Depression Linked With Worsened Non-Motor Symptoms in Parkinson Disease


Patients with Parkinson disease and depression exhibit significantly worse nonmotor symptoms, highlighting the need for comprehensive management including orthostatic hypotension, constipation, and hyposexuality.

Vajiheh Aghamollaii, an associate professor of neurology at Tehran University of Medical Sciences

Vajiheh Aghamollaii

In a recently published comparison study, findings revealed that patients with Parkinson disease (PD) who had depression had significantly worse nonmotor symptoms than those without, with major differences observed in orthostatic hypotension, constipation, and hyposexuality. Overall, these data could be beneficial for the diagnosis of the disease, which eventually could make a considerable difference in the management of patients with PD.1

The analysis, published in Health Science Reports, included 93 patients with PD with depression and 67 without depression who were compared on several nonmotor outcomes. Led by Vajiheh Aghamollaii, an associate professor of neurology at Tehran University of Medical Sciences, the study excluded those with any confirmed prior psychiatric disorder including anxiety disorders, bipolar disorder, schizophrenia, and substance abuse, or any other neurologic disorders including epilepsy, dementia, stroke, or head trauma.

Among patients with depression, with mean Beck Depression Inventory (BDI) score for depression was 35.80. In total, 11 (11.8%) patients had mild depression, 19 (20.4%) had moderate depression, and 63 (67.7%) patients had severe depression according to the BDI questionnaire. Between the 2 groups, patients with depression showed significantly higher rates of orthostatic hypotension, constipation, and hyposexuality compared with the control group (P <.001; P = .029; P <.001, respectively). These symptoms were reported in 41.9%, 54.8%, and 48.4% of those with depression vs 10.4%, 37.3%, and 16.4% of control subjects, respectively.

The study found no between-group differences in the prevalence of hyposmia (P = .079), as well as no significant difference on the Epworth Sleepiness Scale (P = .586), Pain and Sleep Questionnaire (PSQ; P = .418), REM Sleep Behavior Disorder Screening Questionnaire (P = .779), and Montreal Cognitive Assessment (P = .289). Notably, PSQ score was significantly associated with Hoehn and Yahr staging (P = .005), PD duration (P = .001), depression duration (P = .030), and levodopa equivocate daily dose (P = .001).

"As there is a well-known close relationship between dopamine and sexual disorders, hyposexuality is relatively common among patients with PD, associated with many factors including motor disabilities, autonomic dysfunction, sleep disturbances, pain, mood disorders, cognitive abnormalities, and medications. However, hyposexuality and orgasmic dysfunction are often neglected because of patients' embarrassment and clinicians’ focus on more apparent motor symptoms," Aghamollaii et al wrote.

The study authors added, "It should be noted that hyposexuality could be also related to depression medications such as selective serotonin reuptake inhibitors, which could specifically impact our results and interpretations. The high rates of constipation among PD patients are also concerning since gastroparesis and small intestine bacterial overgrowth can lead to malabsorption of PD medication in patients and, therefore, exacerbate motor symptoms."


In a subgroup analysis, BDI did not show a significant correlation with ESS, RBDSQ, PSQ, and MoCA scores (P = .220; P = .895; P = .775; and P = .626) among patients with mild depression. Moreover, the BDI score was not associated with hyposmia, orthostatic hypotension, constipation, and hyposexuality (P = .662; P = .931; P = .329; P = .133, respectively). A similar pattern was also yielded in the moderate depression group, and no significant association of the BDI score with non-motor scores was observed (p = 0.270, 0.770, 0.089, and 0.468, respectively).

Investigators reported that in the severely depressed group, MoCA scores had a significant negative association with the BDI score (P = .042), while other scores did not show any significant result (P = .674; P = .959; P = .679, respectively). This group had significantly higher BDI scores for patients positive for orthostatic hypotension (P = .004) and those with hyposexuality (P = .028), but no differences in the hyposmia (P = .901) and constipation groups (P = .586).

"It should be noted that the results of this study should be interpreted in light of some limitations,” the study authors wrote. “Our work found a significant association of depression score with sleep quality, cognitive performance, and hyposexuality, which were consistent with the former studies in this area. However, it is noteworthy that all three disturbed sleep quality, cognitive decline, and hyposexuality could be manifestations of both depression and PD; therefore, the exact relationship whether its causative or associative should be further investigated."

1. Mayeli M, Shafie M, Shiravi M, et al. Depression is associated with the nonmotor symptoms of Parkinson’s disease: a comparative analysis. Health Science Report. 2024;7(5):e2106. doi:10.1002/hsr2.2106
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