DESCRIPTION (provided by applicant): Young Veterans of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) may be at heightened risk for alcoholism and other psychopathologies as the result of brain damage associated with heavy episodic or binge drinking (BD) during adolescence. Our young Veterans have come of age in a milieu in which BD is highly prevalent. Over 50% of OEF/OIF/OND Veterans were born after 1980 and transitioned through adolescence and into adulthood in the 1990's and 2000's when the problem of BD in young people became apparent. A large literature has amassed indicating that the period of adolescence is a critical time of brain maturation for neural systems, notably prefrontal regions and the limbic system [37] that are associated with the acquisition of complex executive functions, including response inhibition that is critical for behavioral regulation. Recent work suggests that neuropathological damage known to occur in adult chronic alcohol abusers is present in young BD's (e.g., reduced cerebellar volumes, changes in white matter integrity, abnormal cortical thickness, etc. [49; 56; 76]). As such, it is possible that BD during the vulnerable time period of adolescent brain development may interfere with normal maturation and have persisting effects [59]. We suggest that the combination of neural compromise in essential circuitry for the very cognitive functions that are required to remain in control of one' desires and impulsive tendencies is contributing to the high rates of alcohol dependence and abuse we currently see in young Veterans. [In the proposed research we test the overarching hypothesis that a pattern of BD during adolescence results in altered white matter development in the brain, which then interferes with the normal maturation of executive functions that are essential for inhibitory control and sound decision-making. The proposed study will examine 120 Veterans of OEF/OIF/OND, ranging in age from 25-35 years. Sixty Veterans will have a history of BD that began during adolescence; half will be male (MBD) and half will be female (FBD). The two BD groups will be matched for total lifetime consumption of alcohol, months of binge drinking episodes, and severity of posttraumatic stress symptoms. They will be compared to a group of 60 control (CON) Veterans; 30 male (MCON) and 30 female (FCON), matched with regard to important demographic factors to the BD groups, but will have no history of BD. We will use innovative neuroimaging procedures to link clinical and cognitive information to alterations in brain structure and function. In doing so, we will address three aims: (1) determine if a history of BD influences specific brain circuitry linked to inhibitory control in Veterans; (2 link white matter integrity and functional connectivity to inhibitory control and impulsiveness in Veterans with a history of adolescent BD; and (3) examine whether gender differences are present in alterations in brain circuitry (Aim 1) or in the relationships between WM integrity, functional connectivity, and inhibitory control and impulsiveness (Aim 2). We also propose a limited pilot study using simultaneous PET/MRI to compare dopamine release in subgroups of BD's compared to CON's. Through this research, we will gain an understanding of the underlying mechanisms that may promote alcohol abuse and dependence, as well as other psychopathologies, in adulthood. This understanding can lead to interventions targeted to those at greatest risk for the development of chronic abuse. This study may reveal biomarkers of risk for alcoholism and other psychopathologies.

PUBLIC HEALTH RELEVANCE: Binge drinking (BD) is a popular form of entertainment in teenagers and is highly prevalent in military service members. Increasing evidence suggests that BD during adolescence may have life-long neurobiological and cognitive consequences. This is a time in life where cognitive systems and the underlying neural architecture necessary to modulate increased desires to engage in risky behaviors are developing but not yet mature and may be vulnerable to alcohol- related damage. In the proposed work we investigate the impact that adolescent binge drinking has on the neural and cognitive health of Veterans of OEF/OIF/OND. We suspect that adolescent binge drinking will be associated with damage to the very brain regions that are necessary to modulate risky behaviors, like excessive alcohol consumption, which sets up a vicious cycle of vulnerability to drink and further damage to the brain.