Inhibitory control develops in early childhood, and atypical development may be a measurable marker of risk for the later development of psychosis. Additionally, inhibitory control may be a target for intervention.

Behavioral performance on a developmentally appropriate Go/No-Go task including a frustration manipulation completed by children ages 3–5 years (early childhood; n = 107) was examined in relation to psychotic-like experiences (PLEs; ‘tween’; ages 9–12), internalizing symptoms, and externalizing symptoms self-reported at long-term follow-up (pre-adolescence; ages 8–11). ERP N200 amplitude for a subset of these children (n = 34) with electrophysiological data during the task was examined as an index of inhibitory control.

Children with lower accuracy on No-Go trials compared to Go trials in early childhood (F(1,101) = 3.976, p = 0.049), evidenced higher PLEs at the transition to adolescence 4–9 years later, reflecting a specific deficit in inhibitory control. No association was observed with internalizing or externalizing symptoms. Decreased accuracy during the frustration manipulation predicted higher internalizing, F(2,202) = 5.618, p = 0.004, and externalizing symptoms, F(2,202) = 4.663, p = 0.010. Smaller N200 amplitudes were observed on No-Go trials for those with higher PLEs, F(1,101) = 6.075, p = 0.020; no relationship was observed for internalizing or externalizing symptoms.

Long-term follow-up demonstrates for the first time a specific deficit in inhibitory control behaviorally and electrophysiology, for individuals who later report more PLEs. Decreases in task performance under frustration induction indicated risk for internalizing and externalizing symptoms. These findings suggest that pathophysiological mechanisms for psychosis are relevant and discriminable in early childhood, and further, suggest an identifiable and potentially modifiable target for early intervention.

Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement.

Children and adolescents aged 6–17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses.

Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control.

Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.

Long-term efficacy of brief psychotherapies for refugees in low-resource settings is insufficiently understood. Integrative adapt therapy (IAT) is a scalable treatment addressing refugee-specific psychosocial challenges.

We report 12-month post-treatment data from a single-blind, active-controlled trial (October 2017–August 2019) where 327 Myanmar refugees in Malaysia were assigned to either six sessions of IAT (n = 164) or cognitive behavioral treatment (CBT) (n = 163). Primary outcomes were posttraumatic stress disorder (PTSD), depression, anxiety, and persistent complex bereavement disorder (PCBD) symptom scores at treatment end and 12-month post-treatment. Secondary outcome was functional impairment.

282 (86.2%) participants were retained at 12-month follow-up. For both groups, large treatment effects for common mental disorders (CMD) symptoms were maintained at 12-month post-treatment compared to baseline (d = 0.75–1.13). Although participants in IAT had greater symptom reductions and larger effect sizes than CBT participants for all CMDs at treatment end, there were no significant differences between treatment arms at 12-month post-treatment for PTSD [mean difference: −0.9, 95% CI (−2.5 to 0.6), p = 0.25], depression [mean difference: 0.1, 95% CI (−0.6 to 0.7), p = 0.89), anxiety [mean difference: −0.4, 95% CI (−1.4 to 0.6), p = 0.46], and PCBD [mean difference: −0.6, 95% CI (−3.1 to 1.9), p = 0.65]. CBT participants showed greater improvement in functioning than IAT participants at 12-month post-treatment [mean difference: −2.5, 95% CI (−4.7 to −0.3], p = 0.03]. No adverse effects were recorded for either therapy.

Both IAT and CBT showed sustained treatment gains for CMD symptoms amongst refugees over the 12-month period.

Self-harm in pregnancy or the year after birth (‘perinatal self-harm’) is clinically important, yet prevalence rates, temporal trends and risk factors are unclear.

A cohort study of 679 881 mothers (1 172 191 pregnancies) was conducted using Danish population register data-linkage. Hospital treatment for self-harm during pregnancy and the postnatal period (12 months after live delivery) were primary outcomes. Prevalence rates 1997–2015, in women with and without psychiatric history, were calculated. Cox regression was used to identify risk factors.

Prevalence rates of self-harm were, in pregnancy, 32.2 (95% CI 28.9–35.4)/100 000 deliveries and, postnatally, 63.3 (95% CI 58.8–67.9)/100 000 deliveries. Prevalence rates of perinatal self-harm in women without a psychiatric history remained stable but declined among women with a psychiatric history. Risk factors for perinatal self-harm: younger age, non-Danish birth, prior self-harm, psychiatric history and parental psychiatric history. Additional risk factors for postnatal self-harm: multiparity and preterm birth. Of psychiatric conditions, personality disorder was most strongly associated with pregnancy self-harm (aHR 3.15, 95% CI 1.68–5.89); psychosis was most strongly associated with postnatal self-harm (aHR 6.36, 95% CI 4.30–9.41). For psychiatric disorders, aHRs were higher postnatally, particularly for psychotic and mood disorders.

Perinatal self-harm is more common in women with pre-existing psychiatric history and declined between 1997 and 2015, although not among women without pre-existing history. Our results suggest it may be a consequence of adversity and psychopathology, so preventative intervention research should consider both social and psychological determinants among women with and without psychiatric history.

Observational studies suggest a correlation between post-traumatic stress disorder (PTSD) and gastrointestinal tract (GIT) disorders. However, the genetic overlap, causal relationships, and underlining mechanisms between PTSD and GIT disorders were absent.

We obtained genome-wide association study statistics for PTSD (23 212 cases, 151 447 controls), peptic ulcer disease (PUD; 16 666 cases, 439 661 controls), gastroesophageal reflux disease (GORD; 54 854 cases, 401 473 controls), PUD and/or GORD and/or medications (PGM; 90 175 cases, 366 152 controls), irritable bowel syndrome (IBS; 28 518 cases, 426 803 controls), and inflammatory bowel disease (IBD; 7045 cases, 449 282 controls). We quantified genetic correlations, identified pleiotropic loci, and performed multi-marker analysis of genomic annotation, fast gene-based association analysis, transcriptome-wide association study analysis, and bidirectional Mendelian randomization analysis.

PTSD globally correlates with PUD (rg = 0.526, p = 9.355 × 10−7), GORD (rg = 0.398, p = 5.223 × 10−9), PGM (rg = 0.524, p = 1.251 × 10−15), and IBS (rg = 0.419, p = 8.825 × 10−6). Cross-trait meta-analyses identify seven genome-wide significant loci between PTSD and PGM (rs13107325, rs1632855, rs1800628, rs2188100, rs3129953, rs6973700, and rs73154693); three between PTSD and GORD (rs13107325, rs1632855, and rs3132450); one between PTSD and IBS/IBD (rs4937872 and rs114969413, respectively). Proximal pleiotropic genes are mainly enriched in immune response regulatory pathways, and in brain, digestive, and immune systems. Gene-level analyses identify five candidates: ABT1, BTN3A2, HIST1H3J, ZKSCAN4, and ZKSCAN8. We found significant causal effects of GORD, PGM, IBS, and IBD on PTSD. We observed no reverse causality of PTSD with GIT disorders, except for GORD.

PTSD and GIT disorders share common genetic architectures. Our work offers insights into the biological mechanisms, and provides genetic basis for translational research studies.

The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes.

A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63).

Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months.

The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

The adolescent brain may be susceptible to the influences of illicit drug use. While compensatory network reorganization is a unique developmental characteristic that may restore several brain disorders, its association with methamphetamine (MA) use-induced damage during adolescence is unclear.

Using independent component (IC) analysis on structural magnetic resonance imaging data, spatially ICs described as morphometric networks were extracted to examine the effects of MA use on gray matter (GM) volumes and network module connectivity in adolescents (51 MA users v. 60 controls) and adults (54 MA users v. 60 controls).

MA use was related to significant GM volume reductions in the default mode, cognitive control, salience, limbic, sensory and visual network modules in adolescents. GM volumes were also reduced in the limbic and visual network modules of the adult MA group as compared to the adult control group. Differential patterns of structural connectivity between the basal ganglia (BG) and network modules were found between the adolescent and adult MA groups. Specifically, adult MA users exhibited significantly reduced connectivity of the BG with the default network modules compared to control adults, while adolescent MA users, despite the greater extent of network GM volume reductions, did not show alterations in network connectivity relative to control adolescents.

Our findings suggest the potential of compensatory network reorganization in adolescent brains in response to MA use. The developmental characteristic to compensate for MA-induced brain damage can be considered as an age-specific therapeutic target for adolescent MA users.