From Genes to Behavior: What does being “genetically at risk” for addiction really mean? Keith Chen Danielle M. Dick, Ph.D. Virginia Commonwealth University Departments of Psychology and Human & Molecular Genetics

Things we know about substance use problems We’re not all equally at risk Genetic influences are important

How do we know something is genetically influenced? MZ Twins DZ Twins 100% shared genetic variation 100% shared home environment 50% shared genetic variation 100% shared home environment If MZs > DZs → Genetic Influence If DZs = MZs → Shared Environmental Influence If MZs < 1 → Unique Environmental Influence

Psychiatric Disorders Other Important Familial Traits ~zero Heritability Psychiatric Disorders Other Important Familial Traits ~zero Language Religious Affiliation 20-40% Anxiety disorders Depression Bulimia Myocardial Infarction Personality, Breast Cancer, Hip Fracture 40-70% Alcohol and drug dependence, Antisocial Behavior Blood Pressure, Asthma Plasma cholesterol, Prostate Cancer, Adult-onset diabetes 70-80% Schizophrenia Bipolar Illness Weight, Bone Mineral Density 80-100% Autism Height, Brain Volume This is how the heritability of alcohol and drug dependence compares to other biomedical traits and disorders. But knowing that a disorder is under genetic influence is really only the first step in understanding genetic influences on addiction. There are a variety of more complex questions we can address about how genetic influences act… Slide courtesy of Ken Kendler, M.D.

Psychiatric Disorders Other Important Familial Traits ~zero Heritability Psychiatric Disorders Other Important Familial Traits ~zero Language Religious Affiliation 20-40% Anxiety disorders Depression Bulimia Myocardial Infarction Personality, Breast Cancer, Hip Fracture 40-70% Alcohol and drug dependence, Antisocial Behavior Blood Pressure, Asthma Plasma cholesterol, Prostate Cancer, Adult-onset diabetes 70-80% Schizophrenia Bipolar Illness Weight, Bone Mineral Density 80-100% Autism Height, Brain Volume This is how the heritability of alcohol and drug dependence compares to other biomedical traits and disorders. But knowing that a disorder is under genetic influence is really only the first step in understanding genetic influences on addiction. There are a variety of more complex questions we can address about how genetic influences act…

Psychiatric Disorders Other Important Familial Traits ~zero Heritability Psychiatric Disorders Other Important Familial Traits ~zero Language Religious Affiliation 20-40% Anxiety disorders Depression Bulimia Myocardial Infarction Personality, Breast Cancer, Hip Fracture 40-70% Alcohol and drug dependence, Antisocial Behavior Blood Pressure, Asthma Plasma cholesterol, Prostate Cancer, Adult-onset diabetes 70-80% Schizophrenia Bipolar Illness Weight, Bone Mineral Density 80-100% Autism Height, Brain Volume This is how the heritability of alcohol and drug dependence compares to other biomedical traits and disorders. But knowing that a disorder is under genetic influence is really only the first step in understanding genetic influences on addiction. There are a variety of more complex questions we can address about how genetic influences act…

Psychiatric Disorders Other Important Familial Traits ~zero Heritability Psychiatric Disorders Other Important Familial Traits ~zero Language Religious Affiliation 20-40% Anxiety disorders Depression Bulimia Myocardial Infarction Personality, Breast Cancer, Hip Fracture 40-70% Alcohol and drug dependence, Antisocial Behavior Blood Pressure, Asthma Plasma cholesterol, Prostate Cancer, Adult-onset diabetes 70-80% Schizophrenia Bipolar Illness Weight, Bone Mineral Density 80-100% Autism Height, Brain Volume This is how the heritability of alcohol and drug dependence compares to other biomedical traits and disorders. But knowing that a disorder is under genetic influence is really only the first step in understanding genetic influences on addiction. There are a variety of more complex questions we can address about how genetic influences act…

Psychiatric Disorders Other Important Familial Traits ~zero Heritability Psychiatric Disorders Other Important Familial Traits ~zero Language Religious Affiliation 20-40% Anxiety disorders Depression Bulimia Myocardial Infarction Personality, Breast Cancer, Hip Fracture 40-70% Alcohol and drug dependence, Antisocial Behavior Blood Pressure, Asthma Plasma cholesterol, Prostate Cancer, Adult-onset diabetes 70-80% Schizophrenia Bipolar Illness Weight, Bone Mineral Density 80-100% Autism Height, Brain Volume This is how the heritability of alcohol and drug dependence compares to other biomedical traits and disorders. But knowing that a disorder is under genetic influence is really only the first step in understanding genetic influences on addiction. There are a variety of more complex questions we can address about how genetic influences act…

GENE for…

Bodies and Brains Substance Use Problems Genes

Things we know about substance use problems We’re not all equally at risk Genetic influences are important There is no one predisposition or genetic pathway to substance use problems Shows up in different ways across development

Just an example from another project showing different pathways of risk

Pathways of Genetically Influenced Risk for Substance Use Outcomes Physiological: the way our bodies respond to a drug Externalizing: impulsivity, sensation-seeking Internalizing: anxious, depressed, drinking to cope So what we know from our research is that there are different pathways by which individuals engage in risky drinking. One factor is physiological response…Other people are more high sensation-seeking, others drink to cope. So there are very different reasons why people drink, but alcohol programming is all one size fits all. Imagine if when you went in to your primary care physician for a wellness check, instead of asking you about you’re your behavior and talking to you about your risks, they rattled off all the health risks for someone of your age. Probably not the most effective way to go. We can do better. (We all have our own unique combination)

Physiological Response Alcohol dehydrogenase genes – involved in the breakdown of ethanol Unpleasant response – less likely to develop problems! Low level of response to alcohol more drinks to experience intoxicating effects have to drink more than average to experience effects heavier drinking can lead to more problems

Pathways of Risk for Substance Use Outcomes Physiological: the way our bodies respond to a drug Externalizing: impulsivity, sensation-seeking Internalizing: anxious, depressed, drinking to cope So what we know from our research is that there are different pathways by which individuals engage in risky drinking. One factor is physiological response…Other people are more high sensation-seeking, others drink to cope. So there are very different reasons why people drink, but alcohol programming is all one size fits all. Imagine if when you went in to your primary care physician for a wellness check, instead of asking you about you’re your behavior and talking to you about your risks, they rattled off all the health risks for someone of your age. Probably not the most effective way to go. We can do better.

So what do we know about how genes influence addiction? There are no genes “for” substance problems Genes influence the way our bodies respond to drugs, as well as our personalities and temperaments, which can put us more or less at risk for developing problems Dispositions are not destiny

COLLEGE BEHAVIORAL AND EMOTIONAL HEALTH INSTITUTE cobe.vcu.edu