Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait
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Drug induced parkinsonism (DIP) is directly related to dopamine D2 receptor blockade. However, there are many references describing parkinsonian signs (PS) in naive-patients. In our previous study, we observed lower DAT binding in a group of first-episode schizophrenic patients after short-term treatment with risperidone, compared with age-matched healthy controls.
To clarify if DAT decrease could be an illness trait, excluding the effect of antipsychotics on DAT availability, and to determine whether DAT availability before treatment with antipsychotics may predict subsequent development of PS.
Materials and methods
A new series of 20 neuroleptic-naive schizophrenic patients and 15 healthy subjects was recruited. SPECT with [123I] FP-CIT (DaTSCAN®) was performed before starting antipsychotics and after 4 weeks of treatment. PS and psychopathological status were assessed by the Simpson–Angus (SAS), CGI and PANSS scales. Quantitative analyses of SPECTs were performed using ROIs placed in the caudate, putamen and occipital cortex.
Schizophrenic patients showed lower DAT binding compared with the healthy subjects at baseline (p<0.001) and after a 4-week-treatment period (p=0.001). Six out of eight schizophrenic patients of the DIP group were symptomatic for PS at baseline, in comparison to two out of 12 in the NoDIP group. Nonetheless, no differences were observed on DAT between DIP and NoDIP, neither at baseline (p=0.360) nor at endpoint (p=0.984). Finally, no differences between baseline–endpoint DAT binding were observed, neither in the DIP group (p=0.767) nor in the NoDIP group (p=0.093).
Our new series of first-episode naive-schizophrenic patients (1) points out DAT dysfunction as an illness trait due to the significantly lower DAT binding in schizophrenic patients in comparison to healthy subjects; (2) supports the results of other authors who describe PS in never-treated patients; (3) confirms that [123I] FP-CIT does not allow us to predict which patients will develop parkinsonism due to the lack of differences between DIP and NoDIP patients; and (4) confirms a null effect of antipsychotics on DAT due to the lack of differences in [123I] FP-CIT before and after a 4-week-treatment period.
KeywordsNeuroleptic-naive Schizophrenia Parkinsonism Dopamine transporter SPECT
Grants from the Hospital Clínic of Barcelona (Premi Fi de Residencia 2001), Marató TV3 (Enfermedades Psiquiátricas Graves; 2001) and FIS PI02/0485 are gratefully acknowledged. Thanks to Mr. Jover L, Ph.D., and to Ms. Sugranyes G, M.D., for their statistical and English assistance, respectively.
- American Psychiatric Association (APA) (1994) Diagnostic and statistical manual of mental disorders, 4th edn. Washington, USAGoogle Scholar
- Bernardo M, Parellada E, Lomeña F, Catafau A, Font M, Gómez J, Lopez-Carrero C, Gutierrez F, Pavia J, Salamero M (2001) Double-blind olanzapine vs. haloperidol D2 dopamine receptor blockade in schizophrenic patients: a baseline–endpoint [123I] IBZM SPECT study. Psychiatry Research Neuroimaging 107:87–97CrossRefGoogle Scholar
- Bleuler E (1911) Dementia praecox or the group of schizophrenias (trans. J. Zinkin: Dementia Praecox ode der Gruppe der Schizophrenien. In: Aschaffenburg PG (ed) Handbuch der Geiteskrankheiten. Leipzig: Deutike). International Universities Press, New York, 1950Google Scholar
- Burn DJ, Brooks DJ (1993) Nigral dysfunction in drug-induced parkinsonism: an 18F-DOPA PET study. Neurology 43:552–556Google Scholar
- Caliguri M, Lohr J, Jeste D (1993) Parkinsonism in neuroleptic-naive schizophrenic patients. Am J Psychiatry 150:1343–1348Google Scholar
- First MB, Spitzer RL, Williams JBW, Gibbon M (1994) Structured clinical interview for DSM-IV-Patients edition (SCID-P). American Psychiatric Press, Washington, DCGoogle Scholar
- Guy W (1976) Early clinical drug evaluation unit (ECDEU), vol 76. National Institute of Mental Health, Rockville, USA, p 338Google Scholar
- Kay SR, Fisbein S, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:262–273Google Scholar
- Kraepelin E (1919) Dementia praecox and paraphrenia. University of Edinburgh, EdinburghGoogle Scholar
- Mateos JJ, Lomeña F, Parellada E, Font M, Fernandez E, Pavia J, Prats A, Pons F, Bernardo M (2005) Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism. Psychopharmacology 181:401–406PubMedCrossRefGoogle Scholar
- Peralta V, Cuesta M, Campos MS (2002) Síntomas extrapiramidales en pacientes esquizofrénicos nunca tratados con neurolépticos. Aula Médica Psiquiátrica 4:269–280Google Scholar
- Rajput AH, Rozdilsky B, Hornykiewicz O, Shannak K, Lee T, Seeman P (1982) Reversible drug-induced parkinsonism. Clinicopathologic study of two cases. Arch Neurol 10:644–646Google Scholar
- Schmitt GJ, Frodl T, Dresel S, La Fougere C, Bottlender R, Koutsouleris N, Hahn K, Moller Hj, Meisenzahl EM (2006) Striatal dopamine transporter availability is associated with the productive psychotic state in first episode, drug-naive schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 256:115–121PubMedCrossRefGoogle Scholar
- Seeman MV (1997) Psychopathology in women and men: focus on female hormones. Am J Psychiatry 154:1641–1647Google Scholar
- Simpson GM, Angus JW (1970) A rating scale for extra-pyramidal side effects. Acta Psychiatr Scand 212(Suppl):11–19Google Scholar
- Tatsch K, Scherer J, Linke R, Kerner M, Hahn K (1999) Decrease of dopamine transporter binding in neuroleptic-free schizophrenic patients assessed with IPT-SPECT (abstr.). J Nucl Med 40:31Google Scholar
- Tsukada H, Harada N, Nishiyama S, Ohba H, Kakiuchi T (2000) Cholinergic neuronal modulation alters dopamine d2 receptor availability in vivo by regulating receptor affinity induced by facilitated synaptic dopamine turnover: positron emission tomography studies with microdialysis in the conscious monkey brain. J Neurosci 20:7067–7073PubMedGoogle Scholar