Brainstem Pathologies Correlate With Depression and Psychosis in Parkinson's Disease

Fischer, Nicole; Hinkle, Jared T.; Perepezko, Kate; Bakker, Catherine C.; Morris, Meaghan; Broen, Martijn P. G.; Butala, Ankur; Dawson, Ted M.; Leentjens, Albert F.G.; Mari, Zoltán; Marvel, Cherie L.; Mills, Kelly A.; Rosenthal, Liana S.; Shepard, Melissa; Pantelyat, Alexander; Bakker, Arnold B.; Pletniková, Olga; Troncoso, Juan C.; Wang, Jiangxia; Pontone, Gregory M.

doi:10.1016/j.jagp.2020.12.009

Cited by 17 publications

(18 citation statements)

References 34 publications

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“…13,15,16 However, LBD researchers have suggested that depression occurring in LBD is associated with degeneration of the LC. 9,10 Although there have been no quantitative immunohistochemical studies of the DRN, our results indicated that depression in LBD is more likely to be associated with abnormalities in the noradrenergic system than in the serotonergic system. A previous study reported that the accumulation of α-synuclein in the LC was not associated with depression; however, the subjects did not have dementia, suggesting that they might have had relatively low levels of α-synuclein.…”

Section: Discussionmentioning

confidence: 55%

Neuropathological studies of serotonergic and noradrenergic systems in Lewy body disease patients with delusion or depression

Mizutani

Sano

Ohira

et al. 2022

Psychiatry Clin Neurosci

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Aim The association between psychiatric symptoms in Lewy body disease (LBD) and the noradrenergic and serotonergic systems is still controversial. This study investigated the quantitative relationships of depression and delusion with these systems. Methods We studied 24 postmortem tissues from individuals with a pathological diagnosis of LBD with sufficient clinical history. The numbers of neurons and Lewy bodies (LBs) in the locus coeruleus (LC) and dorsal raphe nucleus (DRN) were counted, and the density of neurons in the DRN was analyzed. In addition, the densities of tryptophan hydroxylase‐positive neurites and norepinephrine transporter‐positive neurites in the amygdala and dorsal prefrontal cortex were measured. Finally, we divided the cases into two groups: with or without depressive mood, and with or without delusion. Quantitative histological data were compared between the groups. Results The group with depressive mood had a significantly smaller number of neurons in the LC compared with the group without depressive mood. The group with delusion had a significantly larger number of LBs in the DRN compared with the group without delusion. The density of norepinephrine transporter‐positive neurites in the dorsal prefrontal cortex was significantly correlated with the number of neurons in the LC. Conclusions The accumulation of LBs in the DRN of individuals with LBD was associated with delusion, whereas a decrease in the number of neurons in the LC was associated with depressive mood. These neurodegenerative changes involved the serotonergic and noradrenergic systems and may be associated with the formation of delusion and depression, respectively, in LBD.

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Section: Discussionmentioning

confidence: 55%

Neuropathological studies of serotonergic and noradrenergic systems in Lewy body disease patients with delusion or depression

Mizutani

Sano

Ohira

et al. 2022

Psychiatry Clin Neurosci

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“…However, the neuropathological substrate responsible for other symptoms in PS is not fully understood. Depression in the general population was linked to lesions in the basal ganglia receiving dopaminergic input from the SN [38]. Furthermore, it was associated with neuronal loss and gliosis in the SN in patients with PD [38].…”

Section: Discussionmentioning

confidence: 99%

“…Depression in the general population was linked to lesions in the basal ganglia receiving dopaminergic input from the SN [38]. Furthermore, it was associated with neuronal loss and gliosis in the SN in patients with PD [38]. Pathology of the ventral tegmental area and locus coeruleus could also underlie depressive symptoms [39,40].…”

Section: Discussionmentioning

confidence: 99%

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Clinical, pathological and genetic characteristics of Perry disease—new cases and literature review

Dulski

Cerquera-Cleves

Milanowski

et al. 2021

Euro J of Neurology

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Background and purpose: Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease. Methods: Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed.Results: Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed.There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play.

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“…Taking a similar approach would thus be optimal to disentangle depressive symptoms in patients with prodromal LBD to probe for the relationship between early affective symptoms in DLB and LC dysfunction. A recent study (Fischer et al, 2021) investigated the neurodegeneration within the LC and SN and correlation between the observed degeneration in these nuclei and the occurrence of psychiatric symptoms such as anxiety, depression, and psychosis. Surprisingly, they found no association in PD patients between the aforementioned symptoms and neuronal loss and gliosis in the LC, but in the SN.…”

Section: Degeneration Of the Locus Coeruleus In Dementia With Lewy Bomentioning

confidence: 99%

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

Hansen

2021

Front. Aging Neurosci.

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Background: The locus coeruleus (LC) is a nucleus in the human brainstem with a variety of noradrenaline-driven functions involved in cognition, emotions, and perception. Dementia with Lewy bodies (DLB) constitutes a neurodegenerative disease involving deposits of alpha-synuclein, first appearing in the brainstem. The goal of this narrative review is to delineate the relationship between the expression of psychiatric symptoms as an early-onset of DLB and the degeneration of the LC's noradrenaline system.Methods: We searched in PubMed for relevant articles concerning LC degeneration and psychiatric symptoms in prodromal DLB in this narrative review. We rely on the McKeith criteria for prodromal psychiatric DLB.Results: We found four studies that document neuronal loss, deposits of Lewy bodies and other hints for neurodegeneration in the LC in patients with DLB. Furthermore, we reviewed theories and studies on how the degenerated noradrenaline LC system contributes to psychiatric DLB's phenotype. We hypothesized how anxiety, hallucinations, delusions, and depressive symptoms might occur in DLB patients due to degenerated noradrenergic neurons entailing consecutive altered noradrenergic transmission in the LC's projection areas.Conclusions: LC degeneration in prodromal DLB might cause psychiatric symptoms as the first and non-motor manifestation of DLB, as the LC is affected earlier by degeneration than are dopaminergic structures such as the substantia nigra, which are impaired later in the disease course.

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Brainstem Pathologies Correlate With Depression and Psychosis in Parkinson's Disease

Cited by 17 publications

References 34 publications

Neuropathological studies of serotonergic and noradrenergic systems in Lewy body disease patients with delusion or depression

Neuropathological studies of serotonergic and noradrenergic systems in Lewy body disease patients with delusion or depression

Clinical, pathological and genetic characteristics of Perry disease—new cases and literature review

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

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