scholarly journals Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use

2020 ◽  
Author(s):  
Emma Logtenberg ◽  
Martin F Overbeek ◽  
Joelle A Pasman ◽  
Abdel Abdellaoui ◽  
Maartje Luijten ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Alcohol Dependence ◽  
Genetic Variants ◽  
Brain Volume ◽  
Hippocampal Volume ◽  
Causal Effects ◽  
Subcortical Brain ◽  
Wide Range ◽  
Causal Nature

Background: Structural variation in subcortical brain regions has been linked to substance use, including the most prevalent substances nicotine and alcohol. It may be that pre-existing differences in subcortical brain volume affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. We assess the causal nature of this complex relationship with bi-directional Mendelian randomization (MR). Methods: MR uses genetic variants predictive of a certain trait (exposure) as instrumental variables to test causal effects on a certain outcome. Due to random assortment at meiosis, genetic variants shouldnt be associated with confounders, allowing less biased causal inference. We employed summary-level data of the largest available genome-wide association studies of subcortical brain region volumes (nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus; n=50,290) and smoking and alcohol use (smoking initiation, n=848,460; cigarettes per day, n=216,590; smoking cessation, n=378,249; alcohol drinks per week, n=630,154; alcohol dependence, n=46,568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. Results: There was strong evidence that alcohol dependence decreased amygdala and hippocampal volume and that smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. Conclusions: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and most likely mental health, warranting more recognition in public health efforts.

scholarly journals Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use

2021 ◽  
pp. 1-9
Author(s):  
Emma Logtenberg ◽  
Martin F. Overbeek ◽  
Joëlle A. Pasman ◽  
Abdel Abdellaoui ◽  
Maartje Luijten ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Genetic Variants ◽  
Brain Volume ◽  
Hippocampal Volume ◽  
Causal Effects ◽  
Mendelian Randomisation ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Causal Nature ◽  
Relationship Of

Background Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. Aims We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. Method Mendelian randomisation uses genetic variants predictive of a certain ‘exposure’ as instrumental variables to test causal effects on an ‘outcome’. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. Results There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. Conclusions Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.

scholarly journals Causal relationships between substance use and insomnia

2020 ◽  
Author(s):  
Joëlle A. Pasman ◽  
Dirk J.A. Smit ◽  
Lilian Kingma ◽  
Jacqueline M. Vink ◽  
Jorien L. Treur ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Alcohol Dependence ◽  
Strong Evidence ◽  
Smoking Initiation ◽  
Causal Effects ◽  
Sensitivity Analyses ◽  
Poor Sleep ◽  
A Genome ◽  
Bidirectional Effects

AbstractBackgroundPoor sleep quality and insomnia have been associated with the use of tobacco, alcohol, and cannabis, but it is unclear if there is a causal link. In this Mendelian Randomization (MR) study we examine if insomnia causes substance use and/or if substance use causes insomnia.MethodsMR uses summary effect estimates from a genome-wide association study (GWAS) to create a genetic instrumental variable for a proposed ‘exposure’ variable and then identifies that same genetic instrument in an ‘outcome’ GWAS. With data of GWAS of insomnia, smoking (initiation, heaviness, cessation), alcohol use (drinks per week, dependence), and cannabis initiation, bi-directional causal effects were tested. Multiple sensitivity analyses were applied to assess the robustness of the findings.ResultsThere was strong evidence for positive causal effects of insomnia on all substance use phenotypes (smoking traits, alcohol dependence, cannabis initiation), except alcohol per week. The effects on alcohol dependence and cannabis initiation were attenuated after filtering out pleiotropic SNPs. In the other direction, there was strong evidence that smoking initiation increased chances of insomnia (smoking heaviness and cessation could not be tested as exposures). We found no evidence that alcohol use per week, alcohol dependence, or cannabis initiation causally affect insomnia.ConclusionsThere were unidirectional effects of insomnia on alcohol dependence and cannabis initiation, and bidirectional effects between insomnia and smoking measures. Bidirectional effects between smoking and insomnia might give rise to a vicious circle. Future research should investigate if interventions aimed at insomnia are beneficial for substance use treatment.

scholarly journals Investigating causal pathways between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization

2019 ◽  
Author(s):  
Jorien L Treur ◽  
Ditte Demontis ◽  
George Davey Smith ◽  
Hannah Sallis ◽  
Tom G Richardson ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Smoking Initiation ◽  
Cannabis Use ◽  
Causal Effects ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Causal Pathways

ABSTRACTBackgroundAttention-deficit hyperactivity disorder (ADHD) has consistently been associated with substance (ab)use, but the nature of this association is not fully understood. In view of preventive efforts, a vital question is whether there are causal effects, from ADHD to substance use and/or from substance use to ADHD.MethodsWe applied bidirectional Mendelian randomization using summary-level data from the largest available genome-wide association studies (GWASs) on ADHD, smoking (initiation, cigarettes/day, cessation, and a compound measure of lifetime smoking), alcohol use (drinks/week and alcohol use disorder), cannabis use (initiation and cannabis use disorder (CUD)) and coffee consumption (cups/day). Genetic variants robustly associated with the ‘exposure’ were selected as instruments and then identified in the ‘outcome’ GWAS. Effect estimates from individual genetic variants were combined with inverse-variance weighted regression and five sensitivity analyses were applied (weighted median, weighted mode, MR-Egger, generalized summary-data-based MR, and Steiger filtering).ResultsWe found strong evidence that liability to ADHD increases likelihood of smoking initiation and also cigarettes per day among smokers, decreases likelihood of smoking cessation, and increases likelihood of cannabis initiation and CUD. In the other direction, there was evidence that liability to smoking initiation and CUD increase ADHD risk. There was no clear evidence of causal effects between liability to ADHD and alcohol or caffeine consumption.ConclusionsWe find evidence for causal effects of liability to ADHD on smoking and cannabis use, and of liability to smoking and cannabis use on ADHD risk, indicating bidirectional pathways. Further work is needed to explore causal mechanisms.

scholarly journals “A place to be safe, feel at home and get better”: Including the experiential knowledge of potential users in the design of the first wet service in Montreal, Canada

2021 ◽  
Author(s):  
ROSSIO MOTTA OCHOA ◽  
Natalia Incio-Serra ◽  
Hélène Poliquin ◽  
Sue-Ann MacDonald ◽  
Christophe Huỳnhe ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Dependence ◽  
Harm Reduction ◽  
Research Approach ◽  
Structured Interviews ◽  
Complex Needs ◽  
Barriers To Access ◽  
Wide Range ◽  
A Site ◽  
Alcohol Programs

Abstract BackgroundThe harmful use of alcohol is one of the leading health risk factors for people’s health worldwide, but some populations, like people who experience homelessness, are more vulnerable to its detrimental effects. In the past decades, harm reduction interventions that target these complex issues has been developed. For example, wet services include a wide range of arrangements (wet shelters, drop-in centers, transitory housing, etc.) that allow indoor alcohol use and Managed Alcohol Programs provide regulated doses of alcohol in addition to accommodation and services. Although the positive impacts of these interventions have been reported, little is known about how to integrate the knowledge of people experiencing homelessness and alcohol dependence into the design of such programs. The aim of this study is to present the findings of such an attempt in a first wet service in Montreal, Canada. MethodsCommunity based participatory research approach and qualitative methods–including semi-structured interviews and focus groups–were used to collect the knowledge of potential users (n = 34) of the wet service. The data collected was thematically analyzed. ResultsParticipants reported experiencing harsh living conditions, poverty, stigmatization and police harassment, which increased their alcohol use. The intersection between participants’ alcohol dependence and homelessness with the high barriers to access public services translated into their exclusion from several of such services. Participants envisioned Montreal’s wet service as a safe space to drink, a place that would provide multiple services, a home, and a site of recovery. ConclusionsIntegrating the knowledge of potential users into the design of harm reduction interventions is essential to develop better and more adapted services to meet complex needs. We propose that it could fosters users’ engagement and contribute to their sense of empower, which is crucial for a group that is typically discriminated against and suffers from marginalization.

scholarly journals Genetic variation within GRIN2B in adolescents with alcohol use disorder may be associated with larger left posterior cingulate cortex volume

2016 ◽  
Vol 29 (4) ◽  
pp. 252-258 ◽  
Author(s):  
Shareefa Dalvie ◽  
Samantha J. Brooks ◽  
Valerie Cardenas ◽  
George Fein ◽  
Raj Ramesar ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Genetic Variants ◽  
Alcohol Use Disorder ◽  
Brain Volume ◽  
Cingulate Cortex ◽  
Posterior Cingulate Cortex ◽  
Magnetic Resonance Images ◽  
Mixed Ancestry ◽  
Posterior Cingulate ◽  
Left Posterior

ObjectiveBrain structure differences and adolescent alcohol dependence both show substantial heritability. However, exactly which genes are responsible for brain volume variation in adolescents with substance abuse disorders are currently unknown. The aim of this investigation was to determine whether genetic variants previously implicated in psychiatric disorders are associated with variation in brain volume in adolescents with alcohol use disorder (AUD).MethodsThe cohort consisted of 58 adolescents with DSM-IV AUD and 58 age and gender-matched controls of mixed ancestry ethnicity. An Illumina Infinium iSelect custom 6000 bead chip was used to genotype 5348 single nucleotide polymorphisms (SNPs) in 378 candidate genes. Magnetic resonance images were acquired and volumes of global and regional structures were estimated using voxel-based morphometry. To determine whether any of the genetic variants were associated with brain volume, association analysis was conducted using linear regression in Plink.ResultsFrom the exploratory analysis, the GRIN2B SNP rs219927 was associated with brain volume in the left posterior cingulate cortex (p<0.05), whereby having a G-allele was associated with a bigger volume.ConclusionThe GRIN2B gene is involved in glutamatergic signalling and may be associated with developmental differences in AUD in brain regions such as the posterior cingulate cortex. Such differences may play a role in risk for AUD, and deserve more detailed investigation.

scholarly journals Comorbidity of Major Depression with Substance Use Disorders

2005 ◽  
Vol 50 (10) ◽  
pp. 660-666 ◽  
Author(s):  
Shawn R Currie ◽  
Scott B Patten ◽  
Jeanne VA Williams ◽  
JianLi Wang ◽  
Cynthia A Beck ◽  
...  
Keyword(s):  
Mental Health ◽  
Substance Use ◽  
Major Depression ◽  
Alcohol Use ◽  
Alcohol Dependence ◽  
Substance Use Disorder ◽  
Drug Dependence ◽  
Well Being ◽  
Suicidal Thoughts ◽  
Harmful Alcohol

Objectives: In the Canadian adult population, we aimed to 1) estimate the 12-month prevalence of major depressive disorder (MDD) in persons with a diagnosis of harmful alcohol use, alcohol dependence, and drug dependence; 2) estimate the 12-month prevalence of harmful alcohol use, alcohol dependence, and drug dependence in persons with a 12-month and lifetime diagnosis of MDD; 3) identify socioeconomic correlates of substance use disorder–major depression comorbidity; 4) determine how comorbidity impacts the prevalence of suicidal thoughts; and 5) determine how comorbidity affects mental health care used. Methods: We examined data from the Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2). Results: The 12-month prevalences of MDD in persons with a substance use disorder (SUD) were 6.9% for harmful alcohol use (95% confidence interval [CI], 5.2 to 8.5), 8.8% for alcohol dependence (95%CI, 6.6 to 11.0), and 16.1% for drug dependence (95%CI, 10.3 to 21.9). Conversely, the 12-month prevalences of harmful alcohol use, alcohol dependence, and drug dependence in persons with a 12-month diagnosis of MDD were 12.3% (95%CI, 9.4 to 15.2), 5.8% (95%CI, 4.3 to 7.3), and 3.2% (95%CI, 2.0 to 4.4), respectively. Regression modelling did not identify any socioeconomic predictors of SUD–MDD comorbidity. Substance dependence and MDD independently predicted higher prevalence of suicidal thoughts and mental health treatment use. Conclusions: SUDs cooccur with a high frequency in cases of MDD. Clinicians and mental health services should consider routine assessment of SUDs in depression patients.

scholarly journals An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings

2018 ◽  
Vol 48 (3) ◽  
pp. 713-727 ◽  
Author(s):  
Eleanor Sanderson ◽  
George Davey Smith ◽  
Frank Windmeijer ◽  
Jack Bowden
Keyword(s):  
Genetic Variants ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Causal Effects ◽  
Single Sample ◽  
Uk Biobank ◽  
Level Data ◽  
Wide Range ◽  
Using Data ◽  
Summary Data

Abstract Background Mendelian randomization (MR) is a powerful tool in epidemiology that can be used to estimate the causal effect of an exposure on an outcome in the presence of unobserved confounding, by utilizing genetic variants that are instrumental variables (IVs) for the exposure. This has been extended to multivariable MR (MVMR) to estimate the effect of two or more exposures on an outcome. Methods and results We use simulations and theory to clarify the interpretation of estimated effects in a MVMR analysis under a range of underlying scenarios, where a secondary exposure acts variously as a confounder, a mediator, a pleiotropic pathway and a collider. We then describe how instrument strength and validity can be assessed for an MVMR analysis in the single-sample setting, and develop tests to assess these assumptions in the popular two-sample summary data setting. We illustrate our methods using data from UK Biobank to estimate the effect of education and cognitive ability on body mass index. Conclusion MVMR analysis consistently estimates the direct causal effect of an exposure, or exposures, of interest and provides a powerful tool for determining causal effects in a wide range of scenarios with either individual- or summary-level data.

scholarly journals Adolescent alcohol use is a risk factor for adult alcohol and drug dependence: evidence from a twin design

2005 ◽  
Vol 36 (1) ◽  
pp. 109-118 ◽  
Author(s):  
JULIA D. GRANT ◽  
JEFFREY F. SCHERRER ◽  
MICHAEL T. LYNSKEY ◽  
MICHAEL J. LYONS ◽  
SETH A. EISEN ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Environmental Factors ◽  
Alcohol Dependence ◽  
Family Environment ◽  
Age Of Onset ◽  
Twin Design ◽  
Environmental Correlations ◽  
Other Substances ◽  
Twin Models

Background. Early alcohol use is associated with abuse and dependence of licit and illicit substances later in life. The role of genetic and environmental factors in this association is not conclusive.Method. In 1992, data on substance use, abuse/dependence and psychiatric disorders were collected from 8169 male twin members of the Vietnam Era Twin Registry. The interview obtained age of onset of regular drinking (one drink/month for 6 or more months). Regression analyses of twin pairs discordant for early alcohol use tested whether the association between early drinking (before age 17) and adult substance use and abuse/dependence remained after controlling for genetic factors, family environment and covariates. Twin models tested for common genetic and/or environmental influences on early drinking and adult alcohol dependence and ever use and abuse/dependence on marijuana and other drugs.Results. Co-twin analyses suggested the association between early regular alcohol use and adult alcohol dependence, marijuana and other drug use, and marijuana and other drug abuse/dependence could not be entirely explained by common genetic and shared family environmental factors. Genetic contributions to early regular drinking were significantly correlated with those on use of marijuana (rA=0·59), use of other drugs (rA=0·64), alcohol dependence (rA=0·54) and abuse/dependence of marijuana and other drugs (rA=0·63 and 0·66). Small but significant unique environmental correlations (rE range 0·11–0·22) indicated that familial factors could not entirely explain the association between early alcohol use and later substance use, abuse and dependence.Conclusions. Early regular drinking is associated with later alcohol dependence and use, abuse/dependence on drugs. The association is not entirely explained by genetic or shared family environmental factors. This suggests unique environmental factors contribute to transitions from early regular alcohol drinking to use, abuse and dependence on alcohol and other substances.

DSM-5 alcohol use disorder features among treatment-seeking older adults

2018 ◽  
Vol 64 (4) ◽  
pp. 185-196 ◽  
Author(s):  
Silke Behrendt ◽  
Barbara Braun ◽  
Randi Bilberg ◽  
Gerhard Bühringer ◽  
Michael Bogenschutz ◽  
...  
Keyword(s):  
Older Adults ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
The Elderly ◽  
Treatment Seeking ◽  
Controlled Clinical Trial ◽  
Dsm 5 ◽  
Wide Range ◽  
And Gender ◽  
International Multicenter

Abstract. Background: The number of older adults with alcohol use disorder (AUD) is expected to rise. Adapted treatments for this group are lacking and information on AUD features in treatment seeking older adults is scarce. The international multicenter randomized-controlled clinical trial “ELDERLY-Study” with few exclusion criteria was conducted to investigate two outpatient AUD-treatments for adults aged 60+ with DSM-5 AUD. Aims: To add to 1) basic methodological information on the ELDERLY-Study by providing information on AUD features in ELDERLY-participants taking into account country and gender, and 2) knowledge on AUD features in older adults seeking outpatient treatment. Methods: baseline data from the German and Danish ELDERLY-sites (n=544) were used. AUD diagnoses were obtained with the Mini International Neuropsychiatric Interview, alcohol use information with Form 90. Results: Lost control, desired control, mental/physical problem, and craving were the most prevalent (> 70 %) AUD-symptoms. 54.9 % reported severe DSM-5 AUD (moderate: 28.2 %, mild: 16.9 %). Mean daily alcohol use was 6.3 drinks at 12 grams ethanol each. 93.9 % reported binging. More intense alcohol use was associated with greater AUD-severity and male gender. Country effects showed for alcohol use and AUD-severity. Conclusion: European ELDERLY-participants presented typical dependence symptoms, a wide range of severity, and intense alcohol use. This may underline the clinical significance of AUD in treatment-seeking seniors.

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