Impulsivity is among the strongest correlates of substance involvement (i.e. a broad continuum of substance-related behaviors), and distinct domains (e.g. sensation seeking [SS] and urgency) are differentially correlated, phenotypically and genetically, with unique substance involvement stages. Examining whether polygenic influences for distinct impulsivity domains are differentially predictive of early substance use initiation – a major risk factor for later problematic use – may improve our understanding of the role of impulsivity in addiction etiology.

Data collected from participants of genetically inferred European ancestry enrolled in the Adolescent Brain Cognitive Development StudySM (n = 4,808) were used to estimate associations between polygenic scores (PGSs) for UPPS-P impulsivity domains (i.e. SS, lack of premeditation [LPREMED]/perseverance [LPERSEV], and negative/positive urgency [NU/PU]) and substance (i.e. any, alcohol, nicotine, and cannabis) use initiation by age 15 years. Mediation models examined whether child impulsivity (ages 9–11 years) mediated links between PGSs and substance use initiation.

SS-PGS was significantly associated with any substance and alcohol use initiation (odds ratio [ORs] > 1.10, psFDR < 0.05). LPERSEV and NU/PU PGSs were nominally associated with alcohol and nicotine use initiation, respectively (ORs > 1.06, ps < 0.05, psFDR > 0.05). No significant associations were observed for LPREMED-PGS or cannabis use initiation. Measured impulsivity domains accounted for 5–9% of associations between UPPS-P PGSs and substance use initiation.

Genetic influences for distinct impulsivity domains have differential associations with early substance use initiation, with SS showing the most robust associations, highlighting valuable etiological insight into the earliest stages of substance involvement that may be leveraged to improve prevention and intervention strategies.

Loneliness is associated with several physical and mental health problems, yet its costs to the healthcare system remain unclear.

The current study aimed to review literature on the health and social care impacts of loneliness, and review economic evaluations of loneliness interventions.

We conducted a systematic review of studies published from 2008 to April 2025 by searching five bibliographic databases, grey literature and reference lists of systematic reviews. Studies estimating health and social care cost/expenditure, and on health resource utilisation, were included to assess the impact of loneliness on the health system. Return on investment, social return on investment and cost-effectiveness evaluations were included to assess the economic impact of loneliness interventions. We conducted quality appraisal and narrative synthesis of results.

We included 53 studies. Eight estimated the healthcare cost/expenditure of loneliness, 33 reported healthcare resource use and 19 were economic evaluations of interventions. Findings relating to the cost/expenditure of loneliness and service use were inconsistent: some studies reported excess costs/expenditure and service use, whereas others found lower costs/expenditure and service use. Economic evaluation studies indicated that loneliness interventions can be cost-effective, but were not consistently cost-saving or effective in reducing loneliness.

Findings on the impact of loneliness on the healthcare system and economic evaluations of loneliness interventions were varied. Therefore, we cannot derive confident conclusions from this review. To address evidence gaps, future research relating to social care, younger populations, direct healthcare costs of loneliness and randomised controlled trials with long-term follow-ups should be prioritised.

Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

Although cognitive remediation (CR) improves cognition and functioning, the key features that promote or inhibit its effectiveness, especially between cognitive domains, remain unknown. Discovering these key features will help to develop CR for more impact.

To identify interrelations between cognition, symptoms, and functioning, using a novel network analysis approach and how CR affects these recovery outcomes.

A secondary analysis of randomized controlled trial data (N = 165) of CR in early psychosis. Regularized partial correlation networks were estimated, including symptoms, cognition, and functioning, for pre-, post-treatment, and change over time. Pre- and post-CR networks were compared on global strength, structure, edge invariance, and centrality invariance.

Cognition, negative, and positive symptoms were separable constructs, with symptoms showing independent relationships with cognition. Negative symptoms were central to the CR networks and most strongly associated with change in functioning. Verbal and visual learning improvement showed independent relationships to improved social functioning and negative symptoms. Only visual learning improvement was positively associated with personal goal achievement. Pre- and post-CR networks did not differ in structure (M = 0.20, p = 0.45) but differed in global strength, reflecting greater overall connectivity in the post-CR network (S = 0.91, p = 0.03).

Negative symptoms influenced network changes following therapy, and their reduction was linked to improvement in verbal and visual learning following CR. Independent relationships between visual and verbal learning and functioning suggest that they may be key intervention targets to enhance social and occupational functioning.

The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.

Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.

In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.

Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.

Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.

Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.

Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.

While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.

Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms.

We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities.

By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18–100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates.

This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.

COVID-19 misinformation proliferating online has led to adverse health and societal consequences. Older adults are a particularly vulnerable population due to increased risk for both COVID-19 related complications and susceptibility to, as well as sharing of, misinformation on social networking sites. The present study aimed to: 1) investigate differences in COVID-19 headline accuracy discernment and online sharing of COVID-19 misinformation in older and younger adults; and 2) examine individual differences in global cognition, health literacy and verbal IQ in online sharing of COVID-19 misinformation.

Fifty-two younger (age 18 to 35 years) and fifty older adults (age 50 and older) completed a telephone neurocognitive battery, health literacy and numeracy measures and self-report questionnaires. Participants also completed a social media headline-sharing experiment (Pennycook et al.,2020) in which they were presented true and false COVID-19 headlines and asked to indicate: 1) the likelihood that they would share the story on social media; and 2) the factual accuracy of the story.

A repeated measures multivariate analysis of variance controlling for gender and race/ethnicity showed no effects of age (p=.099), but a significant interaction between actual COVID-19 headline accuracy and likelihood of sharing (p<.001), such that accuracy is more strongly related to sharing false headlines (r=-.64) versus true headlines (r=-.43). Moreover, higher likelihood of sharing false COVID-19 headlines was associated with lower verbal IQ and numeracy skills in older adults (rs=-.51--.40; ps<.01) and with lower verbal IQ, numeracy, and global cognition in younger adults (rs=-.66--.60; ps<.01).

Findings indicate that headline accuracy judgements are an important predictor of sharing COVID-19 misinformation in both older and younger adults. Further, individual differences in cognition, IQ, and numeracy may predict the likelihood of misinformation sharing in younger adults, while IQ and numeracy skills may act as important antecedents of misinformation sharing in older adults. Future work might leverage modern, neuropsychologically-based psychoeducation approaches to improving health and science literacy related to COVID-19.

In England, a range of mental health crisis care models and approaches to organising crisis care systems have been implemented, but characteristics associated with their effectiveness are poorly understood.

To (a) develop a typology of catchment area mental health crisis care systems and (b) investigate how crisis care service models and system characteristics relate to psychiatric hospital admissions and detentions.

Crisis systems data were obtained from a 2019 English national survey. Latent class analyses were conducted to identify discernible typologies, and mixed-effects negative binomial regression models were fitted to explore associations between crisis care models and admissions and detention rates, obtained from nationally reported data.

No clear typology of catchment area crisis care systems emerged. Regression models suggested that provision of a crisis telephone service within the local crisis system was associated with a 11.6% lower admissions rate and 15.3% lower detention rate. Provision of a crisis cafe was associated with a 7.8% lower admission rates. The provision of a crisis assessment team separate from the crisis resolution and home treatment service was associated with a 12.8% higher admission rate.

The configuration of crisis care systems varies considerably in England, but we could not derive a typology that convincingly categorised crisis care systems. Our results suggest that a crisis phone line and a crisis cafe may be associated with lower admission rates. However, our findings suggest crisis assessment teams, separate from home treatment teams, may not be associated with reductions in admission and detentions.

Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a ‘next-step’. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted.

The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored.

Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to ‘next-step’ treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI.

SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.