RESULTS Images are displayed in Fig 2 at p < 0.05 uncorrected.

1. Figure 1. TASK STIMULI • Shuffled Non-Alcohol Alcohol • INTRODUCTION • Adolescence is a high-risk period for initiating alcohol use and problem drinking. The biological mechanisms underlying the transition to problem drinking remain to be fully elucidated. Family history of alcohol use disorders has been found to be a predictor of future dysfunctional alcohol use. This, in part, may be due to altered processing of alcohol-specific cues by reward-related neural systems in the brain. The purpose of this study was to compare alcohol cue reactivity in in adolescents with vs. those without a family history of alcoholism and light vs. heavy drinkers of alcohol. • HYPOTHESIS • Adolescent alcohol users with a family history of alcoholism (FHP) in 1 or more 1st degree relatives will be more responsive to alcohol-specific cues than family history negative (FHN) persons as evidenced by increased amygdala and nucleus accumbens activation during a cue-based functional MRI task. • Heavy drinkers (Hi), as identified by lifetime AL score, will be more responsive to alcohol-specific cues than light drinkers (Low) as evidenced by increased amygdala and nucleus accumbens activation. The Effects of Family History and Alcohol Use on Alcohol Cue Reactivity: an fMRI Study B.M. Anderson1, M.C. Stevens1,2, M. Ginley1, R Rosen1, R Jiantonio1, S. Raskin3, H. Tennen4, C. Austad5, C.R. Fallahi5, R. Wood5, G.D. Pearlson1,2 1Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, Hartford, CT; 2Dept. of Psychiatry, Yale University School of Medicine, New Haven, CT; 3Dept. of Psychology, Trinity College, Hartford, CT; 4University of Connecticut Health Center, Farmington, CT; 5Dept. of Psychology, Central Connecticut State University, New Britain, CT • RESULTS • Images are displayed in Fig 2 at p < 0.05 uncorrected. • FHP participants’ nucleus accumbens (NAcc) showed diminished response to alcohol cues compared to FHN, in a pattern that pointed to a specific effect of alcohol-content, not simply a less responsive reward system. • In contrast,in participants with high dysfunctional drinking scores, NAcc showed an enhanced response to alcohol cues. This may have resulted from less activation to alcohol images in light drinkers. DISCUSSION This study shows there are differences in reward processing of alcohol cues in the NAcc between family history positive and negative individuals and between those with low and high dysfunctional drinking scores. FHP showed less Nacc response to alcohol cues than FHN while participants with high dysfunctional drinking scores showed enhanced response to alcohol cues. CONCLUSIONS There are differences in reward processing of alcohol cues in NAcc related to both alcoholism family history and degree of alcohol use. The diminished rather than enhanced Nacc activity in FHP raise questions about the applicability of adult “craving” neurobiological models to the study of younger persons at- risk for alcoholism. The results also suggest that reward processing abnormalities in FHP may be complex and not explained simply by reward deficiency models. • MATERIALS AND METHODS • College age freshman students in an ongoing NIAAA-funded longitudinal study (Brain and Alcohol Research with College Students) were recruited to participate in a modified functional imaging alcohol cue reactivity task. • Participants (n= 59; average age = 18.7 ± 2.6 years; 33 female, 26 male) were divided by family history of alcoholism status (positive and negative) and current alcohol dysfunction scores low dysfunction < =10; high dysfunction > 10) based on the AL interview (a portion of the Semi-Structured Assessment for the Genetics of Alcoholism). • 16 FHN low; 25 FHN hi; 6 FHP low; 12 FHP hi • Participants viewed a series of 22 alcohol, 22 matched soft drink/bottled water and 44 degraded/shuffled beverage pictures. (See Figure 1.) Each picture was presented for 1750 msec with intermittent fixation periods. The entire task lasted 5 minutes and 54 seconds. Participants responded with a key press whether they liked, disliked or were neutral towards the images. Fig. 2 c. INTERACTION Alcohol –vs. – Baseline Fig. 2 b. EFFECT OF AL INTERVIEW Low > Hi Alcohol –vs. – Baseline Fig. 2 a. EFFECT OF FAMILY HISTORY FHN > FHP Alcohol –vs. – Baseline • IMAGE ACQUISITION & PROCESSING • Functional data were acquired on a Siemens Allegra 3T scanner at the Olin Neuropsychiatry Research Center, with an EPI sequence of TR/TE 1500/28ms, flip angle 65 degrees, FOV 24 cm x 24 cm, 64 x 64 matrix, 3.4 mm x 3.4 mm in plane resolution, 5 mm effective slice thickness, 30 slices. • SPM5 was used to correct head motion (INRIAlign), correct slice timing acquisition, spatially normalize to MNI space and to smooth (9mm FWMH) EPI timeseries data. • The effect of alcohol vs. non-alcohol images, alcohol vs. shuffled images, and non-alcohol images vs. shuffled images was examined using SPM5 factorial models (2 family history status x 2 alcohol drinking level) • The effect of family history, effect of drinking level, and interaction of family history x drinking level were evaluated at an exploratory threshold of p < 0.05 uncorrected. Supported by NIAAA grant AA016599-02. and funding from the ABMRF/The Foundation for Alcohol Research.