Unlocking the puzzle of anxiety and depression

Study examines genetic basis for internalizing disorders

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A current Virginia Commonwealth University study hopes to begin unlocking the key to understanding anxiety and depressive syndromes – conditions that are known as internalizing disorders (IDs).

One in four people will suffer from an anxiety disorder in their lifetime, and between 15 and 20 percent of individuals will experience a depressive episode. Even with these high lifetime prevalence rates, very little is currently known regarding the genetic basis of IDs and how it relates to other internalizing risk factors.

John “Jack” Hettema, M.D., Ph.D., associate professor of psychiatry in the VCU School of Medicine, is leading a study that hopes to illuminate the genetic basis for developing IDs and provide insight into the mechanisms and sets of causes that lead to these disorders.

“Internalizing disorders represent common, debilitating conditions, the etiology of which is not well understood,” said Hettema, who is also a faculty member in the Virginia Institute for Psychiatric and Behavioral Genetics (VIPBG) at VCU. “We’re studying twins, aged 9 to 13, to investigate what measures might predict which children will develop ID. Previous studies have shown that this age group is at the cusp of developing these disorders.”

The study will examine 500 twin pairs recruited through the Mid-Atlantic Twin Registry (MATR), an organization of twins and their families who are willing to consider taking part in twin-based, health-related research. Based at VCU, MATR registers twins of any age, ethnicity and zygosity (identical or fraternal), as well as higher order multiples such as triplets, quadruplets and quintuplets. Most of the twins registered in the MATR are from Virginia, North Carolina and South Carolina, but twins from around the world are welcome to register.

The twins in this study will be given a comprehensive list of questions and experimental tasks and assessed for current and lifetime psychiatric syndromes and symptoms, including IDs, as well as a broad array of childhood risk and protective factors.

“The expected outcome is to provide insights into the mechanisms by which genes and environment confer risk to internalizing disorders,” Hettema said. “Twins have been used for more than a century to study the genetic basis of human traits and medical conditions. The differential genetic relatedness between identical and fraternal twins allows researchers to tease apart the contributions from genes – ‘nature’ – and environment – ‘nurture.’”

The study is funded through the National Institute of Mental Health (NIMH) within the National Institutes of Health. It is one of the first set of grants funded through a new NIMH initiative, the Research Domain Criteria (RDoC) project. RDoC is part of NIMH’s strategic plan to develop new ways of classifying disorders based on dimensions of observable behaviors and brain functions.

Collaborating with Hettema on the study is Roxann Roberson-Nay, Ph.D., assistant professor of psychiatry and faculty member in VIPBG, and Daniel Pine, M.D., chief of the Development and Affective Neuroscience Section at the NIMH.

“This collaboration is ideal as we are combining our expertise. Drs. Pine and Robertson-Nay have conducted numerous research studies of childhood IDs, and we at VIPBG have led or participated in several prior large twin projects,” Hettema said. “With this novel study, we expect to produce numerous groundbreaking articles and expand communication, exchange and collaboration with other experts in the field.”

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