Monoamine transporter availability in Parkinson’s disease patients with or without depression

PurposeDepression is a common symptom in patients suffering from Parkinson’s disease (PD) and markedly reduces their quality of life. As post-mortem studies have shown, its presence may reflect extensive cell loss in the midbrain and brainstem with imbalances in monoaminergic neurotransmitters. However, in vivo evidence of specific monoaminergic deficits in depressed PD patients is still sparse. Therefore, we studied PD patients with depression (PD+D) and without depression (PD−D) using high-resolution single-photon emission computed tomography (SPECT) and the monoamine transporter marker [123I]FP-CIT.MethodsA magnetic resonance imaging-based region-of-interest analysis was applied to quantify the specific-to-nondisplaceable [123I]FP-CIT binding coefficient V3″ in the striatum, thalamus and midbrain/brainstem regions.ResultsPD+D patients had significantly lower V3″ compared with PD−D patients in the striatum (p<0.001), thalamus (p=0.002), and midbrain/brainstem (p=0.025). Only PD+D patients without selective serotonin reuptake inhibitor (SSRI) treatment showed lower thalamic and midbrain V3″ than controls (p<0.001, p=0.029). In a small sub-group of SSRI-treated PD+D patients neither thalamic V3″ nor midbrain/brainstem V3″ differed from those in PD−D patients (p=0.168, p=0.201) or controls (p=0.384, p=0.318).ConclusionOur data indicate that depression in PD is associated with a more pronounced loss of striatal dopamine transporter availability that is most likely secondary to increased dopaminergic degeneration. In addition, depressed PD patients have a lower availability of midbrain/brainstem monoamine transporters than nondepressed PD patients. These findings provide in vivo evidence in support of the known post-mortem data demonstrating more extensive nerve cell loss in PD with depression and indicate that SPECT imaging can help to identify pathophysiological changes underlying nonmotor symptoms in this common movement disorder.

[1]  W. Poewe,et al.  Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology , 2006, Neurology.

[2]  Osama Sabri,et al.  Investigating dopaminergic neurotransmission with 123I-FP-CIT SPECT: comparability of modern SPECT systems. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  R. Baldessarini,et al.  N-Substituted Analogues of 2β-Carbomethoxy-3β-(4′-iodophenyl) tropane (β-CIT) with Selective Affinity to Dopamine or Serotonin Transporters in Rat Forebrain. , 1996 .

[4]  P Slomka,et al.  [Multimodal SPECT and MRT imaging data analysis for an improvement in the diagnosis of idiopathic Parkinson's syndrome]. , 2000, Der Radiologe.

[5]  C. Clarke,et al.  Systematic review of antidepressant therapies in Parkinson's disease. , 2003, Parkinsonism & related disorders.

[6]  H. Marín,et al.  Treatment of depression in Parkinson’s disease , 2006, Current psychiatry reports.

[7]  M. Fujita,et al.  Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines. , 1998, Nuclear medicine and biology.

[8]  Mitsutoshi Yamamoto Depression in Parkinson's disease: its prevalence, diagnosis, and neurochemical background , 2001, Journal of Neurology.

[9]  K. Lesch,et al.  The serotonin transporter in Alzheimer's and Parkinson's disease. , 2000, Journal of neural transmission. Supplementum.

[10]  Multimodale SPECT- und MRT-Bilddatenanalyse zur Verbesserung der Diagnostik des idiopathischen Parkinson-Syndroms , 2000, Der Radiologe.

[11]  P. Nathan,et al.  Molecular Imaging of the Dopaminergic System and its Association with Human Cognitive Function , 2006, Biological Psychiatry.

[12]  S. Hesse,et al.  Possible impact of dopamine SPECT on decision-making for drug treatment in Parkinsonian syndrome , 2006, Journal of Neural Transmission.

[13]  N. Volkow,et al.  Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects. , 1997, The American journal of psychiatry.

[14]  U. Dillmann,et al.  Striatal FP-CIT uptake differs in the subtypes of early Parkinson’s disease , 2007, Journal of Neural Transmission.

[15]  S. Asenbaum,et al.  SPECT and PET imaging of the dopaminergic system in Parkinson's disease , 2000, Journal of Neurology.

[16]  L. Lamberg Psychiatric symptoms common in neurological disorders. , 2001, JAMA.

[17]  L. Reneman,et al.  Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers , 2000, European Journal of Nuclear Medicine.

[18]  A. Antonini,et al.  [123I]FP-CIT striatal binding in early Parkinson's disease patients with tremor vs. akinetic-rigid onset , 2007, Neuroreport.

[19]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[20]  H. Reichmann,et al.  Parkinson’s disease and depression: evidence for an alteration of the basal limbic system detected by transcranial sonography , 1997, Journal of neurology, neurosurgery, and psychiatry.

[21]  L. Chia,et al.  Studies of dementia, depression, electrophysiology and cerebrospinal fluid monoamine metabolites in patients with Parkinson's disease , 1995, Journal of the Neurological Sciences.

[22]  William W. McDonald,et al.  Depression rating scales in Parkinson's disease: Critique and recommendations , 2007, Movement disorders : official journal of the Movement Disorder Society.

[23]  R. Vanninen,et al.  Midbrain binding of [123I]nor-β-CIT in atypical depression , 2006, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[24]  A. Sidhu,et al.  Modulation of the trafficking of the human serotonin transporter by human alpha‐synuclein , 2006, The European journal of neuroscience.

[25]  D. V. von Cramon,et al.  In vivo evidence for differential association of striatal dopamine and midbrain serotonin systems with neuropsychiatric symptoms in Parkinson's disease. , 2001, The Journal of neuropsychiatry and clinical neurosciences.

[26]  Daniel Weintraub,et al.  Psychiatric complications in Parkinson disease. , 2005, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[27]  H. Braak,et al.  Parkinson’s disease: the thalamic components of the limbic loop are severely impaired by α-synuclein immunopositive inclusion body pathology , 2002, Neurobiology of Aging.

[28]  Nora Turjanski,et al.  Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system. , 2005, Brain : a journal of neurology.

[29]  I. Katz,et al.  Effect of Psychiatric and Other Nonmotor Symptoms on Disability in Parkinson's Disease , 2004, Journal of the American Geriatrics Society.

[30]  Sylvain Houle,et al.  Lower dopamine transporter binding potential in striatum during depression , 2001, Neuroreport.

[31]  R. Baldessarini,et al.  Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: potential positron emission tomography (PET) imaging agents for the dopamine transporter. , 2001, Bioorganic & medicinal chemistry letters.

[32]  J. Booij,et al.  Quantification of striatal dopamine transporters with 123I-FP-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double-blind, placebo-controlled, crossover study in healthy control subjects. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[33]  D. Nutt The role of dopamine and norepinephrine in depression and antidepressant treatment. , 2006, The Journal of clinical psychiatry.

[34]  R. Albin,et al.  Spared Caudal Brainstem SERT Binding in Early Parkinson's Disease , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[35]  K. Ikeda,et al.  Depression is associated with impairment of ADL, not motor function in Parkinson disease , 2006, Neurology.

[36]  J. Yesavage,et al.  Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version. , 1986 .

[37]  A. Antonini,et al.  Loss of thalamic serotonin transporters in early drug-naïve Parkinson’s disease patients is associated with tremor: an [123I]β-CIT SPECT study , 2008, Journal of Neural Transmission.

[38]  Alan A. Wilson,et al.  Brain serotonin transporter binding in non‐depressed patients with Parkinson's disease , 2007, European journal of neurology.

[39]  David J. Brooks,et al.  Imaging in Parkinson’s Disease: The Role of Monoamines in Behavior , 2006, Biological Psychiatry.

[40]  U. Müller,et al.  Advances in in vivo imaging of serotonergic neurons in neuropsychiatric disorders , 2004, Neuroscience & Biobehavioral Reviews.

[41]  B. Olivier,et al.  Serotonin, dopamine and norepinephrine transporters in the central nervous system and their inhibitors. , 2000, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[42]  John Hilton,et al.  Positron emission tomography of striatal serotonin transporters in Parkinson disease. , 2003, Archives of neurology.

[43]  W. Weiner,et al.  Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology , 2006, Neurology.

[44]  Ulrich Müller,et al.  Is correction for age necessary in neuroimaging studies of the central serotonin transporter? , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[45]  R Todd Ogden,et al.  Lower serotonin transporter binding potential in the human brain during major depressive episodes. , 2006, The American journal of psychiatry.

[46]  I. Katz,et al.  Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[47]  D. Brooks,et al.  [123I]β-CIT SPECT imaging of dopamine and serotonin transporters in Parkinson’s disease and multiple system atrophy , 2003, Nuklearmedizin.

[48]  Jens Volkmann,et al.  Depression and Parkinson’s disease , 2004, Journal of Neurology.

[49]  R. Baldessarini,et al.  N-Substituted Analogs of 2β-Carbomethoxy-3β-(4‘-iodophenyl)tropane (β-CIT) with Selective Affinity to Dopamine or Serotonin Transporters in Rat Forebrain , 1996 .

[50]  F. Verhey,et al.  Serotonergic mechanisms in Parkinson’s disease: opposing results from preclinical and clinical data , 2005, Journal of Neural Transmission.

[51]  T. L. Brink,et al.  Clinical Gerontology: A Guide to Assessment and Intervention , 1986 .