Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-23T23:09:38.294Z Has data issue: false hasContentIssue false

Bilateral hippocampal increase following first-episode psychosis is associated with good clinical, functional and cognitive outcomes

Published online by Cambridge University Press:  18 July 2013

J. M. Lappin*
Affiliation:
Institute of Psychiatry, King's College London, London, UK
C. Morgan
Affiliation:
Institute of Psychiatry, King's College London, London, UK
S. Chalavi
Affiliation:
Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
K. D. Morgan
Affiliation:
Department of Psychology, University of Westminster, London, UK
A. A. T. S. Reinders
Affiliation:
Institute of Psychiatry, King's College London, London, UK
P. Fearon
Affiliation:
Department of Psychiatry, Trinity College Dublin, Dublin, Republic of Ireland
M. Heslin
Affiliation:
Institute of Psychiatry, King's College London, London, UK
J. Zanelli
Affiliation:
Institute of Psychiatry, King's College London, London, UK
P. B. Jones
Affiliation:
Department of Psychiatry, University of Cambridge, Cambridge, UK
R. M. Murray
Affiliation:
Institute of Psychiatry, King's College London, London, UK
P. Dazzan
Affiliation:
Institute of Psychiatry, King's College London, London, UK
*
*Address for correspondence: J. M. Lappin, Ph.D., Department of Psychosis Studies, PO Box 43, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. (Email: [email protected])

Abstract

Background

Hippocampal pathology has been proposed to underlie clinical, functional and cognitive impairments in schizophrenia. The hippocampus is a highly plastic brain region; examining change in volume, or change bilaterally, over time, can advance understanding of the substrate of recovery in psychosis.

Method

Magnetic resonance imaging and outcome data were collected at baseline and 6-year follow-up in 42 first-episode psychosis subjects and 32 matched controls, to investigate whether poorer outcomes are associated with loss of global matter and hippocampal volumes. Bilateral hippocampal increase (BHI) over time, as a marker of hippocampal plasticity was hypothesized to be associated with better outcomes. Regression analyses were performed on: (i) clinical and functional outcomes with grey matter volume change and BHI as predictor variables; and (ii) cognitive outcome with BHI as predictor.

Results

BHI was present in 29% of psychosis participants. There was no significant grey matter loss over time in either patient or control groups. Less severe illness course and lesser symptom severity were associated with BHI, but not with grey matter change. Employment and global function were associated with BHI and with less grey matter loss. Superior delayed verbal recall was also associated with BHI.

Conclusions

BHI occurs in a minority of patients following their first psychotic episode and is associated with good outcome across clinical, functional and cognitive domains.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2013 

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

Andreasen, NC (1982). Negative symptoms in schizophrenia. Definition and reliability. Archives of General Psychiatry 39, 784788.CrossRefGoogle ScholarPubMed
Andreasen, NC, Nopoulos, P, Magnotta, V, Pierson, R, Ziebell, S, Ho, BC (2011). Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biological Psychiatry 70, 672679.Google Scholar
Annett, M (1970). A classification of hand preference by association analysis. British Journal of Psychiatry 61, 303321.Google Scholar
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, 986996.CrossRefGoogle ScholarPubMed
Barch, DM, Csernansky, JG, Conturo, T, Snyder, AZ (2002). Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism? Journal of Abnormal Psychology 111, 478494.CrossRefGoogle Scholar
Bora, E, Yucel, M, Pantelis, C (2009). Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study. British Journal of Psychiatry 195, 475482.Google Scholar
Cahn, W, Hulshoff Pol, HE, Lems, EB, van Haren, NE, Schnack, HG, van der Linden, JA, Schothorst, PF, van Engeland, H, Kahn, RS (2002). Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Archives of General Psychiatry 59, 10021010.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, 2631.Google Scholar
Dale, AM, Fischl, B, Sereno, MI (1999). Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9, 179194.Google Scholar
Dazzan, P, Morgan, KD, Orr, K, Hutchinson, G, Chitnis, X, Suckling, J, Fearon, P, McGuire, PK, Mallett, RM, Jones, PB, Leff, J, Murray, RM (2005). Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study. Neuropsychopharmacology 30, 765774.CrossRefGoogle ScholarPubMed
Dazzan, P, Morgan, KD, Orr, KG, Hutchinson, G, Chitnis, X, Suckling, J, Fearon, P, Salvo, J, McGuire, PK, Mallett, RM, Jones, PB, Leff, J, Murray, RM (2004). The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study. Brain 127, 143153.CrossRefGoogle ScholarPubMed
DeLisi, LE, Sakuma, M, Maurizio, AM, Relja, M, Hoff, AL (2004). Cerebral ventricular change over the first 10 years after the onset of schizophrenia. Psychiatry Research 130, 5770.CrossRefGoogle ScholarPubMed
Endicott, J, Spitzer, RL, Fleiss, JL, Cohen, J (1976). The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 33, 766771.Google Scholar
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, 341355.CrossRefGoogle ScholarPubMed
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. Biological Psychiatry 64, 774781.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, 145152.Google Scholar
Harrison, G, Hopper, K, Craig, T, Laska, E, Siegel, C, Wanderling, J, Dube, KC, Ganev, K, Giel, R, an der Heiden, W, Holmberg, SK, Janca, A, Lee, PW, León, CA, Malhotra, S, Marsella, AJ, Nakane, Y, Sartorius, N, Shen, Y, Skoda, C, Thara, R, Tsirkin, SJ, Varma, VK, Walsh, D, Wiersma, D (2001). Recovery from psychotic illness: a 15- and 25-year international follow-up study. British Journal of Psychiatry 178, 506517.CrossRefGoogle ScholarPubMed
Heinrichs, RW, Zakzanis, KK (1998). Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12, 426445.Google Scholar
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, 22332245.CrossRefGoogle ScholarPubMed
Kasai, K, Shenton, ME, Salisbury, DF, Hirayasu, Y, Onitsuka, T, Spencer, MH, Yurgelun-Todd, DA, Kikinis, R, Jolesz, FA, McCarley, RW (2003). Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Archives of General Psychiatry 60, 766775.CrossRefGoogle ScholarPubMed
Keshavan, MS, Haas, GL, Kahn, CE, Aguilar, E, Dick, EL, Schooler, NR, Sweeney, JA, Pettegrew, JW (1998). Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible? Journal of Psychiatric Research 32, 161167.CrossRefGoogle ScholarPubMed
Lappin, JM, Morgan, K, Morgan, C, Hutchison, G, Chitnis, X, Suckling, J, Fearon, P, McGuire, PK, Jones, PB, Leff, J, Murray, RM, Dazzan, P (2006). Gray matter abnormalities associated with duration of untreated psychosis. Schizophrenia Research 83, 145153.Google Scholar
Lodge, DJ, Grace, AA (2011). Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia. Trends in Pharmacological Sciences 32, 507513.Google Scholar
Mondelli, V, Cattaneo, A, Belvederi, MM, Di Forti, M, Handley, R, Hepgul, N, Miorelli, A, Navari, S, Papadopoulos, AS, Aitchison, KJ, Morgan, C, Murray, RM, Dazzan, P, Pariante, CM (2011). Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume. Journal of Clinical Psychiatry 72, 16771684.Google Scholar
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, 7578.Google Scholar
Morey, RA, Dolcos, F, Petty, CM, Cooper, DA, Hayes, JP, LaBar, KS, McCarthy, G (2009). The role of trauma-related distractors on neural systems for working memory and emotion processing in posttraumatic stress disorder. Journal of Psychiatric Research 43, 809817.Google Scholar
Nelson, HE (1991). National Adult Reading Test (Part II): Test Manual. NFER-Nelson: Windsor.Google Scholar
Olabi, B, Ellison-Wright, I, McIntosh, AM, Wood, SJ, Bullmore, E, Lawrie, SM (2011). Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biological Psychiatry 70, 8896.Google Scholar
Pajonk, FG, Wobrock, T, Gruber, O, Scherk, H, Berner, D, Kaizl, I, Kierer, A, Muller, S, Oest, M, Meyer, T, Backens, M, Schneider-Axmann, T, Thornton, AE, Honer, WG, Falkai, P (2010). Hippocampal plasticity in response to exercise in schizophrenia. Archives of General Psychiatry 67, 133143.Google Scholar
Reuter, M, Schmansky, NJ, Rosas, HD, Fischl, B (2012). Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage 61, 14021418.CrossRefGoogle ScholarPubMed
Schaufelberger, MS, Lappin, JM, Duran, FL, Rosa, PG, Uchida, RR, Santos, LC, Murray, RM, McGuire, PK, Scazufca, M, Menezes, PR, Busatto, GF (2011). Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study. Psychological Medicine 41, 16771689.CrossRefGoogle ScholarPubMed
Sled, JG, Zijdenbos, AP, Evans, AC (1998). A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Transactions on Medical Imaging 17, 8797.Google Scholar
Spreen, O, Strauss, E (1991). A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary. Oxford University Press: New York.Google Scholar
Steen, RG, Mull, C, McClure, R, Hamer, RM, Lieberman, JA (2006). Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. British Journal of Psychiatry 188, 510518.CrossRefGoogle ScholarPubMed
Suckling, J, Sigmundsson, T, Greenwood, K, Bullmore, ET (1999). A modified fuzzy clustering algorithm for operator independent brain tissue classification of dual echo MR images. Magnetic Resonance Imaging 17, 10651076.Google Scholar
Tamminga, CA, Stan, AD, Wagner, AD (2010). The hippocampal formation in schizophrenia. American Journal of Psychiatry 167, 11781193.CrossRefGoogle ScholarPubMed
van Haren, NE, Hulshoff Pol, HE, Schnack, HG, Cahn, W, Brans, R, Carati, I, Rais, M, Kahn, RS (2008). Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood. Biological Psychiatry 63, 106113.CrossRefGoogle ScholarPubMed
van Haren, NE, Hulshoff Pol, HE, Schnack, HG, Cahn, W, Mandl, RC, Collins, DL, Evans, AC, Kahn, RS (2007). Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology 32, 20572066.Google Scholar
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, 139149.CrossRefGoogle ScholarPubMed
Weiss, AP, Schacter, DL, Goff, DC, Rauch, SL, Alpert, NM, Fischman, AJ, Heckers, S (2003). Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia. Biological Psychiatry 53, 4855.CrossRefGoogle ScholarPubMed
Whitworth, AB, Kemmler, G, Honeder, M, Kremser, C, Felber, S, Hausmann, A, Walch, T, Wanko, C, Weiss, EM, Stuppaeck, CH, Fleischhacker, WW (2005). Longitudinal volumetric MRI study in first- and multiple-episode male schizophrenia patients. Psychiatry Research 140, 225237.CrossRefGoogle ScholarPubMed
Wing, JK, Sturt, E (1978). The PSE-ID-CATEGO System: Supplementary Manual. Medical Research Council: London.Google Scholar
Wood, SJ, Velakoulis, D, Smith, DJ, Bond, D, Stuart, GW, McGorry, PD, Brewer, WJ, Bridle, N, Eritaia, J, Desmond, P, Singh, B, Copolov, D, Pantelis, C (2001). A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia. Schizophrenia Research 52, 3746.Google Scholar
World Health Organization (1994). Schedules for Clinical Assessment in Neuropsychiatry (SCAN). World Health Organization: Geneva.Google 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, 1625.Google Scholar
Yoshida, T, McCarley, RW, Nakamura, M, Lee, K, Koo, MS, Bouix, S, Salisbury, DF, Morra, L, Shenton, ME, Niznikiewicz, MA (2009). A prospective longitudinal volumetric MRI study of superior temporal gyrus gray matter and amygdala–hippocampal complex in chronic schizophrenia. Schizophrenia Research 113, 8494.Google Scholar
Zipursky, RB, Reilly, TJ, Murray, RM (2012). The myth of schizophrenia as a progressive brain disease. Schizophrenia Bulletin. Published online 7 12 2012 . doi:10.1093/schbul/sbs135.Google Scholar
Supplementary material: File

Lappin Supplementary Material

Appendix

Download Lappin Supplementary Material(File)
File 37.9 KB