Serotonin-dependent depression in Parkinson's disease: a role for the subthalamic nucleus?
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.
Department of Neuroscience, Maastricht University, Maastricht, The Netherlands. s.tan@maastrichtuniversity.nl
Sonny K H
SK
Tan
Henrike
H
Hartung
Trevor
T
Sharp
Yasin
Y
Temel
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D046690:Deep Brain Stimulation / Q000009:adverse effects; D003863:Depression / Q000150:complications* / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000150:complications* / Q000378:metabolism* / Q000628:therapy; D011903:Raphe Nuclei / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000378:metabolism*; D009435:Synaptic Transmission
D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin