Depression

The prevalence of clinically relevant depressive symptoms in patients with PD ranges from 30 to 35% according to most studies. A study on a very large sample of PD patients showed that this prevalence was higher in female than males, at advanced stages of the disease and in patients with dementia.

Core symptoms of depression in PD are sadness, depressed mood, loss of pleasure, feelings of worthless, and guilt.

According to the last version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), patients with PD may present minor, major or persistent depressive disorders. Depression is often comorbid with anxiety in PD.

Most of PD patients with depression are treated with selective serotonin reuptake inhibitors (SSRIs). The efficacy of dopamine agonists to counteract depression is still controversial as pramipexole induced positive results but not rotigotine.

Anxiety

The prevalence of anxiety disorders in PD ranges from 25 to 43%. It is higher than in other diseases causing similar disability.

It is considered as “not otherwise specified” (NOS) anxiety disorder. It refers to PD-specific anxiety, like phobia of falling, of driving, social phobia related to potentially embarrassing symptoms (drooling, dysarthria), anxiety related to withdrawal of DA medication or to wearing-off of medication in patients with fluctuations, panic-like disorder related to OFF periods, among others.

Adverse effects of DA medication can also generate significant anxiety as in patients with ICD, DA dysregulation syndrome, or hallucinations.

The main manifestations of anxiety in PD are inability to relax, feeling tense, excessive concern, restlessness. Somatic symptoms may also be observed as palpitations, shortness of breath, sweating, digestive upset, etc. Usually, all the parkinsonian symptoms worsen with anxiety. Moreover, anxiety frequently implies emotion regulation deficits, irritability, excessive tiredness and difficulties falling asleep.

Anxiety-like behaviors, which could be improved by chronic L-DOPA or diazeapam

This anxiety-like behavior may also corrected by pramipexole (but not by L-DOPA) and reboxetine (a selective noradrenaline reuptake inhibitor)

Apathy

Clinically, apathy refers to a set of behavioral, emotional and cognitive manifestations, such as reduced interest and participation in the main activities of daily life, loss of initiative, lack of perseverance, indifference, and flattening of affect.

Psychosis

In PD, psychosis encompasses a set of symptoms including illusions, hallucinations, delusions, and related symptoms.

They usually form a continuum progressing with the course of the disease. Passage (feeling like something is passing at the outer visual field) and presence (feeling that someone is close by) hallucinations as well as illusions (mis- or distorted perception of an actual stimulus) are the most common symptoms at early stage of the disease.

Finally, while haloperidol reduced those behaviors but increases motor symptoms, clozapine and quietapine reduced them without exacerbating parkinsonian disability.

Impulse control disorders refer to a class of psychiatric disorders characterized by impulsivity, i.e., an urge or failure to resist to temptation. In the DSM-5, it is included in a new section labeled “disruptive, impulse control, and conduct disorders.”

In PD, four major forms of ICDs have been described: pathological gambling, compulsive buying, pathological sexual behavior, and compulsive eating.

Dopamine replacement therapy, namely DA agonist use, is the main risk factor for ICDs. In the DOMINION study, ICDs were more frequent in patients receiving DA agonists (17.1%) than in patients only treated by levodopa (6.9%).

To date, there is no available treatment for ICDs.

Neuropsychiatric disorders are among the most common and disabling non-motor manifestations of PD. Their negative impact on quality of life of both the patients and caregivers is indubitable. They also result in a heavy socio-economic cost. In spite of that, the underlying mechanisms remain largely unknown.

Available data suggest that both dopaminergic and non-dopaminergic (serotonergic, noradrenergic, cholinergic, glutamatergic, and GABAergic) systems are involved in the expression or modulation of these disorders. Translational studies with valid animal models of PD and well-characterized group of patients are needed to continue deciphering the affected processes and propose efficient therapeutic strategies.