Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

KarXT combines the M1/M4 preferring muscarinic receptor agonist xanomeline and the peripherally restricted anticholinergic trospium. In the phase 2 EMERGENT-1 study, KarXT met the primary endpoint of a significant reduction in Positive and Negative Syndrome Scale (PANSS) total score through week 5 vs placebo, improved other key secondary efficacy measures, and was generally well tolerated.

EMERGENT-2 was a phase 3, randomized, double-blind, placebo-controlled, 5-week trial of KarXT in acutely psychotic patients with schizophrenia in the inpatient setting. Eligible patients were randomized 1:1 to KarXT or matched placebo. Dosing of KarXT (mg xanomeline/mg trospium) started at 50 mg/20 mg BID and increased to a maximum of 125 mg/30 mg BID. The primary efficacy endpoint was change from baseline to week 5 in PANSS total score. Key secondary endpoints included change from baseline to week 5 in PANSS positive subscale, PANSS negative subscale, and PANSS negative Marder factor scores compared with placebo. Efficacy analyses were performed using the modified intent-to-treat population (patients with ≥1 dose of study medication, a baseline PANSS assessment, and ≥1 postbaseline PANSS assessment). All patients receiving ≥1 dose of study drug were included in safety analyses.

252 US patients were enrolled. KarXT demonstrated a statistically significant and clinically meaningful 9.6-point reduction from baseline to week 5 (effect size=0.61) in PANSS total score vs placebo (p<0.0001); a significant improvement in PANSS total score was demonstrated starting at week 2 (first postbaseline rating) and continued through the study end. KarXT also met key secondary endpoints. Results at week 5 included a 2.9-point reduction in PANSS positive subscale score with KarXT vs placebo (p<0.0001), a 1.8-point reduction in PANSS negative subscale score with KarXT vs placebo (p=0.0055), and a 2.2-point reduction in PANSS negative Marder factor score with KarXT vs placebo (p=0.0022). KarXT was generally well tolerated. Overall discontinuation rates were similar with KarXT (25%) and placebo (21%). The overall treatment-emergent adverse events (TEAEs) rate for KarXT and placebo was 75% and 58%, respectively. Discontinuation rates related to TEAEs were similar between KarXT (7%) and placebo (6%). Rates of serious TEAEs were similar with KarXT and placebo (2%, each group); no serious TEAEs were determined to be drug related. The most common TEAEs (≥5%) with KarXT were all mild to moderate in severity and included constipation, dyspepsia, nausea, vomiting, headache, blood pressure increases, dizziness, gastroesophageal reflux disease, abdominal discomfort, and diarrhea. KarXT was not associated with sedation/somnolence, weight gain, and extrapyramidal symptoms.

KarXT has the potential to be the first in a new class of treatments for patients with schizophrenia and a promising alternative to postsynaptic dopamine D2 receptor antagonists.

Karuna Therapeutics, Inc.

Predeath grief conceptualizes complex feelings of loss experienced for someone who is still living and is linked to poor emotional well-being. The Road Less Travelled program aimed to help carers of people with rarer dementias identify and process predeath grief. This study evaluated the feasibility, acceptability, and preliminary effectiveness of this program.

Pre–post interventional mixed methods study.

Online videoconference group program for carers across the UK held in 2021.

Nine family carers of someone living with a rare form of dementia. Eight were female and one male (mean age 58) with two facilitators.

The Road Less Travelled is an online, facilitated, group-based program that aims to help carers of people with rarer dementias to explore and accept feelings of grief and loss. It involved six fortnightly 2-hour sessions.

We collected measures for a range of well-being outcomes at baseline (T1), post-intervention (T2), and 3 months post-intervention (T3). We conducted interviews with participants and facilitators at T2.

Participant attendance was 98% across all sessions. Findings from the semistructured interviews supported the acceptability of the program and identified improvements in carer well-being. Trends in the outcome measures suggested an improvement in quality of life and a reduction in depression.

The program was feasible to conduct and acceptable to participants. Qualitative reports and high attendance suggest perceived benefits to carers, including increased acceptance of grief, and support the need for a larger-scale pilot study to determine effectiveness.

For decades, quantitative psychologists have recommended that authors report effect sizes to convey the magnitude and potential clinical relevance of statistical associations. However, fewer than one-third of neuropsychology articles published in the early 2000s reported effect sizes. This study re-examines the frequency and extent of effect size reporting in neuropsychology journal articles by manuscript section and over time.

A sample of 326 empirical articles were drawn from 36 randomly selected issues of six neuropsychology journals at 5-year intervals between 1995 and 2020. Four raters used a novel, reliable coding system to quantify the extent to which effect sizes were included in the major sections of all 326 articles.

Findings showed medium-to-large increases in effect size reporting in the Methods and Results sections of neuropsychology journal articles that plateaued in recent years; however, there were only very small and nonsignificant changes in effect size reporting in the Abstract, Introduction, and Discussion sections.

Authors in neuropsychology journals have markedly improved their effect size reporting in the core Methods and Results sections, but are still unlikely to consider these valuable metrics when motivating their study hypotheses and interpreting the conceptual and clinical implications of their findings. Recommendations are provided to encourage more widespread integration of effect sizes in neuropsychological research.

The internet serves an increasingly critical role in how older adults manage their personal health. Electronic patient portals, for example, provide a centralized platform for older adults to access lab results, manage prescriptions and appointments, and communicate with providers. This study examined whether neurocognition mediates the effect of older age on electronic patient portal navigation.

Forty-nine younger (18–35 years) and 35 older adults (50–75 years) completed the Test of Online Health Records Navigation (TOHRN), which is an experimenter-controlled website on which participants were asked to log-in, review laboratory results, read provider messages, and schedule an appointment. Participants also completed a neuropsychological battery, self-report questionnaires, and measures of health literacy and functional capacity.

Mediation analyses revealed a significant indirect effect of older age on lower TOHRN accuracy, which was fully mediated by the total cognitive composite.

Findings indicate that neurocognition may help explain some of the variance in age-related difficulties navigating electronic patient health portals. Future studies might examine the possible benefits of both structural (e.g., human factors web design enhancement) and individual (e.g., training and compensation) cognitive supports to improve the navigability of electronic patient health portals for older adults.

People living with HIV (PLWH) often experience deficits in the strategic/executive aspects of prospective memory (PM) that can interfere with instrumental activities of daily living. This study used a conceptual replication design to determine whether cognitive intraindividual variability, as measured by dispersion (IIV-dispersion), contributes to PM performance and symptoms among PLWH.

Study 1 included 367 PLWH who completed a comprehensive clinical neuropsychological test battery, the Memory for Intentions Test (MIsT), and the Prospective and Retrospective Memory Questionnaire (PRMQ). Study 2 included 79 older PLWH who completed the Cogstate cognitive battery, the Cambridge Prospective Memory Test (CAMPROMPT), an experimental measure of time-based PM, and the PRMQ. In both studies, a mean-adjusted coefficient of variation was derived to measure IIV-dispersion using normative T-scores from the cognitive battery.

Higher IIV-dispersion was significantly associated with lower time-based PM performance at small-to-medium effect sizes in both studies (mean r s  = −0.30). The relationship between IIV-dispersion and event-based PM performance was comparably small in magnitude in both studies (r s  = −0.19, −0.20), but it was only statistically significant in Study 1. IIV-dispersion showed very small, nonsignificant relationships with self-reported PM symptoms in both samples (r s < 0.10).

Extending prior work in healthy adults, these findings suggest that variability in performance across a cognitive battery contributes to laboratory-based PM accuracy, but not perceived PM symptoms, among PLWH. Future studies might examine whether daily fluctuations in cognition or other aspects of IIV (e.g., inconsistency) play a role in PM failures in everyday life.