Past meta-analyses have confirmed robust associations between childhood traumatic experiences and the risk of psychosis. However, the dose–response relationship between cumulative adversity exposure and psychosis risk observed in some, but not all, previous studies in this area has not been specifically scrutinized or substantiated via recommended meta-analytic methods. This meta-analysis aimed to synthesize the available evidence on dose–response effects between childhood trauma and psychosis outcomes.

PsycINFO, PubMed, EMBASE, Web of Science, CNKI, and WANFANG were searched from inception to July 2024 to identify observational studies reporting odds ratios for psychosis outcomes across multiple levels of childhood trauma exposure. Dose–response effects were extracted from eligible studies and synthesized via robust error meta-regression analyses.

Twenty-one studies comprising 59,975 participants were included in the meta-analysis. A significant nonlinear relationship was observed between the number of childhood adversities and the risk of future psychosis experiences (p for nonlinearity = .021). The pooled odds ratio for psychosis increased from 1.76 (95% confidence interval [CI]: 1.39–2.22) for 1 exposure to 6.46 (95% CI: 4.37–9.53) for 5+ exposures compared to no traumatic experience.

This meta-analysis provides robust evidence for a dose–response relationship between cumulative childhood adversity and psychosis risk, with nonlinear patterns suggestive of an accelerating, more pronounced, risk at higher levels of trauma exposure. These findings underscore the importance of considering childhood traumatic experiences as a putative and potentially causative risk factor for psychotic experiences, as well as early prevention and intervention efforts targeting childhood adversity to reduce the risk of psychosis.

Catatonia has many potential underlying causes, but in some patients, no clear etiology is identified, sparking growing interest in its genetic basis. We aimed to provide the first comprehensive synthesis of genetic abnormalities in catatonia.

In this systematic review (PROSPERO CRD42023455118) we searched MEDLINE All, Embase Classic + Embase, PsycINFO, and AMED up to August 15, 2023, for studies on genetic testing and catatonia phenotyping in all age groups. Catatonia was diagnosed using specified diagnostic criteria or description of clinical features. Risk of bias was assessed using the Joanna Briggs Institute quality assessment tools. Results were summarized with a narrative synthesis.

We included 99 studies involving 8600 individuals. Sex was reported for 6080 individuals, of whom 3208 (52.8%) were male. Mean age at onset of catatonia was 28.8 years (SD 16.3). The median duration of the index catatonic episode was 180 days (IQR 38 to 668). Stupor and mutism were the most frequently reported symptoms. Forty-seven genetic conditions were reported in catatonia, including Phelan-McDermid syndrome (n = 80), 22q11.2 deletion syndrome (n = 23), and Down’s syndrome (n = 19). Study quality was good in 29 studies, moderate in 53, and poor in 17. The major focus of association studies has centered on periodic catatonia; despite identifying candidate genes at both 22q13 and 15q15, none have been replicated.

Catatonia can manifest in a wide range of genetic syndromes, suggesting a shared vulnerability across diverse genetic and developmental disorders. We did not identify a unique phenomenology or treatment response profile in genetic associations of catatonia.

Insight in nonverbal correlates of paranoid ideation can potentially help improve diagnostic procedures and guide interventions. The aim was to systematically evaluate the scientific evidence investigating nonverbal correlates of paranoid ideation.

The review follows the PRISMA guidelines. Databases PsycINFO, PubMed, Web of Science, and Cinahl were searched for studies concerning the use of standardized instruments for both verbal and nonverbal measurements of paranoid ideation in adult participants. Quality of studies was evaluated using the Effective Public Health Practice Project tool. Data were systematically extracted and summarized thematically and narratively. This review was registered with PROSPERO (CRD42022288001).

The search strategy yielded 3962 results of which 22 papers met inclusion criteria. Half (n = 11) of the included articles included patients with a diagnosis on the psychosis spectrum, the other articles (n = 11) studied healthy populations. Identified nonverbal categories were spatial behavior (n = 6), brain region activity (n = 5), visual perception (n = 5), stress physiology (n = 4), information processing (n = 3), and aggression (n = 1). Some studies investigated multiple nonverbal categories.

Evidence was strongest for spatial behavior and brain region activity as nonverbal correlates of paranoid ideation. Evidence for stress physiology, information processing, and aggression as potential nonverbal correlates was less robust, due to inconsistent findings and small numbers of publications. Using nonverbal methods to assess paranoid ideation requires more investigation and evaluation. The integration of nonverbal assessments might offer new diagnostic possibilities that move beyond traditional verbal methods.

Psychiatric symptoms are typically highly inter-correlated at the group level. Collectively, these correlations define the architecture of psychopathology – informing taxonomic and mechanistic models in psychiatry. However, to date, it remains unclear if this architecture differs between etiologically distinct subgroups, despite the core relevance of this understanding for personalized medicine. Here, we introduce a new analytic pipeline to probe group differences in the psychopathology architecture – demonstrated through the comparison of two distinct neurogenetic disorders.

We use a large questionnaire battery in 300 individuals aged 5–25 years (n = 102 XXY/KS, n = 64 XYY, n = 134 age-matched XY) to characterize the structure of correlations among 53 diverse measures of psychopathology in XXY/KS and XYY syndrome – enabling us to compare the effects of X- versus Y-chromosome dosage on the architecture of psychopathology at multiple, distinctly informative levels.

Behavior correlation matrices describe the architecture of psychopathology in each syndrome. A comparison of matrix rows reveals that social problems and externalizing symptoms are most differentially coupled to other aspects of psychopathology in XXY/KS versus XYY. Clustering the difference between matrices captures coordinated group differences in pairwise coupling between measures of psychopathology: XXY/KS shows greater coherence among externalizing, internalizing, and autism-related features, while XYY syndrome shows greater coherence in dissociality and early neurodevelopmental impairment.

These methods offer new insights into X- and Y-chromosome dosage effects on behavior, and our shared code can now be applied to other clinical groups of interest – helping to hone mechanistic models and inform the tailoring of care.

Interventions at frequently used suicide locations that restrict access to means, encourage help-seeking, and increase the likelihood of intervention by a third party are effective in preventing suicide at such sites. However, there have been concerns that such efforts may displace suicides to other sites. It is important to synthesize the evidence on suicide displacement effects.

We conducted a systematic search of Medline, PsycINFO, Scopus, and Google for eligible studies from their inception to February 20, 2025. Meta-analyses were conducted to assess the pooled effects of interventions on suicides at frequently used locations and other sites, and on overall suicides involving the same method.

Our search identified 17 studies. Meta-analyses showed a reduction in suicides at the intervention sites (pooled incidence rate ratio [IRR] 0.09, 95% confidence interval [95% CI] 0.04–0.21) and no evidence of changes in suicides at other sites after restricting access to means was deployed alone. The pooled IRR for nearby sites (same type) was 0.99 (95% CI 0.72–1.38); for other sites (same type), it was 0.99 (95% CI 0.76–1.29); and for other sites (different/unspecified type), it was 1.19 (95% CI 0.90–1.58). There was an overall reduction in suicides involving the same method during the post-intervention period (IRR 0.77, 95% CI 0.65–0.92). Similar patterns were observed when restricting access to means was assessed alone or with other interventions.

Suicide numbers at other sites did not change after interventions such as restricting access to means were deployed at frequently used locations.

Anger may increase the risk for prolonged grief disorder (PGD) after violent loss. A source of anger for violently bereaved people can be the criminal proceedings that ensue following the loss. The present study explored the reciprocal associations between PGD and state anger and whether aspects of involvement in the criminal justice system (CJS) relate to PGD and state anger.

We analyzed data of 237 MH17-bereaved people collected 67, 79, 88, and 103 months after the loss. Cross-lagged panel modeling was employed to examine the reciprocal associations between PGD and state anger. In the optimal model, we regressed PGD and state anger levels on different aspects of CJS involvement.

Higher PGD levels significantly predicted higher state anger levels at each wave (β = .112–.130) but not the other way around. This was found while constraining autoregressive and cross-lagged paths. When adding predictors and covariates to the model, PGD levels still consistently predicted state anger levels over time (β = .107–.121), with state anger levels predicting PGD levels to a lesser extent (β = .064–.070). None of the aspects of CJS involvement were related to either PGD or state anger levels.

If replicated, a clinical implication could be that targeting PGD levels in treatment may reduce state anger levels and, to a lesser extent, vice versa. Also, CJS involvement does not seem to have an impact on PGD and state anger in people confronted with violent loss.

Low-income, publicly insured youth face numerous barriers to adequate mental health care, which may be compounded for those with multiple marginalized identities. However, no research has examined how identity and diagnosis may interact to shape the treatment experiences of under-resourced youth with psychiatric conditions. Applying an intersectional lens to treatment disparities is essential for developing targeted interventions to promote equitable care.

Analyses included youth ages 7–18 with eating disorders (EDs; n = 3,311), mood/anxiety disorders (n = 3,219), or psychotic disorders (n = 3,035) enrolled in California Medicaid. Using state billing records, we examined sex- and race and ethnicity-based disparities in receipt of core services – outpatient therapy, outpatient medical care, and inpatient treatment – in the first year after diagnosis and potential differences across diagnostic groups.

Many youth (50.7% across diagnoses) received no outpatient therapy, and youth with EDs were least likely to receive these services. Youth of color received fewer days of outpatient therapy than White youth, and Latinx youth received fewer therapy and medical services across outpatient and inpatient contexts. Sex- and race and ethnicity-based disparities were especially pronounced for youth with EDs, with particularly low levels of service receipt among boys and Latinx youth with EDs.

Results raise concerns for unmet treatment needs among publicly insured youth, which are exacerbated for youth with multiple marginalized identities and those who do not conform to historical stereotypes of affected individuals (e.g., low-income boys of color with EDs). Targeted efforts are needed to ensure equitable care.

There is growing evidence that smoking increases the risk of developing psychiatric disorders, but the underlying mechanisms are largely unknown. We examine brain structure as a potential pathway between smoking and psychiatric disease liability.

We test associations between smoking (initiation, cigarettes per day, cessation, lifetime use) and depression, bipolar disorder, and schizophrenia, with and without correcting for volume of the amygdala, hippocampus, lateral and medial orbitofrontal cortex, superior frontal context, and cortical thickness and surface area. We use three methods that use summary statistics of genome-wide association studies to investigate genome-wide and local genetic overlap (genomic structural equation modeling, local analysis of (co)variant association), as well as causal associations (Mendelian randomization).

While we find causal effects of smoking on brain volume in different brain areas, and with psychiatric disorders, brain volume did not seem to mediate the effect of smoking on psychiatric disorders.

While these findings are limited by characteristics of the included summary statistics (e.g. sample size), we conclude that brain volume of these areas is unlikely to explain a substantial part of any effect of smoking on psychiatric disorders. Nevertheless, genetic methods are valuable tools for exploring other potential mechanisms, such as brain functional connectivity, foregoing the need to collect all phenotypes in one dataset.

Major depressive disorder (MDD) is a complex and heterogeneous disorder, and this heterogeneity poses a significant challenge for advancing precision medicine in patients with MDD. MRI-based subtyping analysis has been widely employed to address the heterogeneity of MDD patients. In this study, we investigated the subtypes of first-episode and drug-naive (FEDN) MDD patients based on the individualized structural covariance network (IDSCN).

In this study, we used T1-weighted anatomical images of 164 FEDN MDD patients and 164 healthy controls from the REST-meta-MDD consortium. The IDSCN of participants was obtained using the network template perturbation method. Subtypes of FEDN MDD were identified using k-means clustering analysis, and differences in neuroimaging findings and clinical symptoms between the identified subtypes were compared using two-sample t-tests.

This study identified two subtypes of FEDN MDD: subtype 1 (n = 117) and subtype 2 (n = 47) by characterizing 10 edges that were significantly altered in at least 5% of patients (i.e., 8 patients) in the IDSCN. Compared with subtype 2, subtype 1 had significantly higher anxiety symptom scores, stronger structural covariance edges in 9 edges within the thalamus, and a significantly reduced gray matter volume (GMV) in the frontal and parietal regions, and in the thalamus.

Our results suggest that patients with FEDN MDD can be classified into two different subtypes based on their IDSCN, providing an important reference for personalized treatment and precision medicine for patients with FEDN MDD.

Mild cognitive impairment with Lewy bodies (MCI-LB) may be identified prospectively based on the presence of cognitive impairment and several core clinical features (visual hallucinations, cognitive fluctuations, parkinsonism, and REM sleep behavior disorder). MCI-LB may vary in its presenting features, which may reflect differences in underlying pathological pattern, severity, or comorbidity.

We aimed to assess how clinical features of MCI-LB accumulate over time, and whether this is associated with the rate of cognitive decline.

In this cohort study, 74 individuals seen with MCI-LB prospectively underwent repeated annual cognitive and clinical assessment up to nine years. Relationships between clinical features (number of core features present and specific features present) and cognitive change on the Addenbrooke’s Cognitive Examination–Revised (ACE-R) were examined with time-varying mixed models. The accumulation of core clinical features over time was examined with a multi-state Markov model.

When an individual with MCI-LB endorsed more clinical features, they typically experienced a faster cognitive decline (ACE-R Score Difference β = −1.1 [−1.7 to −0.5]), specifically when experiencing visual hallucinations (β = −2.1 [−3.5 to −0.8]) or cognitive fluctuations (β = −3.4 [−4.8 to −2.1]).

Individuals with MCI-LB typically acquired more clinical features with the passage of time (25.5% [20.0–32.0%] one-year probability), limiting the prognostic utility of baseline-only features.

The clinical presentation of MCI-LB may evolve over time. The accumulation of more clinical features of Lewy body disease, in particular visual hallucinations and cognitive fluctuations, may be associated with a worse prognosis in clinical settings.

Weight suppression represents the difference between highest and current body weight and predicts maintenance of bulimia nervosa and related syndromes (BN-S). This study tested a biobehavioral model of binge-eating severity in which greater weight suppression links to reduced leptin, which links to reduced glucagon-like peptide 1 (GLP-1) release, which links to both decreased reward satiation and increased reward valuation, which link, respectively, to excessive food intake and loss of control while eating – the defining features of DSM-5 binge-eating episodes.

Women (N = 399) who met DSM-5 criteria for bulimia nervosa or another eating disorder with binge eating (n = 321) or had no lifetime eating disorder symptoms (n = 78) participated in a multi-visit protocol, including structured clinical interviews, height, weight, weight history, percent body fat, fasting leptin, post-prandial GLP-1 response to a fixed meal, and self-report and behavioral assessments of food reward satiation (ad lib meal) and food and nonfood reward valuation (progressive ratio tasks).

A structural equation model (SEM) demonstrated excellent fit to data with significant pathways from greater weight suppression to lower leptin, to blunted GLP-1 response, to lower reward satiation, to larger eating/binge-eating episode size, with significant indirect paths through leptin, GLP-1, and reward satiation. SEM with paths via reward valuation to loss of control eating demonstrated inadequate fit.

Findings specifically link reduced GLP-1 response to severity of binge-episode size and support weight history assessment in eating disorders, DSM-5 over ICD-11 criteria for binge eating, and may inform future clinical trials of GLP-1 agonists for BN-S.

Parental psychopathology is a known risk factor for child autistic-like traits. However, symptom-level associations and underlying mechanisms are poorly understood.

We utilized network analyses and cross-lagged panel models to investigate the specific parental psychopathology related to child autistic-like traits among 8,571 adolescents (mean age, 9.5 years at baseline), using baseline and 2-year follow-up data from the Adolescent Brain Cognitive Development study. Parental psychopathology was measured by the Adult Self Report, and child autistic-like traits were measured by three methods: the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5 autism spectrum disorder (ASD) subscale, the Child Behavior Checklist ASD subscale, and the Social Responsiveness Scale. We also examined the mediating roles of family conflict and children’s functional brain connectivity at baseline.

Parental attention-deficit/hyperactivity problems were central symptoms and had a direct and the strongest link with child autistic-like traits in network models using baseline data. In longitudinal analyses, parental attention-deficit/hyperactivity problems at baseline were the only significant symptoms associated with child autistic-like traits at 2-year follow-up (β = 0.014, 95% confidence interval [0.010, 0.018], FDR q = 0.005), even accounting for children’s comorbid behavioral problems. The observed association was significantly mediated by family conflict (proportion mediated = 11.5%, p for indirect effect <0.001) and functional connectivity between the default mode and dorsal attention networks (proportion mediated = 0.7%, p for indirect effect = 0.047).

Parental attention-deficit/hyperactivity problems were associated with elevated autistic-like traits in offspring during adolescence.

Based on an efficacious face-to-face theory-driven psychological therapy for persecutory delusions in the context of psychosis, we set out to develop a scalable guided 6-month online program. The aim was an intervention that patients can easily access and use, produces large clinical effects, and can be supported by a range of mental health professionals in less contact time than face-to-face therapy. We report here the proof-of-concept testing. At least moderate-sized clinical effects were required to progress to a randomized controlled trial (RCT).

In the 6-month Feeling Safer online program, a certified medical device, patients complete a brief assessment and then are provided with up to 10 modules that match their difficulties. Regular remote meetings with a mental health professional also take place. These may be supplemented by in-person visits. A pre- to post-treatment cohort trial was conducted with 14 patients with persistent persecutory delusions. The primary outcome was the Psychotic Symptoms Rating Scale (PSYRATS)-Delusions.

Satisfaction and usability ratings of the program were high. Very large reductions in persecutory delusions were observed (PSYRATS mean reduction = 7.1, 95% C.I. = 3.4, 10.8, n = 13, Cohen’s d = 3.0). There were large improvements in paranoia, anxiety, depression, agoraphobic distress, psychological wellbeing, meaningful activity, personal recovery, recovering quality of life, and moderate improvements in insomnia, agoraphobic avoidance, and quality of life.

The clinical effects associated with Feeling Safer were very high, comparable to those seen in the evaluations of the face-to-face therapy, and enable progression to an RCT.

Despite the high prevalence of generalized anxiety among young adults, studies investigating factors that shape the course of these symptoms during the twenties are scarce. In addition, generalized anxiety can manifest in different ways, but it is unclear whether symptoms cluster under distinct dimensions in this age group. The current study addressed these gaps using data from the Twins Early Development Study. First, we examined genetic and environmental contributions to continuity and change in generalized anxiety symptoms in young adulthood and the heritability of a latent factor reflecting stability over this period. Next, to explore potential dimensions of generalized anxiety, we investigated the factorial structure of symptoms as well as etiological influences underpinning the different factors.

The sample comprised 6,429 twin pairs. Generalized anxiety was assessed at six waves (age 23–26 years).

Genetic factors largely accounted for continuity and environmental factors for change in symptom severity. Furthermore, the heritability of stable generalized anxiety (60%) was substantially higher than that at any single time point (39–46%). Regarding the factorial structure of symptoms, we found evidence of two dimensions: worry-avoidance and somatic-distress symptoms. Genetic correlations (rG = 0.77–0.91) between the two dimensions were higher than environmental correlations (rE = 0.26–0.65).

The current findings suggest that extracting temporal stability provides the strongest opportunity to identify genetic influences on generalized anxiety. Moreover, the results indicate that differences between generalized anxiety dimensions are more likely attributable to environmental than genetic effects.