Depression Preceding Parkinson’s Disease Onset

Review Article

Austin Alzheimers J Parkinsons Dis. 2015; 2(1): 1023.

Depression Preceding Parkinson’s Disease Onset

Nagayama H* and Kimura K

Department of Neurological Science, Graduate School of Medicine, Japan

*Corresponding author: Hiroshi Nagayama, Department of Neurology, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan

Received: February 26, 2015; Accepted: August 08, 2015; Published: August 13, 2015


Parkinson’s disease (PD) is characterized by many non-motor symptoms, some of which appear prior to motor symptom onset. This preceding period is called the preclinical stage, and some symptoms such as depression are observed during this period. In this report, we review the characteristics of depression observed during the preclinical stage of PD. We included studies retrieved from a MEDLINE search of the following: (1) published between 1970 and March 2014, (2) included Medical Subject Heading (MESH) terms including Parkinson’s disease and MESH terms for depression. There were 18 reports that mentioned preclinical depression or depression-related disorders in PD. Most of these reports were case-control studies and a few were cohort studies; there were no prospective studies. PD diagnosis criteria were variable, and some reports did not include these criteria. The diagnosis of depression was also variable, and was based on questionnaires, interviews, medical record reviews, and database searches. Most of these reports indicated that depression preceding PD onset was a significant risk factor for developing PD, with odds ratios of 1.50–3.40. In particular, a history of depression within 5 years of PD diagnosis correlated with PD development. These results should be interpreted with caution because the criteria for depression and PD varied among studies; however, depression preceding the onset of PD may be a risk factor for developing PD.

Keywords: Parkinson’s disease; Depression; Preclinical stage; Serotonin


PD: Parkinson’s Disease; NMS: Non-motor Symptom; MESH: Medical Subject Heading; DSM: Diagnostic and Statistical Manual of Mental Disorders; H-ICDA: Hospital International Classification of Diseases Adapted; ICPC: International Classification of Primary Care; ICD: International Classification of Disease; 5-HIAA: 5-hydroxyindoleacetic Acid


Symptoms other than motor symptoms have recently been characterized in Parkinson’s disease (PD): non-motor symptoms (NMSs). Some NMSs appear prior to the onset of motor symptoms, such as a kinesis, tremor, and rigidity [1]. The onset of PD is usually marked by the onset of motor symptoms; therefore, the preceding period between the onset of non-motor and motor symptoms is called the preclinical stage. Some of the NMSs observed in the preclinical stage of PD are constipation, hyposmia, rapid eye movement (REM) sleep behavior disorder (RBD), and depression [2].

Psychotic symptoms are reportedly one of the main NMSs observed in PD. In 1913, the correlation between PD and personality was studied [3]; most patients with PD were diligent and socially respectable people. Subsequently, the personality of patients with PD was described as depressive, introversive, and prudent [4–10]. These personality traits likely became apparent during the preclinical stage of PD. Patrick and Levy first reported on depression in patients having PD in 1922 [11]. Today, it is known that the prevalence of depression in patients with PD is higher than that in the general population, and the main symptom is a hedonic [12]. Depression and PD may share a common pathophysiological mechanism [13- 15]. Moreover, some reports suggested that a history of depression is related to developing PD [16-32]. In this report, we review whether preclinical depression may be a risk factor for developing PD, and how preclinical depression is related to the pathophysiological mechanisms involved in developing PD.

Literature search

Our literature search encompassed psychological terms meaning depression because the criteria and/or definition of depression as changed over time. This review will focus only on research that examined the association between PD and preceding depression. We determined whether previous review reports existed regarding the association between preclinical depression and PD by executing a MEDLINE search for all reviews of PD and risk factors from 1970 to March 2014. Results of reviews that met the assessment criteria are reported along with additional relevant results. We used the following Medical Subject Heading (MESH) terms in our search: Parkinson’s disease and one or more of the following, including depression, depressive disorder, affective disorder (psychotic), bipolar disorder, and adjustment disorder. We included reports that clearly mentioned preclinical depression in the examined PD cohort; however, clinical diagnostic criteria for depression or PD were irrelevant. If depression was indicated in the report even just a little, we adopted the reports as widely as possible, and the contents were commented respectively.

Outline of previous reports

There were 18 reports that mentioned depression or disorders including depression preceding PD onset [16–33]; one was a review [33]. The limited number of reports may be due to difficulty evaluating events that precede PD onset. The oldest report was from 1972. However, most reports were from the 1990s to the early 2000s. The review [33] systematically and precisely covered many studies; however, it did not include all the studies that we included in this report. Most previous reports were case-control studies [16–28], a few were cohort studies [29–32], and there were no prospective studies. In most of the case-control studies, PD patients were enrolled in the each hospital or region, and the risk of depression for the developing PD was compared with sex and age matched controls. The cohort study used a regional registration system/database(e.g., general practitioner/public hospital system or National Health Insurance Research Database), which contained10,000 to more than 100,000 subjects to calculate the prevalence of a history of depression in patients with PD [29,31] or the prevalence of newly developed PD in patients with depression [30,32]. However, even in the latter studies, the prevalence of newly developed PD was determined retrospectively in a patient cohort diagnosed with depression during a certain period (i.e., not a prospective study). The control group in these studies was a non-PD group of the same cohort; however, the control group in one study consisted of individuals diagnosed with another disease, such as diabetes mellitus or osteoarthritis [29].

The PD diagnostic methods were variable. Explicit diagnostic criteria were used in several reports [22-24,26]: Criteria for Diagnosing Parkinson’s Disease described by Calne [34,22], British Brain Bank criteria for the clinical diagnosis of PD[23,26,35,36], and Research diagnostic criteria for Parkinson’s disease described by Ward and Gibb [37,24]. In some studies, diagnostic criteria were included [16,17,19,21,28,29,32] or a diagnosis was made based on the combination of cardinal symptoms included in other reports [18,20,25,27,30,31].

Depression diagnostic methods were also variable. A history of depression was detected by a lack of unification, as determined using questionnaires [20-22], interviews [16-18,24,26,28], medical record reviews [19,23,25], and hospital or regionally based registration database searches[29-32]. A few reports evaluated depression and other psychiatric disorders (i.e., disorders that should be clearly distinguished from depression) as a single group. Kessler [16,17] and Raj put et al. [19] described some psychiatric disorders, including depression, as a nervous breakdown or psychoneurosis/ psychosomatic disorder, respectively. In the former, the term nervous breakdown included a wide range of psychiatric disorders, such as a manic state and neurosis. In the latter, psychoneurosis/psychosomatic disorders included hysteria and irritable bowel syndrome, in addition to depression. Diagnostic criteria of these psychiatric disorders, including depression, were not described.

Questionnaire and interview results were retrospectively evaluated and classified according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the Hospital International Classification of Diseases Adapted (H-ICDA) [38] in some reports [18,25,27,28,32]. However, the remaining reports [20-22,24,26] simply stated whether the questionnaire or interview results indicated the presence of depression, without any explicit criteria. Disorders (e.g., depression, mood disorder, or depressive state) differed among most database cohort studies [23,29-31], even though objective disorders were classified according to the International Classification of Primary Care (ICPC) [39] or International Classification of Disease (ICD). Furthermore, Yang et al. reported a correlation between developing PD and a history of antidepressant administration [21]. Therefore, because the diagnosis of depression and the meaning of the term “depression” were diverse, the results of these previous reports should be interpreted with caution.

The risk of developing PD in patients with a history of depression

Past reports were divided into two types. The first group included reports in which the main objective was to determine epidemiological factors involved in developing PD, and where psychiatric symptoms, including depression, were evaluated as a part of these factors [16,17,19-22,24,27]. The second group comprised reports that only focused on psychiatric disorders surrounding the depression, and where the relationship between the risk of developing PD and a history of psychiatric depression was evaluated [18,23,25,26,28-32].

A. Reports that evaluated depression as an epidemiological factor related to developing PD: Most of these reports were casecontrol studies from the 1970s–1990s. The odds ratio summary is shown in (Figure 1). Some of these studies evaluated disorders other than depression, as mentioned above [16,17,19]; therefore, we excluded them in (Figure 1). These four out of five of reports, indicated that a history of depression was a significant risk factor for developing PD (odds ratio: 1.54–3.40) [20-22,24,27]. Behari et al. divided their cohort into two groups according to the preceding period of depression before the onset of PD, and a history of depression was a significant risk factor only in the group whose preceding period was 10 years or shorter [27].