The pathobiological basis of depression in Parkinson disease: challenges and outlooks

Abstract

Depression, with an estimated prevalence of about 40% is a most common neuropsychiatric disorder in Parkinson disease (PD), with a negative impact on quality of life, cognitive impairment and functional disability, yet the underlying neurobiology is poorly understood. Depression in PD (DPD), one of its most common non-motor symptoms, can precede the onset of motor symptoms but can occur at any stage of the disease. Although its diagnosis is based on standard criteria, due to overlap with other symptoms related to PD or to side effects of treatment, depression is frequently underdiagnosed and undertreated. DPD has been related to a variety of pathogenic mechanisms associated with the underlying neurodegenerative process, in particular dysfunction of neurotransmitter systems (dopaminergic, serotonergic and noradrenergic), as well as to disturbances of cortico-limbic, striato-thalamic-prefrontal, mediotemporal-limbic networks, with disruption in the topological organization of functional mood-related, motor and other essential brain network connections due to alterations in the blood–oxygen-level-dependent (BOLD) fluctuations in multiple brain areas. Other hypothetic mechanisms involve neuroinflammation, neuroimmune dysregulation, stress hormones, neurotrophic, toxic or metabolic factors. The pathophysiology and pathogenesis of DPD are multifactorial and complex, and its interactions with genetic factors, age-related changes, cognitive disposition and other co-morbidities awaits further elucidation.

Disrupted topologic efficiency of brain functional connectome in de novo Parkinson's disease with depression

“…We speculated that pathological damage could involve reorganizing the hubs of the functional network during the early stages of DPD, particularly the temporal‐occipital regions engaged in receiving and processing information. Additionally, the present study also explored that DPD exhibits recruited hubs primarily in the limbic cortico‐basal ganglia circuit with regional dysfunction mentioned in previous DPD studies (Jellinger, 2022). However, the current study explored no correlation between the regional topological properties and depressive symptoms.…”

The effects of paroxetine therapy on depressive symptom and motor function in the treatment of depression with Parkinson’s disease: A meta-analysis

“…Studies have shown that the occurrence of dPD is associated with dysfunction of brain neurotransmitters, blockade of neurotransmitter signal transduction pathways, and neurodegeneration. [ 46 ] Deficiency of dopamine, norepinephrine and serotonin may be happened in the substantia nigra, striatum, limbic system and raphe nuclei. Dopaminergic neuron degeneration is found in the substantia nigra pars compacta and ventral tegmental area of midbrain, serotonergic and adrenergic neurons in the raphe nuclei and hypothalamus also have morphological changes.…”

Health phenome of Parkinson’s patients reveals prominent mood-sleep cluster

“…Mood disorders, sleep disorders, and PD may share some common pathogenic mechanisms, including degeneration or dysfunction of dopaminergic, serotonergic, and noradrenergic circuits [19][20][21] . PD is de ned by loss of dopaminergic neurons in striatonigral pathway, with relative preservation of the mesocortical and mesolimbic pathways.…”