The neurobiology of stress: Vulnerability, resilience, and major depression

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(49)

Published: Nov. 27, 2023

The global agri-food system is simultaneously a major contributor to, and severely affected by, climate change. Agroecological farming systems can contribute to creating resilient systems. Based on multiyear qualitative case study, ...Supporting transitions sustainable, important ensure stable food supply in the face of growing extremes. Agroecology, or diversified based ecological principles, such ...

Language: Английский

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Examining intergenerational risk factors for conduct problems using polygenic scores in the Norwegian Mother, Father and Child Cohort Study

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(4), P. 951 - 961

Published: Jan. 16, 2024

The aetiology of conduct problems involves a combination genetic and environmental factors, many which are inherently linked to parental characteristics given parents' central role in children's lives across development. It is important disentangle what extent links between heritable behaviour due transmission risk or indirect influences via the environment (i.e., nurture). We used 31,290 genotyped mother-father-child trios from Norwegian Mother, Father Child Cohort Study (MoBa), testing nurture effects on using 13 polygenic scores (PGS) spanning psychiatric conditions, substance use, education-related other factors. Maternal self-reports at ages 8 14 years were available for up 15,477 children. found significant 12 out PGS age (strongest association: smoking, β = 0.07, 95% confidence interval [0.05, 0.08]) 4 externalising problems, 0.08, 0.11]). Conversely, we did not find our selection PGS. Our findings provide evidence association child problems. results may also indicate that traits indexed by limited aetiological importance problems-though small magnitude captured included remain possibility.

Language: Английский

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Drinking motives and alcohol sensitivity mediate multidimensional genetic influences on alcohol use behaviors

Alcohol Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Abstract Background Genetic influences account for a substantial proportion of individual differences in alcohol use behaviors (AUBs). However, multiple distinct sets genes are linked to different AUBs via uncertain causal links. Here, we explore whether intermediate neurobiological traits mediate the relationship between polygenic scores (PGSs) and AUBs, with aim better understand processes captured by genetic profiles. Methods We derived four alcohol‐related PGSs participants from Spit Science, longitudinal study college students United States ( n = 4549). Using linear regression, tested 22 potential mediators, including personality, expectancies, drinking motives, sensitivity. Nominally significant effects were carried forward mediation model estimate direct indirect on measured (frequency, quantity, disorder symptoms [AUDsx], maximum drinks 24 h). Results In univariable indexing per week (DPW) problematic (PAU) predicted higher levels impulsivity motives as well lower BeerPref (indexing variable pattern problems preference beer) negative urgency Mediational models indicated DPW social/enhancement sensitivity, PAU AUDsx, PGS frequency AUDsx joint effect mediators Conclusions These findings provide evidence that associated partially mediated cognitive factors, which may be more amenable intervention. Greater focus sensitivity is warranted research, attention heterogeneous pathways linking outcomes.

Language: Английский

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Generalized genetic liability to substance use disorders

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(11)

Published: June 2, 2024

Lifetime and temporal co-occurrence of substance use disorders (SUDs) is common compared with individual SUDs characterized by greater severity, additional psychiatric comorbidities, worse outcomes. Here, we review evidence for the role generalized genetic liability to various SUDs. Coaggregation has familial contributions, twin studies suggesting a strong contribution additive influences undergirding variety substances (including alcohol, nicotine, cannabis, others). GWAS have documented similarly large correlations between opioid disorders. Extending these findings, recent identified multiple genomic loci that contribute risk problematic tobacco use, implicating dopaminergic regulatory neuronal development mechanisms in pathophysiology SUD liability, certain signals demonstrating cross-species translational validity. Overlap other externalizing behaviors, while substantial, does not explain entirety signal SUD. Polygenic scores (PGS) derived from outperform PGS prediction serious mental health medical comorbidities. Going forward, it will be important further elucidate etiology incorporating SUDs, evaluating clinical presentation across lifespan, increasing granularity investigation (e.g., specific transdiagnostic criteria) ultimately improve nosology, prevention, treatment

Language: Английский

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Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural Equation Modeling

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 27, 2024

Abstract Externalizing behaviors encompass manifestations of risk-taking, self-regulation, aggression, sensation-/reward-seeking, and impulsivity. research often includes substance use (SU), disorder (SUD), other (non-SU/SUD) “behavioral disinhibition” (BD) traits. Genome-wide twin have pointed to overlapping genetic architecture within across SUB, SUD, BD. We created single-factor measurement models—each describing or BD traits--based on mutually exclusive sets European ancestry genome-wide association study (GWAS) statistics exploring externalizing variables. then applied trivariate Cholesky decomposition these factors in order identify BD-specific genomic variation assess the partitioning BD’s covariance with each facets. Even when residuals for indicators relating same were correlated SUB SUD factors, two yielded a large zero-order correlation (r g =.803). strongly =.774) =.778). In our initial decompositions, 33% total variance remained after removing associated SUB. The majority between SU was shared all factors. When only nicotine/tobacco, cannabis, alcohol included SUB/SUD their increased r =.861; corresponding decreased 27%. summary, BD, SU, highly genetically at latent factor level, significant minority not and/or SUD. Further can better elucidate properties by its genetic/molecular correlates.

Language: Английский

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Genome-wide association studies of lifetime and frequency cannabis use in 131,895 individuals

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 16, 2024

Cannabis is one of the most widely used drugs globally. Decriminalization cannabis further increasing consumption. We performed genome-wide association studies (GWASs) lifetime (N=131,895) and frequency (N=73,374) use. Lifetime use GWAS identified two loci, near CADM2 (rs11922956, p=2.40E-11) another GRM3 (rs12673181, p=6.90E-09). Frequency locus (rs4856591, p=8.10E-09; r2 =0.76 with rs11922956). Both traits were heritable genetically correlated previous GWASs disorder (CUD), as well other substance cognitive traits. Polygenic scores (PGSs) for associated phenotypes in AllofUs participants. Phenome-wide study PGS a hospital cohort replicated associations mood disorders, uncovered celiac infectious diseases. This work demonstrates value CUD transition risk factors.

Language: Английский

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Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural Equation Modeling

Behavior Genetics, Journal Year: 2024, Volume and Issue: 54(5), P. 386 - 397

Published: July 9, 2024

Language: Английский

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Drinking motives and alcohol sensitivity mediate multi-dimensional genetic influences on alcohol use behaviors

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Abstract Background Genetic influences account for a substantial proportion of individual differences in alcohol use behaviors (AUBs). However, multiple distinct sets genes are linked to different AUBs, which may explain their dramatic variability risk factors and manifestations. In this study, we explore whether intermediate neurobiological traits alcohol-related cognitions mediate the relationship between polygenic scores (PGS) with aim better understand processes captured by genetic profiles. Methods Using results from prior genome-wide association studies, derived PGS 6 AUBs participants Spit Science, longitudinal study college students U.S. (n=4,549). Self-report measures included personality traits, expectancies, drinking motivations, sensitivity as well frequency, quantity, disorder (AUD) symptoms, maximum drinks 24 hours. linear regression mediation models, investigated direct indirect effects on AUBs. Results univariable results, PGSs indexing broad AUB dimensions such per week (DPW) AUD predicted higher levels sensation-seeking motives, while BeerPref (indexing variable pattern problems associated preference beer) negative urgency lower sensitivity. Mediational models indicated strong DPW via social/enhancement motives sensitivity, symptoms coping all joint effect mediators including Conclusions These findings provide initial evidence that partially mediated cognitive factors, be more amenable intervention. Greater focus is warranted research, attention heterogeneous pathways linking outcomes.

Language: Английский

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Genetic and shared environmental factors explain the association between adolescent polysubstance use and high school noncompletion.

Psychology of Addictive Behaviors, Journal Year: 2023, Volume and Issue: 38(1), P. 114 - 123

Published: March 13, 2023

Examine the nature of relationship between adolescent polysubstance use and high school noncompletion.

Language: Английский

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Executive Function as an Underlying Mechanism of Alcohol Use, Aggression, and ADHD

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Abstract Background Executive functioning (EF) has been proposed as a transdiagnostic risk factor for externalizing disorders and behavior more broadly, including attention-deficit/hyperactivity disorder (ADHD), aggression, alcohol use. Previous research demonstrated both phenotypic genetic overlap among these behaviors, but yet to examine EF common causal mechanism. The current study examined reciprocal associations between several behaviors using Mendelian randomization (MR) approach. Methods Two-sample MR was conducted test behaviors. Summary statistics from genome-wide association studies (GWASs) were used in analyses, GWASs of EF, ADHD diagnostic status, drinks per week, aggressive behavior, use (AUD) status. Multiple estimation methods employed account horizontal pleiotropy (e.g., inverse variance weighted, MR-PRESSO, MR-MIX). Results significant relationships with (P < 0.01), AUD 0.03), consumption 0.01) across methods. Reciprocally, showed influence on 0.03). Nonetheless, caution should be when interpreting findings there some evidence the effect heterogeneity variant effects other relations tested. There no aggression. Conclusions Findings suggest that may mechanism underlying use, also lead lower performance tasks.

Language: Английский

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