Adolescence is a key developmental period associated with an increased risk of experiencing cannabis-related problems. Identifying modifiable risk factors prior to the onset of cannabis use could help inform preventative interventions.

Analysis nested within a UK prospective birth cohort study, the Avon Longitudinal Study of Parents and Children. Participants (n = 6,049) provided data on cannabis use and symptoms of cannabis problems using the Cannabis Abuse Screening Test at two or more time points between the ages of 15–24 years. Risk factors included internalizing and externalizing disorders assessed at age 10 years, and cognitive function assessed at age 8 years via short-term memory, emotion recognition, divided attention, and listening comprehension.

Participants were mostly female (59.1%) and white (95.73%). Five patterns of adolescent cannabis use problems were identified using longitudinal latent class analysis: stable-no problems (n = 5,157, 85%), early-onset high (n = 104, 2%), late-onset high (n = 153, 3%), early onset low (n = 348, 6%), and late-onset low (n = 287, 5%). In adjusted models, externalizing disorders were associated with early-onset high [RR, 95% CI: 2.82 (1.72, 4.63)], late-onset high [RR, 95% CI: 1.62 (1.02, 2.57)], and early-onset low [RR, 95% CI: 1.82 (1.30, 2.55)] compared to the stable-no problems class. Internalizing disorders were associated with late-onset low only [RR, 95% CI: .50 (.26, .96)], and short-term memory with late-onset high only [RR, 95% CI: 1.09 (1.01, 1.18) compared to the stable-no problems class.

Childhood externalizing disorders were consistently associated with increased risk of problematic patterns of cannabis use over adolescence, particularly early-onset and high levels of problems.

Observational studies consistently report associations between tobacco use, cannabis use and mental illness. However, the extent to which this association reflects an increased risk of new-onset mental illness is unclear and may be biased by unmeasured confounding.

A systematic review and meta-analysis (CRD42021243903). Electronic databases were searched until November 2022. Longitudinal studies in general population samples assessing tobacco and/or cannabis use and reporting the association (e.g. risk ratio [RR]) with incident anxiety, mood, or psychotic disorders were included. Estimates were combined using random-effects meta-analyses. Bias was explored using a modified Newcastle–Ottawa Scale, confounder matrix, E-values, and Doi plots.

Seventy-five studies were included. Tobacco use was associated with mood disorders (K = 43; RR: 1.39, 95% confidence interval [CI] 1.30–1.47), but not anxiety disorders (K = 7; RR: 1.21, 95% CI 0.87–1.68) and evidence for psychotic disorders was influenced by treatment of outliers (K = 4, RR: 3.45, 95% CI 2.63–4.53; K = 5, RR: 2.06, 95% CI 0.98–4.29). Cannabis use was associated with psychotic disorders (K = 4; RR: 3.19, 95% CI 2.07–4.90), but not mood (K = 7; RR: 1.31, 95% CI 0.92–1.86) or anxiety disorders (K = 7; RR: 1.10, 95% CI 0.99–1.22). Confounder matrices and E-values suggested potential overestimation of effects. Only 27% of studies were rated as high quality.

Both substances were associated with psychotic disorders and tobacco use was associated with mood disorders. There was no clear evidence of an association between cannabis use and mood or anxiety disorders. Limited high-quality studies underscore the need for future research using robust causal inference approaches (e.g. evidence triangulation).

Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.

We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls).

Medication-free participants with MDD (n = 192: 110 female, 81 male, 1 other) and controls (n = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (−1019, −1007, −681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF.

Recent stress correlated positively with blood monocyte methylation at the −681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the −1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD.

These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.

A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.

Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).

Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.

To conduct a contemporary detailed assessment of outpatient antibiotic prescribing and outcomes for positive urine cultures in a mixed-sex cohort.

Multicenter retrospective cohort review.

The study was conducted using data from 31 Veterans’ Affairs medical centers.

Outpatient adults with positive urine cultures.

From 2016 to 2019, data were extracted through a nationwide database and manual chart review. Positive urine cultures were reviewed at the chart, clinician, and aggregate levels. Cases were classified as cystitis, pyelonephritis, or asymptomatic bacteriuria (ASB) based upon documented signs and symptoms. Preferred therapy definitions were applied for subdiagnoses: ASB (no antibiotics), cystitis (trimethoprim-sulfamethoxazole, nitrofurantoin, β-lactams), and pyelonephritis (trimethoprim-sulfamethoxazole, fluoroquinolone). Outcomes included 30-day clinical failure or hospitalization. Odds ratios for outcomes between treatments were estimated using logistic regression.

Of 3,255 cases reviewed, ASB was identified in 1,628 cases (50%), cystitis was identified in 1,156 cases (36%), and pyelonephritis was identified in 471 cases (15%). Of all 2,831 cases, 1,298 (46%) received preferred therapy selection and duration for cases where it could be defined. The most common antibiotic class prescribed was a fluoroquinolone (34%). Patients prescribed preferred therapy had lower odds of clinical failure: preferred (8%) versus nonpreferred (10%) (unadjusted OR, 0.74; 95% confidence interval [CI], 0.58–0.95; P = .018). They also had lower odds of 30-day hospitalization: preferred therapy (3%) versus nonpreferred therapy (5%) (unadjusted OR, 0.55; 95% CI, 0.37–0.81; P = .002). Odds of clinical treatment failure or hospitalization was higher for β-lactams relative to ciprofloxacin (unadjusted OR, 1.89; 95% CI, 1.23–2.90; P = .002).

Clinicians prescribed preferred therapy 46% of the time. Those prescribed preferred therapy had lower odds of clinical failure and of being hospitalized.

Increasing numbers of adolescents seek help for gender-identity questions. Consequently, requests for medical treatments, such as puberty suppression, are growing. However, studies investigating the neurobiological substrate of gender incongruence (when birth-assigned sex and gender identity do not align) are scarce, and knowledge about the effects of puberty suppression on the developing brain of transgender youth is limited.

Here we cross-sectionally investigated sex and gender differences in regional fractional anisotropy (FA) as measured by diffusion MR imaging, and the impact of puberty on alterations in the white-matter organization of 35 treatment-naive prepubertal children and 41 adolescents with gender incongruence, receiving puberty suppression. The transgender groups were compared with 79 age-matched, treatment-naive cisgender (when sex and gender align) peers.

We found that transgender adolescents had lower FA in the bilateral inferior fronto-occipital fasciculus (IFOF), forceps major and corpus callosum than cisgender peers. In addition, average FA values of the right IFOF correlated negatively with adolescents' cumulative dosage of puberty suppressants received. Of note, prepubertal children also showed significant FA group differences in, again, the right IFOF and left cortico-spinal tract, but with the reverse pattern (transgender > cisgender) than was seen in adolescents.

Importantly, our results of lower FA (indexing less longitudinal organization, fiber coherence, and myelination) in the IFOF of gender-incongruent adolescents replicate prior findings in transgender adults, suggesting a salient neural correlate of gender incongruence. Findings highlight the complexity with which (pubertal) sex hormones impact white-matter development and add important insight into the neurobiological substrate associated with gender incongruence.

Prevention programs that are ‘transdiagnostic’ may be more cost-effective and beneficial, in terms of reducing levels of psychopathology in the general population, than those focused on a specific disorder. This randomized controlled study evaluated the efficacy of one such intervention program called Resilience Training (RT).

College students who reported mildly elevated depressive or subclinical psychotic symptoms (‘psychotic experiences' (PEs)) (n = 107) were randomized to receiving RT (n = 54) or to a waitlist control condition (n = 53). RT consists of a four-session intervention focused on improving resilience through the acquisition of mindfulness, self-compassion, and mentalization skills. Measures of symptoms and these resilience-enhancing skills were collected before and after the 4-week RT/waitlist period, with a follow-up assessment 12-months later.

Compared to the waitlist control group, RT participants reported significantly greater reductions in PEs, distress associated with PEs, depression, and anxiety, as well as significantly greater improvements in resilience, mindfulness, self-compassion, and positive affect, following the 4-week RT/waitlist period (all p < 0.03). Moreover, improvements in resilience-promoting skills were significantly correlated with symptom reductions (all p < 0.05). Lastly, the RT-related reductions in PEs and associated distress were maintained at the 12-month follow-up assessment.

RT is a brief, group-based intervention associated with improved resilience and reduced symptoms of psychopathology, with sustained effects on PEs, in transdiagnostically at-risk young adults. Follow-up studies can further assess the efficacy of RT relative to other interventions and test whether it can reduce the likelihood of developing a serious mental illness.

It has not yet been determined if the commonly reported cannabis–psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders.

We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort.

PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects.

These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis–psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

To test the effectiveness of a social network intervention (SNI) to improve children’s healthy drinking behaviours.

A three-arm cluster randomised control trial design was used. In the SNI, a subset of children were selected and trained as ‘influence agents’ to promote water consumption–as an alternative to sugar-sweetened beverages (SSB)–among their peers. In the active control condition, all children were simultaneously exposed to the benefits of water consumption. The control condition received no intervention.

Eleven schools in the Netherlands.

Four hundred and fifty-one children (Mage = 10·74, SDage = 0·97; 50·8 % girls).

Structural path models showed that children exposed to the SNI consumed 0·20 less SSB per day compared to those in the control condition (β = 0·25, P = 0·035). There was a trend showing that children exposed to the SNI consumed 0·17 less SSB per day than those in the active control condition (β = 0·20, P = 0·061). No differences were found between conditions for water consumption. However, the moderation effects of descriptive norms (β = –0·12, P = 0·028) and injunctive norms (β = 0·11–0·14, both P = 0·050) indicated that norms are more strongly linked to water consumption in the SNI condition compared to the active control and control conditions.

These findings suggest that a SNI promoting healthy drinking behaviours may prevent children from consuming more SSB. Moreover, for water consumption, the prevailing social norms in the context play an important role in mitigating the effectiveness of the SNI.