Neuroinflammation tied to mood disturbance in early Parkinson’s

Study shows link to worse anxiety, depression in newly diagnosed patients

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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A person looking dejected lies facing down on a bed, head resting on one arm with the other arm dangling over the side.

New study findings strengthen scientists’ belief that neuroinflammation — an inflammatory response in the central nervous system — is linked to mood disturbance in people with early Parkinson’s disease.

Specifically, elevated levels of pro-inflammatory signaling molecules in the cerebrospinal fluid (CSF) were found to be significantly correlated with worse anxiety and depression in newly diagnosed Parkinson’s patients who had yet to receive treatment. The CSF is the fluid surrounding the central nervous system, comprised of the brain and spinal cord.

These findings strengthen the hypothesis that “neuroinflammation may play a role in mood disorders in PD [Parkinson’s disease],” the researchers wrote.

“Better understanding of [the development] of mood disorders may help to explain clinical [diversity] in PD and is important to develop novel therapeutic strategies,” the team wrote.

Results from their small study were detailed in “Mood disturbances in newly diagnosed Parkinson’s Disease patients reflect intrathecal inflammation,” which was published in the journal Parkinsonism & Related Disorders.

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Investigating the impact of inflammation in the brain and spinal cord

Mood disturbance, which can manifest as depression and anxiety, is a common nonmotor symptom among people with Parkinson’s disease. The progressive neurological condition is marked by the dysfunction of certain nerve cells in the brain.

Such disturbances often can be seen in the early stages of the disease, even before the onset of Parkinson’s hallmark motor symptoms.

Inflammation is known to play a role in nerve cell loss in Parkinson’s and has been implicated in the development of mood disturbance in several other conditions.

Building on these findings, a team of scientists in Italy investigated whether neuroinflammation in people with Parkinson’s disease is related to mood disturbances, specifically depression and anxiety.

The study enrolled 45 newly diagnosed Parkinson’s patients who had yet to receive treatment. These individuals had a median age at diagnosis of 60, and about 40% — 19 altogether — were women. A group of 44 people with other disorders served as controls.

To assess neuroinflammation, the team measured the levels of pro-inflammatory immune signaling molecules, called cytokines, in the CSF.

The analysis revealed significantly higher levels of four pro-inflammatory molecules in patients’ CSF compared with controls: interleukin-6 (IL-6), interleukin-9 (IL-9), IFN-alpha, and GCSF.

A comparison of cytokine levels with demographic and clinical characteristics across all participants found no notable correlations with age, sex, disease duration, disease severity, or cognitive abilities. There also were no correlations of note between either diabetes or body mass index, a ratio of weight to height that’s used as a measure of body fat.

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Focus was on link between inflammation, mood disturbance

To investigate a potential relationship between neuroinflammation and mood disorders, levels of pro-inflammatory cytokines were compared with scores from two mood assessment tools: the Beck Depression Inventory-Second Edition (BDI-II) and the State-Trait Anxiety Inventory-form Y (STAI-Y).

Higher BDI-II scores, or worse depression, significantly correlated with elevated CSF levels of IL-6 and interleukin-8 (IL-8), after adjusting for age, sex, disease duration, and the severity of motor symptoms, as assessed by the Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-III).

STAI-Y assessed two types of anxiety: state and trait anxiety. State anxiety refers to a short-term response to an event perceived as adverse, with feelings of tension, apprehension, nervousness, and worry. Trait anxiety indicates a predisposition to perceive stressful situations as dangerous or threatening.

Higher, or worse, STAI-Y state scores significantly correlated with elevated levels of IL-6 and interleukin-12 (IL-12) after adjustments. Higher STAI-Y trait scores were significantly associated with levels of interleukin-2 (IL-2), IL-6, IL-8, IL-12, and interleukin-17 (IL-17).

In addition, elevated levels of IL-8 were linked with worse patient-assessed quality of life, as indicated by lower scores on the Parkinson’s Disease Questionnaire-8 (PDQ-8).

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No differences between men, women seen in mood disturbance severity

While the severity of depression and anxiety did not differ between men and women, PDQ-8 scores were significantly worse in women.

In men with Parkinson’s, higher CSF levels of IL-6 and IL-8 correlated with worse scores on the BDI-II, STAI-Y state, STAI-Y trait, and PDQ-8. Having an older age at diagnosis for men also correlated with levels of the cytokines MIP-1a and MCP-1.

In women, having an older age at diagnosis was related to levels of IL-17 and MIP-1a, with higher levels of CSF eotaxin correlating with worse motor function at diagnosis. Correlations also were found between more severe depression and higher IL-9 and TNF.

Higher STAI-Y state scores matched IL-12 and GCSF levels, while worse STAI-Y trait scores correlated with interleukin-7 (IL-7), IL-9, GCSF, and TNF. Despite these findings, no correlations were found between PDQ-8 and CSF cytokines in female patients.

In newly diagnosed PD [Parkinson’s disease] patients, increased expression [activity] of specific proinflammatory cytokines [immune signaling molecules] is associated with higher levels of depression and anxiety, further strengthening the hypothesis that neuroinflammation may play a role in mood disorders in PD.

Overall, the researchers concluded that “in newly diagnosed PD patients, increased expression [activity] of specific proinflammatory cytokines is associated with higher levels of depression and anxiety, further strengthening the hypothesis that neuroinflammation may play a role in mood disorders in PD.”

These findings “suggest that a proinflammatory CSF milieu may be associated with higher levels of depression and anxiety in the early phases of the disease,” the team wrote.

As study limitations, the team noted the small sample size and the lack of follow-up data.