3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described.

We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.5% male, mean age = 14.5 ± 8.3 years). All participants were also evaluated with gold-standard neuropsychiatric and cognitive assessments. High-resolution structural magnetic resonance imaging was performed on a subset of participants (n = 24).

We found global deficits in EF; individuals with 3q29del scored higher than the population mean on the BRIEF global executive composite (GEC) and all subscales. In total, 81.3% of study subjects (n = 26) scored in the clinical range on at least one BRIEF subscale. BRIEF GEC T scores were higher among 3q29del participants with a diagnosis of attention deficit/hyperactivity disorder (ADHD), and BRIEF GEC T scores were associated with schizophrenia spectrum symptoms as measured by the Structured Interview for Psychosis-Risk Syndromes. BRIEF GEC T scores were not associated with cognitive ability. The BRIEF-2 ADHD form accurately (sensitivity = 86.7%) classified individuals with 3q29del based on ADHD diagnosis status. BRIEF GEC T scores were correlated with cerebellar white matter and subregional cerebellar cortex volumes.

Together, these data expand our understanding of the phenotypic spectrum of 3q29del and identify EF as a core feature linked to both psychiatric and neuroanatomical features of the syndrome.

Post-traumatic stress disorder (PTSD) has been shown to predict psychotic symptomology. However, few studies have examined the relative contribution of PTSD compared to broader post-traumatic sequelae in maintaining psychosis. Complex PTSD (cPTSD), operationalized using ICD-11 criteria, includes core PTSD (intrusions, avoidance, hyperarousal) as well as additional “disturbances of self-organisation” (DSO; emotional dysregulation, interpersonal difficulties, negative self-concept) symptoms, more likely to be associated with complex trauma histories. It was hypothesized that DSOs would be associated with positive psychotic symptoms (paranoia, voices, and visions) in daily life, over and above core PTSD symptoms.

This study (N = 153) employed a baseline subsample of the Study of Trauma And Recovery (STAR), a clinical sample of participants with comorbid post-traumatic stress and psychosis symptoms. Core PTSD, DSO and psychosis symptoms were assessed up to 10 times per day at quasi-random intervals over six consecutive days using Experience Sampling Methodology.

DSOs within the preceding 90 min predicted paranoia, voices, and visions at subsequent moments. These relationships persisted when controlling for core PTSD symptoms within this timeframe, which were themselves significant. The associations between DSOs and paranoia but not voices or visions, were significantly stronger than those between psychosis and core PTSD symptoms.

Consistent with an affective pathway to psychosis, the findings suggest that DSOs may be more important than core PTSD symptoms in maintaining psychotic experiences in daily life among people with comorbid psychosis and cPTSD, and indicate the potential importance of addressing broad post-traumatic sequelae in trauma-focused psychosis interventions.

Adolescence is marked by a sharp increase in the incidence of depression, especially in females. Identification of risk for depressive disorders (DD) in this key developmental stage can help prevention efforts, mitigating the clinical and public burden of DD. While frequently used in diagnosis, nonverbal behaviors are relatively understudied as risk markers for DD. Digital technology, such as facial recognition, may provide objective, fast, efficient, and cost-effective means of measuring nonverbal behavior.

Here, we analyzed video-recorded clinical interviews of 359 never-depressed adolescents females via commercially available facial emotion recognition software.

We found that average head and facial movements forecast future first onset of depression (AUC = 0.70) beyond the effects of other established self-report and physiological markers of DD risk.

Overall, these findings suggest that digital assessment of nonverbal behaviors may provide a promising risk marker for DD, which could aid in early identification and intervention efforts.

While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship.

Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n = 221), and healthy controls (HC, n = 220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups.

There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation – lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation – higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course.

Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

Access to psychedelic drugs is liberalizing, yet responses are highly unpredictable. It is therefore imperative that we improve our ability to predict the nature of the acute psychedelic experience to improve safety and optimize potential therapeutic outcomes. This study sought to validate the ‘Imperial Psychedelic Predictor Scale’ (IPPS), a short, widely applicable, prospective measure intended to be predictive of salient dimensions of the psychedelic experience.

Using four independent datasets in which the IPPS was completed prospectively – two online surveys of ‘naturalistic’ use (N = 741, N = 836) and two controlled administration datasets (N = 30, N = 28) – we conducted factor analysis, regression, and correlation analyses to assess the construct, predictive, and convergent validity of the IPPS.

Our approach produced a 9-item scale with good internal consistency (Cronbach's α = 0.8) containing three factors: set, rapport, and intention. The IPPS was significantly predictive of ‘mystical’, ‘challenging’, and ‘emotional breakthrough’ experiences. In a controlled administration dataset (N = 28), multiple regression found set and rapport explaining 40% of variance in mystical experience, and simple regression found set explained 16% of variance in challenging experience. In another (N = 30), rapport was related to emotional breakthrough explaining 9% of variance.

Together, these data suggest that the IPPS is predictive of relevant acute features of the psychedelic experience in a broad range of contexts. We hope that this brief 9-item scale will be widely adopted for improved knowledge of psychedelic preparedness in controlled settings and beyond.

Exposure to adversity in childhood is a risk factor for lifetime mental health problems. Altered pace of biological aging, as measured through pubertal timing, is one potential explanatory pathway for this risk. This study examined whether pubertal timing mediated the association between adversity (threat and deprivation) and adolescent mental health problems (internalizing and externalizing), and whether this was moderated by sex.

Aims were examined using the Adolescent Brain and Cognitive Development study, a large community sample from the United States. Data were used from three timepoints across the ages of 9–14 years. Latent scores from confirmatory factor analysis operationalized exposure to threat and deprivation. Bayesian mixed-effects regression models tested whether pubertal timing in early adolescence mediated the relationship between adversity exposure and later internalizing and externalizing problems. Sex was examined as a potential moderator of this pathway.

Both threat and deprivation were associated with later internalizing and externalizing symptoms. Threat, but not deprivation, was associated with earlier pubertal timing, which mediated the association of threat with internalizing and externalizing problems. Sex differences were only observed in the direct association between adversity and internalizing problems, but no such differences were present for mediating pathways.

Adversity exposure had similar associations with the pace of biological aging (as indexed by pubertal timing) and mental health problems in males and females. However, the association of adversity on pubertal timing appears to depend on the dimension of adversity experienced, with only threat conferring risk of earlier pubertal timing.

Very late-onset psychosis (VLOP) is associated with higher rates of dementia but the proportion who develop dementia with Lewy bodies (DLB) is unknown. We aimed to identify individuals with VLOP who develop dementia and DLB and characterize the risk factors for progression.

Anonymized data were retrieved from electronic records for individuals with VLOP. Patients developing dementia after psychosis were identified, in addition to those with >2 core features of DLB at the time of dementia or DLB identified by a natural language processing application (NLP-DLB). Demographic factors, Health of the National Outcome Scale (HoNOS) and symptoms at index psychosis were explored as predictors of progression to dementia.

In 1425 patients with VLOP over 4.29 years (mean) follow up, 197 (13.8%) received a subsequent diagnosis of dementia. Of these, 24.4% (n = 48) had >2 core features of DLB and 6% (n = 12) had NLP-DLB. In cox proportional hazard models, older age and cognitive impairment at the time of psychosis were associated with increased risk of incident dementia. Visual hallucinations and 2+ core features of DLB at index psychosis were associated with increased risk of dementia with 2+ symptoms of DLB but not all-cause dementia. Two or more core features of DLB at index psychosis were associated with 81% specificity and 67% sensitivity for incident NLP-DLB.

In patients with VLOP who develop dementia, core features of DLB are common. Visual hallucinations or two core features of DLB in VLOP should prompt clinicians to consider DLB and support further investigation.

Mood and anxiety disorders are heterogeneous conditions with variable course. Knowledge on latent classes and transitions between these classes over time based on longitudinal disorder status information provides insight into clustering of meaningful groups with different disease prognosis.

Data of all four waves of the Netherlands Mental Health Survey and Incidence Study-2 were used, a representative population-based study of adults (mean duration between two successive waves = 3 years; N at T0 = 6646; T1 = 5303; T2 = 4618; T3 = 4007; this results in a total number of data points: 20 574). Presence of eight mood and anxiety DSM-IV disorders was assessed with the Composite International Diagnostic Interview. Latent class analysis and latent Markov modelling were used.

The best fitting model identified four classes: a healthy class (prevalence: 94.1%), depressed-worried class (3.6%; moderate-to-high proportions of mood disorders and generalized anxiety disorder (GAD)), fear class (1.8%; moderate-to-high proportions of panic and phobia disorders) and high comorbidity class (0.6%). In longitudinal analyses over a three-year period, the minority of those in the depressed-worried and high comorbidity class persisted in their class over time (36.5% and 38.4%, respectively), whereas the majority in the fear class did (67.3%). Suggestive of recovery is switching to the healthy class, this was 39.7% in the depressed-worried class, 12.5% in the fear class and 7.0% in the high comorbidity class.

People with panic or phobia disorders have a considerably more persistent and chronic disease course than those with depressive disorders including GAD. Consequently, they could especially benefit from longer-term monitoring and disease management.

Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.

A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC–MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.

A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.

The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Preserved ratio impaired spirometry (PRISm) is a new lung function impairment phenotype and has been recognized as a risk factor for various adverse outcomes. We aimed to examine the associations of this new lung function impairment phenotype with depression and anxiety in longitudinal studies.

We included 369 597 participants from the UK Biobank cohort, and divided them into population 1 without depression or anxiety and population 2 with depression or anxiety at baseline. Cox proportional hazard models were performed to evaluate the associations of lung function impairment phenotype with adverse outcomes of depression and anxiety, as well as their subtypes.

At baseline, 38 879 (10.5%) participants were diagnosed with PRISm. In population 1, the adjusted hazard ratios (HRs) for PRISm (v. normal spirometry) were 1.12 (95% CI 1.07–1.18) for incident depression, and 1.11 (95% CI 1.06–1.15) for incident anxiety, respectively. In population 2, PRISm was a risk factor for mortality in participants with depression (HR: 1.46; 95% CI 1.31–1.62) and anxiety (HR: 1.70; 95% CI 1.44–2.02), compared with normal spirometry. The magnitudes of these associations were similar in the phenotypes of lung function impairment and the subtypes of mental disorders. Trajectory analysis showed that the transition from normal spirometry to PRISm was associated with a higher risk of mortality in participants with depression and anxiety.

PRISm and airflow obstruction have similar risks of depression and anxiety. PRISm recognition may contribute to the prevention of depression and anxiety.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

Structural anomalies in the frontal lobe and basal ganglia have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, these findings have been not always consistent because of ADHD diversity. This study aimed to identify ADHD subtypes based on cognitive function and find their distinct brain structural characteristics.

Using the data of 656 children with ADHD from the Adolescent Brain Cognitive Development (ABCD) Study, we applied unsupervised machine learning to identify ADHD subtypes using the National Institutes of Health Toolbox Tasks. Moreover, we compared the regional brain volumes between each ADHD subtype and 6601 children without ADHD (non-ADHD).

Hierarchical cluster analysis automatically classified ADHD into three distinct subtypes: ADHD-A (n = 212, characterized by high-order cognitive ability), ADHD-B (n = 190, characterized by low cognitive control, processing speed, and episodic memory), and ADHD-C (n = 254, characterized by strikingly low cognitive control, working memory, episodic memory, and language ability). Structural analyses revealed that the ADHD-C type had significantly smaller volumes of the left inferior temporal gyrus and right lateral orbitofrontal cortex than the non-ADHD group, and the right lateral orbitofrontal cortex volume was positively correlated with language performance in the ADHD-C type. However, the volumes of the ADHD-A and ADHD-B types were not significantly different from those of the non-ADHD group.

These results indicate the presence of anomalies in the lateral orbitofrontal cortex associated with language deficits in the ADHD-C type. Subtype specificity may explain previous inconsistencies in brain structural anomalies reported in ADHD.