title: Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [18F]DOPA PET Study.
abstract: Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia. However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls (n=12), patients treated with clozapine (n=12) who had not responded to first-line antipsychotics, and patients who had responded to first-line antipsychotics (n=12) were recruited. Participants were matched for age and sex and symptomatic severity level in patient groups. Participants' dopamine synthesis capacity was measured by using [18F]DOPA PET. We found that patients treated with clozapine show lower dopamine synthesis capacity than patients who have responded to first-line treatment (Cohen's d=0.9191 (whole striatum), 0.7781 (associative striatum), 1.0344 (limbic striatum), and 1.0189 (sensorimotor striatum) in line with the hypothesis that the dopaminergic function is linked to treatment response. This suggests that a different neurobiology may underlie treatment-resistant schizophrenia and that dopamine synthesis capacity may be a useful biomarker to predict treatment responsiveness.
authors.affiliation: Department of Neuropsychiatry, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.
authors.forename: Euitae
authors.initials: E
authors.lastname: Kim
authors.affiliation: Psychiatric Imaging, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London, UK.|Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Mattia
authors.initials: M
authors.lastname: Veronese
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Beck
authors.affiliation: Department of Brain & Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.|Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seongho
authors.initials: S
authors.lastname: Seo
authors.affiliation: Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Brain & Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.|Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yun-Sang
authors.identifier: http://orcid.org/0000-0003-1640-2090
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Brain & Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.|Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Kwon
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D003024:Clozapine; D004298:Dopamine