Increased left striatal dopamine transmission in unaffected siblings of schizophrenia patients in response to acute metabolic stress

被引:31
作者
Brunelin, Jerome [1 ,2 ,3 ,4 ,5 ]
d'Amato, Thierry [2 ,3 ,4 ]
Van Os, Jim [5 ,6 ]
Costes, Nicolas [7 ]
Chagny, Marie-Francoise Suaud [2 ,3 ,4 ]
Saoud, Mohamed [2 ,3 ,4 ]
机构
[1] CH Le Vinatier, EA 4166, Serv Pr Amato, F-69677 Bron, France
[2] Univ Lyon, F-69003 Lyon, France
[3] Univ Lyon 1, EA4166, F-69365 Lyon, France
[4] Hop Neurol, IFNL, F-69394 Lyon, France
[5] Maastricht Univ, Med Ctr, Dept Psychiat & Neuropsychol, S Limburg Mental Hlth Res & Teaching Network,EURO, NL-6200 MD Maastricht, Netherlands
[6] Inst Psychiat, Div Psychol Med, London SE5 8AF, England
[7] PET Dept, CERMEP Imagerie Vivant, F-69667 Bron, France
关键词
Schizophrenia; Dopamine; PET; Vulnerability; Stress; 2DG; POSITRON-EMISSION-TOMOGRAPHY; PITUITARY-ADRENAL AXIS; MAGICAL IDEATION; HEALTHY-VOLUNTEERS; RELEASE; SENSITIZATION; ASYMMETRY; HUMANS; HYPERACTIVITY; MODULATION;
D O I
10.1016/j.pscychresns.2009.10.002
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
A genetic alteration in sensitivity to stress, mediated by mesolimbic hyperdopaminergia, is thought to play a role in the onset, exacerbation and relapse of schizophrenia. Dopamine sensitivity to stress was tested in individuals at higher than average genetic risk for schizophrenia (siblings of patients). Using a PET paradigm of [(11)C]raclopride in a bolus plus constant infusion tracer injection, the central DA response to acute metabolic stress (bolus of 2-Deoxy-D-Glucose, 40mg/kg) in unaffected siblings of patients with schizophrenia (n=8) and healthy controls (n=10) was measured by BPND of [(11)C]raclopride before and after the 2DG challenge. After metabolic stress, controls but not siblings displayed a significant decrease in BPND of [(11)C]raclopride in the striatum; no such differences were apparent in the ventral striatum. Siblings but not controls displayed significant asymmetry (L>R) in the stress-induced DA release, especially in ventral striatum, which correlated strongly with psychometric measures of psychosis liability. The results suggest that asymmetry in the mesolimbic DA response to stress is associated with genetic risk for schizophrenia, possibly reflecting the functional consequences of structural disconnectivity underlying psychotic symptoms. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:130 / 135
页数:6
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