, Volume 60, Issue 2, pp 199–205 | Cite as

Evidence for regional hippocampal damage in patients with schizophrenia

  • Sadhana Singh
  • Subash KhushuEmail author
  • Pawan Kumar
  • Satnam Goyal
  • Triptish Bhatia
  • Smita N Deshpande
Functional Neuroradiology



Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy (1H MRS) procedures.


1H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel).


Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia.


Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients.


Proton magnetic resonance spectroscopy Voxel-based morphometry Schizophrenia Hippocampus 


Compliance with ethical standards


This study was funded by DRDO R&D Project No. INM-311(4.1) and funded in part by grant from the Fogarty International Centre, NIH, The Impact of Yoga Supplementation on Cognitive Function Among Indian Outpatients Grant #1R01TW008289 to TB.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Mueller S, Keeser D, Reiser MF, Teipel S, Meindl T (2012) Functional and structural MR imaging in neuropsychiatric disorders, part 2: application in schizophrenia and autism. AJNR Am J Neuroradiol 33(11):2033–2037. CrossRefPubMedGoogle Scholar
  2. 2.
    Penn DL, Spaulding W, Reed D, Sullivan M, Mueser KT, Hope DA (1997) Cognition and social functioning in schizophrenia. Psychiatry 60(4):281–291. CrossRefPubMedGoogle Scholar
  3. 3.
    Goldberg TEGM (2002) Neurocognitive functioning in patients with schizophrenia: an overview. In: Davis KLCD, Coyle JT, Nemeroff C (eds) Neuropsychopharmacology—fifth generation of progress, pp 657–669Google Scholar
  4. 4.
    Mulholland CCS (2000) The symptom of depression in schizophrenia and its management. Adv Psychiatr Treat 6(3):169–177. CrossRefGoogle Scholar
  5. 5.
    Harvey PD (2011) Mood symptoms, cognition, and everyday functioning: in major depression, bipolar disorder, and schizophrenia. Innov Clin Neurosci 8(10):14–18PubMedPubMedCentralGoogle Scholar
  6. 6.
    Harrison PJ (2004) The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications. Psychopharmacology 174(1):151–162. CrossRefPubMedGoogle Scholar
  7. 7.
    Heckers S (2001) Neuroimaging studies of the hippocampus in schizophrenia. Hippocampus 11(5):520–528. CrossRefPubMedGoogle Scholar
  8. 8.
    Wible CG (2013) Hippocampal physiology, structure and function and the neuroscience of schizophrenia: a unified account of declarative memory deficits, working memory deficits and schizophrenic symptoms. Behav Sci (Basel) 3(2):298–315. CrossRefGoogle Scholar
  9. 9.
    Tamminga CA, Stan AD, Wagner AD (2010) The hippocampal formation in schizophrenia. Am J Psychiatry 167(10):1178–1193. CrossRefPubMedGoogle Scholar
  10. 10.
    Shepherd AM, Laurens KR, Matheson SL, Carr VJ, Green MJ (2012) Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia. Neurosci Biobehav Rev 36(4):1342–1356. CrossRefPubMedGoogle Scholar
  11. 11.
    Glahn DC, Laird AR, Ellison-Wright I, Thelen SM, Robinson JL, Lancaster JL, Bullmore E, Fox PT (2008) Meta-analysis of gray matter anomalies in schizophrenia: application of anatomic likelihood estimation and network analysis. Biol Psychiatry 64(9):774–781. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Asami T, Bouix S, Whitford TJ, Shenton ME, Salisbury DF, McCarley RW (2012) Longitudinal loss of gray matter volume in patients with first-episode schizophrenia: DARTEL automated analysis and ROI validation. NeuroImage 59(2):986–996. CrossRefPubMedGoogle Scholar
  13. 13.
    Williams LM (2008) Voxel-based morphometry in schizophrenia: implications for neurodevelopmental connectivity models, cognition and affect. Expert Rev Neurother 8(7):1049–1065. CrossRefPubMedGoogle Scholar
  14. 14.
    Steen RG, Hamer RM, Lieberman JA (2005) Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology 30(11):1949–1962. CrossRefPubMedGoogle Scholar
  15. 15.
    Deicken RF, Zhou L, Schuff N, Fein G, Weiner MW (1998) Hippocampal neuronal dysfunction in schizophrenia as measured by proton magnetic resonance spectroscopy. Biol Psychiat 43(7):483–488. CrossRefPubMedGoogle Scholar
  16. 16.
    van Elst LT, Valerius G, Buchert M, Thiel T, Rusch N, Bubl E, Hennig J, Ebert D, Olbrich HM (2005) Increased prefrontal and hippocampal glutamate concentration in schizophrenia: evidence from a magnetic resonance spectroscopy study. Biol Psychiatry 58(9):724–730. CrossRefPubMedGoogle Scholar
  17. 17.
    Rusch N, van Elst LT, Valerius G, Buchert M, Thiel T, Ebert D, Hennig J, Olbrich HM (2008) Neurochemical and structural correlates of executive dysfunction in schizophrenia. Schizophr Res 99(1–3):155–163. CrossRefPubMedGoogle Scholar
  18. 18.
    Hutcheson NL, Reid MA, White DM, Kraguljac NV, Avsar KB, Bolding MS, Knowlton RC, den Hollander JA, Lahti AC (2012) Multimodal analysis of the hippocampus in schizophrenia using proton magnetic resonance spectroscopy and functional magnetic resonance imaging. Schizophr Res 140(1–3):136–142. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kraguljac NV, White DM, Reid MA, Lahti AC (2013) Increased hippocampal glutamate and volumetric deficits in unmedicated patients with schizophrenia. Jama Psychiat 70(12):1294–1302. CrossRefGoogle Scholar
  20. 20.
    Hasan A, Wobrock T, Falkai P, Schneider-Axmann T, Guse B, Backens M, Ecker UKH, Heimes J, Galea JM, Gruber O, Scherk H (2014) Hippocampal integrity and neurocognition in first-episode schizophrenia: a multidimensional study. World J Biol Psychia 15(3):188–199. CrossRefGoogle Scholar
  21. 21.
    Nurnberger JI, Blehar MC, Kaufmann CA, Yorkcooler C, Simpson SG, Harkavyfriedman J, Severe JB, Malaspina D, Reich T, Miller M, Bowman ES, Depaulo JR, Cloninger CR, Robinson G, Modlin S, Gershon ES, Maxwell E, Guroff JJ, Kirch D, Wynne D, Berg K, Tsuang MT, Faraone SV, Pepple JR, Ritz AL (1994) Diagnostic interview for genetic studies—rationale, unique features, and training. Arch Gen Psychiat 51(11):849–859. CrossRefPubMedGoogle Scholar
  22. 22.
    Deshpande SN, Mathur MNL, Das SK, Bhatia T, Sharma S, Nimgaonkar VL (1998) A Hindi version of the diagnostic interview for genetic studies. Schizophrenia Bull 24(3):489–493. CrossRefGoogle Scholar
  23. 23.
    Ashburner J (2010) VBM TutorialGoogle Scholar
  24. 24.
    Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33(3):341–355. CrossRefPubMedGoogle Scholar
  25. 25.
    Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnet Reson Med 30(6):672–679. CrossRefGoogle Scholar
  26. 26.
    Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14(4):260–264. CrossRefPubMedGoogle Scholar
  27. 27.
    Cavassila S, Deval S, Huegen C, van Ormondt D, Graveron-Demilly D (2001) Cramer-Rao bounds: an evaluation tool for quantitation. NMR Biomed 14(4):278–283. CrossRefPubMedGoogle Scholar
  28. 28.
    da Silva Alves F, Boot E, Schmitz N, Nederveen A, Vorstman J, Lavini C, Pouwels PJ, de Haan L, Linszen D, van Amelsvoort T (2011) Proton magnetic resonance spectroscopy in 22q11 deletion syndrome. PLoS One 6(6):e21685. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Chang L, Friedman J, Ernst T, Zhong K, Tsopelas ND, Davis K (2007) Brain metabolite abnormalities in the white matter of elderly schizophrenic subjects: implication for glial dysfunction. Biol Psychiatry 62(12):1396–1404. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kegeles LS, Mao X, Stanford AD, Girgis R, Ojeil N, Xu X, Gil R, Slifstein M, Abi-Dargham A, Lisanby SH, Shungu DC (2012) Elevated prefrontal cortex gamma-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry 69(5):449–459. CrossRefPubMedGoogle Scholar
  31. 31.
    de la Fuente-Sandoval C, Leon-Ortiz P, Azcarraga M, Favila R, Stephano S, Graff-Guerrero A (2013) Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study. Int J Neuropsychopharmacol 16(2):471–475. CrossRefPubMedGoogle Scholar
  32. 32.
    Olbrich HM, Valerius G, Rusch N, Buchert M, Thiel T, Hennig J, Ebert D, Van Elst LT (2008) Frontolimbic glutamate alterations in first episode schizophrenia: evidence from a magnetic resonance spectroscopy study. World J Biol Psychiatry 9(1):59–63. CrossRefPubMedGoogle Scholar
  33. 33.
    Nenadic I, Maitra R, Basu S, Dietzek M, Schonfeld N, Lorenz C, Gussew A, Amminger GP, McGorry P, Reichenbach JR, Sauer H, Gaser C, Smesny S (2015) Associations of hippocampal metabolism and regional brain grey matter in neuroleptic-naive ultra-high-risk subjects and first-episode schizophrenia. Eur Neuropsychopharmacol 25(10):1661–1668. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Sadhana Singh
    • 1
  • Subash Khushu
    • 1
    Email author
  • Pawan Kumar
    • 1
  • Satnam Goyal
    • 2
  • Triptish Bhatia
    • 2
  • Smita N Deshpande
    • 2
  1. 1.NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS)DRDODelhiIndia
  2. 2.Post Graduate Institute of Medical Education and Research (PGIMER)RML HospitalNew DelhiIndia

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