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Approved research

Comorbidities between addiction and mental disorders ? association of genetics, biomarkers and environment (e.g. lifestyle) with mental health and cognitive function

Principal Investigator: Professor Helgi Schioth
Approved Research ID: 30172
Approval date: April 6th 2018

Lay summary

We aim to investigate interactions between genetics and environmental factors e.g. lifestyle in relation to mental health and addiction. We will examine whether environmental and other risk factors (psychiatric comorbidities) influence addiction besides having overlapping genetic risk factors crucial for prevention and treatment strategies, study genetic variants with known associations to addictions and psychiatric disorders and perform genome-wide exploratory analyses for novel variants. We will investigate the association and modulating effects of genetic variation between mental health and addiction, including pharmacogenetics, known and novel biomarkers, SNPs role in drug effects and cognitive function to understand susceptibility to addiction. Addictions and drug abuse are severe common psychiatric disorders, among the leading causes of morbidity and preventable mortality, and often linked with other psychiatric diseases as consequences or potential cause of addictive behavior (Agrawal, 2012). We will evaluate the impact of genetic and environmental risk factors on comorbidities of addiction and common psychiatric disorders. Better understanding how neural circuitry, genetics and environmental factors interact in the etiology of addiction and other psychiatric diseases offer better treatment strategies. Novel insights into molecular biology, genetic, pharmacogenetics and epigenetic mechanisms underlying these associations will improve public-health related decisions for health professionals. Statistical models will be utilized to analyze associations between genotype, cognitive function and mental health while controlling for demographics such as age, gender, medications, personality traits, physical activity, etc. as well as comorbidities. To examine causal effects of these genes, Mendelian randomization will be applied. Novel genetic variants will be derived from two-thirds of the cohort and validated in the remaining third. Linear models will be used to study the association between environmental factors, cognitive function and addictive behavior. Modifying effects of biomarkers on cognitive function and mental health will be assessed by incorporating it through generalized linear models. To maximize power, the full cohort will be included in the project. We would also like to include the new data from additional participants (still to be released).

Current scope

We aim to investigate interactions between genetics and environmental factors e.g. lifestyle in relation to mental health and addiction. We will examine whether environmental and other risk factors (psychiatric comorbidities) influence addiction besides having overlapping genetic risk factors crucial for prevention and treatment strategies, study genetic variants with known associations to addictions and psychiatric disorders and perform genome-wide exploratory analyses for novel variants. We will investigate the association and modulating effects of genetic variation between mental health and addiction, including pharmacogenetics, known and novel biomarkers, SNPs role in drug effects and cognitive function to understand susceptibility to addiction.

In addition, we aim to investigate the determinants of and the relationships among mental health, cognitive functions, sexual orientation, and addictions. First, we will examine the interactional effect of genetics and environmental factors (e.g., early life conditions) on addictions, psychiatric disorders, cognitive functions, and/or sexual orientation. Second, we will investigate the relationships among addictions, psychiatric disorders, cognitive functions, and sexual orientation (e.g., the prevalence of addictive substance use and psychiatric disorders among sexual minority groups, whether psychiatric disorders are associated with a higher likelihood of addictive substance use and impaired cognitive functions, whether good cognitive functions can buffer against addiction initiation and the severity of psychiatric disorders). Third, we will examine brain structures and resting-state functional connectivity associated with addictions, psychiatric disorders, cognitive functions, and/or sexual orientation.

Extended scope

We are expanding our research question to investigate the connections between genetics and various health aspects more broadly. First, we will explore the interplay between genetics and anthropometric, metabolic, and lifestyle factors related to cardiometabolic health and energy balance. Specifically, we will focus on genetic variants in key appetite-regulating hormones (GHSR, ghrelin, LEAP2) and their relationship with/role in food intake, lipids, glucose metabolism and homeostasis, and body weight regulation. Secondly, we will investigate the role of genetics, inflammatory and co-morbidity profile, life style and personality aspects in neurological disorders, such as headache disorders including migraine, trigeminal neuralgia (TN) and traumatic brain injury (TBI), as well as in the broad spectrum of psychiatric disorders and mental health conditions. This involves studying independent genetic variants (SNPs) associated with neurological and psychiatric disorders, and association analyses regarding co-morbidity, lifestyle, biomarkers and personality traits in order to explore their pathophysiological role, their interplay with environmental factors, and their connections with mental health, and cognitive functions. These studies will additionally require resources such as pain questionnaires and protein biomarkers.