Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-13T02:01:12.717Z Has data issue: false hasContentIssue false
  • English
  • Français

Reactivity to uncertain threat as a familial vulnerability factor for alcohol use disorder

Published online by Cambridge University Press:  14 September 2016

S. M. Gorka ,
D. Hee ,
L. Lieberman ,
V. A. Mittal ,
K. L. Phan  and
S. A. Shankman
S. M. Gorka*
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
D. Hee
Affiliation:
Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA
L. Lieberman
Affiliation:
Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA
V. A. Mittal
Affiliation:
Department of Psychology, Northwestern University, Evanston, IL, USA
K. L. Phan
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA Mental Health Service Line, Jesse Brown VA Medical Center, Chicago, IL, USA Department of Anatomy and Cell Biology and the Graduate Program in Neuroscience, University of Illinois, Chicago, IL, USA
S. A. Shankman
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA
*
*Address for correspondence: Dr S. M. Gorka, University of Illinois at Chicago, 1747 Roosevelt Road, Chicago, IL 60608, USA. (Email: sgorka2@uic.edu)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

When sober, problematic drinkers display exaggerated reactivity to threats that are uncertain (U-threat). Since this aversive affective state can be alleviated via acute alcohol intoxication, it has been posited that individuals who exhibit heightened reactivity to U-threat at baseline are motivated to use alcohol as a means of avoidance-based coping, setting the stage for excessive drinking. To date, however, no study has attempted to characterize the dispositional nature of exaggerated reactivity to U-threat and test whether it is a vulnerability factor or exclusively a disease marker of problematic alcohol use.

Method

The current investigation utilized a family study design to address these gaps by examining whether (1) reactivity to U-threat is associated with risk for problematic alcohol use, defined by family history of alcohol use disorder (AUD) and (2) reactivity to U-threat is correlated amongst adult biological siblings. A total of 157 families, and 458 individuals, participated in the study and two biological siblings completed a threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Startle potentiation was collected as an index of aversive responding.

Results

Within biological siblings, startle potentiation to U-threat [intraclass correlation (ICC) = 0.35] and P-threat (ICC = 0.63) was significantly correlated. In addition, independent of an individuals’ own AUD status, startle potentiation to U-threat, but not P-threat, was positively associated with risk for AUD (i.e. AUD family history).

Conclusion

This suggests that heightened reactivity to U-threat may be a familial vulnerability factor for problematic drinking and a novel prevention target for AUD.

Keywords

Alcohol use disorderstartle potentiationuncertain threatvulnerability factor
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 16 , December 2016 , pp. 3349 - 3358
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alvarez, RP, Chen, G, Bodurka, J, Kaplan, R, Grillon, C (2011). Phasic and sustained fear in humans elicits distinct patterns of brain activity. Neuroimage 1, 389–400.CrossRefGoogle Scholar
Anokhin, AP, Golosheykin, S, Heath, AC (2007). Genetic and environmental influences on emotion-modulated startle reflex: a twin study. Psychophysiology 44, 106–112.Google Scholar
APA (2015). Structured clinical interview for DSM-5 (SCID-5). (http://www.appi.org/products/structured-clinical-interview-for-dsm-5-scid-5/).Google Scholar
Anokhin, AP, Heath, AC, Myers, E, Ralano, A, Wood, S (2003). Genetic influences on prepulse inhibition of startle reflex in humans. Neuroscience Letters 353, 45–48.CrossRefGoogle ScholarPubMed
Avery, SN, Clauss, JA, Blackford, JU (2016). The human BNST: functional role in anxiety and addiction. Neuropsychopharmacology 41, 126–141.Google Scholar
Baker, TB, Piper, ME, McCarthy, DE, Majeskie, MR, Fiore, MC (2004). Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychological Review 111, 33–51.CrossRefGoogle ScholarPubMed
Barlow, DH (2000). Unraveling the mysteries of anxiety and its disorders from the perspective of emotion theory. American Psychologist 55, 1247–1263.Google Scholar
Blumenthal, TD, Cuthbert, BN, Filion, DL, Hackley, S, Lipp, OV, Van Boxtel, A (2005). Committee report: guidelines for human startle eyeblink electromyographic studies. Psychophysiology 42, 1–15.CrossRefGoogle ScholarPubMed
Boelen, PA, Reijntjes, A (2009). Intolerance of uncertainty and social anxiety. Journal of Anxiety Disorders 23, 130–135.Google Scholar
Bradford, DE, Curtin, JJ, Piper, ME (2015). Anticipation of smoking sufficiently dampens stress reactivity in nicotine-deprived smokers. Journal of Abnormal Psychology 124, 128–136.Google Scholar
Bradford, DE, Shapiro, BL, Curtin, JJ (2013). How bad could it be? Alcohol dampens stress responses to threat of uncertain intensity. Psychological Science 24, 2541–2549.CrossRefGoogle ScholarPubMed
Carleton, RN (2016 a). Into the Unknown: a review and synthesis of contemporary models involving uncertainty. Journal of Anxiety Disorders 39, 30–43.CrossRefGoogle ScholarPubMed
Carleton, RN (2016 b). Fear of the unknown: one fear to rule them all? Journal of Anxiety Disorders 41, 5–21.Google Scholar
Carleton, RN, Fetzner, MG, Hackl, JL, McEvoy, P (2013). Intolerance of uncertainty as a contributor to fear and avoidance symptoms of panic attacks. Cognitive Behaviour Therapy 42, 328–341.CrossRefGoogle ScholarPubMed
Carlson, SR, Katsanis, J, Iacono, WG, McGue, M (1997). Emotional modulation of the startle reflex in twins: preliminary findings. Biological Psychology 46, 235–246.Google Scholar
D'Amato, MR (1974). Derived motives. Annual Review of Psychology 25, 83–106.Google Scholar
Davis, M (2006). Neural systems involved in fear and anxiety measured with fear-potentiated startle. American Psychologist 61, 741–756.CrossRefGoogle ScholarPubMed
Davis, M, Walker, DL, Miles, L, Grillon, C (2010). Phasic v. sustained fear in rats and humans: role of the extended amygdala in fear v. anxiety. Neuropsychopharmacology 35, 105–135.CrossRefGoogle Scholar
Gentes, EL, Ruscio, AM (2011). A meta-analysis of the relation of intolerance of uncertainty to symptoms of generalized anxiety disorder, major depressive disorder, and obsessive–compulsive disorder. Clinical Psychology Review 31, 923–933.Google Scholar
Gorka, SM, Lieberman, L, Phan, KL, Shankman, SA (2016). Association between problematic alcohol use and reactivity to uncertain threat in two independent samples. Drug and Alcohol Dependence 164, 89–96.Google Scholar
Gorka, SM, Liu, H, Sarapas, C, Shankman, SA (2015). Time course of threat responding in panic disorder and depression. International Journal of Psychophysiology 98, 87–94.Google Scholar
Gorka, SM, Nelson, BD, Shankman, SA (2013). Startle response to unpredictable threat in comorbid panic disorder and alcohol dependence. Drug Alcohol Dependence 132, 216–222.CrossRefGoogle ScholarPubMed
Grillon, C, Dierker, L, Merikangas, KR (1998). Fear-potentiated startle in adolescent offspring of parents with anxiety disorders. Biological Psychiatry 44, 990–997.CrossRefGoogle ScholarPubMed
Grillon, C, Franco-Chaves, JA, Mateus, CF, Ionescu, DF, Zarate, CA (2013). Major depression is not associated with blunting of aversive responses; evidence for enhanced anxious anticipation. PLoS ONE 8, e70969.Google Scholar
Grillon, C, Heller, R, Hirschhorn, E, Kling, MA, Pine, DS, Schulkin, J, Vythilingam, M (2011). Acute hydrocortisone treatment increases anxiety but not fear in healthy volunteers: a fear-potentiated startle study. Biological Psychiatry 69, 549–555.Google Scholar
Grillon, C, Lissek, S, Rabin, S, McDowell, D, Dvir, S, Pine, DS (2008). Increased anxiety during anticipation of unpredictable but not predictable aversive stimuli as a psychophysiologic marker of panic disorder. American Journal of Psychiatry 165, 898–904.CrossRefGoogle Scholar
Grillon, C, Pine, DS, Lissek, S, Rabin, S, Bonne, O, Vythilingam, M (2009). Increased anxiety during anticipation of unpredictable aversive stimuli in posttraumatic stress disorder but not in generalized anxiety disorder. Biological Psychiatry 66, 47–53.Google Scholar
Grillon, C, Warner, V, Hille, J, Merikangas, KR, Bruder, GE, Tenke, CE, Nomura, Y, Leite, P, Weissman, MM (2005). Families at high and low risk for depression: a three-generation startle study. Biological Psychiatry 57, 953–960.Google Scholar
Grupe, DW, Nitschke, JB (2013). Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nature Reviews Neuroscience 14, 488–501.Google Scholar
Hasenkamp, W, Epstein, MP, Green, A, Wilcox, L, Boshoven, W, Lewison, B, Duncan, E (2010). Heritability of acoustic startle magnitude, prepulse inhibition, and startle latency in schizophrenia and control families. Psychiatry Research 178, 236–243.Google Scholar
Hefner, KR, Curtin, JJ (2012). Alcohol stress response dampening: selective reduction of anxiety in the face of uncertain threat. Journal of Psychopharmacology 26, 232–245.Google Scholar
Hefner, KR, Moberg, CA, Hachiya, LY, Curtin, JJ (2013). Alcohol stress response dampening during imminent v. distal, uncertain threat. Journal of Abnormal Psychology 122, 756.CrossRefGoogle Scholar
Hefner, KR, Starr, MJ, Curtin, JJ (2015). Altered subjective reward valuation among drug-deprived heavy marijuana users: aversion to uncertainty. Journal of Abnormal Psychology 125, 138–150.Google Scholar
Hesselbrock, VM, Stabenau, JR, Hesselbrock, MN, Meyer, RE, Babor, TF (1982). The nature of alcoholism in patients with different family histories for alcoholism. Progress in Neuro-Psychopharmacology and Biological Psychiatry 6, 607–614.Google Scholar
Hogle, JM, Kaye, JT, Curtin, JJ (2010). Nicotine withdrawal increases threat-induced anxiety but not fear: neuroadaptation in human addiction. Biological Psychiatry 68, 719–725.Google Scholar
Holaway, RM, Heimberg, RG, Coles, ME (2006). A comparison of intolerance of uncertainty in analogue obsessive-compulsive disorder and generalized anxiety disorder. Journal of Anxiety Disorders 20, 158–174.Google Scholar
Hong, RY, Cheung, MWL (2015). The structure of cognitive vulnerabilities to depression and anxiety evidence for a common core etiologic process based on a meta-analytic review. Clinical Psychological Science 3, 892–912.Google Scholar
Ingram, RE, Luxton, DD (2005). Vulnerability-stress models. In Development of Psychopathology: A Vulnerability-Stress Perspective (ed. Hankin, B. L. and Abela, J. R. Z.), pp. 32–46. Sage Publications: California.CrossRefGoogle Scholar
Kassel, JD, Jackson, SI, Unrod, M (2000). Generalized expectancies for negative mood regulation and problem drinking among college students. Journal of Studies on Alcohol and Drugs 61, 332.CrossRefGoogle ScholarPubMed
Kendler, KS, Davis, CG, Kessler, RC (1997). The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: a family history study. British Journal of Psychiatry 170, 541–548.Google Scholar
Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR, Walters, EE (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 593–602.Google Scholar
Khantzian, EJ (1997). The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harvard Review of Psychiatry 4, 231–244.Google Scholar
Klein, DN, Glenn, CR, Kosty, DB, Seeley, JR, Rohde, P, Lewinsohn, PM (2013). Predictors of first lifetime onset of major depressive disorder in young adulthood. Journal of Abnormal Psychology 122, 1.Google Scholar
Koob, GF (2013). Negative reinforcement in drug addiction: the darkness within. Current Opinion in Neurobiology 23, 559–563.CrossRefGoogle Scholar
Koob, GF (2003). Alcoholism: allostasis and beyond. Alcoholism Clinical and Experimental Research 27, 232–243.Google Scholar
Koob, GF, Le Moal, M (2001). Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24, 97–129.Google Scholar
Koob, GF, Volkow, ND (2010). Neurocircuitry of addiction. Neuropsychopharmacology 35, 217–238.Google Scholar
Lejuez, CW, Eifert, GH, Zvolensky, MJ, Richards, JB (2000). Preference between onset predictable and unpredictable administrations of 20% carbon-dioxide-enriched air: implications for better understanding the etiology and treatment of panic disorder. Journal of Experimental Psychology: Applied 6, 349–358.Google ScholarPubMed
Merikangas, KR, Stolar, M, Stevens, DE, Goulet, J, Preisig, MA, Fenton, B, Zhang, H, O'Malley, SS, Rounsaville, BJ (1998). Familial transmission of substance use disorders. Archives of General Psychiatry 55, 973–979.Google Scholar
Miller, GA, Chapman, JP (2001). Misunderstanding analysis of covariance. Journal of Abnormal Psychology 110, 40.Google Scholar
Moberg, CA, Curtin, JJ (2009). Alcohol selectively reduces anxiety but not fear: startle response during unpredictable v. predictable threat. Journal of Abnormal Psychology 118, 335–347.Google Scholar
Nelson, BD, McGowan, SK, Sarapas, C, Robison-Andrew, EJ, Altman, SE, Campbell, ML, Gorka, SM, Katz, AC, Shankman, SA (2013). Biomarkers of threat and reward sensitivity demonstrate unique associations with risk for psychopathology. Journal of Abnormal Psychology 122, 662–671.Google Scholar
Oglesby, ME, Boffa, JW, Short, NA, Raines, AM, Schmidt, NB (2016). Intolerance of uncertainty as a predictor of post-traumatic stress symptoms following a traumatic event. Journal of Anxiety Disorders 41, 82–87.Google Scholar
Rohde, P, Lewinsohn, PM, Seeley, JR (1997). Comparability of telephone and face-to-face interviews assessing Axis I and II disorders. American Journal of Psychiatry 154, 1593–1598.Google Scholar
Rollman, GB, Harris, G (1987). The detectability, discrimability, and perceived magnitude of painful electrical shock. Perception & Psychophysics 42, 257–268.CrossRefGoogle ScholarPubMed
Rosenberg, DR, Sweeney, JA, Squires-Wheeler, E, Keshavan, MS, Cornblatt, BA, Erlenmeyer-Kimling, L (1997). Eye-tracking dysfunction in offspring from the New York High-Risk Project: diagnostic specificity and the role of attention. Psychiatry Research 66, 121–130.Google Scholar
Schmitz, A, Grillon, C (2012). Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test). Nature Protocols 7, 527–532.Google Scholar
Shankman, SA, Nelson, BD, Sarapas, C, Robison-Andrew, EJ, Campbell, ML, Altman, SE, McGowan, SK, Katz, AC, Gorka, SM (2013). A psychophysiological investigation of reward and threat sensitivity in individuals with depression and/or panic disorder. Journal of Abnormal Psychology 122, 322–338.Google Scholar
Shihata, S, McEvoy, PM, Mullan, BA, Carleton, RN (2016). Intolerance of uncertainty in emotional disorders: what uncertainties remain? Journal of Anxiety Disorders 41, 115–124.Google Scholar
Vaidyanathan, U, Malone, SM, Miller, MB, McGue, M, Iacono, WG (2014). Heritability and molecular genetic basis of acoustic startle eye blink and affectively modulated startle response: a genome-wide association study. Psychophysiology 51, 1285–1299.CrossRefGoogle ScholarPubMed
Zubin, J, Spring, B (1977). Vulnerability: a new view of schizophrenia. Journal of Abnormal Psychology 86, 103.Google Scholar