The Interrelationship Between Depression and Parkinson's Disease

In his Leçons du Mardi of 12 June 1888 Jean-Martin Charcot described the facial expression of a patient with Parkinson’s disease as follows:

"The muscles of the face are motionless; there is even a remarkable fixity of look, and the features present a permanent expression of mournfulness, sometimes of stolidness or stupidity … This particular face was not originally appreciated. It is not in Parkinson’s description. I believe I am the first to draw attention to its features that are so arresting and that in fact suffice to establish with ease the proper diagnosis.”

Although it is correct that James Parkinson had not provided a clear description of the characteristic facial appearance in An Essay on the Shaking Palsy in his discussion he did draw attention to a description of a similar case provided by Dr Maty in the Third Volume of the Medical Observations and Inquiries:

" … a more melancholy object I never beheld. The patient naturally a handsome middle-sized sanguine man of cheerful disposition, and an active mind, appeared much emaciated, stooping, and dejected."

Although it is very uncommon for people to present to a physician with concerns about a change in their facial appearance or expression unless they are on the stage, it is not uncommon for family members with the eye of hindsight to report that they had noticed their relative had stopped smiling despite maintaining a good sense of humour, and that they had seemed more distant and emotionally cold. Occasionally they also comment spontaneously on a fixed, staring gaze or a 'poker face'. The description of the face by doctors as 'masked' is inaccurate because expression is not lost only frozen. It is impossible to distinguish the face of a person with severe depression from one with Parkinson’s disease from a photograph.

The hangdog posture, quiet, flat speech, and reduced spontaneous movement seen in some people with severe depression may be confused with Parkinson’s disease in its earliest stages.. Constipation, insomnia, and weight loss are other shared complaints. Tiredness, loss of a joie de vivre, and increased anxiety often over trivia are common early non-specific symptoms of Parkinson’s disease that might suggest depression.

People who develop Parkinson’s disease tend to be low novelty seekers, over-controlled, somewhat inflexible, and prone to depressive breakdown but it has so far proved impossible to determine whether these attributes indicate a pre-morbid personality risk factor or are behaviours linked to the incipient pathological process. A slight slowness of response and difficulty with repartee may also be early changes in Parkinson's disease that can precede slowness, stiffness, and trembling.

Depression that fulfills DSM-IV criteria is common in Parkinson’s disease and has been claimed to occur more frequently than in other chronically disabling physical disorders such as rheumatoid arthritis. Usually it is mild and dysphoria, irritability, loss of joie de vivre, and rumination are frequent symptoms. As the motor impairment worsens over time the frequency of depression increases and may include suicidal ideation. Severe psychotic depression, however, occurs in only about 5 percent of people with Parkinson’s disease and suicide is rare. Anxiety and apathy are also common.. Depression can temporarily increase slowness and stiffness and increase the chance of incident dementia in Parkinson’s disease.

Reserpine and tetrabenazine deplete monoamines in the brain and can cause both depression and reversible Parkinsonism. The motor symptoms that characterise Parkinson’s disease arise from severe nigrostriatal dopamine deficiency but although some post-mortem, spinal fluid, and functional imaging studies have reported a mild reduction of brain monoamines in depression, its biological substrate remains obscure. Many neurologists believe that noradrenergic reuptake inhibitors such as mirtazapine and venlafaxine, and dopamine agonists such as pramipexole are more effective anti-depressants for people with Parkinson’s disease than the serotonin reuptake inhibitors.

A woman with a diagnosis of chronic severe depression whose facial appearance suggests Parkinson's disease

Source: used with permission from Dr. Richard Hunter

Depression is considered to be a risk factor for Parkinson’s disease (odds versus risk ratio of 1.9) and about 15% of confirmed cases report a history of depression prior to the diagnosis. Sometimes this occurs for the first time in young adult life but it is more common for late-onset depression to usher in the disorder of movement. People with isolated late-onset depression have been shown to have an increased frequency of subtle soft motor and non-motor signs, similar to those sometimes reported in early Parkinson’s disease. Interestingly, in some of these research volunteers a mild reduction of dopamine transporter binding in the striatum has been found using single photon emission computed tomography.

Long-term prospective studies of people with late-onset depression and further post-mortem brain neurochemical studies may help to unravel the biological causes of depression and its intriguing interplay with Parkinson’s disease.