Background: Depression associated with Parkinson disease (PD) has a different symptom profile to endogenous depression. The etiology of depression in PD remains uncertain though abnormal serotonergic neurotransmission could play a role.

Objective: To assess with PET serotonergic function via in vivo serotonin transporter (5-HTT) availability in antidepressant-naive patients with PD.

Methods: Thirty-four patients with PD and 10 healthy matched control subjects had a clinical battery of tests including the patient-report Beck Depression Inventory-II (BDI-II), the clinician-report Hamilton Rating Scale for Depression (HRSD), and the structured clinical interview for DSM-IV Axis I Disorders (SCID-I). They underwent ¹¹C-DASB PET, a selective in vivo marker of 5-HTT binding in humans.

Results: BDI-II scores correlated with HRSD scores. Ten of 34 patients with PD (29.4%) had BDI-II and HRSD scores above the discriminative cutoff for PD depression though only half of these patients could be classed on SCID-I criteria as having an anxiety/mood disorder. Patients with PD with the highest scores for depression symptoms showed significantly raised ¹¹C-DASB binding in amygdala, hypothalamus, caudal raphe nuclei, and posterior cingulate cortex compared to low score cases, while ¹¹C-DASB binding values in other regions were similarly decreased in depressed and nondepressed patients with PD compared to healthy controls.

Conclusion: Depressive symptoms in antidepressant-naive patients with PD correlate with relatively higher 5-HTT binding in raphe nuclei and limbic structures possibly reflecting lower extracellular serotonin levels. Our data are compatible with a key role of abnormal serotonergic neurotransmission contributing to the pathophysiology of PD depression and justify the use of agents acting on 5-HTT.