Transdiagnostic biomarkers of mental illness across the lifespan: A systematic review examining the genetic and neural correlates of latent transdiagnostic dimensions of psychopathology in the general population.

This systematic review synthesizes evidence from research investigating the biological correlates of latent transdiagnostic dimensions of psychopathology (e.g., the p-factor, internalizing, externalizing) across the lifespan. Eligibility criteria captured genomic and neuroimaging studies investigating general and/or specific dimensions in general population samples across all age groups. MEDLINE, Embase, and PsycINFO were searched for relevant studies published up to March 2023 and 46 studies were selected for inclusion. The results revealed several biological correlates consistently associated with transdiagnostic dimensions of psychopathology, including polygenic scores for ADHD and neuroticism, global surface area and global gray matter volume. Shared and unique associations between symptom dimensions are highlighted, as are potential age-specific differences in biological associations. Findings are interpreted with reference to key methodological differences across studies. The included studies provide compelling evidence that the general dimension of psychopathology reflects common underlying genetic and neurobiological vulnerabilities that are shared across diverse manifestations of mental illness. Substantive interpretations of general psychopathology in the context of genetic and neurobiological evidence are discussed.

Longitudinal relationships between lifestyle risk factors and neurodevelopment in early adolescence.

OBJECTIVE: The goal of this study is to investigate the cross-sectional and longitudinal relationships between clustered lifestyle risk factors (sleep, physical activity, body mass index [BMI], and screen time) and neurodevelopment over the early adolescent period. METHOD: Data from the ABCD Study Data Release 3.0 consisted of 11,878 participants (aged 9-10 years) at baseline and 6,571 participants (aged 11-12 years) at 2-year follow-up. The interrelationships between lifestyle risk factors and brain structure were analyzed using bivariate multiple indicator latent change score models. Using confirmatory factor analysis, a single lifestyle risk factor domain (measured by sleep, physical activity, BMI, and screen time) was shown to fit the data well. Using exploratory and confirmatory factor analysis, seven brain structure domains were extracted and labeled as temporal-parietal, frontotemporal, occipital, orbitofrontal, temporal, cingulate, parietal, and cuneus domains. All bivariate latent change score models accounted for age, sex at birth, race/ethnicity, parental education, and marital status. RESULTS: Higher lifestyle risk was associated with smaller brain volume at baseline. Higher baseline lifestyle risk was also associated with a greater rate of change (i.e., greater decreases) in brain volume for the temporal-parietal, frontotemporal, orbitofrontal, parietal, and cuneus domains. Effects were not reciprocal; baseline brain volume did not predict changes in lifestyle behaviors over time. CONCLUSION: These findings are important for understanding the biological mechanisms underpinning health risk factors and can be used to target interventions and improve brain health during this critical developmental phase. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The relationship between alcohol use and dementia in adults aged more than 60 years: a combined analysis of prospective, individual-participant data from 15 international studies.

AIM: To synthesize international findings on the alcohol-dementia relationship, including representation from low- and middle-income countries. METHODS: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in six continents. Cox regression investigated the dementia risk associated with alcohol use in older adults aged over 60 years. Additional analyses assessed the alcohol-dementia relationship in the sample stratified by sex and by continent. Participants included 24 478 community dwelling individuals without a history of dementia at baseline and at least one follow-up dementia assessment. The main outcome measure was all-cause dementia as determined by clinical interview. RESULTS: At baseline, the mean age across studies was 71.8 (standard deviation = 7.5, range = 60-102 years), 14 260 (58.3%) were female and 13 269 (54.2%) were current drinkers. During 151 636 person-years of follow-up, there were 2124 incident cases of dementia (14.0 per 1000 person-years). When compared with abstainers, the risk for dementia was lower in occasional [hazard ratio (HR) = 0.78; 95% confidence interval (CI) = 0.68-0.89], light-moderate (HR = 0.78; 95% CI = 0.70-0.87) and moderate-heavy drinkers (HR = 0.62; 95% CI = 0.51-0.77). There was no evidence of differences between life-time abstainers and former drinkers in terms of dementia risk (HR = 0.98; 95% CI = 0.81-1.18). In dose-response analyses, moderate drinking up to 40 g/day was associated with a lower risk of dementia when compared with lif-time abstaining. Among current drinkers, there was no consistent evidence for differences in terms of dementia risk. Results were similar when the sample was stratified by sex. When analysed at the continent level, there was considerable heterogeneity in the alcohol-dementia relationship. CONCLUSIONS: Abstinence from alcohol appears to be associated with an increased risk for all-cause dementia. Among current drinkers, there appears to be no consistent evidence to suggest that the amount of alcohol consumed in later life is associated with dementia risk.

Investigating the molecular genetic, genomic, brain structural, and brain functional correlates of latent transdiagnostic dimensions of psychopathology across the lifespan: Protocol for a systematic review and meta-analysis of cross-sectional and longitudinal studies in the general population.

Background: Research using latent variable modelling has identified a superordinate general dimension of psychopathology, as well as several specific/lower-order transdiagnostic dimensions (e.g., internalising and externalising) within the meta-structure of psychiatric symptoms. These models can facilitate discovery in genetic and neuroscientific research by providing empirically derived psychiatric phenotypes, offering greater validity and reliability than traditional diagnostic categories. The prospective review outlined in this protocol aims to integrate and assess evidence from research investigating the biological correlates of general psychopathology and specific/lower-order transdiagnostic symptom dimensions. Cross-sectional and longitudinal studies investigating general population samples of any age group or developmental period will be included to capture evidence from across the lifespan. Methods and analysis: MEDLINE, Embase, and PsycINFO databases will be systematically searched for relevant literature. The review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligibility criteria were designed to capture psychiatric genetic (i.e., molecular genetic and genomic) and neuroimaging (i.e., brain structural and brain functional) studies investigating latent transdiagnostic dimension(s) or structural model(s) of psychopathology across any age group. Studies which include or exclude participants based on clinical symptoms, disorders, or relevant risk factors (e.g., history of abuse, neglect, and trauma) will be excluded. Biometric genetic research (e.g., twin and family studies), candidate gene studies, neurophysiology studies, and other non-imaging based neuroscientific studies (e.g., post-mortem studies) will be excluded. Study quality and risk of bias will be assessed using the Joanna Briggs Checklist for Analytical Cross-Sectional Studies, the Joanna Briggs Checklist for Cohort Studies, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. Meta-analysis will be conducted if sufficient data is available. Discussion: This protocol outlines the first systematic review to examine evidence from studies investigating the latent structure and underlying biology of psychopathology and to characterise these relationships developmentally across the lifespan. The prospective review will cover a broad range of statistical techniques and models used to investigate latent transdiagnostic dimensions of psychopathology, as well as a numerous genetic and neuroscientific methods. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier[CRD42021262717].

Rethink My Drink: study protocol for a 12-month randomised controlled trial comparing a brief internet-delivered intervention to an online patient information booklet in reducing risky alcohol consumption among older adults in Australia.

BACKGROUND AND AIMS: Alcohol consumption is increasing among older adults. Rethink My Drink is a brief internet-delivered intervention to reduce alcohol consumption and related harms, adapted specifically for older adults. This protocol for a large-scale randomised controlled trial will evaluate whether Rethink My Drink is effective in reducing alcohol consumption and cognitive decline in a sample of older risky drinkers, compared with an active control. DESIGN: 1:1 parallel group, randomised controlled trial. SETTING: Online trial in Australia. PARTICIPANTS: Hazardous or harmful drinkers (defined as those scoring ≥5 on the Alcohol Use Disorders Identification Test [AUDIT]) age 60 to 75 years old (n = 842). Participants will be recruited from August 2021 to August 2022 through online social media advertisements and community networks. INTERVENTION AND COMPARATOR: Participants will be randomly allocated to receive access to Rethink My Drink (intervention) or Alcohol: The Facts (comparator), an online patient information booklet provided by New South Wales (NSW) Health. MEASUREMENTS: Primary outcomes include (i) average weekly standard drinks and (ii) rate of cognitive decline. Secondary outcomes include (i) typical quantity of drinks per drinking day; (ii) heavy episodic drinking; (iii) age-specific risky drinking; (iv) alcohol-related harms; (v) subjective cognitive complaints; and (vi) quality of life. All primary and secondary outcomes will be assessed at baseline, post-intervention (4 weeks) and 12 months. Effectiveness will be evaluated using multilevel linear regression, adjusting for baseline demographic differences. Bonferroni adjustments will be used to control for multiple comparisons. Multiple imputation, regression weighting and sensitivity analyses will assess the effect of attrition. COMMENTS: This will be the first large-scale trial, internationally, to examine whether a brief internet-delivered intervention is effective in reducing alcohol consumption and cognitive decline among older adults. If successful, the intervention will provide an accessible and highly scalable treatment to reduce risky alcohol consumption in older adulthood.

The relationship between brain structure and general psychopathology in preadolescents.

BACKGROUND: An emerging body of literature has indicated that broad, transdiagnostic dimensions of psychopathology are associated with alterations in brain structure across the life span. The current study aimed to investigate the relationship between brain structure and broad dimensions of psychopathology in the critical preadolescent period when psychopathology is emerging. METHODS: This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,875; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. RESULTS: Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, parental education, income, and maternal psychopathology. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There were no statistically significant relationships between psychopathology and cortical thickness in this sample of preadolescents. CONCLUSIONS: The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. Future research may focus on whether the widespread and pervasive relationships between general psychopathology and brain structure reflect cognitive dysfunction that is a feature across a range of mental illnesses.