Journal of Yeungnam Medical Science

Review article

Psychiatry and Mental Health
Prenatal stress and neuroendocrine pathways framing attention-deficit/hyperactivity disorder as a functionally based neurodevelopmental disorder: a narrative review: Sung-Cherl Jung; J Yeungnam Med Sci. 2025;42:67. Published online October 26, 2025; DOI: https://doi.org/10.12701/jyms.2025.42.67

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Abstract PDF: 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 neurotrophic 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.

Review

Psychiatry and Mental Health
Neurobiological Pathophysiology of Attention Deficit Hyperactivity Disorder.: Hyung Bae Park, Yeol Joo; Yeungnam Univ J Med. 2000;17(2):108-122. Published online December 31, 2000; DOI: https://doi.org/10.12701/yujm.2000.17.2.108

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Abstract PDF: BACKGROUND
Models of attention deficit hyperactivity disorder(ADHD) that have proposed a hypodopaminergic state resulting in hypofunction of the prefrontal circuitry have assumed a unitary dopamine system, which largely ignores the distinct functional differences between mesocortical dopamine system and nigrostriatal dopamine system. PURPOSE: The author's goal was to develop a pathophysiological model for ADHD with greater explanotory power than dopaminergic hypofunction hypothesis in prefronal circuitry. MATERIALS AND METHODS: Published clinical findings on ADHD were integrated with data from genetic, pharmacological, neuroimaging studies in human and animals. RESULTS: Molecular genetic studies suggest that three genes may increase the susceptibility to ADHD. The three candidate genes associated with ADHD are each involved in dopaminergic function, and this consistent with the neurobiologic studies implicating catecholamines in the etiology of ADHD. Pharmacological data also provide compelling support for dopamine and noradrenergic hypothesis of ADHD. Neuroimaging studies lend substantial support for the hypothesis that right-sided abnormalities of prefrontal-basal ganglia circuit would be found in ADHD. CONCLUSIONS: The present hypothesis takes advantage of the major differences between the two pertinent dopamine systems. Mesocortical dopamine system, which largely lacks inhibitory autoreceptors, is ideally positioned to regulate cortical inputs, thus improving the signal-to-noise ratio for biologically valued signals. In this circuit, therapeutic doses of stimulants are hypothesized to increase postsynaptic dopamine effects and enhance executive functions. By contrast, symptoms of hyperactivity/impulsivity in ADHD are hypothesized to be associated with relative overactivity of nigrostriatal circuit. This nigrostriatal circuit is tightly regulated by inhibitory autoreceptoors as well as by long distance feedback from the cortex, and slow diffusion of therapeutic doses of stimulant via oral administration is hypothesized to produce a net inhibition of dopaminergic neurotransmission and improves hyperactivity.

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