Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes

Funded by •ERC. Grant Number: 284167 •NIH. Grant Number: 1RO1DK0921127-01 •NWO. Grant Numbers: 463-06-001, 451-04-034Peer reviewedPublisher PD

High-Potency Cannabis, Mental Health and Substance Use in Adolescence:Results from a UK General Population Sample

Importance Cannabis use is consistently linked to poorer mental health outcomes, and there is evidence that use of higher-potency cannabis increases these risks. To date, no studies have described the association between cannabis potency and concurrent mental health in a general population sample or addressed confounding using longitudinal data. Objective To explore the association between cannabis potency and substance use and mental health outcomes, accounting for preceding mental health and frequency of cannabis use. Design, Setting, and Participants This cohort study used data from the Avon Longitudinal Study of Parents and Children, a UK birth cohort of participants born between April 1, 1991, and December 31, 1992. Present data on outcomes and exposures were collected between June 2015 and October 2017 from 1087 participants at 24 years of age who reported recent cannabis use. Exposures Self-reported type of cannabis most commonly used in the past year, coded to a binary exposure of use of high-potency cannabis or lower-potency cannabis. Main Outcomes and Measures Outcomes were reported frequency of cannabis use, reported cannabis use problems, recent use of other illicit drugs, tobacco dependence, alcohol use disorder, depression, generalized anxiety disorder, and psychotic-like experiences. The study used secondary data; consequently, the hypotheses were formulated after data collection. Results Past-year cannabis use was reported by 1087 participants (580 women; mean [SD] age at onset of cannabis use, 16.7 [3.0] years). Of these, 141 participants (13.0%) reported the use of high-potency cannabis. Use of high-potency cannabis was associated with increased frequency of cannabis use (adjusted odds ratio [AOR], 4.38; 95% CI, 2.89-6.63), cannabis problems (AOR, 4.08; 95% CI, 1.41-11.81), and increased likelihood of anxiety disorder (AOR, 1.92; 95% CI, 1.11-3.32). Adjustment for frequency of cannabis use attenuated the association with psychotic experiences (AOR 1.29; 95% CI, 0.67-2.50), tobacco dependence (AOR, 1.42; 95% CI, 0.89-2.27), and other illicit drug use (AOR, 1.29; 95% CI, 0.77-2.17). There was no evidence of association between the use of high-potency cannabis and alcohol use disorder or depression. Conclusions and Relevance To our knowledge, this study provides the first general population evidence suggesting that the use of high-potency cannabis is associated with mental health and addiction. Limiting the availability of high-potency cannabis may be associated with a reduction in the number of individuals who develop cannabis use disorders, the prevention of cannabis use from escalating to a regular behavior, and a reduction in the risk of mental health disorders

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Microglial brain region−dependent diversity and selective regional sensitivities to aging

Microglia play critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific spatially-restricted patterns, the origins of which are unknown. We performed the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse and reveal that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during ageing. Microglial diversity may enable regionally localised homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration

Testing a Level of Response to Alcohol-Based Model of Heavy Drinking and Alcohol Problems in 1,905 17-year-olds

BACKGROUND: The low level of response (LR) to alcohol is one of several genetically-influenced characteristics that increase the risk for heavy drinking and alcohol problems. Efforts to understand how LR operates through additional life influences have been carried out primarily in modest sized U.S.-based samples with limited statistical power, raising questions about generalizability and about the importance of components with smaller effects. This study evaluates a full LR-based model of risk in a large sample of adolescents from the U.K. METHODS: Cross-sectional structural equation models (SEM) were used for the approximate first half of the age 17 subjects assessed by the Avon Longitudinal Study of Parents and Children (ALSPAC), generating data on 1,905 adolescents (0 age 17.8 years, 44.2% males). LR was measured with the Self-Rating of the Effects of Alcohol (SRE) Questionnaire, outcomes were based on drinking quantities and problems, and standardized questionnaires were used to evaluate peer substance use, alcohol expectancies, and using alcohol to cope with stress. RESULTS: In this young and large U.K. sample, a low LR related to more adverse alcohol outcomes both directly and through partial mediation by all three additional key variables (peer substance use, expectancies, and coping). The models were similar in males and females. CONCLUSIONS: These results confirm key elements of the hypothesized LR-based model in a large U.K. sample, supporting some generalizability beyond U.S. groups. They also indicate that with enough statistical power multiple elements contribute to how LR relates to alcohol outcomes, and reinforce the applicability of the model to both genders