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Advanced Neurology Alpha-synuclein, depression and neurodegeneration

Table 6. Bivariate correlations between depression, SNCA allele frequencies, and changes in Parkinson’s disease and Alzheimer’s
disease in the period 1990 – 2019
Variable MDD, baseline Dysthymia, baseline Depression, rs356220 rs2736990 rs3775439
prevalence prevalence baseline prevalence
Parkinson’s disease, change (%)
Unadjusted −0.13 0.07 −0.10 −0.01 −0.09 0.35
Adjusted* −0.13 0.03 −0.11 0.01 −0.11 0.33
Alzheimer’s disease, change (%)
Unadjusted −0.03 0.07 −0.01 0.09 −0.20 0.18
Adjusted* −0.03 0.04 −0.02 0.09 −0.21 0.17
MDD: Major depressive disorder. *Adjusted for changes in life expectancy over the period 1990–2019

Table 7. Bivariate correlations between changes in the prevalence of depressive disorders and that of both PD and
prevalence of depression and both Parkinson’s disease and AlzD at a cross-national level. When longitudinal methods
Alzheimer’s disease in the period 1990 – 2019 of analysis were adopted, two out of the three analyses
(cross-lagged regression and general linear models) were
Variable MDD, Dysthymia, Depression,
change change (%) change (%) suggestive of a prospective association between depression
(%) and the subsequent risk of both neurological disorders
Parkinson’s disease, change (%) (Table 3 and Table 8). These results are consistent with
Unadjusted 0.12 0.11 0.26 a existing evidence on the shared pathogenic mechanisms
and the results of longitudinal
for these disorders
[80-83]
Adjusted* 0.08 0.10 0.23 a research in community samples demonstrating a
Alzheimer’s disease, change (%) prospective link between depressive disorders and
Unadjusted 0.09 0.06 0.17 a neurodegenerative disorders [84-87] . Prior evidence has
Adjusted* 0.05 0.05 0.13 suggested that the links between depression and both PD
MDD: Major depressive disorder. *Adjusted for changes in life and AlzD are mediated by genetic vulnerability [88-90] and
expectancy over the period 1990–2019. Significant at P < 0.05 exposure to environmental risk factors, such as stress and
a
environmental toxins [91-93] . These two sets of risk factors
3.5. General linear model analyses of changes in PD do not operate in isolation. There is preliminary evidence
and AlzD over time that the development of subsequent PD is influenced by
gene-environment interactions between genetic risk and
The results of repeated measures analyses of variance are diabetes mellitus as well as between genetic variants and
presented in Table 8. As observed in the independent pesticide exposure [74,94] .
sample t-tests, there was a significant increase in the
prevalence of both disorders (PD: F = 197.78, P < 0.001; In this study, the cross-sectional association between
AlzD: F = 147.24, P < 0.001) over time. There was a dysthymia and each neurological disorder was stronger
significant effect of the baseline prevalence of all forms of than that observed for MDD (Table 2), and dysthymia
depression on this increase for both PD and AlzD over time. was the only form of depression that showed evidence of
In contrast, no such effect was observed for the frequencies a prospective link with both PD and AlzD in the cross-
of SNCA polymorphisms included in this study. These lagged analyses (Table 3). Dysthymia is defined as a
results are suggestive of a prospective relationship between chronic form of depression, characterized by mild but
persistent depressive symptoms that remain below the
the baseline levels of depression in a population and the diagnostic threshold for MDD . Many patients with
[95]
subsequent risk of both PD and AlzD.
dysthymia have superimposed episodes of MDD, in which
[96]
4. Discussion this is referred to as “double depression” . Dysthymia
has not been studied as extensively as MDD in relation
The current study was conducted to strengthen the to PD or AlzD. According to available data, at least 13%
evidence supporting the association between depressive patients with established PD fulfill the diagnostic criteria
disorders, AlzD, and PD as well as to investigate the for dysthymia . Furthermore, a study has found that 28%
[97]
potential effect of functional polymorphisms of the SNCA of AlzD patients qualify for a diagnosis of dysthymia .
[98]
gene on these associations, while adjusting for confounding The presence of dysthymia has also been found to be
factors. Significant associations were found between the associated with the occurrence of extrapyramidal features

Volume 2 Issue 1 (2023) 7 https://doi.org/10.36922/an.326