Lifestyle Factors Counteract the Neurodevelopmental Impact of Genetic Risk for Accelerated Brain Aging in Adolescence.

BACKGROUND: The transition from childhood to adolescence is characterised by enhanced neural plasticity and a consequent susceptibility to both beneficial and adverse aspects of one's milieu.

METHODS: To understand the implications of the interplay between protective and risk-enhancing factors, we analysed longitudinal data from the Adolescent Brain and Cognitive Development study (N = 834; 394 female). We probed the maturational correlates of positive lifestyle variables (friendships, parental warmth, school engagement, physical exercise, healthy nutrition) and of genetic vulnerability to neuropsychiatric disorders (Major Depressive Disorder, Alzheimer's Disease, Anxiety Disorders, Bipolar Disorder, Schizophrenia), and further sought to elucidate their implications for psychological well-being.

RESULTS: Genetic risk factors and lifestyle buffers showed divergent relationships with later attentional and interpersonal problems. These effects were mediated by distinguishable functional neurodevelopmental deviations spanning the limbic, default mode, visual and control systems. Specifically, greater genetic vulnerability was associated with alterations in the normative maturation of areas rich in dopamine (D2), glutamate and serotonin receptors, and of areas with stronger expression of astrocytic and microglial genes, a molecular signature implicated in the brain disorders discussed here. Greater availability of lifestyle buffers predicted deviations in the normative functional development of higher density GABA-ergic receptor regions. The two profiles of neurodevelopmental alterations showed complementary roles in protection against psychopathology, which varied with environmental stress levels.

CONCLUSIONS: Our results underscore the importance of educational involvement and healthy nutrition in attenuating the neurodevelopmental sequelae of genetic risk factors. They also underscore the importance of characterising early life biomarkers associated with adult-onset pathologies.