Role of Genes in Executive Dysfunction Confirmed by BUSM Researchers

A study led by researchers at Boston University School of Medicine (BUSM) and the McKnight Brain Institute shows specific genetic traits may predispose people to executive dysfunction. The findings, which are published online in the journal Molecular Neurobiology, also suggest that genetic mapping may help identify problems in demonstrating executive function skills and could serve as a therapeutic adjunct for increasing executive functioning capabilities.

This study was done by Marlene Oscar Berman, PhD, professor of neurology, psychiatry, and anatomy and neurobiology at BUSM, Abdalla Bowirrat, MD, PhD, professor of clinical neuroscience and population genetics at the Nazareth English Hospital in Israel and Kenneth Blum, PhD, professor of psychiatry at the McKnight Brain Institute in Florida. Berman, who was Bowirrat’s postdoctoral mentor at BUSM, also is a research psychologist at the Boston VA Medical Center.

The ability to demonstrate executive function skills is unique to humans and requires a set of complex mental abilities that help in evaluating risk, recognizing consequences of future actions, and suppressing unacceptable social responses. Hence, they are key factors in judging whether something is good or bad. Executive function skills also help individuals pay attention and plan behavior when faced with a novel situation.

All behavior, both “normal” (socially acceptable) and “abnormal” (socially unacceptable), is based on an individual’s genetic makeup at birth. Genetic predispositions also are influenced by environmental factors, including family, educational and socioeconomic status, environmental stressors and the availability of psychoactive drugs and unhealthy foods. Predisposition to behavior is based on a set of genes interacting with the environment, which promote a feeling of well-being by way of neurotransmitters interacting in the “reward center” of the brain.

Executive dysfunction in neuropsychiatric disorders is attributed to an issue with the structure or function of brain networks. Brain circuits involving the prefrontal cortex region of the brain receives signals from different neurons associated with a number of neurotransmitters, particularly dopamine. If that system is disrupted, it could lead to executive dysfunction.

“The defects in specific genes may be causing the flawed metabolism of dopamine, as well as other neurotransmitters,” said Berman. These genetic defects may predispose individuals to executive dysfunction, leading to the demonstration of abnormal behaviors. Examples of abnormal behavior include addictions to alcohol, psychostimulants, marijuana, nicotine (smoking) and opiates, as well as sugar binging, pathological gambling, aggression and sex addiction.

“In order to determine executive function ability, a thorough assessment of both genetic and environmental risk factors needs to be conducted,” Berman added.

The researchers conclude that it is necessary to preserve the integrity and function of the complex neural systems by ensuring that neurotransmitters are metabolized efficiently, including how specific genetic defects impact these systems.

The National Institute on Alcohol Abuse and Alcoholism and the Medical Research Service of the US Department of Veterans Affairs provided funding for this study.