Prenatal stress and neuroendocrine pathways framing attention-deficit/hyperactivity disorder as a functionally based neurodevelopmental disorder: a narrative review.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition with a strong genetic underpinning, yet mounting evidence highlights prenatal maternal stress and depression as critical environmental risk factors. Maternal dysregulation of the hypothalamic-pituitary-adrenal axis, with elevated cortisol, corticotropin-releasing hormone, and adrenocorticotropic hormone, can cross the placenta and reprogram the fetal neuroendocrine system. These changes may disrupt dopaminergic signaling, suppress brain-derived neurotropic factor expression, and alter glutamatergic and GABAergic balance, thus impairing synaptic plasticity and executive function. Clinical and animal studies consistently demonstrate that, unlike autism spectrum disorder and intellectual disability, ADHD is characterized less by structural abnormalities and more by functional deficits in neurotransmission and circuit dynamics. Recognizing ADHD as a functionally disrupted but structurally preserved condition reframes its etiology within a developmental perspective. This review integrates epidemiological, mechanistic, and preclinical findings to propose a mechanistic framework in which maternal stress and depression may act through neuroendocrine and dopaminergic pathways to shape the prenatal origins of ADHD, suggesting the potential importance of maternal screening and preventive strategies.