The Adolescent Brain: How Adversity Shapes Mental Health


Adolescence is a significant developmental period in human life, typically spanning from around the age of 10 to the early 20s. It’s characterized by profound physical, psychological, emotional, and social changes. One of the key aspects of adolescence is brain maturation, where neural connections and structures evolve to support improved cognitive control and responses to stress. Studies have shown that accelerated brain aging is closely associated with psychiatric and neurodegenerative risks throughout life. In adults, deviations from normal brain connectivity, both functionally and structurally, are influenced by a combination of genetic predispositions and early-life environmental stressors, however, it’s uncertain whether the same processes observed in adults also apply during the critical transition from childhood to adolescence. A better understanding of these processes could lead to the development of early interventions. A new study, conducted by Dr. Raluca Petrican from the University of Liverpool and Professor Alex Fornito from Monash University, published in the Developmental Cognitive Neuroscience Journal, investigated the role of early-life adversity and genetic vulnerability in shaping psychological functioning during the transition from childhood to adolescence.

The authors took a dimensional approach to explore exposure to deprivation (lack of essential resources) and threat or violence (such as family conflict and neighborhood crime) as indicators of early-life adversity. They also examined genetic vulnerability factors related to Alzheimer’s Disease (AD) and Major Depressive Disorder (MDD), both conditions associated with accelerated brain aging and increased susceptibility to environmental stressors. Recent evidence has suggested a potential causal link between MDD and subsequent AD onset, especially considering that the first signs of depressive symptoms often appear during adolescence. This hypothesis has led to investigations into shared neurobiological mechanisms between the two disorders, particularly focusing on disrupted synaptic transmission in prefrontal cortex (PFC) systems. The PFC is vital for effective coping across development, and any deviations in its maturation can disrupt cognitive control processes.

The researchers conducted a detailed and multifaceted study involving participants from the ongoing Adolescent Brain Cognitive Development (ABCD) study, which consists of 11,500 children and their primary caregivers, who were recruited from 21 different locations across the US and will be tested extensively via behavioral (every 6 months) and neuroimaging (every 2 years) assessments for up to 10 years. The authors included biological parents and offspring, focusing on Caucasian participants. This choice was made because most polygenic risk markers are based on this population, and genetic architecture and risk loci may show racial differences. The study used baseline, two-year, and three-year follow-up data. The final sample comprised 980 Caucasian participants (470 female), predominantly right-handed, aged 9–10 years at baseline. They measured using the Total Problems score from the Child Behavior Checklist. The measure, completed annually by parents, used a 3-point Likert scale to assess participants’ psychological functioning over the previous six months. The study used scores from the two- and three-year follow-up assessments.

The researchers quantified genetic vulnerability using polygenic risk scores (PRS), derived from large genome-wide association studies (GWAS) focused on MDD and AD. For AD, they computed separate APOE region only and no-APOE region PRS, as these forecast different trajectories of neurocognitive impairments and susceptibility to environmental factors. For MDD, they used the most informative variants based on large patient cohorts. The PRS computation involved several preprocessing steps, including filtering based on minor allele frequency, elimination of highly correlated SNPs. Petrican and Fornito approach aimed to uncover the mesoscale (functional connectomic) and molecular (neurochemical and transcriptomic) neurodevelopmental patterns that mediate the joint effect of early-life adversity and genetic vulnerability on adolescent adjustment. Functional connectomic patterns, especially those based on task-related data, provide insights into cognitive and behavioral processes. Molecular indices of brain maturation, including neurotransmitter systems like dopamine (DA), serotonin (5-HT), glutamate (GLU), gamma-aminobutyric acid (GABA), and acetylcholine (ACh), offer indirect tests of synaptic transmission disruption hypotheses in AD and MDD. They focused on two key mental processes during adolescence: inhibitory control and incentive processing. These processes are essential for cognitive control and responses to stress and undergo substantial maturation during adolescence. The research examined how early-life adversity and genetic vulnerability influenced the developmental pace of these processes and their associated brain networks.

The results revealed that exposure to adversity and genetic risk factors for MDD and AD had additive effects on psychopathology risk in adolescence. Specifically, adversity exposure and genetic susceptibility were linked to altered development of the inhibitory control task architecture, with different functional network maturation patterns observed. Furthermore, the authors explored the gene expression profiles associated with these neurodevelopmental alterations. They found that the observed neurodevelopmental profile was enriched for genes implicated in susceptibility to stress, suggesting a potential link between stress susceptibility and the joint impact of adversity and genetic risk on psychological adjustment in adolescence. Notably, their study also identified areas of the brain with higher receptor density for neurotransmitters like GABA, D2, and GLU5R, which are known to play crucial roles in psychopathology, cognitive control, and responses to adversity. These receptor density patterns corresponded to the observed neurodevelopmental alterations, providing further evidence of their relevance in the context of stress susceptibility and genetic risk. Further research into these systems may provide insights into potential therapeutic targets. Finally, the study explored how these neurodevelopmental alterations mediated the link between longitudinal increases in vulnerability to psychopathology and adversity/genetic risk for MDD/AD. The authors’ findings suggested that the observed changes in brain maturation may increase psychopathology risk, particularly among less vulnerable adolescents.

In conclusion, Petrican and Fornito’s study offers valuable knowledge into the complex relationship between early-life adversity, genetic vulnerability, neurodevelopment, and psychopathology during adolescence. Understanding these connections opens up avenues for early interventions and targeted strategies to support the mental health and well-being of young individuals, potentially reducing the long-term risk of conditions like MDD and AD.

The Adolescent Brain: How Adversity Shapes Mental Health - Medicine Innovates

About the author

Alex Fornito is currently a Laureate Fellow of the Australian Research Council, Professor in the School of Psychological Sciences, and Head of the Brain Mapping and Modelling Research Program and Neural Systems and Behaviour Lab at the Turner Institute for Brain and Mental Health, Monash University.

Alex’s research develops new approaches to mapping and modelling the human brain in health and disease. In particular, his work focuses on understanding foundational principles of brain organization and their genetic basis, characterizing brain disturbances in psychiatric disorders, and understanding how individual variability in brain structure and function relate to behaviour.

About the author

Raluca Petrican is currently a Lecturer in the Department of Psychology at the University of Liverpool. Her research falls within the area of Lifespan Developmental Cognitive Neuroscience. The overarching objective of Raluca’s work is to characterise age-specific and age-invariant neuroplasticity processes underpinning positive adjustment to environmental challenges and, thus, facilitate the development of more personalised interventions to enhance psychological resilience. To this end, she uses behavioural, neuroimaging, transcriptomic and polygenic risk methods with neurologically intact and clinical populations.


Petrican R, Fornito A. Adolescent neurodevelopment and psychopathology: The interplay between adversity exposure and genetic risk for accelerated brain ageing. Dev Cogn Neurosci. 2023 ;60:101229. doi: 10.1016/j.dcn.2023.101229.

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