Systematic review of polygenic gene-environment interaction in tobacco, alcohol, and cannabis use

Contains fulltext : 204120.pdf (publisher's version ) (Open Access)Studies testing the effect of single genetic variants on substance use have had modest success. This paper reviewed 39 studies using polygenic measures to test interaction with any type of environmental exposure (GxE) in alcohol, tobacco, and cannabis use. Studies using haplotype combinations, sum scores of candidate-gene risk alleles, and polygenic scores (PS) were included. Overall study quality was moderate, with lower ratings for the polygenic methods in the haplotype and candidate-gene score studies. Heterogeneity in investigated environmental exposures, genetic factors, and outcomes was substantial. Most studies (N = 30) reported at least one significant GxE interaction, but overall evidence was weak. The majority (N = 26) found results in line with differential susceptibility and diathesis-stress frameworks. Future studies should pay more attention to methodological and statistical rigor, and focus on replication efforts. Additional work is needed before firm conclusions can be drawn about the importance of GxE in the etiology of substance use.17 p

Substance use genetics: Uncovering genes and testing gene-environment interplay

Contains fulltext : 237193.pdf (Publisher’s version ) (Open Access)Radboud University, 30 september 2021Promotores : Vink, J.M., Verweij, C.J.H. Co-promotor : Abdellaoui, A.465 p

Stress, childhood trauma, and cognitive functions in functional neurologic disorders

Conversion disorder (CD) has traditionally been ascribed to psychologic factors such as trauma, stress, or emotional conflict. Although reference to the psychologic origin of CD has been removed from the criteria list in DSM-5, many theories still incorporate CD as originating from adverse events. This chapter provides a critical review of the literature on stressful life events in CD and discusses current cognitive and neurobiologic models linking psychologic stressors with conversion symptomatology. In addition, we propose a neurobiologic stress model integrating those cognitive models with neuroendocrine stress research and propose that stress and stress-induced changes in hypothalamus-pituitary-adrenal (HPA) axis function may result in cognitive alterations, that in turn contribute to experiencing conversion symptoms. Experimental studies indeed suggest that basal as well as stress-induced changes in HPA axis responding lead to alterations in attentional processing in CD. Although those changes are stronger in traumatized patients, similar patterns have been observed in patients who do not report a history of traumatic events. We conclude that, whereas adverse events may play an important role in many cases of CD, a substantial proportion of patients do not report a history of traumatization or recent stressful events. Studies integrating effects of stress on cognitive functioning in CD are scarce. We propose that, instead of focusing research on defining etiologic events in terms of symptom-eliciting events, future research should work towards an integrated mechanistic account, assessing alterations in cognitive and biologic stress systems in an integrated manner in patients with CD. Such an account may not only serve early symptom detection, it might also provide a starting point for better-targeted interventions

Investigating genetic correlation and causality between nicotine dependence and ADHD in a broader psychiatric context

People with attention-deficit/hyperactivity disorder (ADHD) or other psychiatric disorders show high rates of nicotine dependence (ND). This comorbidity might be (partly) explained by shared genetic factors. Genetic correlations between ND and ADHD (or other psychiatric disorders) have not yet been estimated. A significant genetic correlation might indicate genetic overlap, but could also reflect a causal relationship. In the present study we investigated the genetic correlation (with LD score regression analyses) between ND and ADHD, as well as between ND and other major psychiatric conditions (major depressive disorder, schizophrenia, anxiety, bipolar disorder, autism spectrum, anorexia nervosa, and antisocial behavior) based on the summary statistics of large Genome Wide Association studies. We explored the causal nature of the relationship between ND and ADHD using two-sample Mendelian randomization. We found a high genetic correlation between ND and ADHD (rg = .53, p = 1.85 × 10-13), and to a lesser extent also between ND-major depressive disorder (rg = .42, p = 3.6 × 10-11) and ND-schizophrenia (rg = .18, p = 1.1 × 10-3). We did not find evidence for a causal relationship from liability for ADHD to ND (which could be due to a lack of power). The strong genetic correlations might reflect different phenotypic manifestations of (partly) shared underlying genetic vulnerabilities. Combined with the lack of evidence for a causal relationship from liability for ADHD to ND, these findings stress the importance to further investigate the underlying genetic vulnerability explaining co-morbidity in psychiatric disorders

Causal relationships between substance use and insomnia

Contains fulltext : 220283.pdf (publisher's version ) (Open Access)Background: Poor 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. Methods: MR 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. Using GWASs 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. Results: There was strong evidence for positive causal effects of liability to insomnia on all substance use phenotypes (smoking traits, alcohol dependence, cannabis initiation), except alcohol per week. In the other direction, there was strong evidence that smoking initiation increased insomnia risk (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 risk. Conclusions: There were unidirectional effects of liability to insomnia on alcohol dependence and cannabis initiation, and bidirectional effects between liability to 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.5 p

High-potency cannabis and incident psychosis: Correcting the causal assumption

Item does not contain fulltextA commentary on Di Forti et al., 2019: 'The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study.'1 p

The prevalence of food addiction in a large sample of adolescents and its association with addictive substances

Item does not contain fulltextThe prevalence of overweight and obesity is increasing, due to, among other factors, increased availability of highly palatable food (food high in fat, salt and/or sugar). It has been proposed that certain foods and/or eating behaviours may be addictive, to a degree comparable to substances of abuse. The Yale Food Addiction Scale (YFAS) measures 'food addiction' by translating the diagnostic criteria for substance use disorder to eating behaviour. So far, only a few studies have examined the prevalence of food addiction in children with the YFAS for children (YFAS-C). Large-scale studies, especially among adolescents, are lacking. Adolescence is of particular interest because it is a period wherein unhealthy eating behaviours or addictive tendencies are likely to develop. The current study examines the prevalence of food addiction using the YFAS-C in a large group of Dutch adolescents (N = 2653) aged 14-21 years. With Generalized Estimation Equation (GEE) analysis we tested the relationship between food addiction symptoms and smoking, cannabis use, alcohol use, and sugar intake through drinks, while controlling for gender, age, educational level and weight class. In the total sample 2.6% met the criteria for a food addiction 'diagnosis', and the average symptom count was 1.0 (SD = 1.3, range 0-7). Symptoms of food addiction were positively associated with smoking, alcohol use, cannabis use and sugar intake. We propose that future studies focus on possible genetic/(neuro)biological mechanisms involved in both food addiction and substance use and that longitudinal designs are needed to examine possible causal pathways.9 p

Corrigendum to "Causal relationships between substance use and insomnia" [Drug Alcohol Dependence 214 (2020) 108151]

Contains fulltext : 226491.pdf (publisher's version ) (Open Access)3 p