Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-19T02:58:23.845Z Has data issue: false hasContentIssue false

Interrelated neuropsychological and anatomical evidence of hippocampal pathology in the at-risk mental state

Published online by Cambridge University Press:  04 April 2008

R. Hurlemann*
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
F. Jessen
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
M. Wagner
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
I. Frommann
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
S. Ruhrmann
Affiliation:
Department of Psychiatry, University of Cologne, Cologne, Germany
A. Brockhaus
Affiliation:
Department of Psychiatry, University of Cologne, Cologne, Germany
H. Picker
Affiliation:
Department of Psychiatry, University of Cologne, Cologne, Germany
L. Scheef
Affiliation:
Department of Radiology, University of Bonn, Bonn, Germany
W. Block
Affiliation:
Department of Radiology, University of Bonn, Bonn, Germany
H. H. Schild
Affiliation:
Department of Radiology, University of Bonn, Bonn, Germany
W. Moller-Hartmann
Affiliation:
Department of Radiology, University of Cologne, Cologne, Germany
B. Krug
Affiliation:
Department of Radiology, University of Cologne, Cologne, Germany
P. Falkai
Affiliation:
Department of Psychiatry, University of Goettingen, Goettingen, Germany
J. Klosterkotter
Affiliation:
Department of Psychiatry, University of Cologne, Cologne, Germany
W. Maier
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
*
*Address for correspondence: R. Hurlemann, M.Sc., M.D., Ph.D., Department of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. (Email: [email protected])

Abstract

Background

Verbal learning and memory deficits are frequent among patients with schizophrenia and correlate with reduced magnetic resonance imaging (MRI) volumes of the hippocampus in these patients. A crucial question is the extent to which interrelated structural-functional deficits of the hippocampus reflect a vulnerability to schizophrenia, as opposed to the disorder per se.

Method

We combined brain structural measures and the Rey Auditory Verbal Learning Test (RAVLT) to assess hippocampal structure and function in 36 never-medicated individuals suspected to be in early (EPS) or late prodromal states (LPS) of schizophrenia relative to 30 healthy controls.

Results

Group comparisons revealed bilaterally reduced MRI hippocampal volumes in both EPS and LPS subjects. In LPS subjects but not in EPS subjects, these reductions were correlated with poorer performance in RAVLT delayed recall.

Conclusions

Our findings suggest progressive and interrelated structural-functional pathology of the hippocampus, as prodromal symptoms and behaviours accumulate, and the level of risk for psychosis increases. Given the inverse correlation of learning and memory deficits with social and vocational functioning in established schizophrenia, our findings substantiate the rationale for developing preventive treatment strategies that maintain cognitive capacities in the at-risk mental state.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2008

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

Achim, AM, Bertrand, MC, Sutton, H, Montoya, A, Czechowska, Y, Malla, AK, Joober, R, Pruessner, JC, Lepage, M (2007). Selective abnormal modulation of hippocampal activity during memory formation in first-episode psychosis. Archives of General Psychiatry 64, 9991014.CrossRefGoogle ScholarPubMed
Achim, AM, Lepage, M (2005). Episodic memory-related activation in schizophrenia: meta-analysis. British Journal of Psychiatry 187, 500509.CrossRefGoogle ScholarPubMed
Aleman, A, Hijman, R, de Haan, EH, Kahn, RS (1999). Memory impairment in schizophrenia: a meta-analysis. American Journal of Psychiatry 156, 13581366.CrossRefGoogle ScholarPubMed
Arndt, S, Cohen, G, Alliger, RJ, Swayze, VW 2nd, Andreasen, NC (1991). Problems with ratio and proportion measures of imaged cerebral structures. Psychiatry Research 40, 7989.CrossRefGoogle ScholarPubMed
Bleuler, E (1911). Dementia Praecox or the Group of Schizophrenias (translated J. Zinkin, 1950). International Universities Press: New York.Google Scholar
Boos, HB, Aleman, A, Cahn, W, Pol, HH, Kahn, RS (2007). Brain volumes in relatives of patients with schizophrenia: a meta-analysis. Archives of General Psychiatry 64, 297304.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, Riecher-Rossler, A, Dazzan, P, Chitnis, X, Aston, J, Drewe, M, Gschwandtner, U, Haller, S, Pfluger, M, Rechsteiner, E, D'Souza, M, Stieglitz, RD, Radu, EW, McGuire, PK (2007). Regional gray matter volume abnormalities in the at risk mental state. Biological Psychiatry 61, 11481156.CrossRefGoogle ScholarPubMed
Boyer, P, Phillips, JL, Rousseau, FL, Ilivitsky, S (2007). Hippocampal abnormalities and memory deficits: new evidence of a strong pathophysiological link in schizophrenia. Brain Research Reviews 54, 92112.CrossRefGoogle Scholar
Brewer, WJ, Francey, SM, Wood, SJ, Jackson, HJ, Pantelis, C, Phillips, LJ, Yung, AR, Anderson, VA, McGorry, PD (2005). Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis. American Journal of Psychiatry 162, 7178.CrossRefGoogle ScholarPubMed
Cannon, TD (2005). Clinical and genetic high-risk strategies in understanding vulnerability to psychosis. Schizophrenia Research 79, 3544.CrossRefGoogle ScholarPubMed
Cook, MJ, Fish, DR, Shorvon, SD, Straughan, K, Stevens, JM (1992). Hippocampal volumetric and morphometric studies in frontal and temporal lobe epilepsy. Brain 115, 10011015.CrossRefGoogle ScholarPubMed
Eastvold, AD, Heaton, RK, Cadenhead, KS (2007). Neurocognitive deficits in the (putative) prodrome and first episode of psychosis. Schizophrenia Research 93, 266277.CrossRefGoogle ScholarPubMed
Feinberg, I (1983). Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? Journal of Psychiatric Research 17, 319334.CrossRefGoogle Scholar
Fletcher, PC, Frith, CD, Rugg, MD (1997). The functional neuroanatomy of episodic memory. Trends in Neurosciences 20, 213218.CrossRefGoogle ScholarPubMed
Free, SL, Bergin, PS, Fish, DR, Cook, MJ, Shorvon, SD, Stevens, JM (1995). Methods for normalization of hippocampal volumes measured with MR. American Journal of Neuroradiology 16, 637643.Google ScholarPubMed
Fusar-Poli, P, Perez, J, Broome, M, Borgwardt, S, Placentino, A, Caverzasi, E, Cortesi, M, Veggiotti, P, Politi, P, Barale, F, McGuire, P (2007) Neurofunctional correlates of vulnerability to psychosis: a systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews 31, 465484.CrossRefGoogle ScholarPubMed
Green, MF (1996). What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry 153, 321330.Google ScholarPubMed
Gross, G, Huber, G (1985). Psychopathology of basic stages of schizophrenia in view of formal thought disturbances. Psychopathology 18, 115125.CrossRefGoogle ScholarPubMed
Hafner, H, Maurer, K, Ruhrmann, S, Bechdolf, A, Klosterkotter, J, Wagner, M, Maier, W, Bottlender, R, Moller, HJ, Gaebel, W, Wolwer, W (2004). Early detection and secondary prevention of psychosis: facts and visions. European Archives of Psychiatry and Clinical Neuroscience 254, 117128.CrossRefGoogle ScholarPubMed
Hafner, H, Riecher-Rossler, A, Hambrecht, M, Maurer, K, Meissner, S, Schmidtke, A, Fatkenheuer, B, Loffler, W, van der Heiden, W (1992). IRAOS: an instrument for the assessment of onset and early course of schizophrenia. Schizophrenia Research 6, 209223.CrossRefGoogle ScholarPubMed
Heckers, S, Konradi, C (2002). Hippocampal neurons in schizophrenia. Journal of Neural Transmission 109, 891905.CrossRefGoogle ScholarPubMed
Helmstaedter, C, Lendt, M, Lux, S (2001). Verbaler Lern- und Merkfähigkeitstest (VLMT). Hogrefe: Göttingen.Google Scholar
Hurlemann, R, Matusch, A, Kuhn, KU, Berning, J, Elmenhorst, D, Winz, O, Kolsch, H, Zilles, K, Wagner, M, Maier, W, Bauer, A (2008). 5-HT2A receptor density is decreased in the at-risk mental state. Psychopharmacology (Berlin) 195, 579590.CrossRefGoogle ScholarPubMed
Hurlemann, R, Tepest, R, Maier, W, Falkai, P, Vogeley, K (2005). Intact hippocampal gray matter in schizophrenia as revealed by automatized image analysis postmortem. Anatomy and Embryology (Berlin) 210, 513517.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.CrossRefGoogle ScholarPubMed
Keefe, RS, Perkins, DO, Gu, H, Zipursky, RB, Christensen, BK, Lieberman, JA (2006). A longitudinal study of neurocognitive function in individuals at-risk for psychosis. Schizophrenia Research 88, 2635.CrossRefGoogle ScholarPubMed
Keshavan, MS, Berger, G, Zipursky, RB, Wood, SJ, Pantelis, C (2005). Neurobiology of early psychosis. British Journal of Psychiatry 48, 818.CrossRefGoogle ScholarPubMed
Klosterkotter, J, Hellmich, M, Steinmeyer, EM, Schultze-Lutter, F (2001). Diagnosing schizophrenia in the initial prodromal phase. Archives of General Psychiatry 58, 158164.CrossRefGoogle ScholarPubMed
Kraepelin, E (1919). Dementia praecox and Paraphrenia (translated R. M. Barclay) (ed. Robertson, G. M.), reprinted 1971. Robert E. Krieger: New York.Google Scholar
Kuroki, N, Kubicki, M, Nestor, PG, Salisbury, DF, Park, HJ, Levitt, JJ, Woolston, S, Frumin, M, Niznikiewicz, M, Westin, CF, Maier, SE, McCarley, RW, Shenton, ME (2006). Fornix integrity and hippocampal volume in male schizophrenic patients. Biological Psychiatry 60, 2231.CrossRefGoogle ScholarPubMed
Lehrl, S (2005). Mehrfachwahl-Wortschatz-Intelligenz-Test, MWT-B, 5th edn. Spitta: Balingen.Google Scholar
Lencz, T, Smith, CW, McLaughlin, D, Auther, A, Nakayama, E, Hovey, L, Cornblatt, BA (2006). Generalized and specific neurocognitive deficits in prodromal schizophrenia. Biological Psychiatry 59, 863871.CrossRefGoogle ScholarPubMed
Lymer, GK, Job, DE, William, T, Moorhead, J, McIntosh, AM, Owens, DG, Johnstone, EC, Lawrie, SM (2006). Brain-behavior relationship in people at high genetic risk of schizophrenia. NeuroImage 33, 275285.CrossRefGoogle ScholarPubMed
McGlashan, TH (1996). Early detection and intervention in schizophrenia: research. Schizophrenia Bulletin 22, 327345.CrossRefGoogle ScholarPubMed
McGlashan, TH, Hoffman, RE (2000). Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Archives of General Psychiatry 57, 637648.CrossRefGoogle ScholarPubMed
McGorry, PD, Yung, AR, Phillips, LJ, Yuen, HP, Francey, S, Cosgrave, EM, Germano, D, Bravin, J, McDonald, T, Blair, A, Adlard, S, Jackson, H (2002). Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Archives of General Psychiatry 59, 921928.CrossRefGoogle Scholar
McKenna, PJ, Tamlyn, D, Lund, CE, Mortimer, AM, Hammond, S, Baddeley, AD (1990) Amnesic syndrome in schizophrenia. Psychological Medicine 20, 967972.CrossRefGoogle ScholarPubMed
Montgomery, SA, Åsberg, M (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382389.CrossRefGoogle ScholarPubMed
Nestor, PG, Kubicki, M, Kuroki, N, Gurrera, RJ, Niznikiewicz, M, Shenton, ME, McCarley, RW (2007). Episodic memory and neuroimaging of hippocampus and fornix in chronic schizophrenia. Psychiatry Research 155, 2128.CrossRefGoogle ScholarPubMed
Niendam, TA, Bearden, CE, Johnson, JK, McKinley, M, Loewy, R, O'Brien, M, Nuechterlein, KH, Green, MF, Cannon, TD (2006). Neurocognitive performance and functional disability in the psychosis prodrome. Schizophrenia Research 84, 100111.CrossRefGoogle ScholarPubMed
Pantelis, C, Velakoulis, D, McGorry, PD, Wood, SJ, Suckling, J, Phillips, LJ, Yung, AR, Bullmore, ET, Brewer, W, Soulsby, B, Desmond, P, McGuire, PK (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361, 281288.CrossRefGoogle ScholarPubMed
Rey, A (1941). L'examen psychologique dans les cas d'encephalopathie traumatique. Archives of Psychology 30, 286340.Google Scholar
Salisbury, DF, Kuroki, N, Kasai, K, Shenton, ME, McCarley, RW (2007). Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia. Archives of General Psychiatry 64, 521529.CrossRefGoogle ScholarPubMed
Scoville, WB, Milner, B (1957). Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery, and Psychiatry 20, 1121.CrossRefGoogle ScholarPubMed
Squire, LR, Stark, CE, Clark, RE (2004). The medial temporal lobe. Annual Review of Neuroscience 27, 279306.CrossRefGoogle ScholarPubMed
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
Strauss, E, Sherman, EMS, Spreen, O (2006). A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary, 3rd edn. Oxford University Press: New York.Google Scholar
Vita, A, de Peri, L, Silenzi, C, Dieci, M (2006). Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies. Schizophrenia Research 15, 7588.CrossRefGoogle Scholar
Vita, A, de Peri, L (2007). Hippocampal and amygdala volume reductions in first-episode schizophrenia. British Journal of Psychiatry 190, 271.CrossRefGoogle ScholarPubMed
Walker, MA, Highley, JR, Esiri, MM, McDonald, B, Roberts, HC, Evans, SP, Crow, TJ (2002). Estimated neuronal populations and volumes of the hippocampus and its subfields in schizophrenia. American Journal of Psychiatry 159, 821828.CrossRefGoogle ScholarPubMed
Yung, AR, McGorry, PD (1996). The prodromal phase of first-episode psychosis: past and current conceptualizations. Schizophrenia Bulletin 22, 353370.CrossRefGoogle ScholarPubMed
Yung, AR, Phillips, LJ, Yuen, HP, Francey, SM, McFarlane, CA, Hallgren, M, McGorry, PD (2003). Psychosis prediction: 12-month follow up of a high-risk (‘prodromal’) group. Schizophrenia Research 60, 2132.CrossRefGoogle ScholarPubMed