In an effort that could vastly improve treatments, psychologists are delving more deeply than ever before into the roles played by genes and gene expression in mental illness, substance abuse and neurodevelopmental disorders. These psychologists are intent on closing an important research loop.
"Over the years, there has been a tremendous amount of work on the molecular side, a tremendous amount of work on the behavioral side, but relatively little precise work that connects the dots between the two, especially in the context of vulnerability," says J. David Jentsch, PhD, professor of psychology at Binghamton University.
This work is garnering major interest from the National Institutes of Health in the form of its Roadmap Epigenomics Project, for example, a research consortium launched in 2007 to develop publicly available epigenome maps of many types of human cells. In addition, individual institutes, including the National Institute of Mental Health, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, are providing generous funding in the area. In 2014 and 2016, NIDA awarded two five-year grants of $12 million each to two groups of researchers to study the link between genes and behavior related to drug abuse. NIDA also pours millions of dollars into the Avenir awards, which fund early-stage investigators in the study of drug abuse genetics and epigenetics.
A fit for psychology
While neurogenetics and epigenetics are embedded within the larger study of genetics, their foci make them particularly attractive areas for psychological study.
Neurogenetics addresses gene-related phenomena related to the brain and central nervous system. Epigenetics—which can encompass neurogenetics or any other form of genetic study—refers to the larger forces that shape gene expression, among them environmental and developmental influences.
At a molecular level, these influences may affect whether a gene is turned on (leading generally to the synthesis of a specific protein), how deeply a gene is located within a DNA coil or how much of an influential biochemical process called methylation is happening inside a DNA molecule, for example. While such processes do not change the gene per se—they are not gene mutations, in other words—they can affect gene expression and thus behavior.
While many players sit at the neurogenetics and epigenetics table—among them molecular biologists, genetic statisticians and developmental biologists, to name a few—psychologists offer unique assets. For one, they already know a lot about the brain's workings and its effects on behavior. The study of epigenetics is particularly compelling for psychologists because it offers the opportunity to examine and control behavioral influences on genetic programming, says Jeremy Day, PhD, who studies the epigenetics and neurogenetics of cocaine addiction in his lab at the University of Alabama, Birmingham.
"We now know that a considerable fraction of your epigenome is modifiable by your experiences—that every major experience you have changes how genes are expressed in some of the cells in your brain," he says.
In terms of addiction research, this means that the aspects of a person's genetic expression that allow him or her to become addicted in the first place could themselves be targets for intervention. If those interventions are successful, they could lessen a person's tendency toward addictive behavior.
That same thinking can be applied to other conditions as well, says Day. Depending on the gene and brain areas involved, such strategies could be used to help people remember important information or stay calm under pressure, for example.
"The thing that intrigues me, and many other people with a psychology background, is that these [epigenetic factors] can be modified"—not necessarily by changing the genetic code, but by changing how genes are turned off and on in different neurons, he says.
Psychologists also bring important perspectives from the field's various subdisciplines. With funding from NIMH, for instance, Virginia Tech psychologist Sarah Clinton, PhD, is studying not only the genetic and epigenetic underpinnings of anxiety and depression in rats, but what those phenomena look like at different developmental stages. Understanding such patterns could help tailor treatments in very young children before these propensities become full-blown disorders.
"This idea of tailoring particular treatment strategies based on molecular biomarkers would ideally be the wave of the future," she says.
Major growth area
New tools are now enabling this work to proceed with unprecedented accuracy, adds Clinton. Five years ago, if researchers wanted to measure DNA methylation, for instance, they had to remove and examine tissue from the brain area they were interested in—a gross measure of this chemical process. But with new technology, researchers can collect specific DNA samples from various animal sources—such as brain tissue, blood or saliva—view the DNA sequence and map out in fine detail the patterns of methylation within a single gene or even a particular gene segment.
Meanwhile, University of Minnesota assistant professor Nicola Grissom, PhD, is attempting to better understand the molecular, genetic and epigenetic phenomena that may fuel neurodevelopmental conditions such as autism and attention-deficit/hyperactivity disorder (ADHD). She's especially interested in examining such processes in the brain areas responsible for goal-directed behavior and executive function, identified in previous research as areas that function differently in people with these conditions.
Grissom and other psychologists add a distinctly human touch to these fields as well. For example, Grissom is interested in testing whether nonpharmacological interventions such as tailored cognitive training can act epigenetically to improve quality of life for those with autism or ADHD. In other efforts, Jentsch, who studies additions and genetics at Binghamton, is intrigued by work suggesting that targeted behavioral interventions—cognitive training or aerobic exercise, for instance—may enhance addicts' ability to exert self-control.
Starting gene-related inquiry with an eye to human behavior and consequences, rather than simply with cells and genes, gives this work added significance, Jentsch believes.
"The findings are more translational, and they can end up impacting on more diseases because we started with the right focus," he says.
