Parkinson´s disease and depression : Clinical and neurobiological studies

Abstract: Parkinson´s disease (PD) is a progressive degenerative movement disorder. PD patients also suffer from several non-motor symptoms including autonomic disturbances, cognitive decline and neuropsychiatric conditions. In this thesis, studies were conducted to increase our knowledge on the pathophysiology and treatment of major depression (MD) in patients with PD. Clinical rating studies on the prevalence as well as neurological and psychiatric symptoms in patients with PD and MD, solely PD and solely MD were performed. The therapeutic responsivity towards the commonly used antidepressant, citalopram, in PD + MD and MD patients was investigated. In parallel with these clinical studies, imaging studies were made and cerebrospinal fluid (CSF) collected. These studies showed that MD in PD is not as frequent in Sweden as has been previously reported. PD patients with a comorbid MD had more severe neurological symptoms than PD patients without depression, indicating an advanced and widespread neurodegenerative process. Treatment with citalopram in PD patients with MD on stable dopaminergic therapy reduced the depressive symptoms as effective as in MD patients without PD. The antidepressive effect occurred earlier in the PD patients. The PD symptoms of hypokinesia and rigidity as well as involuntary movements were reduced during treatment with citalopram. On the other hand, tremor increased during this treatment, possibly a result of increased serotonergic neurotransmission. Imaging studies showed that regional cerebral blood flow differs between PD patients with and without MD, as well as between MD patients with and without PD, both at baseline and regarding the response to treatment with citalopram. However, treatment with citalopram normalizes the mood-related abnormal rCBF pattern in both only MD and PD + MD patients, although in different ways. Biochemical studies of CSF showed that PD patients with MD have significantly lower baseline levels of MHPG, corticosterone and IL-6 when compared to solely MD patients. Moreover, in response to citalopram treatment, patients with solely MD exhibited an expected decrease in 5-HIAA and MHPG levels which was not found in PD patients with MD. Moreover, the levels of BDNF and IL-6 were lower in PD + MD patients compared to solely MD patients after treatment with citalopram in both groups. Taken together, these data suggest that MD in PD could be an indication of a more advanced and widespread neurodegenerative process. These data have also provided imaging and biochemicalevidence that there is a different antidepressant response towards SSRI medication in PD patients with MD compared to MD patients without PD, indicating diverse underlying pathophysiological mechanisms