RESUMO
Parkinson disease (PD) is a neurodegenerative disorder with a complex pathophysiology characterized by the progressive loss of dopaminergic neurons within the substantia nigra. Persons with PD experience several motoric and neuropsychiatric symptoms. Neuropsychiatric features of PD include depression, anxiety, psychosis, impulse control disorders, and apathy. In this chapter, we will utilize the National Institutes of Mental Health Research Domain Criteria (RDoC) to frame and integrate observations from two prevailing disease constructions: neurotransmitter anomalies and circuit physiology. When there is available evidence, we posit how unified translational observations may have clinical relevance and postulate importance outside of PD. Finally, we review the limited evidence available for pharmacologic management of these symptoms.
Assuntos
Encéfalo/fisiopatologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/fisiopatologia , Rede Nervosa/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Inibidores da Captação Adrenérgica/farmacologia , Inibidores da Captação Adrenérgica/uso terapêutico , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêutico , Encéfalo/efeitos dos fármacos , Humanos , Transtornos Mentais/psicologia , Rede Nervosa/efeitos dos fármacos , Doença de Parkinson/psicologia , PsicofarmacologiaRESUMO
INTRODUCTION: Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease the striatal vesicular monoamine transporter (VMAT2), secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical cerebral metabolism. METHODS: PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4-6 months of STN stimulation in seven PD patients (mean age 67⯱â¯7). RESULTS: The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism. CONCLUSIONS: The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.