Depressive symptoms in PD correlate with higher 5-HTT binding in raphe and limbic structures
ABSTRACT 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.
To assess with PET serotonergic function via in vivo serotonin transporter (5-HTT) availability in antidepressant-naive patients with PD.
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.
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.
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.
- SourceAvailable from: Claire O'Callaghan[Show abstract] [Hide abstract]
ABSTRACT: Background Neuropsychiatric symptoms (NPS) in Parkinson’s disease (PD) have been mostly attributed to neurotransmitter imbalances. However, recent findings suggest that grey matter atrophy also contributes to NPS in PD. We contrast PD patients with different levels of NPS, who are well-matched for dopaminergic medication levels and disease stage, to identify the fronto-striatal grey matter atrophy areas associated with NPS in PD. Methods Fifty mild, non-demented PD patients were included. We median-split the group via a neuropsychiatric screening tool (Cambridge Behavioural Inventory—Revised), which resulted in higher vs. lower NPS groups (n = 25 in each group). Using T1 brain scans acquired on a 3 Tesla MRI scanner, voxel-based morphometry analysis was applied to characterise the pattern of fronto-striatal grey matter atrophy associated with elevated NPS. Results We found that the higher NPS group was characterised by greater atrophy in the prefrontal cortex, but not striatal areas. This was further corroborated by a post-hoc analysis cross-correlating the severity of NPS with grey matter loss across the whole PD group, which revealed that atrophy in the orbitofrontal cortex and frontal pole was specifically associated with elevated NPS. Conclusions Prefrontal cortex atrophy in PD has an additional effect to dopamine replacement therapy on the generation of NPS in these patients. These findings are an important step towards the delineation of atrophy versus neurochemical imbalance in PD, and the results emphasise the importance of considering interactions between prefrontal atrophy and neurochemical dysfunction in the genesis of neuropsychiatric symptoms in PD.Parkinsonism & Related Disorders 08/2014; 20(8). DOI:10.1016/j.parkreldis.2014.04.027 · 4.13 Impact Factor
- Etiology and Pathophysiology of Parkinson's Disease, 10/2011; , ISBN: 978-953-307-462-7
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ABSTRACT: Depression is the most common neuropsychiatric co-morbidity in Parkinson's disease (PD). The underlying mechanism of depression in PD is complex and likely involves biological, psychosocial and therapeutic factors. The biological mechanism may involve changes in monoamine systems, in particular the serotonergic (5-hydroxytryptamine, 5-HT) system. It is well established that the 5-HT system is markedly affected in the Parkinsonian brain, with evidence including pathological loss of markers of 5-HT axons as well as cell bodies in the dorsal and median raphe nuclei of the midbrain. However, it remains unresolved whether alterations to the 5-HT system alone are sufficient to confer vulnerability to depression. Here we propose low 5-HT combined with altered network activity within the basal ganglia as critically involved in depression in PD. The latter hypothesis is derived from a number of recent findings that highlight the close interaction between the basal ganglia and the 5-HT system, not only in motor but also limbic functions. These findings include evidence that clinical depression is a side effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN), a treatment option in advanced PD. Further, it has recently been demonstrated that STN DBS in animal models inhibits 5-HT neurotransmission, and that this change may underpin depressive-like side effects. This review provides an overview of 5-HT alterations in PD and a discussion of how these changes might combine with altered basal ganglia network activity to increase depression vulnerability.Neuropharmacology 09/2011; 61(3):387-99. DOI:10.1016/j.neuropharm.2011.01.006 · 4.82 Impact Factor