Glutamatergic function in a genetic high-risk group for psychosis: A proton magnetic resonance spectroscopy study in individuals with 22q11.2 deletion

TY - JOUR

T1 - Glutamatergic function in a genetic high-risk group for psychosis

T2 - A proton magnetic resonance spectroscopy study in individuals with 22q11.2 deletion

AU - Rogdaki, Maria

AU - Hathway, Pamela

AU - Gudbrandsen, Maria

AU - McCutcheon, Robert A

AU - Jauhar, Sameer

AU - Daly, Eileen

AU - Howes, Oliver

N1 - Copyright © 2019 Elsevier B.V. and ECNP. All rights reserved.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Glutamatergic dysregulation is one of the leading theories regarding the pathoaetiolopy of schizophrenia. Meta-analysis of magnetic resonance spectroscopy studies in schizophrenia shows increased levels of glutamate and glutamine (Glx) in the medial frontal cortex and basal ganglia in clinical high-risk groups for psychosis and increased glutamine levels in the thalamus, but it is unclear if this is also the case in people at genetic high risk for psychosis. The aim of this study was to investigate glutamatergic function in the anterior cingulate cortex, striatum and thalamus in carriers of a genetic variant (22q11.2 deletion) associated with a high risk for psychosis. 53 volunteers (23 22q11.2 deletion carriers and 30 controls) underwent proton magnetic resonance spectroscopy imaging and neuropsychological assessments for prodromal psychotic symptoms, schizotypy, anxiety, depression and FSIQ. We did not find any difference between groups in Glx in the anterior cingulate cortex, striatum or thalamus (Glx: t(50)=-1.26, p = 0.21; U = 251, z = -0.7, p = 0.49; U = 316, z= -0.26, p = 0.79, respectively). No correlation was detected between Glx levels in any region and symptomatology or FSIQ. Our findings indicate that glutamatergic function is not altered in people at genetic high risk of psychosis due to the 22q11.2 deletion, which could suggest that this is not the mechanism underlying psychosis risk in 22q11.2 deletion carriers.

AB - Glutamatergic dysregulation is one of the leading theories regarding the pathoaetiolopy of schizophrenia. Meta-analysis of magnetic resonance spectroscopy studies in schizophrenia shows increased levels of glutamate and glutamine (Glx) in the medial frontal cortex and basal ganglia in clinical high-risk groups for psychosis and increased glutamine levels in the thalamus, but it is unclear if this is also the case in people at genetic high risk for psychosis. The aim of this study was to investigate glutamatergic function in the anterior cingulate cortex, striatum and thalamus in carriers of a genetic variant (22q11.2 deletion) associated with a high risk for psychosis. 53 volunteers (23 22q11.2 deletion carriers and 30 controls) underwent proton magnetic resonance spectroscopy imaging and neuropsychological assessments for prodromal psychotic symptoms, schizotypy, anxiety, depression and FSIQ. We did not find any difference between groups in Glx in the anterior cingulate cortex, striatum or thalamus (Glx: t(50)=-1.26, p = 0.21; U = 251, z = -0.7, p = 0.49; U = 316, z= -0.26, p = 0.79, respectively). No correlation was detected between Glx levels in any region and symptomatology or FSIQ. Our findings indicate that glutamatergic function is not altered in people at genetic high risk of psychosis due to the 22q11.2 deletion, which could suggest that this is not the mechanism underlying psychosis risk in 22q11.2 deletion carriers.

KW - Adolescent

KW - Adult

KW - Corpus Striatum/metabolism

KW - Cross-Sectional Studies

KW - DiGeorge Syndrome/genetics

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Glutamic Acid/genetics

KW - Glutamine/genetics

KW - Gyrus Cinguli/metabolism

KW - Humans

KW - Magnetic Resonance Spectroscopy/methods

KW - Male

KW - Psychotic Disorders/genetics

KW - Risk Factors

KW - Thalamus/metabolism

KW - Young Adult

U2 - 10.1016/j.euroneuro.2019.09.005

DO - 10.1016/j.euroneuro.2019.09.005

M3 - Article

C2 - 31648854

SN - 0924-977X

VL - 29

SP - 1333

EP - 1342

JO - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

IS - 12

ER -