Altered Emotion-Modulated Startle in Young Adults With a Family History of Alcoholism Robert Miranda, Jr, Lori A. Meyerson, Tony W. Buchanan, and William R. Lovallo Background: Alcoholism risk may be accompanied by poor regulation of emotions, signaling altered central nervous system processes. This study used the emotion-modulated startle paradigm to test the hypothesis that young adults with a positive paternal history of alcoholism (FH+), relative to family-history- negative persons (FH-), have altered emotional reactivity to environmental cues. Methods: We tested 30 FH+ and 30 FH-, 15 males and 15 females in each group. Participants completed self-report instruments and interviews and had eye blink electromyograms (EMG) measured to acoustic startle probes while viewing color photographs rated as affectively pleasant, neutral, and unpleasant. Results: FH- had the expected linear increase in startle magnitude, with eye blink EMG gaining in strength (F = 18, p  0.0002) from pleasant to neutral to unpleasant slides. In contrast, FH+ did not show EMG potentiation to the unpleasant slides and therefore lacked the same linear trend (F  1, p  0.4). Notably, FH groups rated the emotional valence and arousal of the photographs in similar ways. Self- reported negative affect partly accounted for the lack of startle potentiation in FH+, suggesting that startle modulation differences between the groups may be associated with underlying psychological characteristics. Conclusions: These findings implicate altered limbic outputs to the startle pathway in FH+ despite normal conscious evaluation of emotional arousal and pleasantness of the slides. This method may provide a useful paradigm for testing processing of emotionally relevant stimuli in relation to risk for alcohol use disorders. Key Words: Alcohol Dependence, Family History, Emotion-Modulated Startle Reflex. W HILE MUCH RESEARCH on alcoholism concerns its consequences, identifying factors that predate the disorder is crucial to understanding its etiology. The present study used the emotion-modulated startle tech- nique to examine emotional reactivity in young adults with a family history of alcoholism (FH+) in relation to differ- ences in indicators of temperament. Family prevalence, twin, and adoption studies suggest that alcoholism risk includes both inherited and environ- mental contributions (Schuckit, 1994; Tarter et al., 1999). Inherited factors include biologically rooted individual dif- ferences in behavioral tendencies and self-regulation (Thomas and Chess, 1977). It has been postulated that such dispositions may be related to variations in affective re- sponsivity to environmental cues and are associated with different temperamental styles (Bates, 2000; Strelau, 1983,1994). Within this conceptual framework, alterations in affective responsiveness may impede central inhibitory processes and lead to poor behavioral control and a gen- erally disinhibited temperament (Finn et al., 1994; Goren- stein and Newman, 1980; Gray, 1991). A variety of evidence has shown that FH+ exhibit poor impulse control, antiso- cial tendencies, negative affectivity, and sensation seeking (Finn et al., 1997; Sher et al., 1991) and these, in part, mediate the relationship between family background and the development of alcohol use disorders (Chassin et al., 1999; Finn et al., 2000). Consistent with this formulation, FH+ have shown al- terations of neural systems that regulate physiologic re- sponsiveness to emotionally charged stimuli. In particular, they appear to be hyporesponsive to aversive stimuli. We have observed diminished cortisol secretion in response to physical and mental stress among abstinent alcoholics (Ber- nardy et al., 1996; Errico et al., 1993; Lovallo et al., 2000). Others have observed a stress cortisol hyporesponsiveness in FH+ boys, ages 10 to 12, relative to family-history- negative (FH-) peers (Moss et al., 1995). Notably, nonre- sponders were more likely to smoke nicotine and marijuana From the Department of Psychiatry and Behavioral Sciences and VA Medical Center (RM, WRL), University of Oklahoma Health Sciences Cen- ter, Oklahoma City, Oklahoma; Department of Psychology (RM, LAM), Oklahoma State University, Stillwater, Oklahoma; and Department of Neu- rology (TWB), University of Iowa College of Medicine, Iowa City, Iowa. RM is now at the Center for Alcohol and Addiction Studies, Brown University, Box G-BH, Providence, RI 02912. Received for publication August 3, 2001; accepted January 22, 2002. Supported by the Medical Research Service of the Department of Veterans Affairs, the Alcoholic Beverage Medical Research Foundation, the Oklahoma Center for the Advancement of Science and Technology, and grant AA-05559 from the NIH. Reprint requests: William R. Lovallo, PhD, Veterans Affairs Medical Center (151A), 921 NE 13th Street, Oklahoma City, Oklahoma 73104; Fax: 405-279-5909; E-mail: bill@mindbody1.org Copyright © 2002 by the Research Society on Alcoholism. 0145-6008/02/2604-0441$03.00/0 ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 26, No. 4 April 2002 Alcohol Clin Exp Res, Vol 26, No 4, 2002: pp 441–448 441