Dopamine dysregulation in psychotic relapse after antipsychotic discontinuation: an [18F]DOPA and [11C]raclopride PET study in first-episode psychosis

被引:16
作者
Kim, Seoyoung [1 ]
Shin, Sang Ho [1 ]
Santangelo, Barbara [2 ]
Veronese, Mattia [2 ]
Kang, Seung Kwan [3 ,4 ]
Lee, Jae Sung [3 ,4 ]
Cheon, Gi Jeong [3 ,5 ]
Lee, Woojoo [6 ]
Kwon, Jun Soo [7 ,8 ]
Howes, Oliver D. [9 ,10 ]
Kim, Euitae [1 ,7 ,8 ]
机构
[1] Seoul Natl Univ, Bundang Hosp, Dept Psychiat, Gyeonggi Do, South Korea
[2] Kings Coll London, Ctr Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, London, England
[3] Seoul Natl Univ, Coll Med, Dept Nucl Med, Seoul, South Korea
[4] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul, South Korea
[5] Seoul Natl Univ, Inst Radiat Med, Coll Med, Seoul, South Korea
[6] Seoul Natl Univ, Grad Sch Publ Hlth, Dept Publ Hlth Sci, Seoul, South Korea
[7] Seoul Natl Univ, Dept Psychiat, Coll Med, Seoul, South Korea
[8] Seoul Natl Univ, Coll Nat Sci, Dept Brain & Cognit Sci, Seoul, South Korea
[9] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychosis Studies, London, England
[10] Imperial Coll London, Med Res Council, Clin Sci Ctr, Psychiat Imaging, Hammersmith Hosp Campus, London, England
基金
新加坡国家研究基金会;
关键词
TREATMENT-RESISTANT SCHIZOPHRENIA; POSITRON-EMISSION-TOMOGRAPHY; AMINO-ACID DECARBOXYLASE; SYNTHESIS CAPACITY; NEUROLEPTIC WITHDRAWAL; MAINTENANCE TREATMENT; DEPOLARIZATION BLOCK; DIAGNOSTIC STABILITY; 1ST EPISODE; HUMAN BRAIN;
D O I
10.1038/s41380-020-00879-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although antipsychotic drugs are effective for relieving the psychotic symptoms of first-episode psychosis (FEP), psychotic relapse is common during the course of the illness. While some FEPs remain remitted even without medication, antipsychotic discontinuation is regarded as the most common risk factor for the relapse. Considering the actions of antipsychotic drugs on presynaptic and postsynaptic dopamine dysregulation, this study evaluated possible mechanisms underlying relapse after antipsychotic discontinuation. Twenty five FEPs who were clinically stable and 14 matched healthy controls were enrolled. Striatal dopamine activity was assessed asK(i)(cer)value using [F-18]DOPA PET before and 6 weeks after antipsychotic discontinuation. The D2/3 receptor availability was measured as BPND using [C-11]raclopride PET after antipsychotic discontinuation. Healthy controls also underwent PET scans according to the corresponding schedule of the patients. Patients were monitored for psychotic relapse during 12 weeks after antipsychotic discontinuation. 40% of the patients showed psychotic relapse after antipsychotic discontinuation. The change in K-i(cer) value over time significantly differed between relapsed, non-relapsed patients and healthy controls (Week*Group:F = 4.827, df = 2,253.193,p = 0.009). In relapsed patients, a significant correlation was found between baseline striatal K-i(cer) values and time to relapse after antipsychotic discontinuation (R-2 = 0.518,p = 0.018). BP(ND)were not significantly different between relapsed, non-relapsed patients and healthy controls (F = 1.402, df = 2,32.000,p = 0.261). These results suggest that dysfunctional dopamine autoregulation might precipitate psychotic relapse after antipsychotic discontinuation in FEP. This finding could be used for developing a strategy for the prevention of psychotic relapse related to antipsychotic discontinuation.
引用
收藏
页码:3476 / 3488
页数:13
相关论文
共 73 条
[1]   Antipsychotic Dose Equivalents and Dose-Years: A Standardized Method for Comparing Exposure to Different Drugs [J].
Andreasen, Nancy C. ;
Pressler, Marcus ;
Nopoulos, Peg ;
Miller, Del ;
Ho, Beng-Choon .
BIOLOGICAL PSYCHIATRY, 2010, 67 (03) :255-262
[2]   A CLASSIFICATION OF HAND PREFERENCE BY ASSOCIATION ANALYSIS [J].
ANNETT, M .
BRITISH JOURNAL OF PSYCHOLOGY, 1970, 61 (03) :303-&
[3]  
[Anonymous], 2018, PSYCHOL MED
[4]   Reduced striatal dopamine synthesis capacity in patients with schizophrenia during remission of positive symptoms [J].
Avram, Mihai ;
Brandl, Felix ;
Cabello, Jorge ;
Leucht, Claudia ;
Scherr, Martin ;
Mustafa, Mona ;
Leucht, Stefan ;
Ziegler, Sibylle ;
Sorg, Christian .
BRAIN, 2019, 142 :1813-1826
[5]  
BALDESSARINI RJ, 1995, ARCH GEN PSYCHIAT, V52, P189
[6]   Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study [J].
Bloomfield, Michael A. P. ;
Pepper, Fiona ;
Egerton, Alice ;
Demjaha, Arsime ;
Tomasi, Gianpaolo ;
Mouchlianitis, Elias ;
Maximen, Levi ;
Veroneses, Mattia ;
Turkheimer, Federico ;
Selvaraj, Sudhakar ;
Howes, Oliver D. .
NEUROPSYCHOPHARMACOLOGY, 2014, 39 (10) :2397-2404
[7]   Rates and predictors of relapse following discontinuation of antipsychotic medication after a first episode of psychosis [J].
Bowtell, Meghan ;
Eaton, Scott ;
Thien, Kristen ;
Bardell-Williams, Melissa ;
Downey, Linglee ;
Ratheesh, Aswin ;
Killackey, Eoin ;
McGorry, Patrick ;
O'Donoghue, Brian .
SCHIZOPHRENIA RESEARCH, 2018, 195 :231-236
[8]  
CHOUINARD G, 1978, AM J PSYCHIAT, V135, P1409
[9]   Presynaptic dopaminergic function in the striatum of schizophrenic patients [J].
DaoCastellana, MH ;
PaillereMartinot, ML ;
Hantraye, P ;
AttarLevy, D ;
Remy, P ;
Crouzel, C ;
Artiges, E ;
Feline, A ;
Syrota, A ;
Martinot, JL .
SCHIZOPHRENIA RESEARCH, 1997, 23 (02) :167-174
[10]   The relapse rate and predictors of relapse in patients with first-episode psychosis following discontinuation of antipsychotic medication [J].
Di Capite, Suzanne ;
Upthegrove, Rachel ;
Mallikarjun, Pavan .
EARLY INTERVENTION IN PSYCHIATRY, 2018, 12 (05) :893-899