title: Imaging of the dopamine transporter predicts pattern of disease progression and response to levodopa in patients with schizophrenia and parkinsonism: a 2-year follow-up multicenter study.
abstract: Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinson's Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy.
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Tinazzi
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Italy. Electronic address: fmorgante@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Morgante
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Matinella
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Bovi
authors.affiliation: Department of Cardiovascular and Neurological Sciences, Section of Neurology, University of Cagliari, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Cannas
authors.affiliation: Department of Cardiovascular and Neurological Sciences, Section of Neurology, University of Cagliari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Solla
authors.affiliation: Department of Cardiovascular and Neurological Sciences, Section of Neurology, University of Cagliari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.affiliation: Department "GF Ingrassia", Section of Neurosciences, University of Catania, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nicoletti
authors.affiliation: Department "GF Ingrassia", Section of Neurosciences, University of Catania, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Zappia
authors.affiliation: Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Luca
authors.affiliation: Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Di Stefano
authors.affiliation: Department of Neurosciences, University of Messina, Italy.
authors.forename: Letterio
authors.initials: L
authors.lastname: Morgante
authors.affiliation: UO Parkinson e Disordini del Movimento, Istituto Neurologico Nazionale C. Mondino, IRCCS, Pavia, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pacchetti
authors.affiliation: UO Parkinson e Disordini del Movimento, Istituto Neurologico Nazionale C. Mondino, IRCCS, Pavia, Italy.
authors.forename: Brigida
authors.initials: B
authors.lastname: Minafra
authors.affiliation: UO Parkinson e Disordini del Movimento, Istituto Neurologico Nazionale C. Mondino, IRCCS, Pavia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sciarretta
authors.affiliation: A.O. Pavia, Division of Neurology, The Civil Hospital, Voghera, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dallocchio
authors.affiliation: Department of Neurosciences, Section of Neurology, University of Siena, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Neurosciences, Section of Neurology, University of Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ulivelli
authors.affiliation: Department of Neurosciences, University of Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ceravolo
authors.affiliation: Department of Neurosciences, University of Pisa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Frosini
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cipriani
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D016009:Chi-Square Distribution; D018450:Disease Progression; D015259:Dopamine Agents / Q000627:therapeutic use; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011237:Predictive Value of Tests; D011485:Protein Binding / Q000187:drug effects; D012559:Schizophrenia / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D012720:Severity of Illness Index; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes
chemical_list: D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D007980:Levodopa
keywords: (123)I-FP-CIT SPECT; 123I-FP-CIT SPECT; APs; Antipsychotic drugs; DAT; DIP; DRBA; Dopamine receptor blocking agents; Drug-induced parkinsonism; Levodopa; PD; Parkinson's disease; Schizophrenia; UPDRS III=Unified Parkinson's Disease Rating Scale; antipsychotic drugs; dopamine receptor blocking agents; dopamine transporter; motor section; single photon emission computed tomography of dopamine transporter