Increased left striatal dopamine transmission in unaffected siblings of schizophrenia patients in response to acute metabolic stress.
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 BP(ND) of [(11)C]raclopride before and after the 2DG challenge. After metabolic stress, controls but not siblings displayed a significant decrease in BP(ND) 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.
Brunelin
Jerome
J
Université de Lyon, Lyon, F-69003, France. jerome.brunelin@ch-le-vinatier.fr
d'Amato
Thierry
T
Van Os
Jim
J
Costes
Nicolas
N
Suaud Chagny
Marie-Françoise
MF
Saoud
Mohamed
M
D000328:Adult; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D007839:Functional Laterality / Q000187:drug effects*; D006801:Humans; D008297:Male; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods; D011594:Psychometrics; D020891:Raclopride / Q000493:pharmacokinetics; D012559:Schizophrenia / Q000235:genetics; D035781:Siblings / Q000523:psychology; D013312:Stress, Physiological / Q000235:genetics*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D020891:Raclopride; D003847:Deoxyglucose; D004298:Dopamine