Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence

Abstract

Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function.

Impact of juvenile chronic stress on adult cortico-accumbal function: Implications for cognition and addiction

“…Given the requirement of NMDA receptor-mediated activity within PFC circuits during cognitive tasks (Arnsten & Rubia, 2012), this would presumably result in less recruitment of the PFC as required for effective top-down control. In support of this, reduced neural activity within the PFC when performing a variety of executive function tasks is commonly observed in human adults reporting experience of chronic juvenile stressors (Table 2; e.g., Casement et al, 2015; Fonzo et al, 2016; Philip et al, 2013b; 2016). However, chronic juvenile stress is also associated with increased brain-derived neurotrophic factor (BDNF) in the PFC of adult rats (Table 1; Han et al, 2011b; Meng et al, 2011; Shao et al, 2013), which is surprising given that reduced gray matter, reduced dendritic length or elaboration, and reduced plasticity are often observed in the adult PFC following juvenile stress in both humans and animal models (Tables 1 & 2).…”

Nucleus accumbens functional connectivity at age 20 is associated with trajectory of adolescent cannabis use and predicts psychosocial functioning in young adulthood

“…Therefore, aberrant patterns of neural response to reward among cannabis users are likely to result from a combination of predisposing neural abnormalities and exposure effects that interact across development. Abnormalities in neural reward circuitry may also be influenced by early life stress (49) and/or neurotoxic effects of co-occurring alcohol exposure (71). …”

Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders

“…9) (Makris et al, 2008; Sullivan et al, 2005; Wrase et al, 2008). Whether smaller volumes (Benegal et al, 2007) or altered activation patterns (Acheson et al, 2009; Andrews et al, 2011; Casement et al, 2015; Heitzeg et al, 2008; Heitzeg et al, 2010; Nees et al, 2012; Yau et al, 2012) in reward-related regions can predict higher risk for AUD remains equivocal. While there are inherent difficulties in resolving brain volumes as a function of premorbid condition or outcome of alcohol exposure, another confounding factor may be sex: binge drinking men showed smaller prefrontal, striatal, and medial temporal lobe volumes relative to non-binge drinking men, but binge drinking women showed the inverse pattern of larger volumes of these areas relative to non-binge drinking women (Kvamme et al, 2016).…”