Altered neurotransmitter metabolism in adolescents with high-functioning autism.
Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few1H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using1H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.
Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands.
Gerhard S
GS
Drenthen
Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Behavioral Sciences, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
Evelien M
EM
Barendse
Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands; School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Behavioral Sciences, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.
Albert P
AP
Aldenkamp
School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Behavioral Sciences, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.
Tamar M
TM
van Veenendaal
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
Nicolaas A J
NA
Puts
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
Richard A E
RA
Edden
Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; Department of Behavioral Sciences, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.
Svitlana
S
Zinger
Special Education School de Berkenschutse, Sterkselseweg 65, 5591 VE Heeze, The Netherlands.
Geert
G
Thoonen
Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands; Department of Behavioral Sciences, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.
Marc P H
MP
Hendriks
Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands; Department of Medical Psychology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Roy P C
RP
Kessels
School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: Jacobus.jansen@mumc.nl.
Jacobus F A
JF
Jansen
D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003401:Creatine
Gamma-aminobutyric acid; Glutamate; Magnetic resonance spectroscopy
Magn Reson Imaging. 2011 Apr;29(3):374-9
21232891
Autism Res. 2013 Apr;6(2):119-33
23436782
Neurosci Lett. 2008 Mar 28;434(2):218-23
18313850
Neuroimage. 2014 Feb 1;86:1-9
23707581
J Autism Dev Disord. 2012 May;42(5):827-36
21713591
J Child Adolesc Psychopharmacol. 2015 May;25(4):314-22
25919578
Dev Psychol. 2010 Mar;46(2):530-44
20210511
Neuroscientist. 2003 Dec;9(6):496-507
14678582
J Autism Dev Disord. 2003 Feb;33(1):93-7
12708584
J Neurodev Disord. 2013 Jun 04;5(1):14
23731472
Autism Res. 2013 Feb;6(1):1-10
23166003
Eur Arch Psychiatry Clin Neurosci. 2013 Aug;263(5):379-84
22986449
J Autism Dev Disord. 2003 Oct;33(5):489-507
14594329
Hum Brain Mapp. 2012 Jul;33(7):1553-81
21465627
Front Hum Neurosci. 2015 Jun 22;9:365
26157380
Genet Med. 2006 Sep;8(9):549-56
16980810
Genes Brain Behav. 2003 Oct;2(5):255-67
14606691
Neuroimage. 2014 Feb 1;86:28-34
23370056
Front Hum Neurosci. 2014 Apr 29;8:268
24808851
Clin Radiol. 2009 Jan;64(1):12-21
19070693
J Neuroinflammation. 2014 Nov 19;11:189
25407263
J Magn Reson Imaging. 2014 Dec;40(6):1445-52
25548816
J Child Psychol Psychiatry. 2004 May;45(4):836-54
15056314
Eur J Radiol. 2010 Mar;73(3):526-31
19201120
Med Sci Monit. 2002 Aug;8(8):PR1-6
12165753
J Clin Biochem Nutr. 2012 Nov;51(3):248-9
23170055
J Autism Dev Disord. 2010 Aug;40(8):1028-38
20143145
Adv Med Sci. 2012 Jun 1;57(1):152-6
22472469
Nat Rev Neurosci. 2012 Sep;13(9):636-50
22903221
J Autism Dev Disord. 2009 Feb;39(2):223-30
18821008
NMR Biomed. 1998 Oct;11(6):266-72
9802468
Hum Brain Mapp. 2009 Dec;30(12):4082-107
19530215
Front Hum Neurosci. 2013 Sep 27;7:609
24098278
J Autism Dev Disord. 2011 Apr;41(4):447-54
20652388
Trends Cogn Sci. 2005 Feb;9(2):69-74
15668099
Neuroimage. 2005 Jul 1;26(3):839-51
15955494
Neuroimage. 2014 Oct 1;99:191-6
24875142
Brain. 1997 Apr;120 ( Pt 4):701-22
9153131
J Cogn Neurosci. 2009 Sep;21(9):1736-50
18823226
Prog Nucl Magn Reson Spectrosc. 2012 Jan;60:29-41
22293397
Neuroimage Clin. 2013 Jul 02;3:65-72
24179850
J Autism Dev Disord. 1995 Dec;25(6):579-95
8720028
Child Dev. 2009 Sep-Oct;80(5):1434-47
19765010