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.

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.

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.

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.

Schizophrenia (SZ) and autism spectrum disorders (ASD) are characterized by difficulties in theory of mind (ToM). We examined group differences in performance on a ToM-related test and associations with an estimated IQ.

Participants [N = 1227, SZ (n = 563), ASD (n = 159), and controls (n = 505), 32.2% female] completed the Reading the Mind in the Eyes Test (RMET) and assessments of cognitive ability. Associations between IQ and group on RMET were investigated with regression analyses.

SZ (d = 0.73, p < 0.001) and ASD (d = 0.37, p < 0.001) performed significantly worse on the RMET than controls. SZ performed significantly worse than ASD (d = 0.32, p = 0.002). Adding IQ to the model, SZ (d = 0.60, p < 0.001) and ASD (d = 0.44, p < 0.001) continued to perform significantly worse than controls, but no longer differed from each other (d = 0.13, p = 0.30). Small significant negative correlations between symptom severity and RMET performance were found in SZ (PANSS positive: r = −0.10, negative: r = −0.11, both p < 0.05). A small non-significant negative correlation was found for Autism Diagnostic Observation Schedule scores and RMET in ASD (r = −0.08, p = 0.34).

SZ and ASD are characterized by impairments in RMET. IQ contributed significantly to RMET performance and accounted for group differences in RMET between SZ and ASD. This suggests that non-social cognitive ability needs to be included in comparative studies of the two disorders.

Family members of people with mental illness (MI) may experience a host of psychological adversities such as increased stress, burden, and reduced wellbeing. However, relatively little is known about siblings. This study aimed to characterise the experience of distress (viz. depressive and anxiety symptoms), burden, and wellbeing in siblings of people with MI.

Studies reporting on quantitative measures of depression, anxiety, burden, or wellbeing in siblings; and/or qualitative findings on siblings’ experience were eligible. The literature search was conducted up until 20th October 2022.

Sixty-two studies comprising data from 3744 siblings were included. The pooled mean percentage of depressive symptoms fell in the mild range at 15.71 (k = 28, N = 2187, 95% CI 12.99–18.43) and anxiety symptoms fell in the minimal range at 22.45 (k = 16, N = 1122, 95% CI 17.09–27.80). Moderator analyses indicate that siblings of people with a schizophrenia spectrum disorder experience greater depressive symptoms than siblings of people with other types of MI (β = −16.38, p < 0.001). Qualitative findings suggest that individuals may be particularly vulnerable during their siblings’ illness onset and times of relapse. Limited communication, confusion about MI, and the need to compensate may contribute to siblings’ distress and/or burden. Siblings’ experience of wellbeing and caregiving were closely related.

This review highlights the complex psychological experience of siblings and the need for greater research and clinical support for this important yet often overlooked cohort.

Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another.

Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort.

Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011).

Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.

Previous evidence on antidepressant medication and cardiovascular disease (CVD) among patients with posttraumatic stress disorder (PTSD) has been inconclusive. We estimated the association between antidepressant medication and CVD by applying a marginal structural model.

We analyzed medical utilization records of 27 170 people with PTSD without prior major cardiovascular events in the Korean National Health Insurance Database (NHID). PTSD and CVD were defined in accordance with the recorded ICD-10 diagnostic codes. We acquired information on antidepressant use from the NHID and categorized them by medication type. A composite major adverse cardiovascular events (MACE) outcome was defined as coronary artery disease with revascularization, ischaemic stroke, and/or haemorrhagic stroke. We used inverse probability of treatment weighting to estimate the parameters of a marginal structural discrete-time survival analysis regression model, comparing the resulting estimates to those derived from traditional time-fixed and time-varying Cox proportional hazards regression. We calculated cumulative daily defined doses to test for a dose–response relationship.

People exposed to antidepressants showed a higher hazard of MACE [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.18–1.53]. The estimated effects were strongest for selective serotonin reuptake inhibitors (HR 1.24, 95% CI 1.08–1.44) and TCAs (HR 1.33, 95% CI 1.13–1.56). Exposure to serotonin-norepinephrine reuptake inhibitors did not appear to increase the risk of MACE. People exposed to higher doses of antidepressants showed higher risk of MACE.

In a national cohort of people with PTSD, exposure to antidepressant medications increased the risk of MACE in a dose–response fashion.

Older brain age – as estimated from structural MRI data – is known to be associated with detrimental mental and physical health outcomes in older adults. Social isolation, which has similar detrimental effects on health, may be associated with accelerated brain aging though little is known about how different trajectories of social isolation across the life course moderate this association. We examined the associations between social isolation trajectories from age 5 to age 38 and brain age assessed at age 45.

We previously created a typology of social isolation based on onset during the life course and persistence into adulthood, using group-based trajectory analysis of longitudinal data from a New Zealand birth cohort. The typology comprises four groups: ‘never-isolated’, ‘adult-only’, ‘child-only’, and persistent ‘child-adult’ isolation. A brain age gap estimate (brainAGE) – the difference between predicted age from structural MRI date and chronological age – was derived at age 45. We undertook analyses of brainAGE with trajectory group as the predictor, adjusting for sex, family socio-economic status, and a range of familial and child-behavioral factors.

Older brain age in mid-adulthood was associated with trajectories of social isolation after adjustment for family and child confounders, particularly for the ‘adult-only’ group compared to the ‘never-isolated’ group.

Although our findings are associational, they indicate that preventing social isolation, particularly in mid-adulthood, may help to avert accelerated brain aging associated with negative health outcomes later in life.

Comprehensive Behavioral Intervention for Tics (CBIT) is recommended as a first-line treatment for Tourette syndrome in children and adults. While there is strong evidence proving its efficacy, the mechanisms of reduction in tic severity during CBIT are still poorly understood. In a recent study, our group identified a functional brain network involved in tic suppression in children with TS. We reasoned that voluntary tic suppression and CBIT may share some mechanisms and thus we wanted to assess whether functional connectivity during tic suppression was associated with CBIT outcome.

Thirty-two children with TS, aged 8 to 13 years old, participated in a randomized controlled trial of CBIT v. a treatment-as-usual control condition. EEG was recorded during tic suppression in all participants at baseline and endpoint. We used a source-reconstructed EEG connectivity pipeline to assess functional connectivity during tic suppression.

Functional connectivity during tic suppression did not change from baseline to endpoint. However, baseline tic suppression-related functional connectivity specifically predicted the decrease in vocal tic severity from baseline to endpoint in the CBIT group. Supplementary analyses revealed that the functional connectivity between the right superior frontal gyrus and the right angular gyrus was mainly driving this effect.

This study revealed that functional connectivity during tic suppression at baseline predicted reduction in vocal tic severity. These results suggest probable overlap between the mechanisms of voluntary tic suppression and those of behavior therapy for tics.