The causes of reactive aggression and substance abuse are extremely complex and rooted in the interplay of genetic and environmental factors. Several studies have shown that reactive aggression is associated with monoamine oxidase (MAO) A, the major enzyme for the degradation of monoamine neurotransmitters. In particular, reactive aggression is strongly associated with the interaction of 1) low-activity variants of the MAOA gene (uVNTR) and 2) child abuse/neglect. This interaction has been found to be particularly robust in males, although it may be present also in females to a more limited extent. MAOA genetic variants may also moderate the link between alcohol abuse and aggression, but evidence in this respect remains unclear.
We will study the association between early childhood maltreatment, MAO A genetic variants, impulsive aggression and substance use outcomes in college students.
Dr. Paula Fite’s group will perform extensive psychological surveys in college student volunteers to assess several different factors, including early childhood abuse/neglect, history of drug and alcohol use. We will also examine a number of psychological indices that span a constellation of different emotional and personality traits, such as risk-taking, anger, anxiety and impulsivity. To correlate the psychobiological parameters with MAO A, the groups of Drs. Merlin Butler and Ann Manzardo will collect saliva from volunteers and perform genetic screening to test for the presence of low and high activity MAO A polymorphic variants.
We will use innovative animal models to investigate the effects of adolescent alcohol and THC use on modifying the neurobiological and behavioral alterations underlying reactive aggression.
Dr. Marco Bortolato’s group will employ a novel animal model of gene x environment interactions that feature low genetic MAO A activity and early stress. We will test the aggressive and social behaviors of these animals before, during and after chronic exposure to binge alcohol protocols and THC, the main active ingredient in marijuana. To identify potential molecular biomarkers, Dr. Lundquist’s group will perform transcriptomic analyses and whole gene sequencing studies using RNA from treated and untreated animals.
These studies will provide key insights into the relationship between MAO A and early stress in the ontogeny of aggression and the impact of drugs of abuse on mediating these effects.