Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-26T13:00:29.973Z Has data issue: false hasContentIssue false
  • English
  • Français

Volumetric and morphological characteristics of the hippocampus are associated with progression to schizophrenia in patients with first-episode psychosis

Published online by Cambridge University Press:  23 March 2020

R. Sauras ,
A. Keymer ,
A. Alonso-Solis ,
A. Díaz ,
C. Molins ,
F. Nuñez ,
M. Rabella ,
A. Roldán ,
E. Grasa  and
E. Alvarez
...Show all authors
R. Sauras
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carrer Dr. Aiguader, 88, 1a Planta, 08003Barcelona, Spain
A. Keymer
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain
A. Alonso-Solis
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carrer Dr. Aiguader, 88, 1a Planta, 08003Barcelona, Spain
A. Díaz
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain
C. Molins
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain
F. Nuñez
Affiliation:
Neuroradiology Unit Hospital de Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain
M. Rabella
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain
A. Roldán
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain
E. Grasa
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carrer Dr. Aiguader, 88, 1a Planta, 08003Barcelona, Spain
E. Alvarez
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carrer Dr. Aiguader, 88, 1a Planta, 08003Barcelona, Spain
M.J. Portella*
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carrer Dr. Aiguader, 88, 1a Planta, 08003Barcelona, Spain
I. Corripio
Affiliation:
Psychiatric Department Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), Carrer Sant Antoni M. Claret, 167, 08025Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carrer Dr. Aiguader, 88, 1a Planta, 08003Barcelona, Spain
*
*Corresponding author. Psychiatric Department, Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Sant Antoni M. Claret, 167, 08025 Barcelona. Catalonia, Spain. Fax: +34 935 537 842. E-mail address:[email protected] (M.J. Portella).
Get access

Abstract

Background:

Abnormalities in the hippocampus have been implicated in the pathophysiology of psychosis. However, it is still unclear whether certain abnormalities are a pre-existing vulnerability factor, a sign of disease progression or a consequence of environmental factors. We hypothesized that first-episode psychosis patients who progress to schizophrenia after one year of follow up will display greater volumetric and morphological changes from the very beginning of the disorder.

Methods:

We studied the hippocampus of 41 patients with a first-episode psychosis and 41 matched healthy controls. MRI was performed at the time of the inclusion in the study. After one year, the whole sample was reevaluated and divided in two groups depending on the diagnoses (schizophrenia vs. non-schizophrenia).

Results:

Patients who progressed to schizophrenia showed a significantly smaller left hippocampus volume than control group and no-schizophrenia group (F = 3.54; df = 2, 77; P = 0.03). We also found significant differences in the morphology of the anterior hippocampus (CA1) of patients with first-episode psychosis who developed schizophrenia compared with patients who did not.

Conclusions:

These results are consistent with the assumption of hyperfunctioning dopaminergic cortico-subcortical circuits in schizophrenia, which might be related with an alteration of subcortical structures, such as the hippocampus, along the course of the disease. According with these results, hippocampus abnormalities may serve as a prognostic marker of clinical outcome in patients with a first-episode psychosis.

Keywords

First-episode of psychosisHippocampusShape analysisSchizophrenia
Type
Original article
Information
European Psychiatry , Volume 45 , September 2017 , pp. 1 - 5
Copyright
Copyright © European Psychiatric Association 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

1

Present address. Centre Assistencial Emili Mira i Lopez, Parc de Salut Mar, Universitat Autònoma de Barcelona (UAB), Avinguda Prat de la Riba, 171 (Recinte Torribera), 08921 Santa Coloma de Gramanet, Spain.

References

Gur, RETuretsky, BICowell, PE, et al.Temporolimbic volume reductions in schizophrenia. Arch Gen Psychiatry 2000;57:769–775. http://dx.doi.org/10.1001/archpsyc.57.8.769.CrossRefGoogle Scholar
Nelson, MDSaykin, AJFlashman, LARiorda, HJHippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: A meta-analytic study. Arch Gen Psychiatry 1998;55:433–440. http://dx.doi.org/10.1016/S0920-9964(97)82438-3.CrossRefGoogle ScholarPubMed
Wright, ICRabe-Hesketh, SWoodruff, PWDavid, ASMurray, RMBullmore, ETMeta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 2000;157:16–25. http://dx.doi.org/10.1176/ajp.157.1.16.CrossRefGoogle Scholar
Szeszko, PRGoldberg, EGunduz-Bruce, HAshtari, MRobinson, DMalhotra, AK, et al.Smaller anterior hippocampal formation volume in antipsychotic-naive patients with first-episode schizophrenia. Am J Psychiatry 2003;160:2190–2197. http://dx.doi.org/10.1176/appi.ajp.160.12.2190.CrossRefGoogle ScholarPubMed
Witthaus, HMendes, UBrüne, MÖzgürdal, SBohner, GGudlowski, Y, et al.Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia. J Psychiatry Neurosci 2010;35:33–40. http://dx.doi.org/10.1503/jpn.090013.CrossRefGoogle Scholar
Phillips, LVelakoulis, DPantelis, CWood, SYuen, HYung, A, et al.Non-reduction in hippocampal volume is associated with higher risk of psychosis. Schizophr Res 2002;58:145–158. http://dx.doi.org/10.1016/S0920-9964(01)00392-9.CrossRefGoogle ScholarPubMed
Velakoulis, DWood, SJWong, MTH, et al.Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra–high-risk individuals. Arch Gen Psychiatry 2006;63:139–149. http://dx.doi.org/10.1001/archpsyc.63.2.139.CrossRefGoogle ScholarPubMed
Van Essen, DCA tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature 1997;385:313–318. http://dx.doi.org/10.1038/385313a0.CrossRefGoogle ScholarPubMed
Van Essen, DCDrury, HJoshi, SMiller, MIFunctional and structural mapping of human cerebral cortex: solutions are in the surfaces. Proc Natl Acad Sci U S A 1998;95:788–795. http://dx.doi.org/10.1073/pnas.95.3.788.CrossRefGoogle ScholarPubMed
Moser, EMoser, MBAndersen, PSpatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions. J Neurosci 1993;13:3916 [LP-3925].CrossRefGoogle ScholarPubMed
Szeszko, PRStrous, RDGoldman, RSAshtari, MKnuth, KHLieberman, J, et al.Neuropsychological correlates of hippocampal volumes in patients experiencing a first episode of schizophrenia. Am J Psychiatry 2002;159:217–226. http://dx.doi.org/10.1176/appi.ajp.159.2.217.CrossRefGoogle ScholarPubMed
Roalf, DRVandekar, SNAlmasy, LRuparel, KSatterthwaite, TDElliott, MA, et al.Heritability of subcortical and limbic brain volume and shape in multiplex-multigenerational families with schizophrenia. Biol Psychiatry 2015;77:137–146. http://dx.doi.org/10.1016/j.biopsych.2014.05.009.CrossRefGoogle ScholarPubMed
Csernansky, JGWang, LJones, DRastogi-Cruz, DPosener, JAHeydebrand, G, et al.Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping. Am J Psychiatry 2002;159:2000–2006. http://dx.doi.org/10.1176/appi.ajp.159.12.2000.CrossRefGoogle ScholarPubMed
Csernansky, JGJoshi, SWang, LHaller, JWGado, MMiller, JP, et al.Hippocampal morphometry in schizophrenia by high dimensional brain mapping. Proc Natl Acad Sci U S A 1998;95:11406–11411. http://dx.doi.org/10.1073/pnas.95.19.11406.CrossRefGoogle ScholarPubMed
Zierhut, KCGraßmann, RKaufmann, JSteiner, JBogerts, BSchiltz, KHippocampal CA1 deformity is related to symptom severity and antipsychotic dosage in schizophrenia. Brain 2013;136:804–814. http://dx.doi.org/10.1093/brain/aws335.CrossRefGoogle Scholar
Narr, KLThompson, PMSzeszko, PRobinson, DJang, SWoods, RP, et al.Regional specificity of hippocampal volume reductions in first-episode schizophrenia. Neuroimage 2004;21:1563–1575. http://dx.doi.org/10.1016/j.neuroimage.2003.11.011.CrossRefGoogle ScholarPubMed
Styner, MLieberman, JAPantazis, DGerig, GBoundary and medial shape analysis of the hippocampus in schizophrenia. Med Image Anal 2004;8:197–203. http://dx.doi.org/10.1016/j.media.2004.06.004.CrossRefGoogle Scholar
Lee, J.-M.Kim, SHJang, DPHa, THKim, J.-J.Kim, IY, et al.Deformable model with surface registration for hippocampal shape deformity analysis in schizophrenia. Neuroimage 2004;22:831–840. http://dx.doi.org/10.1016/j.neuroimage.2004.02.004.CrossRefGoogle Scholar
Mamah, DHarms, MPBarch, DStyner, MLieberman, JAWang, LHippocampal shape and volume changes with antipsychotics in early stage psychotic illness. Front Psychiatry 2012;3. http://dx.doi.org/10.3389/fpsyt.2012.00096.Google ScholarPubMed
Schobel, SAChaudhury, NHKhan, UAPaniagua, BStyner, MAAsllani, I, et al.Imaging patients with psychosis and a mouse model establishes a spreading pattern of hippocampal dysfunction and implicates glutamate as a driver. Neuron 2013;78:81–93. http://dx.doi.org/10.1016/j.neuron.2013.02.011.CrossRefGoogle Scholar
Dean, DJOrr, JMBernard, JAGupta, TPelletier-Baldelli, ACarol, EE, et al.Hippocampal shape abnormalities predict symptom progression in neuroleptic-free youth at ultrahigh risk for psychosis. Schizophr Bull 2015. http://dx.doi.org/10.1093/schbul/sbv086 [sbv086].CrossRefGoogle Scholar
Scanlon, CAnderson-Schmidt, HKilmartin, LMcInerney, SKenney, JMcFarland, J, et al.Cortical thinning and caudate abnormalities in first episode psychosis and their association with clinical outcome. Schizophr Res 2014;159:36–42. http://dx.doi.org/10.1016/j.schres.2014.07.030.CrossRefGoogle ScholarPubMed
First, MBSpitzer, RLGibbon, MWilliams, JBWStructured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV); 1997.Google Scholar
Kay, SRFiszbein, AOpler, LAThe positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.CrossRefGoogle Scholar
Patenaude, BSmith, SMKennedy, DNJenkinson, MA Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage 2011;56:907–922. http://dx.doi.org/10.1016/j.neuroimage.2011.02.046.CrossRefGoogle ScholarPubMed
Boos, HBMAleman, ACahn, WPol, HHKahn, RSBrain volumes in relatives of patients with schizophrenia. Arch Gen Psychiatry 2007;64:297. http://dx.doi.org/10.1001/archpsyc.64.3.297.CrossRefGoogle ScholarPubMed
Hu, MLi, JEyler, LGuo, XWei, QTang, J, et al.Decreased left middle temporal gyrus volume in antipsychotic drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings. Schizophr Res 2013;144:37–42. http://dx.doi.org/10.1016/j.schres.2012.12.018.CrossRefGoogle ScholarPubMed
Kubicki, McCarley, Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Neuroimage 2002;17:1711–1719. http://dx.doi.org/10.1016/j.biotechadv.2011.08.021.Secreted.CrossRefGoogle ScholarPubMed
Adriano, FCaltagirone, CSpalletta, GHippocampal volume reduction in first-episode and chronic schizophrenia: a review and meta-analysis. Neuroscientist 2012;18:180–200. http://dx.doi.org/10.1177/1073858410395147.CrossRefGoogle Scholar
Barbas, HBlatt, GJTopographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey. Hippocampus 1995;5:511–533. http://dx.doi.org/10.1002/hipo.450050604.CrossRefGoogle ScholarPubMed
Goldman-Rakic, PSSelemon, LDSchwartz, MLDual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey. Neuroscience 1984;12:719–743.CrossRefGoogle ScholarPubMed
Schobel, SALewandowski, NMCorcoran, CMMoore, HBrown, TMalaspina, D, et al.Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch Gen Psychiatry 2009;66:938–946. http://dx.doi.org/10.1001/archgenpsychiatry.2009.115.CrossRefGoogle ScholarPubMed
Talati, PRane, SKose, SBlackford, JUGore, JDonahue, MJ, et al.Increased hippocampal CA1 cerebral blood volume in schizophrenia. NeuroImage Clin 2014;5:359–364. http://dx.doi.org/10.1016/j.nicl.2014.07.004.CrossRefGoogle Scholar
Ho, B.-C.Magnotta, VHippocampal volume deficits and shape deformities in young biological relatives of schizophrenia probands. Neuroimage 2010;49:3385–3393. http://dx.doi.org/10.1016/j.neuroimage.2009.11.033.CrossRefGoogle ScholarPubMed
Tepest, RWang, LMiller, MIFalkai, PCsernansky, JGHippocampal deformities in the unaffected siblings of schizophrenia subjects. Biol Psychiatry 2003;54:1234–1240. http://dx.doi.org/10.1016/S0006-3223(03)00702-9.CrossRefGoogle ScholarPubMed
Blaha, CDYang, CRFloresco, SBBarr, AMPhillips, AGStimulation of the ventral subiculum of the hippocampus evokes glutamate receptor-mediated changes in dopamine efflux in the rat nucleus accumbens. Eur J Neurosci 1997;9:902–911. http://dx.doi.org/10.1111/j.1460-9568.1997.tb01441.x.CrossRefGoogle ScholarPubMed
Legault, MWise, RAInjections of N-methyl-D-aspartate into the ventral hippocampus increase extracellular dopamine in the ventral tegmental area and nucleus accumbens. Synapse 1999;31:241–249 [doi:10.1002/(SICI)1098-2396(19990315)31:4<241:AID-SYN1>3.0.CO;2-#].3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Lodge, DJGrace, AAHippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia. Trends Pharmacol Sci 2011;32:507–513. http://dx.doi.org/10.1016/j.tips.2011.05.001.CrossRefGoogle ScholarPubMed
Grace, AADopamine system dysregulation by the hippocampus: implications for the pathophysiology and treatment of schizophrenia. Neuropharmacology 2012;62:1342–1348. http://dx.doi.org/10.1016/j.neuropharm.2011.05.011.CrossRefGoogle ScholarPubMed
Ewing, SGWinter, CThe ventral portion of the CA1 region of the hippocampus and the prefrontal cortex as candidate regions for neuromodulation in schizophrenia. Med Hypotheses 2013;80:827–832. http://dx.doi.org/10.1016/j.mehy.2013.03.026.CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.