Original Article| Volume 62, ISSUE 10, P1155-1161, November 15, 2007

Fear-Potentiated Startle to Threat, and Prepulse Inhibition Among Young Adult Nonsmokers, Abstinent Smokers, and Nonabstinent Smokers

  • Christian Grillon
    Address reprint requests to Christian Grillon, Ph.D., 15K North Drive, Building 15K, Room 113, MSC 2670, Bethesda, MD 20892-2670
    Unit of Affective Psychophysiology, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Department of Health and Human Services, Bethesda, Maryland
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  • Shelli Avenevoli
    Section on Developmental Genetic Epidemiology, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Department of Health and Human Services, Bethesda, Maryland

    Department of Psychiatry, The State University of New York at Buffalo, Buffalo, New York.
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  • Elsa Daurignac
    Department of Psychiatry, The State University of New York at Buffalo, Buffalo, New York.
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  • Kathleen R. Merikangas
    Section on Developmental Genetic Epidemiology, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Department of Health and Human Services, Bethesda, Maryland
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      Evidence suggests that the transition from experimental to regular smoking is facilitated by the influence of tobacco on affective and attentional mechanisms. The objective of this study was to examine affective and attentional responses in young adult smokers using fear-potentiated startle and prepulse inhibition.


      Participants were 56 college nonsmokers, nonabstinent smokers, and overnight-abstinent smokers. The fear-potentiated startle test examined phasic responses to imminent threat cues and more sustained responses to unpredictable aversive events. Prepulse inhibition investigated responses to attended and ignored prepulse stimuli.


      Abstinent and nonabstinent smokers showed increased sustained potentiation of startle to contextual cues, compared to controls. Abstinent smokers showed increased fear-potentiated startle to threat cues, compared to nonsmokers. PPI did not discriminate between abstinent or nonabstinent smokers and controls.


      These findings suggest that negative affectivity or anxiety is associated with smoking, particularly during short withdrawal. Potentiated startle may provide a valuable tool in understanding the biologic mechanisms underlying nicotine withdrawal and inform cessation and prevention efforts.

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        • Acri J.B.
        • Morse D.E.
        • Popke E.J.
        • Grunberg N.E.
        Nicotine increases sensory gating measured as inhibition of the acoustic startle reflex in rats.
        Psychopharmacol. 1994; 114: 369-374
        • Brandon T.H.
        • Baker T.B.
        The Smoking Consequences Questionnaire: The subjective expected utility of smoking in college students.
        Psychol Assess. 1991; 3: 484-491
        • Breslau N.N.
        Psychiatric comorbidity of smoking and nicotine dependence.
        Behav Genet. 1995; 25: 95-101
        • Breslau N.N.
        • Johnson E.E.O.
        • Hiripi E.E.
        • Kessler R.R.
        Nicotine dependence in the United States: prevalence, trends, and smoking persistence.
        Arch Gen Psychiatry. 2001; 58: 810-816
        • Cinciripini P.M.
        • Robinson J.D.
        • Carter B.L.
        • Lam C.
        • Wu X.
        • de Moor C.A.
        • et al.
        The effects of smoking deprivation and nicotine administration on emotional reactivity.
        Nicotine Tob Res. 2006; 8: 379-392
        • Davis M.
        Pharmacological and anatomical analysis of fear conditioning using the fear-potientiated startle paradigm.
        Behav Neurosci. 1986; 100: 814-824
        • Davis M.
        Are different parts of the extended amygdala involved in fear versus anxiety?.
        Biol Psychiatry. 1998; 44: 1239-1247
        • DiFranza J.R.J.R.
        • Savageau J.A.J.A.
        • Rigotti N.A.
        • Ockene J.K.J.K.
        • McNeill A.D.
        • Coleman M.M.
        • Wood C.C.
        Trait anxiety and nicotine dependence in adolescents: a report from the DANDY study.
        Addictive Behav. 2004; 29: 911-919
        • Duncan E.
        • Madonick S.
        • Chakravorty S.
        • Parwani A.
        • Szilagyi S.
        • Efferen T.
        • et al.
        Effects of smoking on acoustic startle and prepulse inhibition in humans.
        Psychopharmacol (Berl). 2001; 156: 266-272
        • Fagerstrom K.O.
        • Schneider N.G.
        Measuring nicotine dependence: a review of the Fagerstrom Tolerance Questionnaire.
        J Behav Med. 1989; 12: 159-182
        • Faraday M.M.
        • O’Donoghue V.A.
        • Grunberg N.E.
        Effects of nicotine and stress on startle amplitude and sensory gating depend on rat strain and sex.
        Pharmacol Biochem Behav. 1999; 62: 273-284
        • Filion D.L.
        • Dawson M.E.
        • Schell A.M.
        Modification of the acoustic startle-reflex eyeblink: A tool for investigating early and late attentional processes.
        Biol Psychol. 1993; 35: 185-200
        • Fleming S.E.
        • Lombardo T.W.
        Effects of cigarette smoking on phobic anxiety.
        Addict Behav. 1987; 12: 195-198
        • Geier A.
        • Mucha R.F.
        • Pauli P.
        Appetitive nature of drug cues confirmed with physiological measures in a model using pictures of smoking.
        Psychopharmacol (Berl). 2000; 150: 283-291
        • Geyer M.A.
        • Krebs-Thomson K.
        • Braff D.L.
        • Swerdlow N.R.
        Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.
        Psychopharmacol (Berl). 2001; 156: 117-154
      1. Gilbert DG (1995): Smoking: Individual differences, psychopathology, and emotion. Bristol, PA: Taylor and Francis.

        • Gilbert D.G.
        • Gilbert B.O.
        Personality, psychopathology, and nicotine response as mediators of the genetics of smoking.
        Behav Genet. 1995; 25: 133-147
        • Gilbert D.G.
        • Robinson J.H.
        • Chamberlin C.L.
        • Spielberger C.D.
        Effects of smoking/nicotine on anxiety, heart rate, and lateralization of EEG during a stressful movie.
        Psychophysiol. 1989; 26: 311-320
        • Goodwin R.
        • Hamilton S.P.
        Cigarette smoking and panic: the role of neuroticism.
        Am J Psychiatry. 2002; 159: 1208-1213
        • Grillon C.
        • Ameli R.
        Effects of threat and safety signals on startle during anticipation of aversive shocks, sounds, and airblasts.
        J Psychophysiol. 1998; 12: 329-337
        • Grillon C.
        • Baas J.M.
        A review of the modulation of startle by affective states and its application to psychiatry.
        Clin Neurophysiol. 2003; 114: 1557-1579
        • Grillon C.
        • Baas J.P.
        • Lissek S.
        • Smith K.
        • Milstein J.
        Anxious responses to predictable and unpredictable aversive events.
        Behav Neurosci. 2004; 118: 916-924
        • Grillon C.
        • Dierker L.
        • Merikangas K.
        Startle modulation in children at risk for anxiety disorders and/or alcoholism.
        J Am Acad Child Adolesc Psychiatry. 1997; 36: 925-932
        • Grillon C.
        • Dierker L.
        • Merikangas K.R.
        Fear-potentiated startle in adolescent offspring at risk for anxiety disorder.
        Biol Psychiatry. 1998; 44: 990-997
        • Grillon C.
        • Levenson J.
        • Pine D.S.
        A single dose of the selective serotonin reuptake inhibitor citalopram exacerbates anxiety in humans: a fear-potentiated startle study.
        Neuropsychopharmacol. 2007; 32: 225-231
        • Hogle J.M.
        • Curtin J.J.
        Sex differences in negative affective response during nicotine withdrawal.
        Psychophysiol. 2006; 43: 344-356
        • Hughes J.R.
        • Higgins S.T.
        • Bickel W.K.
        Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities.
        Addiction. 1994; 89: 1461-1470
        • Hutchison K.E.
        • McGeary J.
        • Wooden A.
        • Blumenthal T.
        • Ito T.
        Startle magnitude and prepulse inhibition: effects of alcohol and attention.
        Psychopharmacol. 2003; 167: 235-241
        • Hutchison K.E.
        • Niaura R.
        • Swift R.
        The effects of smoking high nicotine cigarettes on prepulse inhibition, startle latency, and subjective responses.
        Psychopharmacol. 2000; 150: 244-252
        • Jacobsen L.K.
        • Krystal J.H.
        • Mencl W.E.
        • Westerveld M.
        • Frost S.J.
        • Pugh K.R.
        Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers.
        Biol Psychiatry. 2005; 57: 56-66
        • Jones G.M.M.
        • Sahakian B.J.
        • Levy R.
        • Warburton D.M.
        • Gray J.A.
        Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimers’s disease.
        Psychopharmacol. 1992; 108: 437-442
        • Kassel J.D.
        • Stroud L.R.
        • Paronis C.A.
        Smoking, stress, and negative affect: correlation, causation, and context across stages of smoking.
        Psychol Bull. 2003; 129: 270-304
        • Kessler R.C.
        • Üstün T.B.
        The World Mental Health (WMH) survey initiative version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI).
        Int J Methods Psychiatr Res. 2004; 13: 93-121
        • Kumari V.
        • Checkley S.
        • Gray J.
        Effect of cigarette smoking on prepulse inhibition of the acoustic startle reflex in healthy male smokers.
        Psychopharmacol. 1996; 128: 54-60
        • Morris J.S.
        • Ohman A.
        • Dolan R.J.
        Conscious and unconscious emotional learning in the human amygdala.
        Nature. 1998; 393: 467-470
        • Parrott A.C.
        Does cigarette smoking cause stress?.
        Am Psychologist. 1999; 54: 817-820
        • Parrott A.C.
        • Garnham N.J.
        Comparative Mood States and Cognitive Skills of Cigarette Smokers, Deprived Smokers and Nonsmokers.
        Human Psychopharmacol. 1998; 13: 367-376
        • Pomerleau C.S.
        • Pomerleau O.F.
        The effects of a psychological stressor on cigarette smoking and subsequent behavioral and physiological responses.
        Psychophysiol. 1987; 24: 278-285
        • Shiffman S.S.
        Relapse following smoking cessation: a situational analysis.
        J Consult Clin Psychol. 1982; 50: 71-86
        • Swerdlow N.R.
        • Auerbach P.
        • Monroe S.M.
        • Hartston H.
        • Geyer M.A.
        • Braff D.L.
        Men are more inhibited than women by weak prepulses.
        Biol Psychiatry. 1993; 34: 253-260
        • Swerdlow N.R.
        • Geyer M.A.
        • Braff D.L.
        Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges.
        Psychopharmacol (Berl). 2001; 156: 194-215
        • Watson D.
        • Clark L.A.
        • Carey G.
        Positive and negative affectivity and their relation to anxiety and depressive disorders.
        J Abnorm Psychol. 1988; 97: 346-353
        • West R.
        • Hajek P.
        What happens to anxiety levels on giving up smoking?.
        Am J Psychiatry. 1997; 154: 1589-1592