transgender persons (N = 5564) and controls (N = 27 820), aged 16–60 years at 1 January 2011, were followed until the first insurance claim for NAPD in 2011–2019.

The incidence rate ratio (IRR) of NAPD for transgender persons selected exclusively through route 1 (N = 3859, IRR = 2.00, 95%-CI 1.52–2.63) was increased, but significantly lower than the IRRs for those selected exclusively through route 2 (N = 694, IRR = 22.15, 95%-CI 13.91–35.28) and for those found by both routes (N = 1011, IRR = 5.17, 95%-CI 3.57–7.49; p value for differences in IRR < 0.001).

This study supports the social defeat-hypothesis of NAPD. The results also show the presence of a substantial number of transgender persons with severe psychiatric problems who have not (yet) taken steps to gender-affirmative care.

Life engagement represents a holistic concept that encompasses outcomes reflecting life-fulfilment, well-being and participation in valued and meaningful activities, which is recently gaining attention and scientific interest. Despite its conceptual importance and its relevance, life engagement represents a largely unexplored domain in schizophrenia. The aims of the present study were to independently assess correlates and predictors of patient life engagement in a large and well-characterized sample of schizophrenia patients.

To assess the impact of different demographic, clinical, cognitive and functional parameters on life engagement in a large sample of patients with schizophrenia, data from the social cognition psychometric evaluation project were analyzed.

Overall schizophrenia and depressive symptom severity, premorbid IQ, neurocognitive performance, social cognition performance both in the emotion processing and theory of mind domains, functional capacity, social skills performance and real-world functioning in different areas all emerged as correlates of patient life engagement. Greater symptom severity and greater impairment in real-world interpersonal relationships, social skills, functional capacity and work outcomes emerged as individual predictors of greater limitations in life engagement.

Life engagement in people living with schizophrenia represents a holistic and complex construct, with several different clinical, cognitive and functional correlates. These features represent potential treatment targets to improve the clinical condition and also facilitate the process of recovery and the overall well-being of people living with schizophrenia.