On dopamine and depression

                                                 How true is this in Parkinson's???

We are learning ever more about the manifestations of non-motor symptoms in Parkinson's Disease and their presence from even before diagnosis. It's fair to say that for many patients, it's actually the non-motor symptoms rather than the motor symptoms that cause much of the burden of the disease. To effectively target these symptoms it's vital that we understand the underlying cause. 

Neuropsychiatric symptoms (e.g. depression, anxiety, hallucinations) have been assumed to be directly linked with dopamine dysregulation - the same process leading to movement problems.  It makes sense - dopamine regulating drugs can be an effective treatment for people with schizophrenia so dopamine is already implicated in neuropsychiatric symptoms. 

However, there are other potentially blame-worthy processes going on in the course of Parkinson's Disease and teasing out their contributions is the aim of this paper, from a team based in South Korea. The authors looked at a group of newly diagnosed Parkinson's patients who were assessed clinically for neuropsychiatric symptoms then had PET scans specific for the dopamine activity and MRI to look more globally at brain atrophy. 

The first important finding was that a high proportion, almost 60% of patients, had at least one neuropsychiatric symptom. The imaging results paint an intriguing picture, with thinning (neuronal loss) in specific areas being linked to specific symptoms - for example temporal lobe atrophy was associated with aggression/agitation. Dopamine activity, on the other hand, was not linked with any of the symptoms.

There are some issues with the kind of exploratory analysis in this study - when a lot of comparisons are made it is likely that, by chance, there will be some positive results. It is also important to consider that there are likely links between the different neuropsychiatric symptoms that mean they can't be considered independently of each other. But I think it's an important reminder that, just as Parkinson's is more than just a movement problem, it's underlying cause is more than a dopamine problem.  

-Anna

https://www.ncbi.nlm.nih.gov/pubmed/28951497

J Neurol Neurosurg Psychiatry. 2017 Sep 26. pii: jnnp-2017-316075. doi: 10.1136/jnnp-2017-316075. [Epub ahead of print]

Effects of dopaminergic depletion and brain atrophy on neuropsychiatric symptoms in de novo Parkinson's disease.

Ye BS, Jeon S, Yoon S, Kang SW, Baik K, Lee Y, Chung SJ, Oh JS, Moon H, Kim JS, Lee PH, Sohn YH.

Abstract

BACKGROUND:

Neuropsychiatric symptoms impact the patients' quality of life and caregivers' burdens in Parkinson's disease (PD). We aimed to investigate the effects of striatal dopaminergic depletion and brain atrophy on the neuropsychiatric symptoms of patients with PD.

METHODS:

Two hundred and seven patients with de novo drug-naïve PD underwent dopamine transporter (DAT) positron emission tomography and brain MRI scanning. In addition, the patients were assessed with caregiver-administered neuropsychiatric inventory (NPI) questionnaires. To evaluate the effects of DAT uptake, subcortical volume and cortical thinning on the patients' neuropsychiatric symptoms, we performed logistic regression and negative binomial regression analyses on the NPI data after controlling for possible confounders.

RESULTS:

Frontal cortical thinning was associated with the presence of nighttime behaviour and irritability, and the thinning correlated with the severity of the nighttime behaviour. Temporal cortical thinning was associated with the presence of aggression/agitation, and it correlated with the severity of the aggression/agitation. Subcortical atrophy in the accumbens was associated with the presence of disinhibition and correlated with the severity of the disinhibition. Putamen atrophy and insular thinning were independently associated with the presence of apathy, but only insular thinning correlated with the severity of the apathy. Of the predictors, only frontal cortical thinning correlated with the total NPI score.

CONCLUSIONS:

The results of this study suggested that accumbens atrophy and frontotemporal cortical thinning, especially frontal cortical thinning, independently contributed to neuropsychiatric symptoms in patients with PD, while DAT uptake did not affect the neuropsychiatric symptoms.