Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Immediate Communication
  • Published:

Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: a multicentre 1H-MRS study (OPTiMiSE)

Molecular Psychiatry volume 23, pages 2145–2155 (2018)Cite this article

Subjects

Abstract

Conventional antipsychotic medication is ineffective in around a third of patients with schizophrenia, and the nature of the therapeutic response is unpredictable. We investigated whether response to antipsychotics is related to brain glutamate levels prior to treatment. Proton magnetic resonance spectroscopy was used to measure glutamate levels (Glu/Cr) in the anterior cingulate cortex (ACC) and in the thalamus in antipsychotic-naive or minimally medicated patients with first episode psychosis (FEP, n = 71) and healthy volunteers (n = 60), at three sites. Following scanning, patients were treated with amisulpride for 4 weeks (n = 65), then 1H-MRS was repeated (n = 46). Remission status was defined in terms of Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores. Higher levels of Glu/Cr in the ACC were associated with more severe symptoms at presentation and a lower likelihood of being in remission at 4 weeks (P < 0.05). There were longitudinal reductions in Glu/Cr in both the ACC and thalamus over the treatment period (P < 0.05), but these changes were not associated with the therapeutic response. There were no differences in baseline Glu/Cr between patients and controls. These results extend previous evidence linking higher levels of ACC glutamate with a poor antipsychotic response by showing that the association is evident before the initiation of treatment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Meltzer HY. Treatment-resistant schizophrenia--the role of clozapine. Curr Med Res Opin. 1997;14:1–20.

    Article  CAS  Google Scholar 

  2. Knapp M, Mangalore R, Simon J. The global costs of schizophrenia. Schizophr Bull. 2004;30:279–93.

    Article  Google Scholar 

  3. Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M, Abi-Dargham A, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment: meta-analysis of imaging studies. Arch Gen Psychiatry. 2012;69:776–86.

    Article  Google Scholar 

  4. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA. 2000;97:8104–9.

    Article  CAS  Google Scholar 

  5. Demjaha A, Murray RM, McGuire PK, Kapur S, Howes OD. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry. 2012;169:1203–10.

    Article  CAS  Google Scholar 

  6. Wulff S, Pinborg LH, Svarer C, Jensen LT, Nielsen MO, Allerup P, et al. Striatal D(2/3) binding potential values in drug-naive first-episode schizophrenia patients correlate with treatment outcome. Schizophr Bull. 2015;41:1143–52.

    Article  Google Scholar 

  7. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry. 1991;148:1301–8.

  8. Moghaddam B, Adams B, Verma A, Daly D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci. 1997;17:2921–7.

    Article  CAS  Google Scholar 

  9. Moghaddam B, Krystal JH. Capturing the angel in “angel dust”: twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans. Schizophr Bull. 2012;38:942–9.

    Article  Google Scholar 

  10. Egerton A, Brugger S, Raffin M, Barker GJ, Lythgoe DJ, McGuire PK, et al. Anterior cingulate glutamate levels related to clinical status following treatment in first-episode schizophrenia. Neuropsychopharmacology. 2012;37:2515–21.

    Article  CAS  Google Scholar 

  11. Mouchlianitis E, Bloomfield MA, Law V, Beck K, Selvaraj S, Rasquinha N, et al. Treatment-resistant schizophrenia patients show elevated anterior cingulate cortex glutamate compared to treatment-responsive. Schizophr Bull. 2016;42:744–52.

    Article  Google Scholar 

  12. Demjaha A, Egerton A, Murray RM, Kapur S, Howes OD, Stone JM, et al. Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function. Biol Psychiatry. 2013;75:e11–3.

    Article  CAS  Google Scholar 

  13. Aoyama N, Theberge J, Drost DJ, Manchanda R, Northcott S, Neufeld RW, et al. Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia. Br J Psychiatry. 2011;198:448–56.

    Article  Google Scholar 

  14. Goto N, Yoshimura R, Kakeda S, Nishimura J, Moriya J, Hayashi K, et al. Six-month treatment with atypical antipsychotic drugs decreased frontal-lobe levels of glutamate plus glutamine in early-stage first-episode schizophrenia. Neuropsychiatr Dis Treat. 2012;8:119–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Szulc A, Galinska B, Tarasow E, Waszkiewicz N, Konarzewska B, Poplawska R, et al. Proton magnetic resonance spectroscopy study of brain metabolite changes after antipsychotic treatment. Pharmacopsychiatry. 2011;44:148–57.

    Article  CAS  Google Scholar 

  16. de la Fuente-Sandoval C, Leon-Ortiz P, Azcarraga M, Stephano S, Favila R, Diaz-Galvis L, et al. Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: a longitudinal proton magnetic resonance spectroscopy study. JAMA Psychiatry. 2013;70:1057–66.

    Article  Google Scholar 

  17. Szulc A, Galinska B, Tarasow E, Dzienis W, Kubas B, Konarzewska B, et al. The effect of risperidone on metabolite measures in the frontal lobe, temporal lobe, and thalamus in schizophrenic patients. A proton magnetic resonance spectroscopy (1H MRS). Pharmacopsychiatry. 2005;38:214–9.

    Article  CAS  Google Scholar 

  18. Bustillo JR, Rowland LM, Mullins P, Jung R, Chen H, Qualls C, et al. 1H-MRS at 4 Tesla in minimally treated early schizophrenia. Mol Psychiatry. 2010;15:629–36.

    Article  Google Scholar 

  19. Goff DC, Hennen J, Lyoo IK, Tsai G, Wald LL, Evins AE, et al. Modulation of brain and serum glutamatergic concentrations following a switch from conventional neuroleptics to olanzapine. Biol Psychiatry. 2002;51:493–7.

    Article  CAS  Google Scholar 

  20. Egerton A, Bhachu A, Merritt K, McQueen G, Szulc A, McGuire P. Effects of antipsychotic administration on brain glutamate in schizophrenia: a systematic review of longitudinal 1H-MRS studies. Front Psychiatry. 2017;8:66.

    Article  Google Scholar 

  21. Carli M, Calcagno E, Mainolfi P, Mainini E, Invernizzi RW. Effects of aripiprazole, olanzapine, and haloperidol in a model of cognitive deficit of schizophrenia in rats: relationship with glutamate release in the medial prefrontal cortex. Psychopharmacology. 2011;214:639–52.

    Article  CAS  Google Scholar 

  22. Abekawa T, Ito K, Nakagawa S, Nakato Y, Koyama T. Effects of aripiprazole and haloperidol on progression to schizophrenia-like behavioural abnormalities and apoptosis in rodents. Schizophr Res. 2011;125:77–87.

    Article  Google Scholar 

  23. Lopez-Gil X, Babot Z, Amargos-Bosch M, Sunol C, Artigas F, Adell A. Clozapine and haloperidol differently suppress the MK-801-increased glutamatergic and serotonergic transmission in the medial prefrontal cortex of the rat. Neuropsychopharmacology. 2007;32:2087–97.

    Article  CAS  Google Scholar 

  24. Lopez-Gil X, Artigas F, Adell A. Role of different monoamine receptors controlling MK-801-induced release of serotonin and glutamate in the medial prefrontal cortex: relevance for antipsychotic action. Int J Neuropsychopharmacol. 2009;12:487–99.

    Article  CAS  Google Scholar 

  25. Roenker NL, Gudelsky G, Ahlbrand R, Bronson SL, Kern JR, Waterman H, et al. Effect of paliperidone and risperidone on extracellular glutamate in the prefrontal cortex of rats exposed to prenatal immune activation or MK-801. Neurosci Lett. 2011;500:167–71.

    Article  CAS  Google Scholar 

  26. McLoughlin GA, Ma D, Tsang TM, Jones DN, Cilia J, Hill MD, et al. Analyzing the effects of psychotropic drugs on metabolite profiles in rat brain using 1H NMR spectroscopy. J Proteome Res. 2009;8:1943–52.

    Article  CAS  Google Scholar 

  27. Bustillo J, Barrow R, Paz R, Tang J, Seraji-Bozorgzad N, Moore GJ, et al. Long-term treatment of rats with haloperidol: lack of an effect on brain N-acetyl aspartate levels. Neuropsychopharmacology. 2006;31:751–6.

    Article  Google Scholar 

  28. Egerton A, Stone JM, Chaddock CA, Barker GJ, Bonoldi I, Howard RM, et al. Relationship between brain glutamate levels and clinical outcome in individuals at ultra high risk of psychosis. Neuropsychopharmacology. 2014;39:2891–9.

    Article  CAS  Google Scholar 

  29. Chivers JK, Gommeren W, Leysen JE, Jenner P, Marsden CD. Comparison of the in-vitro receptor selectivity of substituted benzamide drugs for brain neurotransmitter receptors. J Pharm Pharmacol. 1988;40:415–21.

    Article  CAS  Google Scholar 

  30. Schoemaker H, Claustre Y, Fage D, Rouquier L, Chergui K, Curet O, et al. Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. J Pharmacol Exp Ther. 1997;280:83–97.

    CAS  PubMed  Google Scholar 

  31. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 2008;371:1085–97.

    Article  CAS  Google Scholar 

  32. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(Suppl 20):22–33. quiz34-57

    PubMed  Google Scholar 

  33. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76.

    Article  CAS  Google Scholar 

  34. Morosini PL, Magliano L, Brambilla L, Ugolini S, Pioli R. Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand. 2000;101:323–9.

    CAS  PubMed  Google Scholar 

  35. Agid O, Kapur S, Arenovich T, Zipursky RB. Delayed-onset hypothesis of antipsychotic action: a hypothesis tested and rejected. Arch Gen Psychiatry. 2003;60:1228–35.

    Article  CAS  Google Scholar 

  36. Leucht S, Busch R, Hamann J, Kissling W, Kane JM. Early-onset hypothesis of antipsychotic drug action: a hypothesis tested, confirmed and extended. Biol Psychiatry. 2005;57:1543–9.

    Article  CAS  Google Scholar 

  37. Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162:441–9.

    Article  Google Scholar 

  38. Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson. 1993;30:672–9.

    Article  CAS  Google Scholar 

  39. Leucht S, Davis JM, Engel RR, Kane JM, Wagenpfeil S. Defining ‘response’ in antipsychotic drug trials: recommendations for the use of scale-derived cutoffs. Neuropsychopharmacology. 2007;32:1903–10.

    Article  CAS  Google Scholar 

  40. Szulc A, Konarzewska B, Galinska-Skok B, Lazarczyk J, Waszkiewicz N, Tarasow E, et al. Proton magnetic resonance spectroscopy measures related to short-term symptomatic outcome in chronic schizophrenia. Neurosci Lett. 2013;547:37–41.

    Article  CAS  Google Scholar 

  41. Robinson DG, Woerner MG, Alvir JM, Geisler S, Koreen A, Sheitman B, et al. Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 1999;156:544–9.

    Article  CAS  Google Scholar 

  42. Demjaha A, Lappin JM, Stahl D, Patel MX, MacCabe JH, Howes OD, et al. Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors. Psychol Med. 2017;47:1981–9.

    Article  CAS  Google Scholar 

  43. Kapur S, Mamo D. Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:1081–90.

    Article  CAS  Google Scholar 

  44. Sarpal DK, Argyelan M, Robinson DG, Szeszko PR, Karlsgodt KH, John M, et al. Baseline striatal functional connectivity as a predictor of response to antipsychotic drug treatment. Am J Psychiatry. 2016;173:69–77.

    Article  Google Scholar 

  45. Lui S, Li T, Deng W, Jiang L, Wu Q, Tang H, et al. Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by “resting state” functional magnetic resonance imaging. Arch Gen Psychiatry. 2010;67:783–92.

    Article  Google Scholar 

  46. Bolding MS, White DM, Hadley JA, Weiler M, Holcomb HH, Lahti AC. Antipsychotic drugs alter functional connectivity between the medial frontal cortex, hippocampus, and nucleus accumbens as measured by H215O PET. Front Psychiatry. 2012;3:105.

    PubMed  PubMed Central  Google Scholar 

  47. Reis Marques T, Taylor H, Chaddock C, Dell’acqua F, Handley R, Reinders AA, et al. White matter integrity as a predictor of response to treatment in first episode psychosis. Brain. 2014;137(Pt 1):172–82.

    Article  Google Scholar 

  48. Ebdrup BH, Raghava JM, Nielsen MO, Rostrup E, Glenthoj B. Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade. J Psychiatry Neurosci. 2016;41:133–41.

    Article  Google Scholar 

  49. Sarpal DK, Robinson DG, Lencz T, Argyelan M, Ikuta T, Karlsgodt K, et al. Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia. JAMA Psychiatry. 2015;72:5–13.

    Article  Google Scholar 

  50. Kegeles LS, Mao X, Stanford AD, Girgis R, Ojeil N, Xu X, et al. Elevated prefrontal cortex gamma-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 2012;69:449–59.

    Article  CAS  Google Scholar 

  51. Choe BY, Suh TS, Shinn KS, Lee CW, Lee C, Paik IH. Observation of metabolic changes in chronic schizophrenia after neuroleptic treatment by in vivo hydrogen magnetic resonance spectroscopy. Invest Radiol. 1996;31:345–52.

    Article  CAS  Google Scholar 

  52. Abekawa T, Ito K, Koyama T. Role of the simultaneous enhancement of NMDA and dopamine D1 receptor-mediated neurotransmission in the effects of clozapine on phencyclidine-induced acute increases in glutamate levels in the rat medial prefrontal cortex. Naunyn Schmiede Arch Pharmacol. 2006;374:177–93.

    Article  CAS  Google Scholar 

  53. Homayoun H, Moghaddam B. Fine-tuning of awake prefrontal cortex neurons by clozapine: comparison with haloperidol and N-desmethylclozapine. Biol Psychiatry. 2007;61:679–87.

    Article  CAS  Google Scholar 

  54. Gao WJ, Wang Y, Goldman-Rakic PS. Dopamine modulation of perisomatic and peridendritic inhibition in prefrontal cortex. J Neurosci. 2003;23:1622–30.

    Article  CAS  Google Scholar 

  55. Seamans JK, Gorelova N, Durstewitz D, Yang CR. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons. J Neurosci. 2001;21:3628–38.

    Article  CAS  Google Scholar 

  56. Bartha R, Williamson PC, Drost DJ, Malla A, Carr TJ, Cortese L, et al. Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 1997;54:959–65.

    Article  CAS  Google Scholar 

  57. Theberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, et al. Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry. 2002;159:1944–6.

    Article  Google Scholar 

  58. Theberge J, Williamson KE, Aoyama N, Drost DJ, Manchanda R, Malla AK, et al. Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia. Br J Psychiatry. 2007;191:325–34.

    Article  Google Scholar 

  59. Galinska B, Szulc A, Tarasow E, Kubas B, Dzienis W, Czernikiewicz A, et al. Duration of untreated psychosis and proton magnetic resonance spectroscopy (1H-MRS) findings in first-episode schizophrenia. Med Sci Monit. 2009;15:CR82–88.

  60. Natsubori T, Inoue H, Abe O, Takano Y, Iwashiro N, Aoki Y, et al. Reduced frontal glutamate + glutamine and N-acetyl aspartate levels in patients with chronic schizophrenia but not in those at clinical high risk for psychosis or with first-episode schizophrenia. Schizophr Bull. 2014;40:1128–39.

    Article  Google Scholar 

  61. Merritt K, Egerton A, Kempton MJ, Taylor MJ, McGuire PK. Nature of glutamate alterations in schizophrenia: a meta-analysis of proton magnetic resonance spectroscopy studies. JAMA Psychiatry. 2016;73:665–74.

    Article  Google Scholar 

  62. Kim SY, Kaufman MJ, Cohen BM, Jensen JE, Coyle JT, Du F, et al. In vivo brain glycine and glutamate concentrations in patients with first-episode psychosis measured by echo time-averaged proton magnetic resonance spectroscopy at 4T. Biol Psychiatry. 2017;83:484–91.

    Article  CAS  Google Scholar 

  63. Ongur D, Prescot AP, Jensen JE, Cohen BM, Renshaw PF. Creatine abnormalities in schizophrenia and bipolar disorder. Psychiatry Res. 2009;172:44–48.

    Article  CAS  Google Scholar 

  64. Kraguljac NV, Reid M, White D, Jones R, den Hollander J, Lowman D, et al. Neurometabolites in schizophrenia and bipolar disorder—a systematic review and meta-analysis. Psychiatry Res. 2012;203:111–25.

    Article  CAS  Google Scholar 

  65. Bustillo JR, Jones T, Chen H, Lemke N, Abbott C, Qualls C, et al. Glutamatergic and neuronal dysfunction in gray and white matter: a spectroscopic imaging study in a large schizophrenia sample. Schizophr Bull. 2017;43:611–9.

    PubMed  Google Scholar 

  66. Wijtenburg SA, Yang S, Fischer BA, Rowland LM. In vivo assessment of neurotransmitters and modulators with magnetic resonance spectroscopy: application to schizophrenia. Neurosci Biobehav Rev. 2015;51:276–95.

    Article  CAS  Google Scholar 

  67. McGuire P, Dazzan P. Does neuroimaging have a role in predicting outcomes in psychosis? World Psychiatry. 2017;16:209–10.

    Article  Google Scholar 

  68. Stevenson JM, Reilly JL, Harris MS, Patel SR, Weiden PJ, Prasad KM, et al. Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes. Transl Psychiatry. 2016;6:e739.

    Article  CAS  Google Scholar 

  69. Bishop JR, Ellingrod VL, Moline J, Miller D. Association between the polymorphic GRM3 gene and negative symptom improvement during olanzapine treatment. Schizophr Res. 2005;77:253–60.

    Article  Google Scholar 

  70. Bishop JR, Miller del D, Ellingrod VL, Holman T. Association between type-three metabotropic glutamate receptor gene (GRM3) variants and symptom presentation in treatment refractory schizophrenia. Human Psychopharmacol. 2011;26:28–34.

    Article  CAS  Google Scholar 

  71. Bishop JR, Reilly JL, Harris MS, Patel SR, Kittles R, Badner JA, et al. Pharmacogenetic associations of the type-3 metabotropic glutamate receptor (GRM3) gene with working memory and clinical symptom response to antipsychotics in first-episode schizophrenia. Psychopharmacology. 2015;232:145–54.

    Article  CAS  Google Scholar 

  72. Fijal BA, Kinon BJ, Kapur S, Stauffer VL, Conley RR, Jamal HH, et al. Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia. Pharm J. 2009;9:311–8.

    CAS  Google Scholar 

  73. Mondelli V, Ciufolini S, Belvederi Murri M, Bonaccorso S, Di Forti M, Giordano A, et al. Cortisol and inflammatory biomarkers predict poor treatment response in first episode psychosis. Schizophr Bull. 2015;41:1162–70.

    Article  Google Scholar 

  74. Pollak TA, Drndarski S, Stone JM, David AS, McGuire P, Abbott NJ. The blood-brain barrier in psychosis. Lancet Psychiatry. 2017; 5:79–92.

    Article  Google Scholar 

  75. Pollak TA, Beck K, Irani SR, Howes OD, David AS, McGuire PK. Autoantibodies to central nervous system neuronal surface antigens: psychiatric symptoms and psychopharmacological implications. Psychopharmacology. 2016;233:1605–21.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by a grant from the European Commission within the 7th Program (HEALTH-F2-2010-242114). We would like to thank the other OPTiMiSE investigators for their on-going support during the study. A.E. received additional support from the Brain and Behaviour Research Foundation (YIA 2012–18777). Research at the London site was supported by the Department of Health via the National Institute for Health Research (NIHR) Specialist Biomedical Research Center for Mental Health award to South London and Maudsley NHS Foundation Trust (SLaM) and the Institute of Psychiatry at King’s College London, London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Author information

Authors and Affiliations

  1. Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK

    A. Egerton, K. Merritt, G. J. Barker, D. J. Lythgoe, R. Perez-Iglesias, K. V. Sendt, J. M. Stone, P. Dazzan & P. McGuire

  2. Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark

    B. V. Broberg, L. Baandrup, S. W. Düring, E. Rostrup & B. Glenthøj

  3. Department of Psychiatry, Brain Center Rudolf Magnus Institute, University Medical Centre, Utrecht, The Netherlands

    N. Van Haren, I. E. Sommer & R. S. Kahn

  4. Functional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine Rigshospitalet, University of Copenhagen, Glostrup, Denmark

    E. Rostrup

  5. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark

    B. Glenthøj

Authors
  1. A. Egerton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. V. Broberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Van Haren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Merritt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. J. Barker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. J. Lythgoe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. Perez-Iglesias
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. Baandrup
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. W. Düring
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K. V. Sendt
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J. M. Stone
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. E. Rostrup
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. I. E. Sommer
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. B. Glenthøj
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. R. S. Kahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. P. Dazzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. P. McGuire
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Egerton.

Ethics declarations

Conflict of interest

G.J.B. received honoraria for teaching from General Electric Healthcare during the course of this study, and acts as a consultant for IXICO. A.E. has received research funding from the Roche and consultancy payment from Heptares Therapeutics. B.G. is the leader of a Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen and other foundations. P.M. has received consultancy payment for Sunovion and Takeda. R.P.I. has received honoraria as a speaker for Lundbeck. J.M.S. has received honoraria from Roche and Janssen and consultancy payment from Takeda. The remaining authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Egerton, A., Broberg, B.V., Van Haren, N. et al. Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: a multicentre 1H-MRS study (OPTiMiSE). Mol Psychiatry 23, 2145–2155 (2018). https://doi.org/10.1038/s41380-018-0082-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-018-0082-9

This article is cited by

Search

Advanced search

Quick links