In Parkinson's disease (PD), there is degeneration of the cholinergic, noradrenergic, and serotonergic systems in addition to dopaminergic projections. Function of these non-dopaminergic systems can be imaged with positron emission tomography (PET) and single photon emission computed tomography (SPECT) and correlated with motor and nonmotor symptomatology. In addition, neuronal loss in PD is associated with microglial activation. The role of microglia in driving the disease process remains uncertain. This review presents and discusses current findings in these areas.
"Depression and anxiety are major non-motor features of Parkinson’s disease; precise prevalence rates vary depending on precise diagnostic criteria and staging of Parkinson’s disease [40, 41]. Such symptoms are often associated with degeneration of the noradrenergic (locus coeruleus) and serotoninergic (midbrain raphé nuclei) systems but definitive evidence is lacking (see [42, 43]). The possible role of dopaminergic neuron loss in these symptoms also needs to be clarified . "
[Show abstract][Hide abstract] ABSTRACT: The definition of Parkinson's disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article - widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic perspective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include - Parkinson's syndrome, Parkinson's syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA).
"Experiments have found that the serotonergic system plays an essential role in both symptoms. Brooks (2007) reports that in order to generate tremors with the characteristic PD frequency of 3-5 Hz in animal models it is necessary to lesion not just nigro-striatal dopaminergic projections but also the midbrain tegmentum, which contains serotonergic cell bodies in the median raphe, rubrospinal, and dentatothalamic tracts. He also notes that loss of midbrain serotonin 5-HT 1A binding correlates with tremor severity in PD, unlike loss of striatal dopaminergic function. "
"A recent review of imaging studies in PD concluded that there is very little evidence to support a major role for serotonergic system in regulating depression in the context of PD . In contrast there is strong evidence for the role of both the noradrenergic  and dopaminergic systems . "
[Show abstract][Hide abstract] ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants for the treatment of depression in patients with Parkinson's Disease (PD) but data on their efficacy are controversial.
We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the efficacy and acceptability of SSRIs in the treatment of depression in PD.
Ten studies were included. In the comparison between SSRIs and Placebo (n = 6 studies), the combined risk ratio (random effects) was 1.08 (95% confidence interval: 0.77 - 1.55, p = 0.67). In the comparison between SSRIs and Tricyclic Antidepressants (TCAs) (n = 3 studies) the combined risk ratio was 0.75 (0.39 - 1.42, p = 0.37). An acceptability analysis showed that SSRIs were generally well tolerated.
These results suggest that there is insufficient evidence to reject the null hypothesis of no differences in efficacy between SSRIs and placebo in the treatment of depression in PD. Due to the limited number of studies and the small sample sizes a type II error (false negative) cannot be excluded. The comparison between SSRIs and TCAs is based on only three studies and further trials with more pragmatic design are needed.
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