Hostname: page-component-6766d58669-nqrmd Total loading time: 0 Render date: 2026-05-19T15:22:40.741Z Has data issue: false hasContentIssue false
  • English
  • Français

A voxel- and source-based morphometry analysis of grey matter volume differences in very-late-onset schizophrenia-like psychosis

Published online by Cambridge University Press:  14 August 2023

Lies Van Assche ,
Akihiro Takamiya Open the ORCID record for Akihiro Takamiya [Opens in a new window] ,
Jan Van den Stock ,
Luc Van de Ven ,
Patrick Luyten ,
Louise Emsell  and
Mathieu Vandenbulcke
Lies Van Assche
Affiliation:
Geriatric Psychiatry, University Psychiatric Center KU Leuven, Leuven, Belgium Neuropsychiatry, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
Akihiro Takamiya*
Affiliation:
Neuropsychiatry, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
Jan Van den Stock
Affiliation:
Geriatric Psychiatry, University Psychiatric Center KU Leuven, Leuven, Belgium Neuropsychiatry, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
Luc Van de Ven
Affiliation:
Geriatric Psychiatry, University Psychiatric Center KU Leuven, Leuven, Belgium
Patrick Luyten
Affiliation:
Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium Research Department of Clinical Educational and Health Psychology, University College London, London, UK
Louise Emsell
Affiliation:
Geriatric Psychiatry, University Psychiatric Center KU Leuven, Leuven, Belgium Neuropsychiatry, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium Translational MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
Mathieu Vandenbulcke
Affiliation:
Geriatric Psychiatry, University Psychiatric Center KU Leuven, Leuven, Belgium Neuropsychiatry, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
*
Corresponding author: Akihiro Takamiya; Email: akihiro.takamiya@kuleuven.be
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Very-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores.

Methods

In this cross-sectional study, we investigated whole-brain GMV differences between 35 individuals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated relationships between GMV differences and cognitive function assessed with an extensive neuropsychological battery.

Results

VBM showed lower GMV in the thalamus, left inferior frontal gyrus and left insula in patients with VLOSLP compared to healthy controls. SBM revealed lower thalamo-temporal GMV in patients with VLOSLP. Processing speed, selective attention, mental flexibility, working memory, verbal memory, semantic fluency and confrontation naming were impaired in patients with VLOSLP. Correlations between thalamic volumes and memory function were significant within the group of individuals with VLOSLP, whereas no significant associations remained in the healthy controls.

Conclusions

Lower GMV in the thalamus and fronto-temporal regions may be part of the underlying neurobiology of VLOSLP, with lower thalamic GMV contributing to memory impairment in the disorder.

Keywords

Late onset psychosisMRIneuroimagingneuropsychology

Information

Type
Original Article
Information
Psychological Medicine , Volume 54 , Issue 3 , February 2024 , pp. 592 - 600
Check for updates
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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.)

Article purchase

Temporarily unavailable

Footnotes

*

Shared first authorship

References

Aleman, A., Hijman, R., de Haan, E. H., & Kahn, R. S. (1999). Memory impairment in schizophrenia: A meta-analysis. The American Journal of Psychiatry, 156(9), 1358–1366. doi:10.1176/ajp.156.9.1358.Google Scholar
Almeida, O. P., Howard, R., Levy, R., David, A. S., Morris, R. G., & Sahakian, B. J. (1995a). Clinical and cognitive diversity of psychotic states arising in late life (late paraphrenia). Psychological Medicine, 25(4), 699–714.Google Scholar
Almeida, O. P., Howard, R., Levy, R., David, A. S., Morris, R. G., & Sahakian, B. J. (1995b). Cognitive features of psychotic states arising in late life (late paraphrenia). Psychological Medicine, 25(4), 685–698.Google Scholar
Andrews, J., Wang, L., Csernansky, J. G., Gado, M. H., & Barch, D. M. (2006). Abnormalities of thalamic activation and cognition in schizophrenia. The American Journal of Psychiatry, 163(3), 463–469. doi:10.1176/appi.ajp.163.3.463.Google Scholar
Baker, J. T., Sanders, A. L., Maccotta, L., & Buckner, R. L. (2001). Neural correlates of verbal memory encoding during semantic and structural processing tasks. Neuroreport, 12(6), 1251–1256. doi:10.1097/00001756-200105080-00039.Google Scholar
Barak, Y., Aizenberg, D., Mirecki, I., Mazeh, D., & Achiron, A. (2002). Very late-onset schizophrenia-like psychosis: Clinical and imaging characteristics in comparison with elderly patients with schizophrenia. Journal of Nervous and Mental Disease, 190(11), 733–736. doi:10.1097/01.nmd.0000038167.15155.d6.Google Scholar
Barta, P. E., Powers, R. E., Aylward, E. H., Chase, G. A., Harris, G. J., Rabins, P. V., … Pearlson, G. D. (1997). Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls. Psychiatry Research, 68(2–3), 65–75.Google Scholar
Behrens, T. E., Johansen-Berg, H., Woolrich, M. W., Smith, S. M., Wheeler-Kingshott, C. A., Boulby, P. A., … Matthews, P. M. (2003). Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nature Neuroscience, 6(7), 750–757. doi:10.1038/nn1075.CrossRefGoogle ScholarPubMed
Benton, A. L. (1968). Differential behavioral effects in frontal lobe disease. Neuropsychologia, 6(1), 53–60.Google Scholar
Brichant-Petitjean, C., Legauffre, C., Ramoz, N., Ades, J., Gorwood, P., & Dubertret, C. (2013). Memory deficits in late-onset schizophrenia. Schizophrenia Research, 151(1–3), 85–90. doi:10.1016/j.schres.2013.08.021.CrossRefGoogle ScholarPubMed
Casanova, M. F. (2010). The pathology of paraphrenia. Current Psychiatry Reports, 12(3), 196–201. doi:10.1007/s11920-010-0108-8.Google Scholar
Cho, K. I. K., Kwak, Y. B., Hwang, W. J., Lee, J., Kim, M., Lee, T. Y., & Kwon, J. S. (2019). Microstructural changes in higher-order nuclei of the thalamus in patients with first-episode psychosis. Biological Psychiatry, 85(1), 70–78. doi:10.1016/j.biopsych.2018.05.019.Google Scholar
Coltheart, M. (2010). The neuropsychology of delusions. Annals of the New York Academy of Sciences, 1191, 16–26. doi:10.1111/j.1749-6632.2010.05496.x.Google Scholar
Copeland, J. R., Dewey, M. E., Scott, A., Gilmore, C., Larkin, B. A., Cleave, N., … McKibbin, P. E. (1998). Schizophrenia and delusional disorder in older age: Community prevalence, incidence, comorbidity, and outcome. Schizophrenia Bulletin, 24(1), 153–161. doi:10.1093/oxfordjournals.schbul.a033307.Google Scholar
Corey-Bloom, J., Jernigan, T., Archibald, S., Harris, M. J., & Jeste, D. V. (1995). Quantitative magnetic resonance imaging of the brain in late-life schizophrenia. The American Journal of Psychiatry, 152(3), 447–449. doi:10.1176/ajp.152.3.447.Google Scholar
Coscia, D., Narr, K., Robinson, D., Hamilton, L., Sevy, S., Burdick, K., … Szeszko, P. (2009). Volumetric and shape analysis of the thalamus in first-episode schizophrenia. Human Brain Mapping, 30, 1236–1245. doi:10.1002/hbm.20595.Google Scholar
Crespo-Facorro, B., Roiz-Santiáñez, R., Pelayo-Terán, J. M., Rodríguez-Sánchez, J. M., Pérez-Iglesias, R., González-Blanch, C., … Vázquez-Barquero, J. L. (2007). Reduced thalamic volume in first-episode non-affective psychosis: Correlations with clinical variables, symptomatology and cognitive functioning. NeuroImage, 35(4), 1613–1623. doi:10.1016/j.neuroimage.2007.01.048.Google Scholar
Doughty, O. J., & Done, D. J. (2009). Is semantic memory impaired in schizophrenia? A systematic review and meta-analysis of 91 studies. Cognitive Neuropsychiatry, 14(6), 473–509. doi:10.1080/13546800903073291.Google Scholar
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198. doi:10.1016/0022-3956(75)90026-6.Google Scholar
Frangou, S. (2010). Cognitive function in early onset schizophrenia: A selective review. Frontiers in Human Neuroscience, 3(79). doi:10.3389/neuro.09.079.2009.Google Scholar
Frangou, S., Hadjulis, M., & Vourdas, A. (2007). The Maudsley early onset schizophrenia study: Cognitive function over a 4-year follow-up period. Schizophrenia Bulletin, 34(1), 52–59. doi:10.1093/schbul/sbm124.Google Scholar
Georgescu, I. A., Popa, D., & Zagrean, L. (2020). The anatomical and functional heterogeneity of the mediodorsal thalamus. Brain Sciences, 10(9). doi:10.3390/brainsci10090624.Google Scholar
Girard, C., Simard, M., Noiseux, R., Laplante, L., Dugas, M., Rousseau, F., … Bernier, P. J. (2011). Late-onset-psychosis: Cognition. International Psychogeriatrics, 23(8), 1301–1316. doi:10.1017/s1041610211000238.Google Scholar
Goodglass, H., Kaplan, E., & Weintraub, S. (1983). Boston naming test. Philadelphia, PA: Lea & Febiger.Google Scholar
Guimond, S., Chakravarty, M. M., Bergeron-Gagnon, L., Patel, R., & Lepage, M. (2015). Verbal memory impairments in schizophrenia associated with cortical thinning. NeuroImage, 11, 20–29. doi:10.1016/j.nicl.2015.12.010.Google Scholar
Gupta, C. N., Calhoun, V. D., Rachakonda, S., Chen, J., Patel, V., Liu, J., … Turner, J. A. (2015). Patterns of gray matter abnormalities in schizophrenia based on an international mega-analysis. Schizophrenia Bulletin, 41, 1133–1142.Google Scholar
Hagino, H., Suzuki, M., Mori, K., Nohara, S., Yamashita, I., Takahashi, T., … Kurachi, M. (2002). Proton magnetic resonance spectroscopy of the inferior frontal gyrus and thalamus and its relationship to verbal learning task performance in patients with schizophrenia: A preliminary report. [10.1046/j.1440-1819.2002.01045.x]. Psychiatry and Clinical Neurosciences, 56(5), 499–507. doi:10.1046/j.1440-1819.2002.01045.x.Google Scholar
Hanssen, M., van der Werf, M., Verkaaik, M., Arts, B., Myin-Germeys, I., van Os, J., … Kohler, S. (2015). Comparative study of clinical and neuropsychological characteristics between early-, late and very-late-onset schizophrenia-spectrum disorders. The American Journal of Geriatric Psychiatry, 23(8), 852–862. doi:10.1016/j.jagp.2014.10.007.Google Scholar
Heaton, R., Paulsen, J. S., McAdams, L. A., Kuck, J., Zisook, S., Braff, D., … Jeste, D. V. (1994). Neuropsychological deficits in schizophrenics. Relationship to age, chronicity, and dementia. Archives of General Psychiatry, 51(6), 469–476. doi:10.1001/archpsyc.1994.03950060033003.Google Scholar
Henderson, A. S., Korten, A. E., Levings, C., Jorm, A. F., Christensen, H., Jacomb, P. A., & Rodgers, B. (1998). Psychotic symptoms in the elderly: A prospective study in a population sample. International Journal of Geriatric Psychiatry, 13(7), 484–492.Google Scholar
Himberg, J., Hyvärinen, A., & Esposito, F. (2004). Validating the independent components of neuroimaging time series via clustering and visualization. NeuroImage, 22, 1214–1222.Google Scholar
Howard, R., Förstl, H., Almeida, O., Burns, A., & Levy, R. (1992a). Computer-assisted CT measurements in late paraphrenics with and without Schneiderian first-rank symptoms: A preliminary report. International Journal of Geriatric Psychiatry, 7(1), 35–38. doi:10.1002/gps.930070106.Google Scholar
Howard, R., Förstl, H., Naguib, M., Burns, A., & Levy, R. (1992b). First-rank symptoms of Schneider in late paraphrenia. Cortical structural correlates. The British Journal of Psychiatry, 160, 108–109.Google Scholar
Howard, R., Rabins, P. V., Seeman, M. V., Jeste, D. V., & The International Late-Onset Schizophrenia Group. (2000). Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: An international consensus. The American Journal of Psychiatry, 157(2), 172–178. doi:10.1176/appi.ajp.157.2.172.Google Scholar
Huang, A. S., Rogers, B. P., Sheffield, J. M., Jalbrzikowski, M. E., Anticevic, A., Blackford, J. U., … Woodward, N. D. (2020). Thalamic nuclei volumes in psychotic disorders and in youths with psychosis spectrum symptoms. The American Journal of Psychiatry, 177(12), 1159–1167. https://doi.org/10.1176/appi.ajp.2020.19101099.Google Scholar
Jellinger, K. A. (2012). Cerebral correlates of psychotic syndromes in neurodegenerative diseases. Journal of Cellular and Molecular Medicine, 16(5), 995–1012. doi:10.1111/j.1582-4934.2011.01311.x.Google Scholar
Jeste, D. V., Harris, M. J., Krull, A., Kuck, J., McAdams, L. A., & Heaton, R. (1995). Clinical and neuropsychological characteristics of patients with late-onset schizophrenia. The American Journal of Psychiatry, 152(5), 722–730. doi:10.1176/ajp.152.5.722.Google Scholar
Jones, G., & Macken, B. (2015). Questioning short-term memory and its measurement: Why digit span measures long-term associative learning. Cognition, 144, 1–13. doi:10.1016/j.cognition.2015.07.009.Google Scholar
Lesser, I. M., Miller, B. L., Swartz, J. R., Boone, K. B., Mehringer, C. M., & Mena, I. (1993). Brain imaging in late-life schizophrenia and related psychoses. Schizophrenia Bulletin, 19(4), 773–782.Google Scholar
Miller, G. A. (1956). The magical number seven, plus or minus two: Some limits on our capacity for processing information. Psychological Review, 63(2), 81–97. doi:10.1037/h0043158.Google Scholar
Naguib, M., & Levy, R. (1987). Late paraphrenia: Neuropsychological impairment and structural brain abnormalities on computed tomography. International Journal of Geriatric Psychiatry, 2(2), 83–90. doi:10.1002/gps.930020205.Google Scholar
Östling, S., Johansson, B., & Skoog, I. (2004). Cognitive test performance in relation to psychotic symptoms and paranoid ideation in non-demented 85-year-olds. Psychological Medicine, 34(3), 443–450. doi:10.1017/S0033291703001144.Google Scholar
Rabin, L. A., Paolillo, E., & Barr, W. B. (2016). Stability in test-usage practices of clinical neuropsychologists in the United States and Canada over a 10-year period: A follow-up survey of INS and NAN members. Archives of Clinical Neuropsychology, 31(3), 206–230. doi:10.1093/arclin/acw007.Google Scholar
Rabins, P., Aylward, E., Holroyd, S., & Pearlson, G. (2000). MRI findings differentiate between late-onset schizophrenia and late-life mood disorder. International Journal of Geriatric Psychiatry, 15(10), 954–960.Google Scholar
Rabins, P., Pearlson, G., Jayaram, G., Steele, C., & Tune, L. (1987). Increased ventricle-to-brain ratio in late-onset schizophrenia. The American Journal of Psychiatry, 144(9), 1216–1218. doi:10.1176/ajp.144.9.1216.Google Scholar
Rey, A. (1964). L'examen clinique en psychologie. Paris: Universitaires de France.Google Scholar
Sachdev, P., Brodaty, H., Cheang, D., & Cathcart, S. (2000). Hippocampus and amygdala volumes in elderly schizophrenic patients as assessed by magnetic resonance imaging. Psychiatry and Clinical Neurosciences, 54(1), 105–112. doi:10.1046/j.1440-1819.2000.00644.x.Google Scholar
Sharma, E. R., Debsikdar, A. V., Naphade, N. M., & Shetty, J. V. (2014). Very late-onset schizophrenia like psychosis: Case series and future directions. Indian Journal of Psychological Medicine, 36(2), 208–210. doi:10.4103/0253-7176.130999.Google Scholar
Sheffield, J. M., Huang, A. S., Rogers, B. P., Giraldo-Chica, M., Landman, B. A., Blackford, J. U., … Woodward, N. D. (2020). Thalamocortical anatomical connectivity in schizophrenia and psychotic bipolar disorder. Schizophrenia Bulletin, 46(5), 1062–1071. doi:10.1093/schbul/sbaa022.Google Scholar
Smith, S. M., & Nichols, T. E. (2009). Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference. NeuroImage, 44(1), 83–98. doi:10.1016/j.neuroimage.2008.03.061.Google Scholar
Strauss, E., Sherman, E., & Spreen, O. (2006). A compendium of neuropsychological tests. New York: Oxford University Press.Google Scholar
Stroop, J. R. (1935). Studies of interference in serial verbal reactions. Journal of Experimental Psychology, 18, 643–662.Google Scholar
Swick, D., Ashley, V., & Turken, A. U. (2008). Left inferior frontal gyrus is critical for response inhibition. BMC Neuroscience, 9, 102. doi:10.1186/1471-2202-9-102.Google Scholar
Tops, M., & Boksem, M. A. S. (2011). A potential role of the inferior frontal gyrus and anterior insula in cognitive control, brain rhythms, and event-related potentials. Frontiers in Psychology, 2, 330. doi:10.3389/fpsyg.2011.00330.Google Scholar
Vahia, I. V., Palmer, B. W., Depp, C., Fellows, I., Golshan, S., Kraemer, H. C., & Jeste, D. V. (2010). Is late-onset schizophrenia a subtype of schizophrenia? Acta Psychiatrica Scandinavica, 122(5), 414–426. doi:10.1111/j.1600-0447.2010.01552.x.Google Scholar
Van Assche, L., Morrens, M., Luyten, P., Van de Ven, L., & Vandenbulcke, M. (2017). The neuropsychology and neurobiology of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: A critical review. Neuroscience & Biobehavioral Reviews, 83, 604–621. doi:10.1016/j.neubiorev.2017.08.024.Google Scholar
Van der Elst, W., Van Boxtel, M. P., Van Breukelen, G. J., & Jolles, J. (2006). The Stroop color-word test: Influence of age, sex, and education; and normative data for a large sample across the adult age range. Assessment, 13(1), 62–79. doi:10.1177/1073191105283427.Google Scholar
Van der Werf, Y. D., Scheltens, P., Lindeboom, J., Witter, M. P., Uylings, H. B., & Jolles, J. (2003). Deficits of memory, executive functioning and attention following infarction in the thalamus: A study of 22 cases with localised lesions. Neuropsychologia, 41(10), 1330–1344. doi:10.1016/s0028-3932(03)00059-9.Google Scholar
Van der Werf, Y. D., Witter, M. P., Uylings, H. B., & Jolles, J. (2000). Neuropsychology of infarctions in the thalamus: A review. Neuropsychologia, 38(5), 613–627. doi:10.1016/s0028-3932(99)00104-9.Google Scholar
van Os, J., Howard, R., Takei, N., & Murray, R. (1995). Increasing age is a risk factor for psychosis in the elderly. Social Psychiatry and Psychiatric Epidemiology, 30(4), 161–164.Google Scholar
Xu, L., Groth, K. M., Pearlson, G., Schretlen, D. J., & Calhoun, V. D. (2009). Source-based morphometry: The use of independent component analysis to identify gray matter differences with application to schizophrenia. Human Brain Mapping, 30(3), 711–724.Google Scholar
Zakzanis, K. K., Kielar, A., Young, D. A., & Boulos, M. (2001). Neuropsychological differentiation of late onset schizophrenia and frontotemporal dementia. Cognitive Neuropsychiatry, 6(1), 63–77. doi:10.1080/13546800042000052.Google Scholar
Supplementary material: File

S0033291723002258sup001.docx

Van Assche et al. supplementary material

Download S0033291723002258sup001.docx(File)
File 638.3 KB