Hostname: page-component-8448b6f56d-xtgtn Total loading time: 0 Render date: 2024-04-17T23:28:20.444Z Has data issue: false hasContentIssue false
  • English
  • Français

Hippocampal volume change relates to clinical outcome in childhood-onset schizophrenia

Published online by Cambridge University Press:  04 May 2015

A. A. Anvari ,
L. A. Friedman ,
D. Greenstein ,
P. Gochman ,
N. Gogtay  and
J. L. Rapoport
A. A. Anvari*
Affiliation:
Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
L. A. Friedman
Affiliation:
Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
D. Greenstein
Affiliation:
Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
P. Gochman
Affiliation:
Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
N. Gogtay
Affiliation:
Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
J. L. Rapoport
Affiliation:
Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
*
*Address for correspondence: A. A. Anvari, B.S., Child Psychiatry Branch, National Institute of Mental Health, Building 10, Room 3N202, 10 Center Drive, Bethesda, MD 20892-1600, USA. (Email: afsoon@anvari.net)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Fixed hippocampal volume reductions and shape abnormalities are established findings in schizophrenia, but the relationship between hippocampal volume change and clinical outcome has been relatively unexplored in schizophrenia and other psychotic disorders. In light of recent findings correlating hippocampal volume change and clinical outcome in first-episode psychotic adults, we hypothesized that fewer decreases in hippocampal volume would be associated with better functional outcome and fewer psychotic symptoms in our rare and chronically ill population of childhood-onset schizophrenia (COS) patients.

Method

We prospectively obtained 114 structural brain magnetic resonance images (MRIs) from 27 COS subjects, each with three or more scans between the ages of 10 and 30 years. Change in hippocampal volume, measured by fit slope and percentage change, was regressed against clinical ratings (Children's Global Assessment Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms) at last scan (controlling for sex, time between scans and total intracranial volume).

Results

Fewer negative symptoms were associated with less hippocampal volume decrease (fit slope: p = 0.0003, and percentage change: p = 0.005) while positive symptoms were not related to hippocampal change. There was also a relationship between improved clinical global functioning and maintained hippocampal volumes (fit slope: p = 0.025, and percentage change: p = 0.043).

Conclusions

These results suggest that abnormal hippocampal development in schizophrenia can be linked to global functioning and negative symptoms. The hippocampus can be considered a potential treatment target for future therapies.

Keywords

Childhood-onset schizophreniahippocampusmagnetic resonance imagingnegative symptomspsychosis
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 12 , September 2015 , pp. 2667 - 2674
Copyright
Copyright © Cambridge University Press 2015 

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.)

References

Ambrosini, PJ, Metz, C, Prabucki, K, Lee, JC (1989). Videotape reliability of the third revised edition of the K-SADS. Journal of the American Academy of Child and Adolescent Psychiatry 28, 723–728.CrossRefGoogle ScholarPubMed
Andreasen, NC (1983). Scale for the Assessment of Negative Symptoms (SANS). University of Iowa: Iowa City.Google Scholar
Andreasen, NC (1984). Scale for the Assessment of Positive Symptoms (SAPS). University of Iowa: Iowa City.Google Scholar
Andreasen, NC, Olsen, S (1982). Negative v positive schizophrenia. Definition and validation. Archives of General Psychiatry 39, 789–794.CrossRefGoogle ScholarPubMed
Brambilla, P, Perlini, C, Rajagopalan, P, Saharan, P, Rambaldelli, G, Bellani, M, Dusi, N, Cerini, R, Pozzi Mucelli, R, Tansella, M, Thompson, PM (2013). Schizophrenia severity, social functioning and hippocampal neuroanatomy: three-dimensional mapping study. British Journal of Psychiatry 202, 50–55.CrossRefGoogle ScholarPubMed
Castellanos, FX, Giedd, JN, Marsh, WL, Hamburger, SD, Vaituzis, AC, Dickstein, DP, Sarfatti, SE, Vauss, YC, Snell, JW, Lange, N, Kaysen, D, Krain, AL, Ritchie, GF, Rajapakse, JC, Rapoport, JL (1996). Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Archives of General Psychiatry 53, 607–616.CrossRefGoogle ScholarPubMed
Chakos, MH, Schobel, SA, Gu, H, Gerig, G, Bradford, D, Charles, C, Lieberman, JA (2005). Duration of illness and treatment effects on hippocampal volume in male patients with schizophrenia. British Journal of Psychiatry 186, 26–31.CrossRefGoogle ScholarPubMed
Collip, D, Habets, P, Marcelis, M, Gronenschild, E, Lataster, T, Lardinois, M, Nicolson, NA, Myin-Germeys, I (2013). Hippocampal volume as marker of daily life stress sensitivity in psychosis. Psychological Medicine 43, 1377–1387.CrossRefGoogle ScholarPubMed
Csernansky, JG, Joshi, S, Wang, L, Haller, JW, Gado, M, Miller, JP, Grenander, U, Miller, MI (1998). Hippocampal morphometry in schizophrenia by high dimensional brain mapping. Proceedings of the National Academy of Sciences 95, 11406–11411.CrossRefGoogle ScholarPubMed
de Castro-Manglano, P, Mechelli, A, Soutullo, C, Landecho, I, Gimenez-Amaya, JM, Ortuno, F, McGuire, P (2011). Structural brain abnormalities in first-episode psychosis: differences between affective psychoses and schizophrenia and relationship to clinical outcome. Bipolar Disorders 13, 545–555.CrossRefGoogle ScholarPubMed
DeLisi, LE, Sakuma, M, Ge, S, Kushner, M (1998). Association of brain structural change with the heterogeneous course of schizophrenia from early childhood through five years subsequent to a first hospitalization. Psychiatry Research 84, 75–88.CrossRefGoogle ScholarPubMed
Fischl, B, Liu, A, Dale, AM (2001). Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex. IEEE Transactions on Medical Imaging 20, 70–80.CrossRefGoogle ScholarPubMed
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, 341–355.CrossRefGoogle ScholarPubMed
Fischl, B, Salat, DH, van der Kouwe, AJ, Makris, N, Segonne, F, Quinn, BT, Dale, AM (2004). Sequence-independent segmentation of magnetic resonance images. NeuroImage 23 (Suppl. 1), S69–S84.CrossRefGoogle ScholarPubMed
Giedd, JN, Jeffries, NO, Blumenthal, J, Castellanos, FX, Vaituzis, AC, Fernandez, T, Hamburger, SD, Liu, H, Nelson, J, Bedwell, J, Tran, L, Lenane, M, Nicolson, R, Rapoport, JL (1999). Childhood-onset schizophrenia: progressive brain changes during adolescence. Biological Psychiatry 46, 892–898.CrossRefGoogle ScholarPubMed
Gogtay, N, Nugent, TF III, Herman, DH, Ordonez, A, Greenstein, D, Hayashi, KM, Clasen, L, Toga, AW, Giedd, JN, Rapoport, JL, Thompson, PM (2006). Dynamic mapping of normal human hippocampal development. Hippocampus 16, 664–672.CrossRefGoogle ScholarPubMed
Gogtay, N, Sporn, A, Clasen, LS, Nugent, TF III, Greenstein, D, Nicolson, R, Giedd, JN, Lenane, M, Gochman, P, Evans, A, Rapoport, JL (2004). Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses. Archives of General Psychiatry 61, 17–22.CrossRefGoogle ScholarPubMed
Goldman, AL, Pezawas, L, Mattay, VS, Fischl, B, Verchinski, BA, Zoltick, B, Weinberger, DR, Meyer-Lindenberg, A (2008). Heritability of brain morphology related to schizophrenia: a large-scale automated magnetic resonance imaging segmentation study. Biological Psychiatry 63, 475–483.CrossRefGoogle ScholarPubMed
Grace, AA (2012). Dopamine system dysregulation by the hippocampus: implications for the pathophysiology and treatment of schizophrenia. Neuropharmacology 62, 1342–1348.CrossRefGoogle ScholarPubMed
Gur, RE, Cowell, P, Turetsky, BI, Gallacher, F, Cannon, T, Bilker, W, Gur, RC (1998). A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures. Archives of General Psychiatry 55, 145–152.CrossRefGoogle ScholarPubMed
Honea, R, Crow, TJ, Passingham, D, Mackay, CE (2005). Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. American Journal of Psychiatry 162, 2233–2245.CrossRefGoogle ScholarPubMed
Johnson, SL, Wang, L, Alpert, KI, Greenstein, D, Clasen, L, Lalonde, F, Miller, R, Rapoport, J, Gogtay, N (2013). Hippocampal shape abnormalities of patients with childhood-onset schizophrenia and their unaffected siblings. Journal of the American Academy of Child and Adolescent Psychiatry 52, 527–536 e2.CrossRefGoogle ScholarPubMed
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, N (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980–988.CrossRefGoogle ScholarPubMed
Lappin, JM, Morgan, C, Chalavi, S, Morgan, KD, Reinders, AA, Fearon, P, Heslin, M, Zanelli, J, Jones, PB, Murray, RM, Dazzan, P (2014). Bilateral hippocampal increase following first-episode psychosis is associated with good clinical, functional and cognitive outcomes. Psychological Medicine 44, 1279–1291.CrossRefGoogle ScholarPubMed
Lieberman, J, Chakos, M, Wu, H, Alvir, J, Hoffman, E, Robinson, D, Bilder, R (2001). Longitudinal study of brain morphology in first episode schizophrenia. Biological Psychiatry 49, 487–499.CrossRefGoogle ScholarPubMed
Lodge, DJ, Grace, AA (2011). Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia. Trends in Pharmacological Sciences 32, 507–513.CrossRefGoogle ScholarPubMed
Mattai, A, Hosanagar, A, Weisinger, B, Greenstein, D, Stidd, R, Clasen, L, Lalonde, F, Rapoport, J, Gogtay, N (2011). Hippocampal volume development in healthy siblings of childhood-onset schizophrenia patients. American Journal of Psychiatry 168, 427–435.CrossRefGoogle ScholarPubMed
McClure, RK, Styner, M, Maltbie, E, Lieberman, JA, Gouttard, S, Gerig, G, Shi, X, Zhu, H (2013). Localized differences in caudate and hippocampal shape are associated with schizophrenia but not antipsychotic type. Psychiatry Research 211, 1–10.CrossRefGoogle Scholar
McKenna, K, Gordon, CT, Lenane, M, Kaysen, D, Fahey, K, Rapoport, JL (1994). Looking for childhood-onset schizophrenia: the first 71 cases screened. Journal of the American Academy of Child and Adolescent Psychiatry 33, 636–644.CrossRefGoogle ScholarPubMed
Mondelli, V, Pariante, CM, Navari, S, Aas, M, D'Albenzio, A, Di Forti, M, Handley, R, Hepgul, N, Marques, TR, Taylor, H, Papadopoulos, AS, Aitchison, KJ, Murray, RM, Dazzan, P (2010). Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis. Schizophrenia Research 119, 75–78.CrossRefGoogle ScholarPubMed
Nelson, MD, Saykin, AJ, Flashman, LA, Riordan, HJ (1998). Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Archives of General Psychiatry 55, 433–440.CrossRefGoogle ScholarPubMed
Nicolson, R, Rapoport, JL (1999). Childhood-onset schizophrenia: rare but worth studying. Biological Psychiatry 46, 1418–1428.CrossRefGoogle ScholarPubMed
Nugent, TF III, Herman, DH, Ordonez, A, Greenstein, D, Hayashi, KM, Lenane, M, Clasen, L, Jung, D, Toga, AW, Giedd, JN, Rapoport, JL, Thompson, PM, Gogtay, N (2007). Dynamic mapping of hippocampal development in childhood onset schizophrenia. Schizophrenia Research 90, 62–70.CrossRefGoogle ScholarPubMed
Plessen, KJ, Bansal, R, Zhu, H, Whiteman, R, Amat, J, Quackenbush, GA, Martin, L, Durkin, K, Blair, C, Royal, J, Hugdahl, K, Peterson, BS (2006). Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder. Archives of General Psychiatry 63, 795–807.CrossRefGoogle ScholarPubMed
R Development Team (2012). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria.Google Scholar
Rogosa, DR, Willett, JB (1983). Demonstrating the reliability of the difference score in the measurement of change. Journal of Educational Measurement 20, 335–343.CrossRefGoogle Scholar
Segonne, F, Dale, AM, Busa, E, Glessner, M, Salat, D, Hahn, HK, Fischl, B (2004). A hybrid approach to the skull stripping problem in MRI. NeuroImage 22, 1060–1075.CrossRefGoogle Scholar
Segonne, F, Pacheco, J, Fischl, B (2007). Geometrically accurate topology-correction of cortical surfaces using nonseparating loops. IEEE Transactions on Medical Imaging 26, 518–529.CrossRefGoogle ScholarPubMed
Shaffer, D, Gould, MS, Brasic, J, Ambrosini, P, Fisher, P, Bird, H, Aluwahlia, S (1983). A Children's Global Assessment Scale (CGAS). Archives of General Psychiatry 40, 1228–1231.CrossRefGoogle ScholarPubMed
Singer, JD, Willett, JB (2003). Applied Longitudinal Data Analysis: Modeling Change and Event Occurrence. Oxford University Press: New York.CrossRefGoogle Scholar
Sporn, AL, Greenstein, DK, Gogtay, N, Jeffries, NO, Lenane, M, Gochman, P, Clasen, LS, Blumenthal, J, Giedd, JN, Rapoport, JL (2003). Progressive brain volume loss during adolescence in childhood-onset schizophrenia. American Journal of Psychiatry 160, 2181–2189.CrossRefGoogle ScholarPubMed
Sporn, AL, Vermani, A, Greenstein, DK, Bobb, AJ, Spencer, EP, Clasen, LS, Tossell, JW, Stayer, CC, Gochman, PA, Lenane, MC, Rapoport, JL, Gogtay, N (2007). Clozapine treatment of childhood-onset schizophrenia: evaluation of effectiveness, adverse effects, and long-term outcome. Journal of the American Academy of Child and Adolescent Psychiatry 46, 1349–1356.CrossRefGoogle ScholarPubMed
Velakoulis, D, Pantelis, C, McGorry, PD, Dudgeon, P, Brewer, W, Cook, M, Desmond, P, Bridle, N, Tierney, P, Murrie, V, Singh, B, Copolov, D (1999). Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study. Archives of General Psychiatry 56, 133–141.CrossRefGoogle ScholarPubMed
Velakoulis, D, Wood, SJ, Wong, MT, McGorry, PD, Yung, A, Phillips, L, Smith, D, Brewer, W, Proffitt, T, Desmond, P, Pantelis, C (2006). 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. Archives of General Psychiatry 63, 139–149.CrossRefGoogle ScholarPubMed
Walter, A, Studerus, E, Smieskova, R, Kuster, P, Aston, J, Lang, UE, Radue, EW, Riecher-Rossler, A, Borgwardt, S (2012). Hippocampal volume in subjects at high risk of psychosis: a longitudinal MRI study. Schizophrenia Research 142, 217–222.CrossRefGoogle ScholarPubMed
Willett, JB (1989). Some results on reliability for the longitudinal measurement of change: implications for the design of studies of individual growth. Educational and Psychological Measurement 49, 587–602.CrossRefGoogle Scholar
Wright, IC, Rabe-Hesketh, S, Woodruff, PW, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 16–25.CrossRefGoogle ScholarPubMed
Zierhut, KC, Grassmann, R, Kaufmann, J, Steiner, J, Bogerts, B, Schiltz, K (2013). Hippocampal CA1 deformity is related to symptom severity and antipsychotic dosage in schizophrenia. Brain 136, 804–814.CrossRefGoogle ScholarPubMed
Zipursky, RB, Reilly, TJ, Murray, RM (2013). The myth of schizophrenia as a progressive brain disease. Schizophrenia Bulletin 39, 1363–1372.CrossRefGoogle ScholarPubMed
Supplementary material: File

Anvari supplementary material

Tables S1-S4

Download Anvari supplementary material(File)
File 19.6 KB
Supplementary material: File

Anvari supplementary material

Appendix

Download Anvari supplementary material(File)
File 65.1 KB