In recent years, the scientific community has witnessed a paradigm shift in how mental health and psychiatric disorders are conceptualized, with growing emphasis on their developmental origins. Breaking away from traditional models that often focused on symptomatic treatment in adulthood, a novel theoretical framework known as the Developmental Origins of Mental Health and Disorders (DOMHaD) is gaining traction. This framework builds upon and extends the established concept of the Developmental Origins of Health and Disease (DOHaD), which historically has explained how early-life environments shape lifelong physical health. By integrating genetic predispositions, epigenetic modifications, and environmental exposures spanning from preconception to adolescence, DOMHaD offers a profound and comprehensive insight into the complex genesis of psychiatric conditions.
The crux of DOMHaD lies in the recognition that virtually all major psychiatric disorders, including those traditionally deemed to have adult onset, find their roots in developmental processes that begin long before clinical manifestations emerge. This perspective compels a reevaluation of neurodevelopmental trajectories, closely examining the orchestration of brain–body interactions across precise spatiotemporal frameworks. The human brain undergoes rapid, dynamic changes from conception through adolescence, influenced by multiple biological and environmental factors that interact with an individual’s genetic background, modifying vulnerability or resilience over time. This continuous interplay shapes whether a developmental path veers towards mental wellness or disordered states.
Genetics, while undeniably foundational, do not act in isolation within this framework. Rather, each individual inherits a unique genome at conception, which establishes a baseline susceptibility or robustness toward various psychiatric disorders. These intrinsic genetic blueprints are overlaid by environmental signals—both internal and external—that originate before conception through parental influences such as epigenetic marks or health status. Maternal and paternal exposures prior to fertilization can epigenetically prime the developing embryo, influencing how genes are expressed or silenced, thereby setting early trajectories with lifelong consequences.
During gestation, in utero conditions exert critical influence over fetal brain development and systemic regulation. Factors such as maternal stress, nutrition, infection, and exposure to toxins can trigger molecular cascades that modify epigenetic landscapes, alter inflammatory pathways, or impact neuroendocrine signaling, all of which bear on the susceptibility to later psychiatric disease. Postnatal environments further sculpt these trajectories by modulating the ongoing maturation of brain circuits, synaptic pruning, and the establishment of neuroimmune interactions. The childhood and adolescent periods—in which cognitive, emotional, and social capacities are refined—represent additional windows of vulnerability or opportunity, where environmental inputs continue to etch themselves upon a genetically primed yet plastic neural canvas.
A defining feature of DOMHaD is its departure from deterministic or reductionist thinking. Instead, it posits psychiatric disorders and mental health as emergent properties of complex, dynamic systems unfolding across critical developmental epochs. Healthy functioning and pathology are not viewed as dichotomous outcomes but rather as two aspects of a single continuum influenced by a mosaic of interacting factors. This conceptualization reconciles why unrelated individuals sharing similar environments manifest different psychiatric outcomes and why some genetically predisposed individuals remain resilient.
Epigenetics occupies a critical role within DOMHaD. It provides a molecular mechanism by which environmental exposures leave lasting “imprints” on the genome without altering the DNA sequence itself. These heritable modifications can regulate gene expression patterns crucial for brain development and stress responses, effectively translating early-life experiences into biological “memories” that shape future mental health trajectories. For example, DNA methylation changes in neurodevelopmentally relevant genes have been linked to risks for disorders such as schizophrenia, depression, and autism spectrum conditions.
Moreover, the brain–body axis is central to DOMHaD’s explanatory power. Neural circuits do not develop in isolation but in concert with systemic regulators including the immune, endocrine, and metabolic systems. Disruptions in this tightly regulated cross-talk can result in maladaptive neurodevelopmental outcomes manifesting as psychiatric symptoms later in life. Elevated inflammatory biomarkers in early life, for instance, have been associated with increased risk for mood and psychotic disorders in adulthood, emphasizing that systemic physiology and brain development are deeply intertwined.
DOMHaD also illuminates the nuanced temporal dynamics of risk and resilience factors. The timing, dose, and duration of exposures influence developmental outcomes in non-linear and often counterintuitive ways. For example, mild prenatal stress might catalyze adaptive stress response mechanisms, whereas severe or chronic prenatal stress could precipitate maladaptive neurobiological changes conferring psychiatric vulnerability. Understanding these complex exposure-response relationships requires longitudinal research paradigms and sophisticated analytic tools capable of modeling developmental trajectories at multiple biological scales.
The implications of the DOMHaD framework reach far beyond theoretical insights, offering transformational possibilities for prevention, diagnosis, and treatment of psychiatric disorders. First, early identification of at-risk individuals through biomarkers reflecting developmental perturbations could enable timely interventions well before symptom onset. Interventions targeting pregnant women, families, or children during sensitive windows could mitigate or reverse maladaptive trajectories, potentially lowering lifetime psychiatric burden.
Second, the framework encourages an integrative approach toward mental health research and clinical practice. Future psychiatric diagnostics might incorporate developmental histories, genetic profiles, epigenetic signatures, and environmental context to generate personalized risk assessments and treatment plans. Such precision psychiatry could harness advances in neuroimaging, multiomics, and wearable technologies to monitor dynamic changes in brain and systemic function, facilitating adaptive intervention strategies.
Third, DOMHaD underscores the importance of public health policies that prioritize maternal and child wellbeing as pillars in the prevention of mental illness. Programs addressing nutrition, environmental toxins, psychosocial stressors, and healthcare access during preconception, pregnancy, and early childhood could profoundly impact population mental health outcomes. Moreover, understanding the interplay between socioeconomic factors and biological processes draws attention to the critical need for reducing health disparities.
Importantly, while DOMHaD expands our conceptual horizons, it also confronts formidable scientific challenges. Disentangling the causal pathways linking genetic, epigenetic, environmental, and neurodevelopmental variables demands rigorous longitudinal cohort studies, meticulously phenotyped populations, and advanced computational modeling. Ethical considerations emerge around predictive testing and early interventions, necessitating sensitive frameworks that balance benefit with autonomy and consent.
In conclusion, the Developmental Origins of Mental Health and Disorders framework represents a compelling, integrative approach that reframes psychiatric conditions as outcomes of complex, multilevel developmental processes starting before birth and extending into adolescence. By embracing this developmental and systems biology perspective, mental health research and clinical care stand poised to move toward more effective, individualized, and preventative paradigms. As science continues to unravel the intricate tapestry of interactions shaping mental health, DOMHaD offers a roadmap for leveraging developmental insights to curb the global burden of psychiatric disorders in ways that were once unimaginable.
Subject of Research: Developmental origins and mechanisms underlying mental health and psychiatric disorders
Article Title: Developmental origins of mental health and disorders (DOMHaD): an approach to understanding, preventing and treating psychiatric disorders.
Article References:
Reisinger, S.N., Hannan, A.J. Developmental origins of mental health and disorders (DOMHaD): an approach to understanding, preventing and treating psychiatric disorders. Nat. Mental Health (2025). https://doi.org/10.1038/s44220-025-00495-3
Image Credits: AI Generated
