Stress Modulates Illness-Course of Substance Use Disorders: A Translational Review

Abstract

Childhood trauma and post-childhood chronic/repeated stress could increase the risk of a substance use disorder by affecting five stages of addiction illness-course: (a) initial experimentation with substances; (b) shifting from experimental to regular use; (c) escalation from regular use to abuse or dependence; (d) motivation to quit; and (e) risk of (re-)lapse. We reviewed the human literature on relationships between stress and addiction illness-course. We explored per illness-course stage: (i) whether childhood trauma and post-childhood chronic/repeated stress have comparable effects and (ii) whether effects cut across classes of substances of abuse. We further discuss potential underlying mechanisms by which stressors may affect illness-course stages for which we relied on evidence from studies in animals and humans. Stress and substances of abuse both activate stress and dopaminergic motivation systems, and childhood trauma and post-childhood stressful events are more chronic and occur more frequently in people who use substances. Stressors increase risk to initiate early use potentially by affecting trait-like factors of risk-taking, decision making, and behavioral control. Stressors also accelerate transition to regular use potentially due to prior effects of stress on sensitization of dopaminergic motivation systems, cross-sensitizing with substances of abuse, especially in people with high trait impulsivity who are more prone to sensitization. Finally, stressors increase risk for abuse and dependence, attenuate motivation to quit, and increase relapse risk potentially by intensified sensitization of motivational systems, by a shift from positive to negative reinforcement due to sensitization of the amygdala by corticotropin releasing factor, and by increased sensitization of noradrenergic systems. Stress generally affects addiction illness-course across stressor types and across classes of substances of abuse.

Stress-related salivary alpha-amylase (sAA) activity in alcohol dependent patients with and without a history of childhood maltreatment

“…Moreover, AD patients with CM (C+ A+) showed the highest ratings of distress during or after the TSST whereas AD patients without CM (C−A+) showed the lowest ratings. This result seems to support the findings from prior studies that linked higher stress vulnerability to a higher risk of relapse (Lijffijt et al 2014). Significant differences could also be found with regard to the mood ratings with C −A+ participants showing the highest values on the mood scale during the entire course of the investigation.…”

“…Childhood maltreatment (CM) presents a risk factor for alcohol dependence (AD) and has been linked to a more severe clinical profile and a higher risk for relapse (Keyes et al 2011;Lijffijt et al 2014). One potential factor that has been discussed to moderate the interaction between CM and AD is an altered functioning of the neurobiological stress systems (Keyes et al 2011;Lijffijt et al 2014).…”

“…One potential factor that has been discussed to moderate the interaction between CM and AD is an altered functioning of the neurobiological stress systems (Keyes et al 2011;Lijffijt et al 2014). Besides the hypothalamic-pituitary-adrenal axis (HPA axis), the noradrenergic (NA)/sympathetic system has been associated with persistent functional changes after CM (De Bellis and Zisk 2014).…”

Stress exposure and the risk for the onset of alcohol use disorders and nicotine dependence in deployed military personnel: The role of prior internalizing disorders

“…This was necessary due to the restricted sample size. However, both incidence and recurrence of SUDs could be equally related to stressful experiences (Lijffijt et al, 2014;Sinha, 2008), wherefore this strategy seemed appropriate for the purpose of this study. Individuals that already met the criteria for a 12-month SUD diagnosis at Time 1 were excluded from the respective analysis ( Fig.…”

“…On a behavioral level, there is some empirical support for the self-medication hypothesis suggesting that individuals use substances to cope with adverse emotional states and psychological symptoms that occur in reaction to SE (Garland, Pettus-Davis, & Howard, 2013;Khantzian, 1997;Magid et al, 2009). It has also been suggested that the link between SE and SUD risk can partially be explained by the effects of SE on individual trait factors such as stress reactivity and behavioral control (Lijffijt, Hu, & Swann, 2014). Addictive Behaviors 43 (2015) [89][90][91][92][93][94][95][96] Importantly, despite noteworthy evidence for a relationship between SE and subsequent SUD, several studies do not find an association between SE and SUD risk Keyes, Hatzenbuehler, Grant, & Hasin, 2012;North et al, 2005;Vlahov et al, 2006).…”