A longitudinal investigation of GABA, glutamate, and glutamine across the insula during antipsychotic treatment of first-episode schizophrenia.
Antipsychotic treatment
First-episode schizophrenia
GABA
Glutamate
Glutamine
Insula
Magnetic resonance spectroscopic imaging
Psychosis
Treatment response
Journal
Schizophrenia research
ISSN: 1573-2509
Titre abrégé: Schizophr Res
Pays: Netherlands
ID NLM: 8804207
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
15
03
2022
revised:
29
06
2022
accepted:
20
08
2022
pubmed:
28
8
2022
medline:
26
10
2022
entrez:
27
8
2022
Statut:
ppublish
Résumé
Individuals with first-episode schizophrenia (FES) typically present with acute psychotic symptoms. Though antipsychotic drugs are the mainstay for treatment, the neurobiology underlying successful treatment remains largely elusive. Recent evidence from functional connectivity studies highlights the insula as a key structure in the neural mechanism of response. However, molecular contributions to response across insular regions remain largely unknown. We used 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to measure glutamate (Glu), Glutamine (Gln), and GABA from anterior and posterior regions of the insula across antipsychotic treatment. A total of 36 participants were examined, including 15 individuals with FES and moderate to severe psychosis who were scanned at two time points, while starting and after 6 weeks of antipsychotic treatment. Symptoms were carefully monitored across the study period to characterize treatment response. GABA, Glu, and Gln levels were calculated relative to creatine in anterior and posterior insular regions, bilaterally. In relation to psychotic symptom reduction, we observed a significant increase in Glu across all insular regions with (p < 0.001), but no corresponding changes in Gln or GABA. In group analyses, the FES cohort showed lower levels of Glu (p < 0.001) and GABA (p = 0.02) at baseline. Finally, in exploratory analyses, treatment remitters demonstrated a normalization of lower insular Glu levels across treatment, unlike non-remitters. Overall, these findings contribute to our understating of molecular changes associated with antipsychotic response and demonstrate abnormalities specific to the insula in FES.
Identifiants
pubmed: 36029656
pii: S0920-9964(22)00310-3
doi: 10.1016/j.schres.2022.08.008
pmc: PMC10018530
mid: NIHMS1877544
pii:
doi:
Substances chimiques
Antipsychotic Agents
0
Glutamine
0RH81L854J
Glutamic Acid
3KX376GY7L
Creatine
MU72812GK0
gamma-Aminobutyric Acid
56-12-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
98-106Subventions
Organisme : NIMH NIH HHS
ID : R01 MH124705
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All authors declare that they have no conflicts of interest.
Références
Schizophr Res. 2010 Nov;123(2-3):93-104
pubmed: 20832997
Mol Psychiatry. 2022 Jan;27(1):744-757
pubmed: 34584230
Acta Psychiatr Scand Suppl. 2009;(438):7-14
pubmed: 19132961
Epidemiol Rev. 2008;30:67-76
pubmed: 18480098
NMR Biomed. 2001 Jun;14(4):260-4
pubmed: 11410943
Neuropsychopharmacology. 2016 Sep;41(10):2606-13
pubmed: 27272768
Biol Psychiatry. 2021 Nov 1;90(9):643-651
pubmed: 34344534
Mol Psychiatry. 2020 Apr;25(4):873-882
pubmed: 29934548
Brain Res Brain Res Rev. 1996 Oct;22(3):229-44
pubmed: 8957561
Science. 2017 Aug 11;357(6351):596-600
pubmed: 28798131
Biol Psychiatry. 2013 Sep 15;74(6):467-74
pubmed: 23623456
Curr Opin Neurobiol. 2014 Jun;26:22-6
pubmed: 24650500
Neurosci Lett. 2013 Jun 28;547:37-41
pubmed: 23665527
Neuroimage. 2010 Jan 15;49(2):1271-81
pubmed: 19819338
Schizophr Res. 2008 Jul;102(1-3):230-40
pubmed: 18423985
Neuropsychopharmacology. 2021 May;46(6):1133-1139
pubmed: 33273706
J Comp Neurol. 1982 Nov 20;212(1):1-22
pubmed: 7174905
Brain Struct Funct. 2010 Jun;214(5-6):519-34
pubmed: 20512376
Transl Psychiatry. 2017 Jun 6;7(6):e1147
pubmed: 28585933
Neuroscience. 1996 Dec;75(4):1065-74
pubmed: 8938742
Am J Psychiatry. 2016 Jan;173(1):69-77
pubmed: 26315980
Am J Psychiatry. 2003 Jan;160(1):13-23
pubmed: 12505794
JAMA Psychiatry. 2021 Jun 1;78(6):667-681
pubmed: 33881460
Mol Psychiatry. 2005 May;10(5):434-49
pubmed: 15700048
Neurology. 2007 Dec 11;69(24):2256-65
pubmed: 18071146
Schizophr Res. 2007 Jan;89(1-3):129-39
pubmed: 17095194
PLoS One. 2012;7(2):e30554
pubmed: 22347384
Magn Reson Med. 2010 Jan;63(1):9-19
pubmed: 19918903
Schizophr Res. 2014 Feb;152(2-3):325-32
pubmed: 24418122
Psychiatry Res. 2009 Apr 30;172(1):44-8
pubmed: 19239984
Schizophr Bull. 2013 Jan;39(1):120-9
pubmed: 21746807
J Neurol Neurosurg Psychiatry. 2010 Jun;81(6):611-8
pubmed: 20522870
Acta Psychiatr Scand. 2006 Feb;113(2):91-5
pubmed: 16423159
Schizophr Res. 2004 Aug 1;69(2-3):277-87
pubmed: 15469199
Transl Psychiatry. 2021 May 27;11(1):322
pubmed: 34045446
Magn Reson Med. 2009 Jun;61(6):1279-85
pubmed: 19319893
Schizophr Bull. 2021 Mar 16;47(2):505-516
pubmed: 32910150
Arch Gen Psychiatry. 1999 Mar;56(3):241-7
pubmed: 10078501
Biol Psychiatry. 2020 Aug 1;88(3):273-281
pubmed: 32312577
Neurobiol Dis. 2019 Nov;131:104414
pubmed: 30849509
Neuropsychopharmacology. 2003 Feb;28(2):265-75
pubmed: 12589379
Biol Psychiatry. 2012 Nov 1;72(9):775-84
pubmed: 22621997
JAMA Psychiatry. 2016 Jul 1;73(7):665-74
pubmed: 27304221
Nat Rev Neurosci. 2009 Jan;10(1):59-70
pubmed: 19096369
Am J Psychiatry. 2005 Mar;162(3):441-9
pubmed: 15741458
Schizophr Bull. 2014 Jul;40(4):904-13
pubmed: 23861539
Magn Reson Med. 2010 Nov;64(5):1237-46
pubmed: 20648684
Neuropsychopharmacology. 2012 Oct;37(11):2515-21
pubmed: 22763619
JAMA Psychiatry. 2013 Oct;70(10):1057-66
pubmed: 23966023
J Neurosci. 2005 Apr 27;25(17):4385-95
pubmed: 15858065
Arch Gen Psychiatry. 1993 May;50(5):369-76
pubmed: 8098203
Neuropsychopharmacology. 2020 Mar;45(4):632-640
pubmed: 31842203
Annu Rev Neurosci. 2002;25:409-32
pubmed: 12052915
Schizophr Bull. 2014 Sep;40(5):1095-104
pubmed: 24243441
Front Psychiatry. 2021 May 19;12:656459
pubmed: 34093272
Brain Struct Funct. 2010 Jun;214(5-6):655-67
pubmed: 20512370
Psychiatry Res. 2011 May 15;187(1-2):42-8
pubmed: 21168920
Biol Psychiatry. 2019 Apr 1;85(7):596-605
pubmed: 30389132
Biol Psychiatry. 2014 Mar 1;75(5):e11-3
pubmed: 23890739
J Clin Neurophysiol. 2017 Jul;34(4):300-306
pubmed: 28644199
Neuropsychopharmacology. 2007 Sep;32(9):1903-10
pubmed: 17287825
Psychol Med. 2016 Nov;46(15):3231-3240
pubmed: 27605254
Schizophr Bull. 2016 May;42(3):744-52
pubmed: 26683625
Magn Reson Med. 2012 Oct;68(4):1007-17
pubmed: 22213108
Arch Gen Psychiatry. 2003 Nov;60(11):1069-77
pubmed: 14609882
Am J Psychiatry. 2019 Jul 1;176(7):564-572
pubmed: 31164007
Psychopharmacol Bull. 1988;24(1):112-7
pubmed: 3387514
Elife. 2020 Jan 24;9:
pubmed: 31975686
Schizophr Res. 2010 Nov;123(2-3):105-15
pubmed: 20724114
Annu Rev Clin Psychol. 2014;10:425-48
pubmed: 24313570
Arch Gen Psychiatry. 1988 Sep;45(9):789-96
pubmed: 3046553
Schizophr Bull. 2008 Nov;34(6):1163-71
pubmed: 18156640
Neuron. 2013 Aug 21;79(4):814-28
pubmed: 23972602
Magn Reson Med. 2006 Dec;56(6):1200-10
pubmed: 17094090
Schizophr Bull. 2011 Jan;37(1):177-88
pubmed: 19633214
JAMA Psychiatry. 2015 Jan;72(1):5-13
pubmed: 25372846