Trait dissociation has not been examined from a structural human brain mapping perspective in healthy adults or children. Non-pathological dissociation shares some features with daydreaming and mind-wandering, but also involves subtle disruptions in affect and autobiographical memory.

To identify neurostructural biomarkers of trait dissociation in healthy children.

Typically developing 9- to 15-year-olds (n = 180) without psychological or behavioural disorders were enrolled in the Developmental Chronnecto-Genomics (DevCoG) study of healthy brain development and completed psychological assessments of trauma exposure and dissociation, along with a structural T1-weighted magnetic resonance imaging. We conducted univariate ANCOVA generalised linear models for each region of the default mode network examining the effects of trait dissociation, including scanner site, age, gender and trauma as covariates and correcting for multiple comparison.

We found that the precuneus was significantly larger in children with higher levels of trait dissociation but this was not related to trauma exposure. The inferior parietal volume was smaller in children with higher levels of trauma but was not related to dissociation. No other regions of interest, including frontal and limbic structures, were significantly related to trait dissociation even before multiple comparison correction.

Trait dissociation reflects subtle cognitive disruptions worthy of study in healthy people and warrants study as a potential risk factor for psychopathology. This neurostructural study of trait dissociation in healthy children identified the precuneus as an essential brain region to consider in future dissociation research.

A combination of olanzapine and samidorphan (OLZ/SAM) that provides the efficacy of olanzapine while mitigating weight gain was recently approved by the FDA for the treatment of schizophrenia and bipolar I disorder. To improve communication of the OLZ/SAM benefit-risk profile, a structured framework was utilized.

The Benefit-Risk Action Team framework was used to evaluate OLZ/SAM, with analyses completed for each pivotal study. ENLIGHTEN-1 evaluated antipsychotic efficacy and safety. ENLIGHTEN-2 evaluated the weight profile of OLZ/SAM vs olanzapine. Benefit-risk outcomes were selected based on study outcome parameters, known risks of olanzapine and samidorphan, and public health importance. A subset of opioid antagonist risks was not assessed due to clinical trial exclusions; however, they were factored into the overall evaluation. Risk differences and confidence intervals were analyzed.

In ENLIGHTEN-1, OLZ/SAM had a lower risk of psychiatric discontinuation and nonresponse to treatment compared with placebo; higher risks of hyperprolactinemia, weight gain (≥7%), sedation, and worsening of fasting triglycerides and glucose, and no difference for fasting total and LDL cholesterol, neutropenia, orthostatic hypotension, and movement disorders. In ENLIGHTEN-2, OLZ/SAM had reduced risks of weight gain and waist circumference increase compared to olanzapine along with similar risks of relapse and psychiatric discontinuation and no difference in metabolic worsening, neutropenia, hyperprolactinemia, orthostatic hypotension, sedation, and movement disorders.

Based on this assessment, OLZ/SAM has comparable efficacy and a safety profile consistent with olanzapine, with reduced weight gain. A structured approach to assessing the benefit-risk profile of a product facilitates transparent evaluation and communication.

Alkermes, Inc.

Patients with single ventricle heart disease are living into adulthood due to medical and surgical advancements but have significant physical comorbidities and an increased risk for psychological comorbidities compared to healthy subjects or those with other CHD diagnoses. This study aimed to systematically review psychological functioning in paediatric single ventricle heart disease.

Literature was searched using PubMed, Embase, PsycInfo, CINAHL Complete and Scopus. Peer-reviewed articles that included patients ages 0–25 years with single ventricle heart disease, and quantitative measures of psychological outcomes were included. Meta-analysis using a fixed-effect model was conducted for internalising and externalising t-scores, utilised by the Achenbach Child Behavior Checklist.

Twenty-nine records met the criteria for inclusion. 13/24 studies demonstrated increased risk for internalising disorders, such as anxiety/depression; 16/22 studies demonstrated risk for externalising disorders, such as attention or behavioural problems. Meta-analysis of four studies revealed that paediatric single ventricle heart disease patients had no significant difference in internalising and externalising t-scores compared to normative values.

The current review demonstrates the need for further studies to better understand psychological functioning in patients with single ventricle heart disease, with a majority of studies showing increased risk for psychological problems despite no difference seen in a small meta-analysis. This summary of the literature underscores the need for regular psychological screening, earlier intervention and integrated mental health therapies in paediatric single ventricle heart disease.