Neurobiological signatures associated with alcohol and drug use in the human adolescent brain

Abstract

Magnetic resonance (MR) techniques provide opportunities to non-invasively characterize neurobiological milestones of adolescent brain development. Juxtaposed to the critical finalization of brain development is initiation of alcohol and substance use, and increased frequency and quantity of use, patterns that can lead to abuse and addiction. This review provides a comprehensive overview of existing MR studies of adolescent alcohol and drug users. The most common alteration reported across substance used and MR modalities is in the frontal lobe (63% of published studies). This is not surprising, given that this is the last region to reach neurobiological adulthood. Comparatively, evidence is less consistent regarding alterations in regions that mature earlier (e.g., amygdala, hippocampus), however newer techniques now permit investigations beyond regional approaches that are uncovering network-level vulnerabilities. Regardless of whether neurobiological signatures exist prior to the initiation of use, this body of work provides important direction for ongoing prospective investigations of adolescent brain development, and the significant impact of alcohol and substance use on the brain during the second decade of life.

The role of experience in adolescent cognitive development: Integration of executive, memory, and mesolimbic systems

“…The nature of vulnerability during this period of development highlights the critical role of experience in affecting neurodevelopmental trajectories throughout the lifespan. For example, previous research in animal models and humans have demonstrated that exposure to drugs of abuse during adolescence results in alterations in HPC volume and neurophysiology that has downstream consequences on drug abuse and affective disorders (see Spear, 2016 and Silveri et al, 2016 in the same issue), which may have downstream consequences on HPC-PFC interactions. Characterizing this period of adolescent development, and its sensitivity to drugs of abuse and other environmental insults, is critical to a greater understanding of normative increases in sensation seeking and psychopathology.…”

Reward-centricity and attenuated aversions: An adolescent phenotype emerging from studies in laboratory animals

“…Even the preference for a natural reward—sweet tastes—was found to be greater early in adolescence (11–15 years) than during late adolescence/emerging adulthood (19–25 years) (Desor and Beauchamp, 1987). A multitude of other studies have demonstrated enhanced sensitivity to rewarding stimuli in human adolescents for both decision-making/risk taking behaviors, as well as for cognitive control and learning behaviors, data that have been recently reviewed (see Andersen et al, 2002; and also in this issue: Luciana et al, 2016; Schulz and Sisk, 2016; Silveri et al, 2016; Spear, 2016; Vanderschuren et al, 2016; van Duijvenvoorde et al, 2016). …”

“…Such propensities for alcohol/drug use during adolescence may not only be encouraged by an adolescent reward-sensitive phenotype, but also by (as we shall see) an attenuated sensitivity to aversive stimuli, including the aversive properties of alcohol, nicotine, and illicit drugs. This pattern of increased rewarding but decreased aversive sensitivities may help to promote high levels of alcohol/drug use among susceptible adolescents—elevated use that has the potential to impact normative developmental changes in brain structure and function during this critical period, thus altering neural processes and behaviors occurring within adolescence, as well as into adulthood (see reviews by Silveri et al, 2016 and Spear, 2016). …”

PPAR‐gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double‐blind randomized controlled pilot trial

“…Multiple studies, both preclinical (17, 18) and human (19–21) show impaired WM integrity is associated with functional consequences, including impulsivity (19), decision making (22) and relapse (23). Importantly, emerging evidence implicates WM integrity across a range of psychiatric disorders and cognitive processes relevant to addiction (24, 25). Based on (1) modulation of cocaine cue reactivity in animal models via PPAR-γ agonism, and (2) evidence for neuroprotective effects of PPAR-γ agonism, we sought to identify analogous effects of PIO treatment in individuals with CUD.…”