Depression and Nigral Neuron Density in Lewy Body Spectrum Diseases

Abstract

Parkinson's disease and other Lewy body spectrum diseases (LBDs) are associated with a specific risk for clinical depression. In the present clinicopathological study with 73 patients with LBD, we observed that the substantia nigra pars compacta dopamine neuron density was markedly lower in patients who had comorbid depression antemortem than in nondepressed patients (1.52 vs 2.32 n/mm2, p = 0.004). There were no differences in cognition, motor disease severity, antiparkinsonian medications, or disease duration between groups. The results implicate the substantia nigra as an important psychomotor modulatory area of mood in patients with Lewy body disorders. ANN NEUROL 2021;;89:1046–1050

Depressive symptoms before and after Parkinson’s diagnosis—A longitudinal analysis

“…For example, in prodromal PD, depressive symptoms may gradually develop as Lewy pathology develops in the lower brainstem such as locus coeruleus and lower raphe nuclei, followed by the substantia nigra, accompanied by neuronal losses [20]. In support, postmortem studies found markedly lower neuron density in these brain regions of PD patients with depression versus without [28][29][30]. Further, neurotransmitter imbalances and alterations in the noradrenergic, serotonergic, and dopaminergic systems have also been found in association with depressive symptoms in PD [31][32][33][34].…”

Delirium-Onset of Prodromal Dementia With Lewy Bodies—Putative Brainstem-Related Pathomechanism and Clinical Relevance

“…For instance, a recent study (Chen et al, 2021) demonstrated that the SN displayed an early pathology also in patients with MCI and Lewy body pathology vs. controls in 3 T MRI analyzed via quantitative susceptibility mapping. Another working group (Saari et al, 2021) showed that those patients with more depressive symptoms and LBD had more sparsely distributed neurons than those with no depressive symptoms. Thus, further research is needed into how certain clinical features are associated with which type of Lewy body pathology and its spread.…”

Height and nigral neuron density in Parkinson’s disease

“…Thirty-six postmortem cases of patients with LBDs and 19 healthy controls were included in this study. The included patients were collected from 168 postmortem cases with neuropathologically confirmed Lewy body pathology (database previously described in [6]). The inclusion criteria were available height and weight information and autopsy data, and acceptable quality of nigral tissue samples for neuronal counting.…”

“…Database selection criteria and neuropathological methods have been described in detail previously [6]. Briefly, formalin-fixed and paraffin-embedded midbrain at the level of origin of the third cranial nerve was sectioned at 8 µm thick sections and stained with Luxol Fast Blue to evaluate borders of substantia nigra pars compacta (magnification 1.0) and with tyrosine hydroxylase (TH) immunohistochemistry for calculation of dopaminergic neurons.…”

“…TH-positive neurons were systematically manually calculated from the SNc (magnification 20.0). The cell count was corrected with the Abercrombie method using the diameter of TH-positive nuclei (magnification 63.0 or higher) as described [6]. The median (range) time from death to autopsy was 5 (2-8) days, and the median time from autopsy to neuropathological examination was 23 (12-73) days (missing data for 2 patients).…”