Skip to main content Accessibility help
×
Home

Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan

  • N. Pujol (a1), R. Penadés (a2), C. Junqué (a3), I. Dinov (a4), C. H. Y. Fu (a5), R. Catalán (a6), N. Ibarretxe-Bilbao (a7), N. Bargalló (a8), M. Bernardo (a9), A. Toga (a4), R. J. Howard (a5) and S. G. Costafreda (a5)...

Abstract

Background

Hippocampal abnormalities have been demonstrated in schizophrenia. It is unclear whether these abnormalities worsen with age, and whether they affect cognition and function.

Aims

To determine whether hippocampal abnormalities in chronic schizophrenia are associated with age, cognition and socio-occupational function.

Method

Using 3 T magnetic resonance imaging we scanned 100 persons aged 19–82 years: 51 were out-patients with stable schizophrenia at least 2 years after diagnosis and 49 were healthy volunteers matched for age and gender. Automated analysis was used to determine hippocampal volume and shape.

Results

There were differential effects of age in the schizophrenia and control samples on total hippocampal volume (group×age interaction: F (1,95) = 6.57, P = 0.012), with steeper age-related reduction in the schizophrenia group. Three-dimensional shape analysis located the age-related deformations predominantly in the mid-body of the hippocampus. In the schizophrenia group similar patterns of morphometric abnormalities were correlated with impaired cognition and poorer socio-occupational function.

Conclusions

Hippocampal abnormalities are associated with age in people with chronic schizophrenia, with a steeper decline than in healthy individuals. These abnormalities are associated with cognitive and functional deficits, suggesting that hippocampal morphometry may be a biomarker for cognitive decline in older patients with schizophrenia.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan
      Available formats
      ×

Copyright

Corresponding author

Dr Sergi G. Costafreda, Institute of Psychiatry, De Crespigny Park, PO Box 70, London SE5 8AF, UK. Email: sergi.1.costafreda@kcl.ac.uk

Footnotes

Hide All

Declaration of interest

None.

Footnotes

References

Hide All
1 Tamminga, CA Stan, AD Wagner, AD The hippocampal formation in schizophrenia. Am J Psychiatry 2010; 167: 1178–93.
2 Small, SA Schobel, SA Buxton, RB Witter, MP, Barnes, CA A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nat Rev Neurosci 2011; 12: 585601.
3 Adriano, F Caltagirone, C Spalletta, G Hippocampal volume reduction in first-episode and chronic schizophrenia: a review and meta-analysis. Neuroscientist 2012; 18: 180200.
4 Velakoulis, D Stuart, GW Wood, SJ Smith, DJ Brewer, WJ Desmond, P, et al. Selective bilateral hippocampal volume loss in chronic schizophrenia. Biol Psychiatry 2001; 50: 531–9.
5 Narr, KL Thompson, PM Szeszko, P Robinson, D Jang, S Woods, RP, et al. Regional specificity of hippocampal volume reductions in first-episode schizophrenia. Neuroimage 2004; 21: 1563–75.
6 Velakoulis, D Wood, SJ Wong, MT McGorry, PD Yung, A Phillips, L, 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: 139–49.
7 Chakos, MH Schobel, SA Gu, H Gerig, G Bradford, D Charles, C, et al. Duration of illness and treatment effects on hippocampal volume in male patients with schizophrenia. Br J Psychiatry 2005; 186: 2631.
8 Wood, SJ Velakoulis, D Smith, DJ Bond, D Stuart, GW McGorry, PD, et al. A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia. Schizophr Res 2001; 52: 3746.
9 Koolschijn, PC van, Haren NE Cahn, W Schnack, HG Janssen, J Klumpers, F et al. Hippocampal volume change in schizophrenia. J Clin Psychiatry 2010; 71: 737–44.
10 Arnold, SE. Contributions of neuropathology to understanding schizophrenia in late life. Harv Rev Psychiatry 2001; 9: 6976.
11 Arnold, SE Trojanowski, JQ Gur, RE Blackwell, P Han, L, Choi, C Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia. Arch Gen Psychiatry 1998; 55: 225–32.
12 Costafreda, SG Dinov, ID Tu, Z Shi, Y Liu, CY Kloszewska, I, et al. Automated hippocampal shape analysis predicts the onset of dementia in mild cognitive impairment. Neuroimage 2011; 56: 212–9.
13 First, MB Spitzer, RL Gibbon, M Williams, JBW Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P) Biometrics Research, New York State Psychiatric Institute, 2002.
14 First, MB Spitzer, RL Gibbon, M Williams, JBW Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP). Biometrics Research, New York State Psychiatric Institute, 2002.
15 Wechsler, D. Wechsler Adult Intelligence Scale – Revised. TEA Ediciones, 1981.
16 Rey, A. L'Examen Clinique en Psychologie. Press Universitaire de France, 1964.
17 Lobo, A Saz, P Marcos, G Día, JL de, la Cámara C Ventura, T et al. Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-Mental Status Examination) in the general geriatric population. Med Clin (Barc) 1999; 112: 767–74.
18 Pfeffer, RI Kurosaki, TT Harrah, CH Chance, JM, Filos, S Measurement of functional activities in older adults in the community. J Gerontol 1982; 37: 323–9.
19 Kay, SR Fiszbein, A Vital-Herne, M Fuentes, LS The Positive and Negative Syndrome Scale – Spanish adaptation. J Nerv Ment Dis 1990; 178: 510–7.
20 Morra, JH Tu, Z Apostolova, LG Green, AE Avedissian, C Madsen, SK, et al. Validation of a fully automated 3D hippocampal segmentation method using subjects with Alzheimer's disease mild cognitive impairment, and elderly controls. Neuroimage 2008; 43: 5968.
21 Fischl, B. Freesurfer. Neuroimage 2012; 62: 774–81.
22 Shi, Y Thompson, PM de Zubicaray, GI Rose, SE Tu, Z Dinov, I et al. Direct mapping of hippocampal surfaces with intrinsic shape context. Neuroimage 2007; 37: 792807.
23 Noble, KG Grieve, SM Korgaonkar, MS Engelhardt, LE Griffith, EY Williams, LM, et al. Hippocampal volume varies with educational attainment across the lifespan. Front Hum Neurosci 2012; 6: 307.
24 Sobel, ME. Asymptotic confidence intervals for indirect effects in structural equation models. Sociol Method 1982; 13: 290312.
25 Friston, KJ Holmes, A Poline, JB Price, CJ, Frith, CD Detecting activations in PET and fMRI: levels of inference and power. Neuroimage 1996; 4: 223–35.
26 Anderson, M Robinson, J. Permutation tests for linear models. Aust NZ J Stat 2001; 43: 7588.
27 West, MJ. Stereological studies of the hippocampus: a comparison of the hippocampal subdivisions of diverse species including hedgehogs, laboratory rodents, wild mice and men. Prog Brain Psychiatry Res 1998; 84: 7588.
28 Csernansky, JG Wang, L Swank, J Miller, JP Gado, M McKeel, D, et al. Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly. Neuroimage 2005; 25: 783–92.
29 Yushkevich, PA Avants, BB Pluta, J Das, S Minkoff, D, Mechanic-Hamilton, D et al. A high-resolution computational atlas of the human hippocampus from postmortem magnetic resonance imaging at 9.4 T. Neuroimage 2009; 44: 385–98.
30 DeLisi, LE Sakuma, M Ge, S, Kushner, M Association of brain structural change with the heterogeneous course of schizophrenia from early childhood through five years subsequent to a first hospitalization. Schizophr Res 2001; 83: 1336.
31 Friedman, JI Harvey, PD Coleman, T Moriarty, PJ Bowie, C Parrella, M, et al. Six-year follow-up study of cognitive and functional status across the lifespan in schizophrenia: a comparison with Alzheimer's disease and normal aging. Am J Psychiatry 2001; 158: 1441–8.
32 Schuster, C Schuller, AM Paulos, C Namer, I Pull, C Danion, JM, et al. Gray matter volume decreases in elderly patients with schizophrenia: a voxel-based morphometry study. Schizophr Bull 2012; 38: 796802.
33 Prestia, A Boccardi, M Galluzzi, S Cavedo, E Adorni, A Soricelli, A, et al. Hippocampal and amygdalar volume changes in elderly patients with Alzheimer's disease and schizophrenia. Psychiatry Res 2011; 192: 7783.
34 Rapp, MA Schnaider-Beeri, M Purohit, DP Reichenberg, A McGurk, SR Haroutunian, V, et al. Cortical neurotic plaques and hippocampal neurofibrillary tangles are related to dementia in elderly schizophrenia patients. Schizophr Res 2010; 116: 90–6.
35 Casanova, MF Stevens, JR Brown, R Royston, C, Bruton, C Disentangling the pathology of schizophrenia and paraphrenia. Acta Neuropathol 2002; 103: 313–20.
36 Posener, JA Wang, L Price, JL Gado, MH Province, MA Miller, MI, et al. High-dimensional mapping of the hippocampus in depression. Am J Psychiatry 2003; 160: 83–9.
37 Cole, J Toga, AW Hojatkashani, C Thompson, P Costafreda, SG Cleare, AJ, et al. Subregional hippocampal deformations in major depressive disorder. J Affect Disord 2010; 126: 272–7.
38 Velakoulis, D Pantelis, C McGorry, PD Dudgeon, P Brewer, W Cook, M, et al. Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study. Arch Gen Psychiatry 1999; 56: 133–41.
39 Pantelis, D Velakoulis, J Suckling, PD McGorry, LJ Phillips, AR Yung, SJ, et al. Left medial temporal volume reduction occurs during the transition from high-risk to first-episode psychosis. Schizophr Res 2000; 41: 35.
40 Lipska, BK Weinberger, DR. A neurodevelopmental model of schizophrenia: neonatal disconnection of the hippocampus. Neurotox Res 2002; 4: 469–75.
41 Thompson, PM Hayashi, KM De Zubicaray, GI Janke, AL Rose, SE Semple, J, et al. Mapping hippocampal and ventricular change in Alzheimer disease. Neuroimage 2004; 22: 1754–66.
42 Penadés, R Boget, T Catalán, R Bernardo, M Gastó, C Salamero, M Cognitive mechanisms, psychosocial functioning, and neurocognitive rehabilitation in schizophrenia. Schizophr Res 2003; 63: 219–27.
43 Green, MF. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry 2006; 67: e12.
44 Panenka, WJ Khorram, B Barr, AM Smith, GN Lang, DJ Kopala, LC, et al. A longitudinal study on the effects of typical versus atypical antipsychotic drugs on hippocampal volume in schizophrenia. Schizophr Res 2007; 94: 288–92.
45 Ebdrup, BH Skimminge, A Rasmussen, H Aggernaes, B Oranje, B Lublin, H, et al. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. Int J Neuropsychopharmacol 2011; 14: 6982.
46 Vernon, AC Natesan, S Modo, M Kapur, S Effect of chronic antipsychotic treatment on brain structure: a serial magnetic resonance imaging study with ex vivo and postmortem confirmation. Biol Psychiatry 2011; 69: 936–44.
Type Description Title
PDF
Supplementary materials

Pujol et al. supplementary material
Supplementary Material

 PDF (187 KB)
187 KB

Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan

  • N. Pujol (a1), R. Penadés (a2), C. Junqué (a3), I. Dinov (a4), C. H. Y. Fu (a5), R. Catalán (a6), N. Ibarretxe-Bilbao (a7), N. Bargalló (a8), M. Bernardo (a9), A. Toga (a4), R. J. Howard (a5) and S. G. Costafreda (a5)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan

  • N. Pujol (a1), R. Penadés (a2), C. Junqué (a3), I. Dinov (a4), C. H. Y. Fu (a5), R. Catalán (a6), N. Ibarretxe-Bilbao (a7), N. Bargalló (a8), M. Bernardo (a9), A. Toga (a4), R. J. Howard (a5) and S. G. Costafreda (a5)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *