A vicious cycle is likely to occur. In trying to cope with stress, people begin to use drugs, thinking this will alleviate their negative mood. But during extended stressful periods, occasional self-medication readily escalates to regular use. This boosts output of stress- related hormones and neurotransmitters, contributing to heightened stress responsivity and negative emotional states, which in turn increase the motivation for continued drug use. Even individuals maintaining drug abstinence prior to Covid were at great risk for relapse during the pandemic, since withdrawal is dominated by negative affect and activation of the stress and anxiety systems that contribute to drug-craving. The Vulnerable Brain A particularly challenging dynamic of the pandemic has been the lack of in-person socialization for children and adolescents. The human brain has evolved to maximize social interaction and connectivity, which are dependent on the precise orchestration of complex neurodevelopmental processes. Forced isolation, lack of peer support, and minimal teacher oversight created a perfect storm for heightened stress and risky decision- making. Although restrictions have eased considerably with new variants, the support of peers and schools that is a central part of children’s daily lives, could disappear again. Friendships, cliques, sports, and extra-curricular activities may again be fundamentally altered. An entire social structure might once more be disrupted. For many children, school is the only predictably safe and nurturing place in their lives. In the 2020 academic year, they were uprooted from this stabilizing force and required to attend school virtually. We know from developmental neurobiology that the adolescent brain is uniquely vulnerable to addiction due to a genetically programmed increase in risk-taking and anxiety-related behaviors driven by the amygdala, coupled with a relatively immature “executive” cognitive control center in the brain (the prefrontal cortex), which does not reach full maturity until the third decade of life. Differences in the development of executive versus emotional networks in the adolescent brain make adolescents more sensitive to rewarding and stressful stimuli than adults . So, as challenging as Covid lockdown was for most adults, it was more difficult and neurobiologically perilous for most teens. Significant neurodevelopment continues well into adolescence, as is evident in various brain structures. Particularly relevant to stress, social connectivity, and
addiction is the profound functional and structural maturing of the amygdala, prefrontal cortex, and ventral striatum. For instance, activation of the ventral striatum in response to reward (including social reward) is stronger in adolescents than in adults and children, which parallels the adolescent maturation of the dopamine system. Adolescence is also a period of enhanced activity in the hypothalamic-pituitary-adrenal (HPA) axis—the neuroendocrine regulator of stress—and hormone levels following puberty enhance the stress response and increase the motivation and value of reward. Another critical maturation process during adolescence is in amygdala- prefrontal cortex connectivity , a key neural circuit for the generation of negative affect and its regulation. The peak in social drive that occurs during adolescence coincides with this period of prefrontal cortex-amygdala maturation. Adolescence is a sensitive period of enhanced amygdala reactivity when emotional stimuli, stress, and social interactions are extremely important. It should be emphasized that this period is also characterized by a relatively immature prefrontal cortex that is responsible for cognitive function. Indeed, cognitive control via inputs from the prefrontal cortex to the amygdala does not fully mature until early adulthood, leaving the ability of the prefrontal cortex to inhibit amygdala activity significantly low during adolescence. Stress further weakens this moderating process. Altogether, the neural signatures of adolescence parallel heightened reward sensitivity, stress sensitivity, and risk-taking as compared to other age groups. It’s not
18 DANA FOUNDATION CEREBRUM | Winter 2022
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