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ALCohoL ReSeARCh: C u r r e n t R e v i e w s
506 Alcohol Research: C u r r e n t R e v i e w s
Resilience to Meet the Challenge of Addiction Psychobiology and Clinical Considerations
Tanja N. Alim, M.D.; William B. Lawson, M.D.; Adriana Feder, M.D.; Brian M. Iacoviello, Ph.D.; Shireen Saxena, M.S.; Christopher R. Bailey; Allison M. Greene, M.S.; and Alexander Neumeister, M.D.
Tanja N. Alim, M.D., is an assis- tant professor and William B. Lawson, M.D., is a professor and chair of the Department of Psychiatry, both at the Department of Psychiatry and Behavioral Sciences, Howard University, Washington, DC.
Adriana Feder, M.D., is an assistant professor; Brian M. Iacoviello, Ph.D., is a postdoctoral fellow; and Shireen Saxena, M.S., Christopher R. Bailey, and Allison M. Greene, M.S., are research associates; all at the Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York.
Alexander Neumeister, M.D., is a professor in the Department of Psychiatry and Radiology, New York University Langone Medical Center, New York, New York.
Acute and chronic stress–related mechanisms play an important role in the development of addiction and its chronic, relapsing nature. Multisystem adaptations in brain, body, behavioral, and social function may contribute to a dysregulated physiological state that is maintained beyond the homeostatic range. In addition, chronic abuse of substances leads to an altered set point across multiple systems. Resilience can be defined as the absence of psychopathology despite exposure to high stress and reflects a person’s ability to cope successfully in the face of adversity, demonstrating adaptive psychological and physiological stress responses. The study of resilience can be approached by examining interindividual stress responsibility at multiple phenotypic levels, ranging from psychological differences in the way people cope with stress to differences in neurochemical or neural circuitry function. The ultimate goal of such research is the development of strategies and interventions to enhance resilience and coping in the face of stress and prevent the onset of addiction problems or relapse. Key WoRDS: Addiction; substance abuse; stress; acute stress reaction; chronic stress reaction; biological adaptation to stress; psychological response to stress; physiological response to stress; resilience; relapse; coping skills; psychobiology
evidence from different disciplinessuggests that acute and chronicstress–related mechanisms play an important role in both the develop- ment and the chronic, relapsing nature of addiction (Baumeister 2003; Baumeister et al. 1994; Brady and Sinha 2005). Stress is defined as the physiological and psychological process resulting from a challenge to homeostasis by any real or perceived demand on the body (Lazarus and Fokman 1984; McEwen 2000; Selye 1976). Stress often induces
multisystem adaptations that occur in the brain and body and affect behavioral and social function. The resulting dynamic condition is a dysregulated physiological state maintained beyond the homeostatic range. This definition and conceptualization of stress was fur- ther developed to explain the chronic abuse of substances and comfort foods and has been studied in the context of behavioral addiction (i.e., pathological gambling) (Dallman et al. 2005; Koob and Le Moal 1997; Koob 2003).
Persistent challenges to an organism through chronic substance use may ultimately lead to an altered set point across multiple systems. This hypothe- sis is consistent with evidence that sug- gests adaptations in brain reward and stress circuits, and local physiology (e.g., energy balance) can contribute to addictive processes. Cravings or urges, decreases in self-control, and a compul- sive engagement in unhealthy behaviors each characterize patients with addiction (Dallman et al. 2005; Kalivas and
Volkow 2005; Koob et al. 2004; Sinha 2001). Alternatively, a person’s ability to successfully cope with high stress is reflected in adaptive physiological and psychological responses (Charney 2004; MacQueen et al. 2003). Resilience, defined as the absence of psychopathology despite exposure to high stress, can be studied by examining interindividual differences in stress responsivity across an organism’s various types (i.e., at multiple phenotypic levels). Responsivity ranges from psychological differences in the way individuals cope with stress to differences in neuro- chemical or neural circuitry function (Cicchetti and Blender 2006). Variability within the genetic makeup and quality of early-life experience, as well as inter- actions between the two, are known to contribute to differences in stress resilience (Enoch 2010; Heim and Nemeroff 2001). Genetic influences can stem from gene–environment interactions, changes in gene expres- sion influenced by the environment (i.e., epigenetic changes), or variation within the actual genetic code. Some examples of genetic influences on resilience include variability in the genes involved in the body’s stress response (i.e., those controlling the hypothalamic– pituitary–adrenal [HPA] axis). These include those coding for the corti- cotropin-releasing factor (CRF) type 1 receptor or the glucocorticoid receptor (GR) (which cortisol can activate) as well as the serotonin transporter cathecol-O-methyltransferase (COMT), neuropeptide Y (NPY), and brain- derived neurotrophic factor (BDNF) genes (Feder et al. 2009) Genetic varia- tion in the gene encoding the CRH1 receptor was found to moderate the impact of stress, for example, among adolescents engaging in heavy drinking (Blomeyer et al. 2008; Schmid et al. 2010). This gene-by-environment interaction predicted the initiation of drinking in adolescence as well as pro- gression to heavy drinking by young adulthood (Schmid et al. 2010). The following sections highlight resilient responses to stress in studies in which stress was identified as an important
factor contributing to the neurobiology of alcohol dependence.
Psychosocial Factors Associated With Resilience
Early studies of children exposed to adversity (Masten 2001; Masten and Coatsworth 1998; Rutter 1985) as well as more recent studies in resilient adults (Ahmad et al. 2010; Alim et al. 2008; Bonanno 2004) have identified a range of psychosocial factors associated with successful adaptation to stressful or traumatic events. For example, the ability to simultaneously experience
both positive and negative emotions when confronted with a high-stress situation increases flexibility of think- ing and problem solving and can buffer individuals from developing stress-induced adverse consequences (Fredrickson 2001; Ong et al. 2006). Likewise, optimism has been associated with resilience to stress-related disorders, including alcohol use disorders (Ahmad et al. 2010; Alim et al. 2008). Unlike personality characteristics associated with increased risk for sub- stance use disorders (e.g., impulsivity, novelty seeking, and negative emotion- ality), positive emotionality, the tendency to experience positive mood frequently, was found to be associated with resilience to substance use in a large longitudinal study of public school students fol- lowed from late childhood through midadolescence (Wills et al. 2001). In this study, positive emotionality was found to buffer the effects of parent–
child conflict and of parental and peer substance use on adolescent substance use. The ability to focus attention on performing and completing tasks was identified as a protective factor against substance use (Wills et al. 2001). The ability to focus attention might relate to the capacity to cope by planning and problem solving in times of stress, both types of coping styles characteris- tic of resilient individuals (Southwick et al. 2005). Veenstra and colleagues (2007) examined the impact of coping style on alcohol use in response to stressful life events in a sample of 1,608 men and 1,645 women drawn randomly from the Dutch Lifestyle and Health Study (Veenstra et al 2007). Individuals who scored high on emotion coping, a coping style focused on feelings and emotional content to cope with stress, used more alcohol when experiencing a negative life event, compared with those who scored low on emotion coping. Alcohol use in times of stress did not vary by cognitive or by action coping, but the study found that cog- nitive coping and having more social contacts was linked to lower alcohol use in general. Another study of more than 1,300 adult drinkers in the gen- eral population from a New York county found stress-induced drinking in a subset of men (but not women) who scored high on avoidance coping and on positive expectancy from alcohol (Cooper et al. 1992). Men with low-avoidance coping and low expectancy from alcohol, on the other hand, actually showed a negative relationship between stressful life events and alcohol use. Of note, low avoidance coping has been linked to stress resilience in general, in several other studies (Alim et al. 2008; Carver et al. 1997).
Neurochemistry of Resilience
“Allostasis” refers to the dynamic pro- cess through which the body adapts to daily stressors and maintains home- ostasis (Sterling and Eyer 1988). Sudden
Resilience to Meet the Challenge of Addiction: Psychobiology and Clinical Considerations 507
The ability to focus attention on performing and completing tasks was identified as a
protective factor against substance use.
stressful events trigger the release of the “flight-or-fight” hormones (i.e., cate- cholamines) and other stress hormones in the brain, preparing the organism to cope with stress and avert harm. This process is mediated by a stress circuit (see figure 1), which is consistently implicated in stress-related disorders such as mood and anxiety disorders and addictive disorders. Interindividual variability in stress resilience results from differences in the coordinated stress response. This response com- prises the function and interactions…
