Understanding the Role of Genes and Environment in Substance Use and Mental Illness

October 30, 2018

We know genetics plays a role in substance use and mental illness, but to what extent is environment a factor? Or does one behavior or condition trigger the other?

These are among the questions Dr. Karin Verweij tries to answer in her studies of cannabis use and its associations with mental illness. She has performed twin studies to estimate the heritability of cannabis and ecstasy use. In a twin study the resemblance of identical twins is compared with that of non-identical twins. If identical twins resemble each other more than non-identical twins, this is an indication that part of the individual differences in a trait is due to genetic differences between people. With complex models it is possible to estimate the proportion of individual differences that is due to genetic influences. In her studies, Karin found heritability estimates of approximately 45% for cannabis use, 55% for problematic cannabis use, and 74% for ecstasy use.

With twin studies she also found genetic correlations between substance use and conduct disorder and between cannabis use and educational attainment, which means that part of the genes that play a role in cannabis use, also play a role in conduct disorder and educational attainment.

Over time Karin has also published several papers (with increasingly large sample sizes) in which DNA data was used to search for the specific genes that play a role in cannabis use. In August, she published a paper in Nature Neuroscience in which the first genetic variants for lifetime cannabis use were reported. In that paper the authors also looked at the genetic association of cannabis use with personality traits and various mental health traits. They found strong associations with openness to experience, risk taking behavior, smoking and alcohol consumption, and several psychiatric disorders (including ADHD and autism). They also looked at the causal association between cannabis use and schizophrenia.

The same genes that influence cannabis use also cause schizophrenia—“not entirely, but there is overlap,” she says.  As cannabis use increases, psychotic symptoms tend to increase as well. Verweij wants to know whether the cannabis use is causing the schizophrenia or perhaps the other way around, that cannabis use is an attempt at self-medicating emerging psychotic symptoms.

“I look at whether genes are causing both substance abuse and psychotic symptoms or causing one of them, which leads to the other.”

The ultimate goal of Verweij’s research would be to use her findings in clinical settings to improve treatment options and diagnoses.  Once pharmaceutical companies know which genes cause substance abuse and mental illness, they can work on drugs targeting those specific genes. And once patients have better medications, they should be able to control or eliminate both dependence on harmful substances and psychotic symptoms.

“Those advances won’t happen in the next few years but in the far future,” she says.

Verweij focuses on cannabis use because several researchers already are looking at genetics and smoking or alcohol, and because sample sizes are not yet available for more potent substances such as heroin.  Indeed, much of her data to date has come from an ongoing, collaborative study involving more than 180,000 people who provided DNA and answered questions on cannabis use.

Cohort data from this study is exclusively European ancestry, Verweij says, explaining that another goal for her is to secure data from African or Asian ancestry, or other populations. “We know there will be some differences in which genes are important in these different populations.” At the moment, most available genotype data are still from people with European ancestry, she notes, but more and more data from other ancestral groups are becoming available. Hopefully, soon there will be enough data to perform the analyses also in cohorts with other ancestry.

Verweij says she segued into psychology and neuroscience after a first attempt at human movement science—a tie-in with her athletic youth in Vianen, the Netherlands.

She took a few psychology courses during her studies in human movement and got hooked.  After exploring different avenues, she chose neuroscience and earned her PhD in 2012 at the University of Queensland in Australia. She returned to the Netherlands to be closer to family and friends, and continues her research there.

Karin Verweij is a recipient of the Federation of Associations in Behavioral & Brain Sciences (FABBS) Early Career Impact Award and was nominated by the Behavior Genetics Association.