On August 27, 2025, at 8:27 a.m., two children were killed and 18 others were injured in a shooting at the Annunciation Catholic School in Minnesota. The 23-year-old perpetrator died of a self-inflicted wound. This horrendous act of homicide and suicide has left deep consequences for the community in its wake. It also offers a salient reminder of why developmental mental health, and the focus of this special issue, are so vital to our field and to society’s future.

On one level, we might hypothesize that the shooter’s life followed a concerning developmental trajectory - beginning with early school behaviors that raised worries among peers, escalating into violent obsessions and depression, and ultimately culminating in this tragic event. On another level, the acute mental health needs of the children and families surviving this trauma are daunting, and must also be met with an explicit developmental lens.

While mass violence like this is rare, its horror is undeniable. More pervasive, however, are the rising rates of youth anxiety, depression, and suicide around the world. These challenges now represent the norm, impairing educational attainment, workforce participation, and social cohesion, ultimately diminishing quality of life and fostering long-term economic and societal consequences.

These realities underscore the central themes of this issue: the pressing need for improved methods of preemptive identification and early intervention for individuals at high risk of adverse mental health outcomes and behaviors. Equally important, the work gathered here emphasizes neurobiological and psychosocial resilience, capitalizing on the inherent sturdiness of children and adolescents and their remarkable capacity for plasticity and adaptation. Together with the critical role of environmental and social support, these efforts represent the guiding priorities for our field in the months and years ahead.

The articles in this issue are organized across levels of scale in the developing brain: first from cellular/molecular mechanisms, then to neural circuits, on to understanding how stress exposure affects these developing circuits and how multilevel adaptations can be harnessed to foster resilience, and in conclusion, how the integration of these themes can inform clinical practice and next-generation interventions. Interwoven with the scientific papers are three “lived experience perspectives” to remind us that these themes– and the work we do– play out in the lives of countless individuals and family members every day.

We open this issue with a mother’s perspective. Linda Spence [1] is a highly educated and articulate woman with strong financial resources, yet despite working for years with the best experts available, the evaluations and treatments her son were offered did little to mitigate a downward mental illness course. In some instances, especially when it came to medication side effects, the treatments may have made the situation worse. Ms. Spence was continuously struck by how little of her son’s care was informed by a deep scientific understanding of what was happening in his brain. Ultimately, the “best available” psychiatric care did not prevent her son’s tragic death at age 22.

And yet, as we showcase in the first four papers, the basic science of brain development has made important strides over the past decade and is poised to inform the next generation of interventions [2,3,4,5]. Our contributors highlight recent findings that elucidate molecular, cellular, and microcircuit fundamentals: what are the regulators and mediators that affect early neuronal function and phases of brain development? How do external stressors exert modifications to these systems, and what molecular and cellular factors contribute to resilience? How do these factors set the stage for later mental health vulnerabilities– and how can we address them as early as possible while leveraging resilience capacities?

This sets the stage for the following seven papers, which focus on the next level of scale– developmental mechanisms in human brain circuits– from sensory processing, to higher order prefrontal control operations, to striatal-hippocampal interactions [6,7,8,9,10,11,12]. We include papers on the organizing principles of brain circuit development and how this must inform neuroimaging-based clinical research in children and youth, how specific systems are maximally malleable during specific periods of development, and the various ways that developing circuits are tuned by experience in directions that promote mental health resilience or that create mental health vulnerability. This section synthesizes evidence that the brain is continuously modeling and remodeling itself through active, multilevel adaptations– processes that provide essential context for building optimally-tuned and optimally-timed interventions. We can thus begin to ask not only what bends developmental trajectories in maladaptive directions, but how we can bend them back.

Stress exposure can have many forms of “bending effects,” and in the next section, we take a closer look at how stressors affect the developing brain and behavior and how we can leverage a range of strengths and supports to bend trajectories back in the right direction. We begin this section with the perspective of an individual whose lived experiences provide a translational bridge: Dean Holmes [13] shares a personal story where several concepts introduced earlier– including genetic liability and early stress exposure– have interacted over time with their capacity for creativity and for seeking healing contexts, to bend their trajectory of mental illness into one of personal recovery and productivity. We then present four scientific papers highlighting key mechanisms by which developmental stress, social determinants of health, and structural racism can get “into the brain” to affect sensory processing, frontal cortical development, and risk for adverse mental health outcomes– as well as approaches that can mitigate these effects [14,15,16,17].

Building firmly upon the scientific foundation of the prior three sections, we conclude with eight papers that present clinical insights and next-generation interventions. This includes current insights on how to define treatment targets (e.g., through neuroimaging, neuromodulation, and computational psychiatry methods), when to act, what kinds of transdiagnostic symptoms to consider, and how to deliver interventions at scale [18,19,20,21,22,23,24,25]. Mr. Holmes’ perspective piece reminds us that mental illness symptoms usually do not fit into neat categorical boxes– for example, when trauma, depression, suicidality, and psychosis are all present and interacting synergistically. Two papers underscore this recurring theme of synergism, examining the emergence in adolescence of suicidal thoughts and behaviors, and the emergence of psychosis. Two linked papers wrap up this section, providing a comprehensive rationale for transdiagnostic early prevention approaches.

We conclude this issue on development with a final lived experience perspective and with the viewpoint of two experienced researchers. Tom White describes what it has been like to live with Tourette’s syndrome as a teenager and young adult, and how he has learned to build on his strengths and engage vigorously with the world around him to support his recovery [26]– the lesson we all ultimately hope to convey to vulnerable children and adolescents. Drs. Gordon and Veensta-Vanderwheele [27] take up the challenge raised at the outset by Linda Spence and identify specific new scientific advances that are likely to change what we can offer to children and adolescents and their families in the coming years.

Working together to integrate research across the levels of neural and behavioral scale described in this issue, we believe that the field is poised to answer a mother’s challenge: to do better in creating precise, effective, and truly scientifically-informed mental health and addiction treatments for children and adolescents.