Objective/Rationale:
Depression occurs in Parkinson’s disease (PD) much more frequently than in the general population, and is a major factor contributing to decreased quality of life for affected patients. Some imaging studies have suggested a loss of serotonin-containing inputs to the cortex in PD with depression (PD-D), but there are conflicting data. We will examine in postmortem samples of the cortex of PD-D subjects and PD subjects without depression, examining different proteins expressed by serotonin neurons.
Project Description:
We will process post-mortem samples from subjects with PD and PD-D, and control subjects without neurological disease, using immunohistochemical methods to reveal serotonergic axons in the cortex and striatum; adjacent sections will also be processed with a marker of dopamine axons. We will quantify the extent of the total serotonergic (and dopaminergic) innervations of these regions using computer-assisted imaging programs. We will also specifically determine if the anticipated loss of the serotonin input to the forebrain differentially involves the two different types of serotonin axons, which originate from different brainstem nuclei, and are functionally different.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Depression in Parkinson’s disease (PD-D) occurs in about half of all PD cases, and is a significant contributor to decreased quality of life. Treatment with antidepressant drugs can reduce depressive symptoms in some patients, but available data suggest that SSRIs (such as Prozac and related drugs) may be less effective than older tricyclic antidepressants. Defining the exact pathology that occurs in PD-D may offer new insights into more effective treatments for depression associated with PD.
Anticipated Outcome:
Based on preliminary data from a small number of cases, we anticipate that we will observe a decrease in the serotonin innervation of the cortex in both PD and PD-D subjects that preferentially involves the thick, varicose type of serotonergic axon. We further hypothesize that the loss of serotonergic innervation will be more extensive in PD-D cases than in PD patients who did not have a history of depression.