Depression in Parkinson's disease.

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The prevalence increases with age, affecting about 1% of people aged above 65 (1). Given the profound aging of the world's population (2), the prevalence of PD will increase further during the next decades. Clinically, PD is characterized by resting tremor, rigidity, akinesia and postural instability. However, research during the last 30 years has shown that a wide range of neuropsychiatric symptoms occur in PD as well (3), the most prevalent being depression. Depression has important consequences for the PD patients' and their caregiver's quality of life (4, 5). In addition to psychological reactions to the impairment and poor prognosis of the disease, it has been suggested that the brain changes associated with PD, such as serotonergic and mesolimbic and mesocortical dopaminergic deficits, may contribute to depression in PD (6, 7). Ten years ago, the critical areas for future research of depression in PD were identified to be large-scale demographic studies, longitudinal studies, and combined imaging and neuropsychological studies of depression in PD (8). Since then, several of these issues have been addressed. However, key questions remain unanswered. Is depression more prevalent in PD compared with other conditions with comparable functional impairment? If not, there is little reason to assume a disease-specific association between PD and depression. Studies of these questions have usually included small samples subject to selection and participation biases. In this issue, Nilsson et al. (9) have used the Danish registers of somatic and psychiatric in-patients to address this question. Such registers are important research tools offering potential insights which cannot easily be derived from other sources. Data from more than 200 000 people were analyzed, and more than 12 000 subjects with PD were identified. Using this large and representative database, the authors found a significant increased risk for hospitalization because of depression in patients with PD compared with subjects with osteoarthritis or diabetes mellitus. The authors suggest that the increased risk was not a mere psychological reaction to the disease but rather because of disease-specific brain changes in PD patients. This study provides important new information. However, only a small proportion of depressed PD patients were addressed, i.e. those who were hospitalized in a psychiatric hospital. Depression in PD is usually not severe, or associated with psychosis or suicidality, and the large majority of depressed PD patients were likely not included. Why is there an increased risk for depression in PD? Identifying the relationship of depression to clinical features with known or presumed neurological correlates may answer this question. Several clinical factors have been found to be associated with increased risk for depression, including akinesia, cognitive impairment, and right-sided symptoms. However, such studies have usually not controlled for demographic factors known to increase the risk for depression in the general population, such as gender, age, and family history. Therefore, potential factors specific for PD which may induce depression cannot be distinguished from overall, non-specific risk factors for depression. These problems were addressed by Leentjens et al. (10). They found that several known risk-factors for depression were found to be markers of depression in PD as well. Among these, a family history of depression was most influential. This finding highlights the close and enigmatic relationship between depression and PD. Not only does PD increase the risk for depression, but as Nilsson and colleagues have shown in a previous paper (11), depression is in fact a risk factor for PD, and may be the presenting symptom in some PD cases (12). Thus, a common neurobiological factor may underlie both depression and PD, or depression may damage dopaminergic nigrostriatal neurons through yet unknown mechanisms. Leentjen et al. found that right-sided dominance was the only disease-specific factor that was related to depression. This finding is consistent with observations both in patients with major depression (13) and in many studies of stroke patients (14), suggesting that injury to the left anterior brain renders it particularly vulnerable to depression. However, there are several other disease-specific factors which could potentially be related to depression but which were not explored in this study, including subtle cognitive impairment and age at onset. The present studies highlight the close relationship between depression and PD, and provide answers to important questions. However, several issues are still unresolved. There is now a need forexploring the neurological and neurochemical underpinnings of depression in PD. Moreover, although preliminary evidence suggests that antidepressants are useful for PD patients, there has not yet been randomized, placebo-controlled clinical trials demonstrating treatment efficacy. Such studies are urgently needed in order to provide clinicians with answers to the most salient question for the patient: how should depression in PD be treated? Acta Psychiatrica Scandinavica Dag Aarsland, Jeffrey L Cummings Invited Guest Editors