Depressive symptoms are common in Parkinson’s disease, especially in elderly patients. Recognition of depression in Parkinson’s disease can be confounded by the symptoms of Parkinson’s disease itself. It is not clear whether the symptoms of depression in Parkinson’s disease differ from those of depression in persons without Parkinson’s disease. Some have suggested that patients with depression in Parkinson’s disease have less guilt and sadness, whereas others have shown no difference when compared with patients with major depression. Anhedonia, or the lack of ability to enjoy, may be a clinical feature of Parkinson’s disease and a key symptom of depression in Parkinson’s disease. Tearfulness and emotionalism can occur in Parkinson’s disease in a similar manner to stroke and must not be confused with depression. Clinicians should be aware of the difficulties in diagnosing mild depression and should have a low threshold for the diagnosis in Parkinson’s disease.

Depression in Parkinson’s disease probably represents a spectrum of mood disturbances from mood changes before Parkinson’s disease motor symptoms through to depression associated with dementia. DSM-IV criteria may not adequately capture the spectrum of mood disorders seen in Parkinson’s disease. A broader definition of mood phenotype to include greater levels of psychological distress and particularly anxiety may be more appropriate in Parkinson’s disease. DSM-IV criteria for depression have been modified for depression in Parkinson’s disease by a consensus group to be more inclusive of symptoms, to include subsyndromal depression, to specify the timing of assessment and to use informants in those who are cognitively impaired³. These modified criteria have been validated prospectively⁴.

In a prospective cohort study of mood states in Parkinson’s disease it has been shown mood disturbance can be divided into depression plus anxiety, depression alone, excessive worry and normal mood⁵.

A variety of rating scales have been used to assess depression in Parkinson’s disease although they may reflect the presence of depressive symptomatology rather than depressive illness. For screening, the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Montgomery and Asberg Depression Rating Scale (MADRS) and the Geriatric Depression Scale (GDS) have been shown to be valid. For measurement of severity of depressive symptoms, the HDRS, MADRS, BDI and Zung Self-Rating Depression Scale (SDS) are recommended. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of Parkinson’s disease severity⁶. The HDRS is based on a structured interview whereas the self-rated GDS takes 5 minutes to complete, has been validated against the HDRS and is used commonly in United Kingdom practice in older patients.

People who are prescribed anti-parkinsonian drugs are more likely than controls or diabetics to be prescribed antidepressant drugs. Recent prescription of antidepressants is associated with an increased risk of developing Parkinson’s disease since depression can be a premorbid sign of early Parkinson’s disease⁷. A prevalence meta-analysis showed the weighted prevalence of major depressive disorder was 17%, and that of minor depression 22% and dysthymia 13%. Clinically significant depressive symptoms were present in 35%⁸. In a study of mood disorders in Parkinson’s disease in the United Kingdom the prevalence of major depression was 2.8% and minor depression was 7.7% although there was a high prevalence of up to 80% of worry and tension⁵. Depression is often unrecognized. In a survey of 1000 patients, 50% reported depressive symptoms but only 1% identified themselves as depressed⁹. This may be because people do not believe themselves to be depressed unless they feel sad. Similarly doctors can miss depression, in the majority of cases.

Age, psychosis and depression in Parkinson’s disease increase mortality, with a relative risk of 2.7 in patients with depression in Parkinson’s disease compared with those without depression, with the increased risk not due to suicide. The prevalence of depression is not related to disease duration. The five-year cumulative risk of depression onset is around 10%. Depression in Parkinson’s disease has a chronic course, and in one study, 56% of patients with major depression at baseline still had major depression at follow-up, while by combining major and minor forms, depression was chronic in 89% of cases¹⁰. Minor depression can lead to major depression in 11% of cases over a year and major depression will lead on to minor depression in 33% of cases and will remain chronic in the majority of cases¹¹.

It is unclear whether cognitive impairment in Parkinson’s disease is a risk factor for depression or vice versa, or whether the two sets of symptoms represent a depressive–executive syndrome. Depression in Parkinson’s disease may be similar in nature to depression associated with the depression–executive dysfunction syndrome of later life, which is associated with a slow or poor response to antidepressants. Depression and dementia combined may represent a subtype of Parkinson’s disease¹². Studies comparing depression in Parkinson’s disease with depression without Parkinson’s disease have shown similar cognitive deficits in both conditions, with reduced verbal fluency and attention deficits in depression and problems of abstract reasoning and set shifting in depression in Parkinson’s disease. Patients with depressive pseudodementia respond to cueing in a similar manner to Parkinson’s disease patients with subcortical dementia, which suggests that similar neural pathways are involved. Defining and diagnosing depression in Parkinson’s disease in the presence of dementia are problematic since most rating scales are unsuitable. The Cornell Scale for Depression in Dementia has been used in research but takes 30 minutes to administer and may not be practical for screening in clinical practice¹³.

It is still unclear how much the depression in Parkinson’s disease is due to the biology of the disease or is the result of psychosocial effects of chronic disease. An organic basis for depression is supported by a number of factors. Depression has been shown to be common in early disease, impairing activities of daily living and increasing the need for symptomatic therapy for Parkinson’s disease¹⁴. One case–control study has shown that initiation of any antidepressant therapy may be associated with a higher risk of Parkinson’s disease in the two years after the start of treatment, which suggests that depressive symptoms could be an early manifestation of Parkinson’s disease, preceding motor dysfunction⁷. The early pathological stages of Parkinson’s disease (Braak stage 1 and 2) with pathology in the brainstem linking to the limbic system before the onset of motor symptoms may be associated with depression and anxiety. Depressed patients are more likely to develop Parkinson’s disease than they are to develop osteoarthritis or diabetes, suggesting some common underlying aetiological factors. At diagnosis, 9.2% of Parkinson’s disease patients have a background history of depression compared with 4% of controls, again suggesting a link between depression and Parkinson’s disease¹⁵.

There is a possible familial aggregation of unipolar depression and Parkinson’s disease. Female gender, young onset, akinesia, postural and gait problems and right hemi-Parkinson’s disease have a significantly higher risk of depression in Parkinson’s disease. Depression is more pronounced in ‘off ’ periods, possibly due to the deregulation of the locus caeruleus similar to that found in rapid cycling bipolar affective disorder. Positron emission tomography (PET) studies of depression in Parkinson’s disease have shown reduced cortical serotonin (5HT) binding and reduced limbic noradrenaline and dopamine but no correlation with basal ganglia dopamine levels¹⁶. Abnormalities of the mesencephalon on MRI and transcranial ultrasound, frontal cortical under-activity on PET scans, and reduced caudate metabolism all suggest an organic basis for depression in Parkinson’s disease.