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Although research suggests depression is common among individuals with Parkinson’s disease (PD), it is unclear how to best assess depression in PD (dPD). We wanted to examine the prevalence of dPD using different definitions of depression, as well as examine factors associated with dPD.
One hundred fifty-eight individuals (68% male; age 66.8 ± 9.6 SD) with a primary diagnosis of PD were assessed for depression using the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) in an outpatient setting at the Movement Disorders Clinic at Massachusetts General Hospital. We defined depression using 4 thresholds based on the HANDS and whether or not an individual was ever on an antidepressant regimen. We also examined potential predictors of the presence of dPD.
The prevalence of depression among study participants ranged from 11% to 57%, depending on which of the 4 definitions of depression was applied. Younger age and longer duration of PD predicted a relatively higher prevalence of depression. Having a history of depression prior to onset of PD also was predictive of dPD.
Depression appears to be relatively common among individuals with PD, and history of depression, younger age, and longer PD duration may be factors associated with dPD.
Previous research has suggested depression (or at least depressive symptoms) is relatively common among individuals with Parkinson’s disease (PD).1 Approximately 40% of individuals with PD experience some form of depression.2,3 Studies also have suggested depression has an impact on PD, in that it appears to compromise the individual’s quality of life, even more so than motoric issues,1,4 and has been associated with greater disease progression.5
Additionally, the relationship between depression and PD is not well understood. One explanation is conceptually, depression may be related to PD-induced neurobiologic changes likely associated with changes in central nervous system levels of dopamine and serotonin.6 Affective functioning may be influenced by the degeneration of neural systems in PD. In addition, PD involves structural changes, including subcortical-cortical neural pathway degeneration, neuronal loss of the substantia nigra, the presence of Lewy body inclusions, and a decline in monoamine neurotransmitter systems.6,7 And, given the high prevalence rates of psychiatric symptoms in PD, some see PD as a neuropsychiatric condition, not simply a movement disorder.8 Depression, therefore, may result from biochemical deficiencies produced by PD, suggesting a neurobiologic basis for the depressive symptoms.7,8 Depression may also occur later in the disease process, again possibly related to neurodegeneration. Alternatively, depression may stem from a psychological reaction to PD; a person may become depressed in response to the stress and disability of this chronic and progressive disease.6
Defining depression in the context of PD (dPD) is challenging, due in part to the overlap of symptoms of both disorders,7 leading to difficulties in accurately diagnosing dPD.8 For example, insomnia, tiredness, psychomotor retardation, difficulty with concentration, and reduced appetite are symptoms of both conditions, which can make it challenging to discern the underlying pathophysiology,7 particularly with concurrent onset. The use of standard, inclusive criteria to diagnose dPD, compared with a more exclusive, diagnostic-etiologic method, has a considerable impact on prevalence rates,9 and the implications for treatment are significant.
The aim of the current study was threefold: 1) to expand on our previous findings10—which examined depressive symptom patterns and predictors of severity of dPD—by using more qualitative classifications for measuring prevalence; 2) to examine the prevalence of depression in individuals with idiopathic PD treated at a tertiary care hospital, using 4 thresholds for depression; and 3) to examine possible predictors of dPD in this outpatient sample.
Two hundred patients with PD, who were consecutively seen at the Movement Disorder Clinic at Massachusetts General Hospital between March 2004 and June 2005, were invited to fill out a self-rated questionnaire aimed at screening for depressive symptoms (Harvard Department of Psychiatry/National Depression Screening Day Scale [HANDS]10). Formal approval to conduct this study was obtained from the Massachusetts General Hospital Institutional Review Board (IRB), and all procedures were conducted in accordance with the Declaration of Helsinki. A cover letter accompanying the HANDS questionnaire asked patients for permission to enroll them in a prevalence study, and if they agreed by providing verbal consent, they were asked to fill out the attached HANDS questionnaire (TABLE 1). The HANDS is a 10-item self-report scale that asks patients to rate on an ordinal scale of 0 (none/little of the time), 1 (some of the time), 2 (most of the time), and 3 (all of the time) how often during the last 2 weeks they have felt decreased energy, self-blame, poor appetite, insomnia, hopelessness, sadness, decreased interest, feelings of worthlessness, suicidal thoughts, and decreased concentration. A total HANDS score is the simple sum of ratings across the 10 items.
We chose the HANDS as our measure of depression because it has a high degree of correspondence with the DSM-III-R criteria for major depression, and it has demonstrated validity consistent with other widely used self-report measures of depression, such as the Zung Self-Rating Depression Scale, Beck Depression Inventory-II, and Hopkins Symptom Depression Checklist.11 A total score cutoff of ≥9 suggests depression, whereas scores between 6 and 9 indicate possible depression, based on comparisons with diagnoses achieved with the Structured Clinical Interview for Mood Disorders (SCID).11,12 We also obtained other clinical and demographic information, including patient age, sex, age of onset of PD, duration of PD, PD severity based on the Hoehn and Yahr (HY) scale,13 presence of dementia, antidepressant use (current or past), and whether the patient had a history of depression prior to being diagnosed with PD. The presence of dementia was evaluated using a standard neurological exam consistent with the criteria for dementia of the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA).14 History of depression was measured based on chart reviews, including recorded psychiatry medication, family member/caregiver information, and patient self-report.
Based on the above considerations, in determining the prevalence of depression, we defined depression based on the HANDS score in 4 ways:
In determining potential predictors of depression, we defined a dichotomous variable, eg, presence/absence of depression, indexed in a given analysis by 1 of the 4 definitions of depression described above. We used a multiple logistic regression analysis with backward elimination (at a cutoff of P ≤ .05) of the simultaneous predictors of age, HY score, duration of PD illness, an indicator variable of presence/absence of dementia, and an indicator variable of presence/absence of history of depression prior to the PD illness. Four separate analyses, each with one of the 4 respective methods of defining depression as the categorical dependent variable, were conducted.
Of the 200 individuals with PD who were to be administered the HANDS, 158 (79%) fully completed the 10 items and thus were included in the study. Of the 42 who did not participate, 15 left certain items on the HANDS unanswered, 19 chose not to participate, and we were not able to give the HANDS to 8 individuals due to scheduling conflicts. There did not appear to be any discernible differences between those completing the forms and those choosing not to participate or not fully completing the forms, although a significantly (P < .03) higher proportion of women than men did not complete the forms (26% vs 13%). There was no significant age difference between completers and noncompleters of the study questionnaire. The effective sample of 158 consisted of 108 men (68%) and 50 women (32%); mean age (years), 66.8 ± 9.6 SD; mean age for PD onset, 57.7 ± 10.8 years; mean HY score, 2.4 ± 1.0 (range, 0 to 5); and mean duration of PD illness (years), 9.1 ± 6.2. Dementia was present in 5 patients (3.2%), and 21 had a history of depression prior to PD illness (13.7%). The mean HANDS total score was 4.8 ± 4.1. There was no significant difference between males (5.0 ± 3.8) and females (4.7 ± 4.2) in terms of mean HANDS score.
Because the HANDS form was administered only once to each subject, we do not have data from our sample on test/retest reliability for the HANDS (which, in any case, would be confounded with any actual trait instability) in this population. We, therefore, provide information on the internal consistency reliability of the instrument, specifically Cronbach’s coefficient alpha, which estimates the proportion of variance of the subjects’ total HANDS scores, which is due to true differences among the subjects, as opposed to measurement error variance. Coefficient alpha for the 10 HANDS items was computed to be 0.84 (raw score) or 0.85 (for the standardized z scores). An alpha >0.7 is usually considered acceptable and >0.8 is good.15 There was no item whose deletion lowered alpha to less than 0.8 or raised it above 0.86. The item-total correlations ranged from r = 0.46 (the “poor appetite” item) to 0.79 (“no interest”). All inter-item correlations were positive and were generally moderate and significant (P < .05; highest r = 0.63 for “hopelessness” vs “worthlessness”), except “poor appetite” had virtually a zero correlation with “suicidal thoughts” partly due to the fact that the latter item had by far the lowest and least variable ratings, with all subjects indicating “none/little of the time” (score, 0) except for 3 who indicated “some of the time” (score, 1).
The prevalence of dPD was 47% to 57%, depending on the HANDS total cutoff score used to define depression and assuming current or past use of an antidepressant categorizes a patient as depressed, regardless of current HANDS score. If we do not include antidepressant use as an additional criterion, our prevalence rate would be between 11.4% and 36.7%. (See TABLE 2 for a breakdown of prevalence rates of dPD, given our 4 thresholds/definitions.) Almost half of our sample (70, or 44%) had been on an antidepressant (past or current), and only 4 (3%) had a HANDS score ≥9 and were never treated with an antidepressant. Individuals exposed to antidepressants were younger than those who had never taken antidepressants (65 vs 69 years of age; P = .043). There was no significant relationship between antidepressant use and HY score (PD severity). Among individuals exposed to antidepressants, 20% endorsed depressive symptoms with a HANDS score ≥9, and 54% had a HANDS score ≥6.
Four separate logistic regressions were run to predict presence of depressive symptoms, using each of the 4 respective definitions of depression indicated in the Methods section. In each case, after backward elimination (at P ≤ .05), only 2 significant predictors remained (each adjusted for the other). History of depression was always one of the significant predictors. When depression was defined solely by a HANDS total score ≥9, increasing duration of PD predicted greater likelihood of depression, whereas for each of the other 3 definitions of depression, younger age was the second significant predictor. With other predictors held constant, a 1-year increase in duration of PD increased the odds of reporting symptoms of depression by a factor of approximately 1.09 (95% confidence interval [CI], 1.003 to 1.175), whereas a 1-year increase in age reduced the odds by a factor of approximately 0.95 (CI, 0.92 to 0.99). Depending on the model, having a pre-PD history of depression increased the odds of endorsing depressive symptoms by a factor of 3.5 (for HANDS scores ≥6) to as much as 15 (for HANDS scores ≥9 or antidepressant use). For each of the 4 regressions, the model as a whole was significant (P ≤ .01), and the area under the receiver operating characteristic (ROC) curves was 0.75 for the HANDS ≥9 criterion, 0.67 for HANDS ≥6, 0.72 for HANDS ≥9 or antidepressant use, and 0.68 for HANDS ≥6 or antidepressant use (FIGURE).
Given the co-occurrence of depression and PD, it seems important to continue to assess their relationship, as well as to how to identify dPD and how to measure depression in the context of PD. Our previous findings were more descriptive of the nature of depression in PD, in that the earlier study focused on the micro symptom pattern and predictors of severity of depression as a continuous variable,10 whereas the current study is more concerned with depression as a qualitative, clinically diagnosed classification, its prevalence, and what variables predict its presence. More specifically, the aim of the current study was to further determine the prevalence of dPD by looking at 4 potential threshold criteria based on the HANDS and antidepressant use, and to examine the relative contributions of age, history of depression, duration of PD, and severity of PD to depression.
Our results suggest the prevalence of dPD in outpatients was 11% to 57%, depending on the HANDS cutoff score. We found duration of PD, younger age, and especially history of depression predicted the prevalence of depression in PD. Others have found sex (female) and more severe PD predicted depression16; however, our findings did not indicate any relationship between sex and total HANDS score. Although our prevalence rates of depression were increased by 1) lowering the HANDS cutoff score from 9 to 6, and also by 2) including antidepressant use in the definition of depression, with respect to ROC area under the curve—or accuracy of prediction of depression—the inclusion of antidepressant use left the sensitivity virtually unaffected, in the case of both the HANDS 6 and 9 cutoffs.
Overall, these data indicate symptoms of depression are common in PD and it may be possible to identify factors that increase the risk of dPD. Furthermore, all things being equal, it is interesting younger age appears to predict depressive symptoms. Future studies are needed to determine if this finding can be replicated. These studies might also test the speculative hypothesis that the prospect of impending disability is more psychologically stressful to those who thought they had more of their life ahead of them, whereas older persons might be more accepting of the illness and less psychologically affected by it.
Twenty-one patients reported being diagnosed with depression prior to the PD diagnosis, possibly suggesting that depression may be an early sign of PD related to neurochemical and neurodegenerative changes involved in both disorders.17 Replication using a larger sample size is necessary in order to address incongruities in reports demonstrating the temporal relationship between diagnosis of major depressive disorder and the onset of PD.18,19
There are several limitations to our study, which include relatively small sample size (N = 158), no clinician-rated measure of depression, and no depressed control group without PD. Although the results reflect the inclusion of 5 patients with dementia, there were no implications for cognitive impairment that would have significantly affected the total HANDS score. Because we included current or past use of antidepressants in 2 of our 4 definitions of depression, our observation that having a history of depression prior to the onset of PD was predictive of dPD could be perceived as a sort of circular reasoning. However, history of depression predicted depression in all 4 of our definitions (HANDS score ≥9; HANDS score ≥6; HANDS score ≥9, or current or past antidepressant use; HANDS score ≥6, or current or past antidepressant use), not exclusively those defined by antidepressant use. Lastly, it is possible our use of more inclusive, standard definitions of depression in which the HANDS score is considered independently of PD symptom severity may overestimate the rate of true comorbidity.
Depression appears to be relatively prevalent in PD and may possibly be underdiagnosed. Further work is needed to determine the best measures to assess dPD and whether a specific measure should be developed or whether standard depression measures are valid. Younger age, longer PD duration, and history of depression prior to onset of PD appear to be factors that increase the risk of dPD. Further studies are needed, both to confirm these results and to further examine the complex relationship between depression and PD. It may be helpful to conceptualize depression as being on a continuum and to further examine whether depression is an early symptom of PD in some cases, as these areas of investigation can have great clinical relevance.
This research was supported by the Harvard Medical School Kaplen Fellowship. Data were collected from NINDS/NIH P50 NS038372.
DISCLOSURES: Dr. Farabaugh has received grant/research support from the National Institute for Mental Health, Harvard Medical School, and NARSAD. She also has been a speaker for Massachusetts General Hospital Academy and the American Psychiatric Association. Dr. Fava has received lifetime research support from Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmith-Kline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson and Johnson Pharmaceutical Research and Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; PharmaviteR LLC; Photothera; Roche; RCT Logic, LLC; sanofi-aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories. He also has advised/consulted for Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Clinical Trials Solutions, LLC; CNS Response, Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Danippon Sumitomo Pharma Co. Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Eli Lilly and Company; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson and Johnson Pharmaceutical Research and Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante, Inc.; Merck, Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; PharmaStar; Pharmavite LLC.; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; Psycho-Genics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; RCT Logic, LLC; sanofi-aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Synthelabo; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda Pharmaceuticals, Inc. Dr. Fava has spoken for/been published in Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute/Physicians Postgraduate Press, Inc.; Eli Lilly and Company; Forest Pharmaceuticals, Inc.; GlaxoSmith-Kline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource,Corp.; Wyeth-Ayerst Laboratories. Dr. Fava has had equity holdings in Compellis. He also has received royalties/other income from Patent for Sequential Parallel Comparison Design (SPCD) and patent application for a combination of azapirones and bupropion in major depressive disorder, copyright royalties for the MGH Cognitive and Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs and Symptoms (DESS), and SAFER. Patent for research and licensing of SPCD with RCT Logic; Lippincott, Williams and Wilkins; World Scientific Publishing Co. Pte. Ltd. Drs. Locascio, Yap, Bitran, and Growdon and Ms. Sousa report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Amy H. Farabaugh, Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA.
Joseph J. Locascio, Movement Disorders Unit, Memory Disorders Unit, Massachusetts General Hospital, Boston, MA, USA.
Liang Yap, Memory Disorders Unit, Massachusetts General Hospital, Boston, MA, USA.
Maurizio Fava, Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA.
Stella Bitran, Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA.
Jessica L. Sousa, Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA.
John H. Growdon, Movement Disorders Unit, Memory Disorders Unit, Massachusetts General Hospital, Boston, MA, USA.