Influences of dopaminergic system dysfunction on late-life depression

Abstract

Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions.

Comparison of Functional and Structural Neural Network Features in Older Adults With Depression With vs Without Apathy and Association With Response to Escitalopram

“…We applied a hypothesis-driven, seed-to-whole-brain rsFC approach focused on the SN. Future studies evaluating other networks that may be disrupted in apathy, including the reward network, 16 , 58 will provide further insights into its etiopathogenesis.…”

“…An emerging hypothesis suggests that apathy and its impact on treatment response in LLD may reflect compromise of the salience network (SN) and its large-scale network connections. 5 , 15 , 16 The SN, which includes the insula and dorsal anterior cingulate cortex (dACC), attributes motivational value to a stimulus. The SN dynamically coordinates the activity of other large-scale networks, including the executive control network and default mode network (DMN), to guide purposeful behavior.…”

Dopamine receptor agonists: standard and non-standard applications in medicine

“…Так, назначение ропинирола при биполярном расстройстве приводило к снижению частоты маниакального переключения и тяжести заболевания, а также уменьшению выраженности депрессии [10]. Существуют достаточно убедительные доказательства эффективности прамипек сола в лечении первичных психиатрических расстройств [10,11]. Несмотря на то что не все исследования дают однозначные результаты, использование АДР для коррекции первичных аффективных расстройств видится весьма перспективным.…”

Effects of age and sex on dendritic D2 autoreceptor inhibition in substantia nigra dopamine neurons

“…Dopamine neurons of the substantia nigra pars compacta (SNc) are integral to motor function and reward learning (Cohen et al, 2009;Schultz, 2007;Yin et al, 2008). Dopaminergic behaviors decline with advancing age, with movement deficits and apathy or depression commonly observed in the elderly population (Seidler et al, 2010;Taylor et al, 2022).…”

“…Dopamine neurons of the substantia nigra pars compacta (SNc) are integral to motor function and reward learning (Cohen et al, 2009; Schultz, 2007; Yin et al, 2008). Dopaminergic behaviors decline with advancing age, with movement deficits and apathy or depression commonly observed in the elderly population (Seidler et al, 2010; Taylor et al, 2022). Moreover, aging is the single largest risk factor for development of Parkinson’s disease (PD, reviewed in Reeve et al (2014), where degeneration of SNc dopamine cells is the main hallmark of the disease and is responsible for the motor symptomatology (Hornykiewicz, 1975).…”