Alcohol, nicotine, and cannabis use problems have a poorer prognosis when they co-occur with internalizing distress (INT). One hypothesis to account for the association between INT and alcohol and substance use problems (SUP) is that people engage in heavy substance use to reduce aversive affective states characteristic of INT (e.g. affective reinforcement). Whether INT operates as a cause or a shared liability with SUP (e.g. shared genetic and environmental risk) over and above an alternative cause (e.g. externalizing problems, EXT) remains unclear.

We tested INT as a developmental pathway for SUP by applying a prospective, co-twin control approach to the Minnesota Twin and Family Study sample (n = 1881 twin pairs). A multilevel modeling framework was used to estimate the between-twin pair effect and the within-twin pair effect of INT over and above EXT on separate SUP outcomes (i.e. alcohol, nicotine, and cannabis use problems) from adolescence (age 14) to young adulthood (age 29).

We failed to detect any non-familial causal effects of INT on SUPs. Instead, their associations were due to common genetic and shared environmental influences. In contrast, EXT had consistent non-familial causal influences on alcohol and cannabis use in adolescence and young adulthood.

The link between INT and SUPs is primarily due to shared, familial influences while EXT likely serves as a unique determinant, with elevated EXT increasing selection into situations that pose SUP risk (e.g. peer environments that normalize and sustain heavy use) over and above common genetic influences.

This study investigated functional connectivity in the default mode, central executive, dorsal attention, and salience networks (SN) and its relation to executive function in youth with traumatic brain injury.

Twenty-three youth with traumatic brain injury (11 with moderate-to-severe injury (6 male, mage = 11.78 ± 2.68 years, mtimesinceinjury = 3.71 ± 2.43 years) and 12 with complicated-mild injury (9 male, mage = 12.59 ± 1.99 years, mtimesinceinjury = 4.55 ± 1.59 years) and 17 youth with orthopedic injury (11 male, mage = 11.75 ± 2.12 years, mtimesinceinjury = 3.95 ± 1.79 years)) completed resting-state functional magnetic resonance imaging and a parent rated their child’s executive function.

We found group differences in the strength of connectivity among four regions in the default mode network (DMN) and two regions of the SN, ps < .05, Eta2 = .151–.229. The orthopedic injury group demonstrated significant negative between-network connectivity, while brain injury groups had negligible negative or, in some cases, positive between-network associations. Groups did not differ on parent ratings of executive function, as all groups fell above the normative mean, reflecting poorer than expected everyday executive behavior. Attenuation of typical negative between-network association between the posterior cingulate in the DMN and two regions of the salience network was associated with worse parent-rated executive behavior (rs = .291–.317, ps < .05).

Findings illustrate the implications of disrupted downregulation of the default mode network by the SN following pediatric brain injury. They also demonstrate how disruption in functional connectivity may underlie poor executive function after childhood traumatic brain injury.

The National Institutes of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) is a validated laptop-based battery of executive functioning tests. A modified tablet version of the EXAMINER was developed on the UCSF Tablet-based Cognitive Assessment Tool (TabCAT-EXAMINER). Here we describe the battery and investigate the reliability and validity of a composite score.

A diagnostically heterogeneous sample of 2135 individuals (mean age = 65.58, SD = 16.07), including controls and participants with a variety of neurodegenerative syndromes, completed the TabCAT-EXAMINER. A composite score was developed using confirmatory factor analysis and item response theory. Validity was evaluated via linear regressions that tested associations with neuropsychological tests, demographics, clinical diagnosis, and disease severity. Replicability of cross-sectional results was tested in a separate sample of participants (n = 342) recruited from a frontotemporal dementia study. As this separate sample also collected longitudinal TabCAT-EXAMINER measures, we additionally assessed test-retest reliability and associations between baseline disease severity and changes in TabCAT-EXAMINER scores.

The TabCAT-EXAMINER score was normally distributed, demonstrated high test-retest reliability, and was associated in the expected directions with independent tests of executive functioning, demographics, disease severity, and diagnosis. Greater baseline disease severity was associated with more rapid longitudinal TabCAT-EXAMINER decline.

The TabCAT-EXAMINER is a tablet-based executive functioning battery developed for observational research and clinical trials. Performance can be summarized as a single composite score, and results of this study support its reliability and validity in cognitive aging and neurodegenerative disease cohorts.

Agitation and aggression occur in up to half of people living with dementia over the course of the disease. Although non-pharmacological interventions are used as first-line treatment strategies, antipsychotics may be indicated in severe cases. A major adverse effect of antipsychotics in dementia is stroke; the mechanism of action of atypical antipsychotic risperidone has been linked to cardiovascular disease (CVD) biological pathways in preclinical studies.

To evaluate the risk of stroke associated with risperidone across different patient subgroups defined by stroke and CVD history.

Anonymised primary care data from the UK-based Clinical Practice Research Datalink were used to identify individuals diagnosed with dementia after the age of 65 years between 2004 and 2023. Risk of stroke over 1 year was compared between individuals initiating risperidone and propensity-score-matched controls across subgroups with and without history of stroke and any CVD.

In the overall cohort (28 403 risperidone users and 136 324 mtatched controls), risperidone was associated with increased risk of stroke (adjusted hazard ratio: 1.28; 95% CI: 1.20–1.37). In the risperidone user group, the incidence rate of stroke was substantially higher in those with a prior history of stroke (incidence rate: 222 per 1000 person-years) and CVD (incidence rate: 94.1 per 1000 person-years) than in the overall cohort (incidence rate: 53.3 per 1000 person-years). Relative risks related to risperidone were similar across all CVD and stroke subgroup comparisons (hazard ratios between 1.23 and 1.44).

People with dementia with a prior history of CVD are at a significant increased risk of stroke, and risperidone further exacerbates this risk. Moreover, risperidone increases risk of stroke in patients without a prior history of CVD. This quantification of stroke risk across subgroups with and without history of CVD may help with communication of risk and aid more judicious prescribing.

Stroke is a devastating disease, but the disability due to stroke can be avoided or reduced through timely access to treatment and care. This study surveyed all designated stroke centres across Canada to better understand the national acute stroke treatment landscape.

An online survey designed to obtain information on each stroke hospital’s designation level, most responsible physician for acute reperfusion treatment decision-making, availability of stroke coordinators, stroke research activity and level of transition to tenecteplase for intravenous thrombolysis was distributed to stroke centres in Canada via a network of stroke administrators and physician leads from each province. The survey responses were collated and audited for completeness and accuracy, and final responses were analysed using descriptive statistics and graphical distributions as appropriate.

There are a total of 205 designated stroke centres in Canada; 13.2% (n = 27) are endovascular thrombectomy (EVT) capable (n = 26 provide 24/7 access), while the rest provide thrombolysis alone, comprising primary stroke centres (n = 70, 34.1%) and thrombolysis-ready centres (n = 108, 52.7%). The presence of neurologists in the thrombolysis-capable centres is minimal, although compensated for by a high use of telestroke in making thrombolysis decisions. Participation rate in stroke clinical trials was heavily restricted to the EVT-capable centres. There were variabilities among provinces in the availability of stroke coordinators.

The acute ischaemic stroke landscape in Canada is variable between provinces, presenting unique opportunities for collaboration. There is a need for greater availability of stroke neurologists and stroke coordinators and for diversifying site participation in clinical trials.

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.

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.