This study aimed to deepen the understanding of the psychological mechanisms underlying the formation and maintenance of clinical high-risk symptoms for psychosis (CHR-P) in real-life contexts. Specifically, it examined whether (i) momentary feelings of stress increase the frequency of CHR-P symptoms, or conversely, (ii) CHR-P symptoms increase the intensity of stress. Additionally, potential moderators of the relationship between stress and CHR-P symptoms were explored.

Using Ecological Momentary Assessment, 79 patients (age: 11–36; 50.6% female) recruited from an early detection center for psychosis, reported their momentary stress levels and the frequency of CHR-P symptoms eight times a day for seven days. Time series data were analyzed using residual dynamic structural equation modeling in a random intercept cross-lagged panel design, comparing differently modeled contemporaneous effects.

There was no evidence of a contemporaneous or temporal link between stress on CHR-P symptoms. However, a contemporaneous effect of CHR-P symptoms on stress was found, while the corresponding temporal effect was not significant. The severity of interview-assessed CHR-P symptoms, age, and type of CHR-P symptoms (i.e., basic symptoms vs. [attenuated] positive symptoms) did not affect the contemporaneous effect of CHR-P symptoms on stress. However, nonperceptive symptoms had a greater contemporaneous effect on stress than perceptive symptoms.

The findings suggest a greater contemporaneous impact of CHR-P symptoms on stress than vice versa. The experience of nonperceptive symptoms, in particular, may alter the appraisal of stress in daily life and represent a target for early interventions in real-time daily life (i.e., ecological momentary interventions).

There is evidence that attachment, trauma, and voice appraisals individually impact voice hearing in psychosis, but their intersectional relationship has not been examined. The aim of this study was to identify subgroups of individuals from the intersectional relationship between these factors and examine differences between subgroups on clinical outcomes.

A latent profile analysis was conducted on baseline data from the AVATAR2 trial (n = 345), to identify statistically distinct subgroups of individuals with psychosis who hear distressing voices based on co-occurring patterns of trauma, fearful attachment, and voice appraisals. The association between profile membership and demographic characteristics, voice severity, posttraumatic stress disorder symptoms, emotional distress, and difficulties with motivation and pleasure was then examined. Experts by experience were consulted throughout the process.

Four profiles were identified: ‘adverse voices and relational trauma’, ‘low malevolent and omnipotent voices’, ‘adverse voices yet low relational trauma’, and ‘high benevolent voices’. Negative voice appraisals occurred in the presence of high and low trauma and attachment adversities. The first profile was associated with being female and/or other non-male genders and had worse voice severity and emotional distress. High adversities and worse emotional distress occurred in the presence of voice benevolence and engagement. Black and South Asian ethnicities were not associated with specific profiles.

The identified profiles had negative and positive voice appraisals associated with higher and lower occurrence of adversities, and different clinical outcomes. These profiles could inform detailed case formulations that could tailor interventions for voice hearers.

Depression has been linked to disruptions in resting-state networks (RSNs). However, inconsistent findings on RSN disruptions, with variations in reported connectivity within and between RSNs, complicate the understanding of the neurobiological mechanisms underlying depression.

A systematic literature search of PubMed and Web of Science identified studies that employed resting-state functional magnetic resonance imaging (fMRI) to explore RSN changes in depression. Studies using seed-based functional connectivity analysis or independent component analysis were included, and coordinate-based meta-analyses were performed to evaluate alterations in RSN connectivity both within and between networks.

A total of 58 studies were included, comprising 2321 patients with depression and 2197 healthy controls. The meta-analysis revealed significant alterations in RSN connectivity, both within and between networks, in patients with depression compared with healthy controls. Specifically, within-network changes included both increased and decreased connectivity in the default mode network (DMN) and increased connectivity in the frontoparietal network (FPN). Between-network findings showed increased DMN–FPN and limbic network (LN)–DMN connectivity, decreased DMN–somatomotor network and LN–FPN connectivity, and varied ventral attention network (VAN)–dorsal attentional network (DAN) connectivity. Additionally, a positive correlation was found between illness duration and increased connectivity between the VAN and DAN.

These findings not only provide a comprehensive characterization of RSN disruptions in depression but also enhance our understanding of the neurobiological mechanisms underlying depression.

Complex post-traumatic stress disorder (cPTSD) is a newly recognized condition characterized by core PTSD symptoms and disturbances in self-organization (DSO) that has been associated with psychotic-like experiences (PLEs). This study employs two psychopathology network approaches to identify which post-traumatic symptoms are related to PLEs in a sample of late adolescents. We propose that cPTSD symptoms play a crucial role in explaining the co-occurrence of trauma and PLEs.

A sample of 1010 late adolescents provided measures of post-traumatic symptomatology and PLEs. We estimated the Gaussian graphical network structure of PTSD/cPTSD symptoms and PLEs and assessed their bridge centrality indices. Bayesian network analysis was then used to estimate a directed acyclic graph (DAG). Gender was set as a moderator in both Gaussian and Bayesian models.

Results show that affect dysregulation, a cPTSD domain, presented the highest bridge connection with the PLE cluster. Bayesian network analysis identified a pathway going from cPTSD items of worthlessness and relational dysregulation, to PLE items of paranoia and social anxiety. Additionally, we found relevant gender differences in network connectivity, with females showing higher connectivity compared to males.

Our findings highlight the central role of affect dysregulation and negative self-concept in linking cPTSD to PLE symptoms, with specific differences according to gender. These insights underscore the need for targeted, gender-sensitive approaches in the prevention and treatment of PLEs among adolescents, emphasizing early intervention and tailored treatment strategies.

Poorer family functioning during childhood is associated with severe mental disorders in adulthood in the general population. However, family functioning is understudied in families with parental schizophrenia or bipolar disorder. We aimed to investigate family functioning in families with 11-year-old children of parents with schizophrenia or bipolar disorder compared with controls. Second, we aimed to examine associations between family functioning and levels of child psychopathology, child global functioning, and parental social functioning.

In this prospective, population-based cohort study, we included 160 families with parental schizophrenia, 95 families with parental bipolar disorder, and 177 control families. Family functioning was measured with the 12-item version of the McMaster Family Assessment Device – General Functional Scale.

Families with parental schizophrenia (Cohen’s d = 0.29; p = .002) and parental bipolar disorder (Cohen’s d = 0.34; p = .004) had significantly poorer family functioning and a significantly higher prevalence of clinically significant family dysfunction (Cohen’s d range = 0.29–0.34; p values = .007) than control families. Across study groups, poorer family functioning was associated with higher levels of child psychopathology and poorer social functioning of the primary caregiver (p values < .001).

Children in families with parental schizophrenia or bipolar disorder are at increased risk of experiencing family dysfunction, and poorer family functioning confers risk for more symptoms of child psychopathology and poorer parental social functioning. Future studies should investigate the potentially predictive value of family dysfunction in relation to later illness onset and other adverse outcomes in these populations.

Patients with schizophrenia experience accelerated aging, accompanied by abnormalities in biomarkers such as shorter telomere length. Brain age prediction using neuroimaging data has gained attention in schizophrenia research, with consistently reported increases in brain-predicted age difference (brain-PAD). However, its associations with clinical symptoms and illness duration remain unclear.

We developed brain age prediction models using structural magnetic resonance imaging (MRI) data from 10,938 healthy individuals. The models were validated on an independent test dataset comprising 79 healthy controls, 57 patients with recent-onset schizophrenia, and 71 patients with chronic schizophrenia. Group comparisons and the clinical associations of brain-PAD were analyzed using multiple linear regression. SHapley Additive exPlanations (SHAP) values estimated feature contributions to the model, and between-group differences in SHAP values and group-by-SHAP value interactions were also examined.

Patients with recent-onset schizophrenia and chronic schizophrenia exhibited increased brain-PAD values of 1.2 and 0.9 years, respectively. Between-group differences in SHAP values were identified in the right lateral prefrontal area (false discovery rate [FDR] p = 0.022), with group-by-SHAP value interactions observed in the left prefrontal area (FDR p = 0.049). A negative association between brain-PAD and Full-scale Intelligence Quotient scores in chronic schizophrenia was noted, which did not remain significant after correction for multiple comparisons.

Brain-PAD increases were pronounced in the early phase of schizophrenia. Regional brain abnormalities contributing to brain-PAD likely vary with illness duration. Future longitudinal studies are required to overcome limitations related to sample size, heterogeneity, and the cross-sectional design of this study.

Neuropsychological evidence suggests that dissociation might disturb emotional learning, which is a fundamental mechanism of psychotherapy. However, a recent meta-analysis on the impact of dissociation on treatment outcomes in psychotherapy trials for posttraumatic stress disorder (PTSD) reported inconsistent results and concluded that further high-quality clinical trials are needed to test whether dissociation affects the efficacy of psychotherapies. We had two main aims: First, to test whether the efficacy of two evidence-based psychotherapies for individuals with trauma-related PTSD is affected by the level of pretreatment dissociation. Second, we investigated whether a significant reduction in dissociation at an early stage of treatment is beneficial for subsequent efficacy.

The potential impact of dissociation on efficacy was studied in 193 women with PTSD related to childhood abuse who were randomized to dialectical behavior therapy for PTSD (DBT-PTSD) or cognitive processing therapy (CPT). Efficacy was operationalized as a change in the Clinician-Administered PTSD Scale (CAPS). Dissociation was assessed with the Dissociation Tension Scale (DSS). The analyses accounted for major confounders (in particular initial PTSD severity).

Two main findings emerged from this study. First, baseline dissociation was a negative predictor for treatment efficacy. Second, a significant drop in dissociation at the initial stages of treatment was beneficial for subsequent efficacy.

Dissociation likely reduces the efficacy of trauma-focused therapies. Accordingly, successful reduction of dissociation at an early stage of treatment assists the efficacy of trauma-focused psychotherapies.

Symptoms of complex post-traumatic stress disorder (cPTSD) may play a role in the maintenance of psychotic symptoms. Network analyses have shown interrelationships between post-traumatic sequelae and psychosis, but the temporal dynamics of these relationships in people with psychosis and a history of trauma remain unclear. We aimed to explore, using network analysis, the temporal order of relationships between symptoms of cPTSD (i.e. core PTSD and disturbances of self-organization [DSOs]) and psychosis in the flow of daily life.

Participants with psychosis and comorbid PTSD (N = 153) completed an experience-sampling study involving multiple daily assessments of psychosis (paranoia, voices, and visions), core PTSD (trauma-related intrusions, avoidance, hyperarousal), and DSOs (emotional dysregulation, interpersonal difficulties, negative self-concept) over six consecutive days. Multilevel vector autoregressive modeling was used to estimate three complementary networks representing different timescales.

Our between-subjects network suggested that, on average over the testing period, most cPTSD symptoms related to at least one positive psychotic symptom. Many average relationships persist in the contemporaneous network, indicating symptoms of cPTSD and psychosis co-occur, especially paranoia with hyperarousal and negative self-concept. The temporal network suggested that paranoia reciprocally predicted, and was predicted by, hyperarousal, negative self-concept, and emotional dysregulation from moment to moment. cPTSD did not directly relate to voices in the temporal network.

cPTSD and positive psychosis symptoms mutually maintain each other in trauma-exposed people with psychosis via the maintenance of current threat, consistent with cognitive models of PTSD. Current threat, therefore, represents a valuable treatment target in phased-based trauma-focused psychosis interventions.

Major depressive disorder (MDD) is a heterogeneous condition characterized by significant intersubject variability in clinical presentations. Recent neuroimaging studies have indicated that MDD involves altered brain connectivity across widespread regions. However, the variability in abnormal connectivity among MDD patients remains understudied.

Utilizing a large, multi-site dataset comprising 1,276 patients with MDD and 1,104 matched healthy controls, this study aimed to investigate the intersubject variability of structural covariance (IVSC) and functional connectivity (IVFC) in MDD.

Patients with MDD demonstrated higher IVSC in the precuneus and lingual gyrus, but lower IVSC in the medial frontal gyrus, calcarine, cuneus, and cerebellum anterior lobe. Conversely, they exhibited an overall increase in IVFC across almost the entire brain, including the middle frontal gyrus, anterior cingulate cortex, hippocampus, insula, striatum, and precuneus. Correlation and mediation analyses revealed that abnormal IVSC was positively correlated with gray matter atrophy and mediated the relationship between abnormal IVFC and gray matter atrophy. As the disease progressed, IVFC increased in the left striatum, insula, right lingual gyrus, posterior cingulate, and left calcarine. Pharmacotherapy significantly reduced IVFC in the right insula, superior temporal gyrus, and inferior parietal lobule. Furthermore, we found significant but distinct correlations between abnormal IVSC and IVFC and the distribution of neurotransmitter receptors, suggesting potential molecular underpinnings. Further analysis confirmed that abnormal patterns of IVSC and IVFC were reproducible and MDD specificity.

These results elucidate the heterogeneity of abnormal connectivity in MDD, underscoring the importance of addressing this heterogeneity in future research.

Loneliness is a risk factor for late-life dementia. There is less consistent evidence of its association with cognitive performance. This study examined the replicability of the association between loneliness and overall and domain-specific cognitive function and informant-rated cognitive decline in cohorts from seven countries: the United States, England, India, China, South Africa, Mexico, and Chile.

Data were from the Harmonized Cognitive Assessment Protocol administered in seven population-based studies (total N > 20,000). Participants reported their loneliness, completed a battery of cognitive tests, and nominated a knowledgeable informant to rate their cognitive decline. Random-effect meta-analyses were used to summarize the associations from each cohort.

Loneliness was associated with poor overall cognitive performance and informant-rated cognitive decline controlling for sociodemographic factors (meta-analytic correlation for overall cognition = −.10 [95% CI = −.13, −.06] and informant-rated decline = .16 [95% CI = .14, .17]). Despite some heterogeneity, the associations were significant across samples from Africa, Asia, Europe, North, Central, and South America. The meta-analysis also indicated an association with specific cognitive domains: episodic memory, speed-attention, visuospatial abilities, numeric reasoning, and verbal fluency. The associations were attenuated but persisted when depressive symptoms were added as a covariate. Depression, cognitive impairment, and sociodemographic factors did not consistently moderate the associations across samples.

Loneliness is associated with poor performance across multiple domains of cognition and observer-rated cognitive decline, associations that replicated across diverse world regions and cultures.

According to the aberrant salience proposal, reward processing abnormality, specifically erroneous reward prediction error (RPE) signaling due to stimulus-independent release of dopamine, underlies delusions in schizophrenia. However, no studies to date have examined RPE-associated brain activations in relation to this symptom.

Seventy-eight patients with a DSM-5 diagnosis of schizophrenia/schizoaffective disorder and 43 healthy individuals underwent fMRI while they performed a probabilistic monetary reward task designed to generate a measure of RPE. Ratings of delusions and referentiality were made in the patients.

Using whole-brain, voxel-based analysis, schizophrenia patients showed only minor differences in RPE-associated activation compared to healthy controls. Within the patient group, however, severity of delusions was inversely associated with RPE-associated activation in areas including the caudate nucleus, the thalamus and the left pallidum, as well as the lateral frontal cortex bilaterally, the pre- and postcentral gyrus and supplementary motor area, the middle cingulate gyrus, and parts of the temporal and parietal cortex. A broadly similar pattern of association was seen for referentiality.

According to this study, while patients with schizophrenia as a group do not show marked alterations in RPE signaling, delusions and referentiality are associated with reduced activation in parts of the prefrontal cortex and the basal ganglia, though not specifically the ventral striatum. The direction of the changes is on the face of it contrary to that predicted by aberrant salience theory.

Cognitive behavioural therapy for insomnia (CBT-I) is the recommended first-line treatment for insomnia. However, scaling this proven effective intervention to areas of high need remains a challenge, necessitating sensitive adaptation and evaluation.

A randomised waitlist-controlled trial evaluated the efficacy of a hybrid digital CBT-I and emotion regulation (dCBT-I + ER) intervention delivered through workplaces. Participants with at least mild insomnia and depression or anxiety symptoms were randomised to the intervention or waitlist control groups. The intervention was delivered via a web-based platform and four video-conferencing therapy sessions. Participants tracked their sleep using actigraphy and a sleep diary that was used to pace the intervention delivered. Assessments occurred at baseline and 8 weeks post-randomisation, measuring insomnia, depression, anxiety, psychological well-being, quality of life, and work productivity.

Of the 159 participants (mean age 43.6 ± 9.4 years, 76.7% female, 80.5% white), 80 received the intervention and 79 were in the control group. The intervention group showed significant improvements in insomnia (F1, 134 = 71.46, p < .0001); depression (F1, 134 = 35.67, p < .0001); and anxiety (F1, 134 = 17.63, p < .0001), with large effect sizes (d = 0.7–1.5). Sleep diary data supported these findings, whereas actigraphy data did not. Improvements in psychological well-being were significant (F1, 132.13 = 10.64, p < 0.001), whereas quality of life, work productivity, and satisfaction outcomes were not.

This study suggests that a hybrid dCBT-I + ER intervention, delivered via workplaces, effectively improves insomnia, depression, and anxiety. It holds promise as a scalable solution, warranting further investigation into its long-term efficacy and economic impact.

Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear.

We used genomic structural equation modeling and genome-wide association studies (N = 79,729–903,147) to examine the latent genetic architecture of nine impulsivity traits and seven substance use (SU) and SUD traits.

We found that the SU and SUD factors were strongly genetically inter-correlated (rG=0.77) but their associations with impulsivity facets differed. Lack of premeditation, negative and positive urgency were equally positively genetically correlated with both the SU (rG=.0.30–0.50) and SUD (rG=0.38–0.46) factors; sensation seeking was more strongly genetically correlated with the SU factor (rG=0.27 versus rG=0.10); delay discounting was more strongly genetically correlated with the SUD factor (rG=0.31 versus rG=0.21); and lack of perseverance was only weakly genetically correlated with the SU factor (rG=0.10). After controlling for the genetic correlation between SU/SUD, we found that lack of premeditation was independently genetically associated with both the SU (β=0.42) and SUD factors (β=0.21); sensation seeking and positive urgency were independently genetically associated with the SU factor (β=0.48, β=0.33, respectively); and negative urgency and delay discounting were independently genetically associated with the SUD factor (β=0.33, β=0.36, respectively).

Our findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.

We conducted a prospective study to advance knowledge of biological factors that predict the future onset of binge eating and compensatory weight control behaviors because few biological risk factors for eating pathology have been identified.

Adolescent girls free of binge eating or compensatory behaviors (N = 88; Mage = 14.5; [SD = 0.9]) completed functional magnetic resonance imaging tasks assessing individual differences in neural responsivity hypothesized to increase risk for onset of binge eating and compensatory behaviors, along with additional self-report measures, and were assessed over a 4-year follow-up.

Elevated responsivity of regions implicated in attention and valuation (dorsal anterior cingulate cortex; ventromedial prefrontal cortex) to thin models and lower responsivity of a reward valuation region (caudate) to anticipated milkshake tastes (which correlated with feeling fat) predicted the future onset of binge eating or compensatory behaviors over 4-year follow-up. Parental history of binge eating and compensatory behaviors, emotionality, weight/shape overvaluation, feeling fat, and elevated BMI also predicted the future onset of binge eating or compensatory behaviors.

The evidence that elevated attentional bias for, and valuation of the thin ideal, in combination with lower valuation of high-calorie foods, predicted the future onset of eating-disordered behaviors are novel findings. The evidence that weight/shape overvaluation, feeling fat, elevated body mass, emotionality, and parental history of eating pathology predicted the future onset of eating-disordered behaviors extend past findings.

Recent research has demonstrated that domains of social determinants of health (SDOH) (e.g. air pollution and social context) are associated with psychosis. However, SDOHs have often been studied in isolation. This study investigated distinct exposure profiles, estimated their associations with persistent distressing psychotic-like experiences (PLE), and evaluated whether involvement in physical activity partially explains this association.

Analyses included 8,145 young adolescents from the Adolescent Brain and Cognitive Development Study. Data from the baseline and three follow-ups were included. Area-level geocoded variables spanning various domains of SDOH, including socioeconomic status, education, crime, built environment, social context, and crime, were clustered using a self-organizing map method to identify exposure profiles. Generalized linear mixed modeling tested the association between exposure profiles and persistent distressing PLE and physical activities (i.e. team and individual sports), adjusting for individual-level covariates including age, sex, race/ethnicity, highest level of parent education, family-relatedness, and study sites.

Five exposure profiles were identified. Compared to the reference Profile 1 (suburban affluent areas), Profile 3 (rural areas with low walkability and high ozone), and Profile 4 (urban areas with high SES deprivation, high crime, and high pollution) were associated with greater persistent distressing PLE. Team sports mediated 6.14% of the association for Profile 3.

This study found that neighborhoods characterized by rural areas with low walkability and urban areas with high socioeconomic deprivation, pollution concentrations, and crime were associated with persistent distressing PLE. Findings suggest that various social-environmental factors may differentially impact the development of psychosis.