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.

Sexual abuse and bullying are associated with poor mental health in adulthood. We previously established a clear relationship between bullying and symptoms of psychosis. Similarly, we would expect sexual abuse to be linked to the emergence of psychotic symptoms, through effects on negative affect.

We analysed English data from the Adult Psychiatric Morbidity Surveys, carried out in 2007 (N = 5954) and 2014 (N = 5946), based on representative national samples living in private households. We used probabilistic graphical models represented by directed acyclic graphs (DAGs). We obtained measures of persecutory ideation and auditory hallucinosis from the Psychosis Screening Questionnaire, and identified affective symptoms using the Clinical Interview Schedule. We included cannabis consumption and sex as they may determine the relationship between symptoms. We constrained incoming edges to sexual abuse and bullying to respect temporality.

In the DAG analyses, contrary to our expectations, paranoia appeared early in the cascade of relationships, close to the abuse variables, and generally lying upstream of affective symptoms. Paranoia was consistently directly antecedent to hallucinations, but also indirectly so, via non-psychotic symptoms. Hallucinosis was also the endpoint of pathways involving non-psychotic symptoms.

Via worry, sexual abuse and bullying appear to drive a range of affective symptoms, and in some people, these may encourage the emergence of hallucinations. The link between adverse experiences and paranoia is much more direct. These findings have implications for managing distressing outcomes. In particular, worry may be a salient target for intervention in psychosis.

Substantial evidence indicates structural abnormalities in the cerebral cortex of patients with schizophrenia (SCZ), although their clinical implications remain unclear. Previous case-control studies have investigated group-level differences in structural abnormalities, although the study design cannot account for interindividual differences. Recent research has focused on the association between the heterogeneity of the cerebral cortex morphometric features and clinical heterogeneity.

We used neuroimaging data from 420 healthy controls and 695 patients with SCZ from seven studies. Four cerebral cortex measures were obtained: surface area, gray matter volume, thickness, and local gyrification index. We calculated the coefficient of variation (CV) and person-based similarity index (PBSI) scores and performed group comparisons. Associations between the PBSI scores and cognitive functions were evaluated using Spearman's rho test and normative modeling.

Patients with SCZ had a greater CV of surface area and cortical thickness than those of healthy controls. All PBSI scores across cortical measures were lower in patients with SCZ than in HCs. In the patient group, the PBSI scores for gray matter volume and all cortical measures taken together positively correlated with the full-scale IQ scores. Patients with deviant PBSI scores for gray matter volume and all cortical measures taken together had lower full-scale IQ scores than those of other patients.

The cerebral cortex in patients with SCZ showed greater regional and global structural variability than that in healthy controls. Patients with deviant similarity of cortical structural profiles exhibited a lower general intelligence than those exhibited by the other patients.

Electroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, monocenter studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers. The objective of this study was to develop and validate neuroimaging biomarkers for ECT outcome in a multicenter setting.

Multimodal data (i.e. clinical, sMRI and resting-state fMRI) were collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluate which data modalities or combinations thereof could provide the best predictions for treatment remission (HAM-D score ⩽7) using a support vector machine classifier.

Remission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82–0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers (N = 109), and remained acceptable when validated using leave-one-site-out cross-validation (0.70–0.73 AUC).

These results show that multimodal neuroimaging data can be used to predict remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. Future development of a clinical decision support tool applying these biomarkers may be feasible.

Intimate partner violence (IPV) and sexual violence (SV) are significant problems world-wide, and they affect women disproportionally. Whether individuals with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of being involved in these types of violence is unclear.

We carried out a systematic review and meta-analysis (PROSPERO registration CRD42022348165) of the associations between ADHD and being the victim or perpetrator of IPV and SV. Ratios of occurrence of violence were pooled in random-effects models and study risk of bias was evaluated using the Newcastle–Ottawa Scale.

A search on multiple databases, carried out on 7 October 2022, yielded 14 eligible studies (1 111 557 individuals). Analyses showed a higher risk of ADHD individuals being involved in IPV as perpetrators (six studies, OR 2.5, 95% CI 1.51–4.15) or victims (four studies, OR 1.78, 95% CI 1.06–3.0). Likewise, individuals with ADHD were at increased risk of being perpetrators (three studies, OR 2.73, 95% CI 1.35–5.51) or victims of SV (six studies, OR 1.84, 95% CI 1.51–2.24). Results were overall robust to different analytical choices.

Individuals with ADHD are at an increased risk of being involved in cases of violence, namely IPV and SV, either as victims or perpetrators. Although the causal path or mediating variables for these results are still unclear, this increased risk should inform evidence-based psychoeducation with individuals with ADHD, their families, and partners about romantic relationships and sexuality.

Childhood trauma may impact the course of schizophrenia spectrum disorders (SSD), specifically in relation to the increased severity of depressive or negative symptoms. The type and impact of trauma may differ between sexes. In a large sample of recent-onset patients, we investigated the associations of depressive and negative symptoms with childhood trauma and whether these are sex-specific.

A total of 187 first-episode psychosis patients in remission (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment study) and 115 recent-onset SSD patients (Simvastatin study) were included in this cross-sectional study (men: n = 218; women: n = 84). Total trauma score and trauma subtypes were assessed using the Childhood Trauma Questionnaire Short Form; depressive and negative symptoms were rated using the Positive And Negative Symptoms Scale. Sex-specific regression analyses were performed.

Women reported higher rates of sexual abuse than men (23.5% v. 7.8%). Depressive symptoms were associated with total trauma scores and emotional abuse ratings in men (β: 0.219–0.295; p ≤ 0.001). In women, depressive symptoms were associated with sexual abuse ratings (β: 0.271; p = 0.011). Negative symptoms were associated with total trauma score and emotional neglect ratings in men (β: 0.166–0.232; p ≤ 0.001). Negative symptoms in women were not linked to childhood trauma, potentially due to lack of statistical power.

Depressive symptom severity was associated with different types of trauma in men and women with recent-onset SSD. Specifically, in women, depressive symptom severity was associated with childhood sexual abuse, which was reported three times as often as in men. Our results emphasize the importance of sex-specific analyses in SSD research.

It is clinically important to predict the conversion of major depression (MD) to bipolar disorder (BD). Therefore, we sought to identify related conversion rates and risk factors.

This cohort study included the Swedish population born from 1941 onward. Data were collected from Swedish population-based registers. Potential risk factors, including family genetic risk scores (FGRS), which were calculated based on the phenotypes of relatives in the extended family and not molecular data, and demographic/clinical characteristics from these registers were retrieved. Those with first MD registrations from 2006 were followed up until 2018. The conversion rate to BD and related risk factors were analyzed using Cox proportional hazards models. Additional analyses were performed for late converters and with stratification by sex.

The cumulative incidence of conversion was 5.84% [95% confidence interval (95% CI) 5.72–5.96] for 13 years. In the multivariable analysis, the strongest risk factors for conversion were high FGRS of BD [hazard ratio (HR) = 2.73, 95% CI 2.43–3.08], inpatient treatment settings (HR = 2.64, 95% CI 2.44–2.84), and psychotic depression (HR = 2.58, 95% CI 2.14–3.11). For late converters, the first registration of MD during the teenage years was a stronger risk factor when compared with the baseline model. When the interactions between risk factors and sex were significant, stratification by sex revealed that they were more predictive in females.

Family history of BD, inpatient treatment, and psychotic symptoms were the strongest predictors of conversion from MD to BD.

There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI).

Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks.

Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular–left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure.

These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.

Studies investigating cognitive impairments in psychosis and depression have typically compared the average performance of the clinical group against healthy controls (HC), and do not report on the actual prevalence of cognitive impairments or strengths within these clinical groups. This information is essential so that clinical services can provide adequate resources to supporting cognitive functioning. Thus, we investigated this prevalence in individuals in the early course of psychosis or depression.

A comprehensive cognitive test battery comprising 12 tests was completed by 1286 individuals aged 15–41 (mean age 25.07, s.d. 5.88) from the PRONIA study at baseline: HC (N = 454), clinical high risk for psychosis (CHR; N = 270), recent-onset depression (ROD; N = 267), and recent-onset psychosis (ROP; N = 295). Z-scores were calculated to estimate the prevalence of moderate or severe deficits or strengths (>2 s.d. or 1–2 s.d. below or above HC, respectively) for each cognitive test.

Impairment in at least two cognitive tests was as follows: ROP (88.3% moderately, 45.1% severely impaired), CHR (71.2% moderately, 22.4% severely impaired), ROD (61.6% moderately, 16.2% severely impaired). Across clinical groups, impairments were most prevalent in tests of working memory, processing speed, and verbal learning. Above average performance (>1 s.d.) in at least two tests was present for 40.5% ROD, 36.1% CHR, 16.1% ROP, and was >2 SDs in 1.8% ROD, 1.4% CHR, and 0% ROP.

These findings suggest that interventions should be tailored to the individual, with working memory, processing speed, and verbal learning likely to be important transdiagnostic targets.