ReviewInternational journal of molecular sciences2026
A Four-Dimensional Model of Attention-Deficit/Hyperactivity Disorder: Toward Improved Recognition of Female ADHD.
Review in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Attention-deficit/hyperactivity disorder (ADHD) is traditionally defined by symptoms of inattention, hyperactivity, and impulsivity. However, growing evidence suggests that this framework incompletely reflects the underlying neurobiology and clinical heterogeneity of the disorder, particularly in females. Current models of dopaminergic neurotransmission propose that ADHD is characterized not by simple dopamine deficiency but by dysregulation of tonic and phasic dopamine signaling. Theoretical models propose that reduced tonic dopamine activity may coexist with enhanced stimulus-dependent phasic responses in ADHD. Whether such signaling differences produce alternating states of underactivation and hyperactivation within the same individual has not been directly demonstrated and constitutes a central hypothesis of the present framework. In this narrative hypothesis paper, I examine evidence linking dopaminergic dysregulation to a broader ADHD phenotype encompassing four functional domains: energy regulation, attention allocation, behavioral activation, and emotional reactivity and awareness. Within these domains, hyperactivity and hypoactivity, inattention and hyperfocus, impulsive responding and difficulty initiating action, and emotional hyperreactivity and alexithymia are treated as potentially related manifestations rather than established psychometric opposites. Neuroimaging studies report alterations in dopamine transporter and receptor availability, while clinical and behavioral studies document associations between ADHD and different, sometimes contrasting manifestations within the proposed domains. Importantly, internally experienced manifestations such as emotional dysregulation, hypoactivity, procrastination, and hyperfocus appear particularly relevant to female presentations of ADHD. I propose that ADHD should be conceptualized as a multidimensional disorder of dopaminergic regulation. This framework may better explain phenotypic diversity, improve identification of underrecognized presentations, and guide future biomarker-driven and precision-medicine approaches to ADHD.
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