The Pharmacogenomics of Opioid Response in Cancer Pain: From Receptor Polymorphisms to Tumour-Mediated Interference-A Narrative-Critical Review.
Authors: Mercadante S
Journal: International journal of molecular sciences
depression treatment
mental health
open access
Abstract
Restless legs syndrome (RLS) is a chronic sensorimotor disorder characterized by unpleasant sensations accompanied by an urge to move the legs, typically worsening during rest and in the evening hours, often leading to sleep disturbance and reduced daytime functioning.
Although historically conceptualized within dopaminergic and sensorimotor frameworks, accumulating neurobiological evidence suggests that RLS involves multisystem dysregulation affecting broader neural networks, including dopaminergic pathways and sleep–wake regulatory circuits.
Clinical and neuroimaging studies have demonstrated abnormalities in thalamic, basal ganglia, and limbic-related networks in RLS, supporting the view that the disorder extends beyond peripheral sensory mechanisms. Nonmotor features of RLS have received increasing attention due to their substantial impact on quality of life, with sleep disruption and mood symptoms being frequently reported.
Studies examining cognitive function in RLS have yielded heterogeneous findings: some report deficits in attention and executive control, particularly in individuals with marked sleep disturbances, whereas others observe preserved overall cognitive performance compared with matched controls.
These inconsistencies suggest that cognitive alterations in RLS may be subtle and domain-specific rather than global in nature. Neurobiological models indicate that RLS involves alterations in basal ganglia–thalamocortical circuits characterized by dopaminergic, glutamatergic, and GABAergic imbalance—mechanisms with theoretical relevance for both cognitive and affective regulation.
Social cognition, encompassing processes such as theory of mind, emotion recognition, and mental-state inference, relies on distributed prefrontal, temporoparietal, and limbic networks that are sensitive to dopaminergic modulation and sleep integrity.
Impairments in social cognition have been documented in neurological conditions involving basal ganglia and dopaminergic dysfunction, including Parkinson's disease and Huntington's disease.
Moreover, sleep-related disorders such as obstructive sleep apnea and chronic insomnia have been associated with alterations in emotional and social-cognitive functioning.
Although historically conceptualized within dopaminergic and sensorimotor frameworks, accumulating neurobiological evidence suggests that RLS involves multisystem dysregulation affecting broader neural networks, including dopaminergic pathways and sleep–wake regulatory circuits.
Clinical and neuroimaging studies have demonstrated abnormalities in thalamic, basal ganglia, and limbic-related networks in RLS, supporting the view that the disorder extends beyond peripheral sensory mechanisms. Nonmotor features of RLS have received increasing attention due to their substantial impact on quality of life, with sleep disruption and mood symptoms being frequently reported.
Studies examining cognitive function in RLS have yielded heterogeneous findings: some report deficits in attention and executive control, particularly in individuals with marked sleep disturbances, whereas others observe preserved overall cognitive performance compared with matched controls.
These inconsistencies suggest that cognitive alterations in RLS may be subtle and domain-specific rather than global in nature. Neurobiological models indicate that RLS involves alterations in basal ganglia–thalamocortical circuits characterized by dopaminergic, glutamatergic, and GABAergic imbalance—mechanisms with theoretical relevance for both cognitive and affective regulation.
Social cognition, encompassing processes such as theory of mind, emotion recognition, and mental-state inference, relies on distributed prefrontal, temporoparietal, and limbic networks that are sensitive to dopaminergic modulation and sleep integrity.
Impairments in social cognition have been documented in neurological conditions involving basal ganglia and dopaminergic dysfunction, including Parkinson's disease and Huntington's disease.
Moreover, sleep-related disorders such as obstructive sleep apnea and chronic insomnia have been associated with alterations in emotional and social-cognitive functioning.