Skip to main content Accessibility help

Hippocampal function in schizophrenia and bipolar disorder

  • J. Hall (a1), H. C. Whalley (a1), K. Marwick (a1), J. McKirdy (a1), J. Sussmann (a1), L. Romaniuk (a1), E. C. Johnstone (a1), H. I. Wan (a2), A. M. McIntosh (a1) and S. M. Lawrie (a1)...



The hippocampus plays a central role in memory formation. There is considerable evidence of abnormalities in hippocampal structure and function in schizophrenia, which may differentiate it from bipolar disorder. However, no previous studies have compared hippocampal activation in schizophrenia and bipolar disorder directly.


Fifteen patients with schizophrenia, 14 patients with bipolar disorder and 14 healthy comparison subjects took part in the study. Subjects performed a face–name pair memory task during functional magnetic resonance imaging (fMRI). Differences in blood oxygen level-dependent (BOLD) activity were determined during encoding and retrieval of the face–name pairs.


The patient groups showed significant differences in hippocampal and prefrontal cortex (PFC) activation during face–name pair learning. During encoding, patients with schizophrenia showed decreased anterior hippocampal activation relative to subjects with bipolar disorder, whereas patients with bipolar disorder showed decreased dorsal PFC activation relative to patients with schizophrenia. During retrieval, patients with schizophrenia showed greater activation of the dorsal PFC than patients with bipolar disorder. Patients with schizophrenia also differed from healthy control subjects in the activation of several brain regions, showing impaired superior temporal cortex activation during encoding and greater dorsal PFC activation during retrieval. These effects were evident despite matched task performance.


Patients with schizophrenia showed deficits in hippocampal activation during a memory task relative to patients with bipolar disorder. The disorders were further distinguished by differences in PFC activation. The results demonstrate that these disorders can distinguished at a group level using non-invasive neuroimaging.


Corresponding author

*Address for correspondence: Dr J. Hall, Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK. (Email:


Hide All
Achim, AM, Lepage, M (2003). Is associative recognition more impaired than item recognition memory in schizophrenia? A meta-analysis. Brain and Cognition 53, 121124.
Achim, AM, Lepage, M (2005). Episodic memory-related activation in schizophrenia: meta-analysis. British Journal of Psychiatry 187, 500509.
Aleman, A, Hijman, R, de Haan, EHF, Kahn, RS (1999). Memory impairment in schizophrenia: a meta-analysis. American Journal of Psychiatry 156, 13581366.
Blumberg, HP, Leung, H-C, Skudlarski, P, Lacadie, CM, Fredericks, CA, Harris, BC, Charney, DS, Gore, JC, Krystal, JH, Peterson, BS (2003). A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Archives of General Psychiatry 60, 601609.
Blumenfeld, RS, Ranganath, C (2007). Prefrontal cortex and long-term memory encoding: an integrative review of findings from neuropsychology and neuroimaging. Neuroscientist 13, 280291.
Boos, HBM, 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.
Callicott, JH, Mattay, VS, Verchinski, BA, Marenco, S, Egan, MF, Weinberger, DR (2003). Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. American Journal of Psychiatry 160, 22092215.
Chen, C-H, Lennox, B, Jacob, R, Calder, A, Lupson, V, Bisbrown-Chippendale, R, Suckling, J, Bullmore, E (2006). Explicit and implicit facial affect recognition in manic and depressed states of bipolar disorder: a functional magnetic resonance imaging study. Biological Psychiatry 59, 3139.
Curtis, VA, Dixon, TA, Morris, RG, Bullmore, ET, Brammer, MJ, Williams, SCR, Sharma, T, Murray, RM, McGuire, PK (2001). Differential frontal activation in schizophrenia and bipolar illness during verbal fluency. Journal of Affective Disorders 66, 111121.
Danion, J-M, Rizzo, L, Bruant, A (1999). Functional mechanisms underlying impaired recognition memory and conscious awareness in patients with schizophrenia. Archives of General Psychiatry 56, 639644.
Deckersbach, T, Dougherty, DD, Savage, C, McMurrich, S, Fischman, AJ, Nierenberg, A, Sachs, G, Rauch, SL (2006). Impaired recruitment of the dorsolateral prefrontal cortex and hippocampus during encoding in bipolar disorder. Biological Psychiatry 59, 138146.
Dolan, RJ, Fletcher, PF (1999). Encoding and retrieval in human medial temporal lobes: an empirical investigation using functional magnetic resonance imaging (fMRI). Hippocampus 9, 2534.
Fletcher, PC, Frith, CD, Rugg, MD (1997). The functional neuroanatomy of episodic memory. Trends in Neurosciences 20, 213218.
Frey, BN, Andreazza, AC, Nery, FG, Martins, MR, Quevedo, J, Soares, JC, Kapczinski, F (2007). The role of hippocampus in the pathophysiology of bipolar disorder. Behavioural Pharmacology 18, 419430.
Haldane, M, Frangou, S (2004). New insights help define the pathophysiology of bipolar affective disorder: neuroimaging and neuropathology findings. Progress in Neuro-Psychopharmacology and Biological Psychiatry 28, 943960.
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 5662.
Heckers, S (2001). Neuroimaging studies of the hippocampus in schizophrenia. Hippocampus 11, 520528.
Heckers, S, Rauch, S, Goff, D, Savage, C, Schacter, D, Fischman, A, Alpert, N (1998). Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nature Neuroscience 1, 318323.
Henson, RNA, Rugg, MD, Shallice, T, Josephs, O, Dolan, RJ (1999). Recollection and familiarity in recognition memory: an event-related functional magnetic resonance imaging study. Journal of Neuroscience 19, 39623972.
Huron, C, Danion, JM, Giacomoni, F, Grange, D, Robert, P, Rizzo, L (1995). Impairment of recognition memory with, but not without, conscious recollection in schizophrenia. American Journal of Psychiatry 152, 17371742.
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.
Kirwan, CB, Stark, CE (2004). Medial temporal lobe activation during encoding and retrieval of novel face–name pairs. Hippocampus 14, 919930.
Lagopoulos, J, Ivanovski, B, Malhi, GS (2007). An event-related functional MRI study of working memory in euthymic bipolar disorder. Journal of Psychiatry and Neuroscience 32, 174184.
Lawrence, NS, Williams, AM, Surguladze, S, Giampietro, V, Brammer, MJ, Andrew, C, Frangou, S, Ecker, C, Phillips, ML (2004). Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression. Biological Psychiatry 55, 578587.
Lepage, M, Habib, R, Tulving, E (1998). Hippocampal PET activations of memory encoding and retrieval: the HIPER model. Hippocampus 8, 313322.
Lisman, JE, Coyle, JT, Green, RW, Javitt, DC, Benes, FM, Heckers, S, Grace, AA (2008). Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends in Neurosciences 31, 234242.
Lodge, DJ, Grace, AA (2007). Aberrant hippocampal activity underlies the dopamine dysregulation in an animal model of schizophrenia. Journal of Neuroscience 27, 1142411430.
Maldjian, JA, Laurienti, PJ, Kraft, RA, Burdette, JH (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19, 12331239.
Mayes, A, Montaldi, D, Migo, E (2007). Associative memory and the medial temporal lobes. Trends in Cognitive Sciences 11, 126135.
McIntosh, AM, Whalley, HC, McKirdy, J, Hall, J, Sussmann, JED, Shankar, P, Johnstone, EC, Lawrie, SM (2008). Prefrontal function and activation in bipolar disorder and schizophrenia. American Journal of Psychiatry 165, 378384.
Monks, PJ, Thompson, JM, Bullmore, ET, Suckling, J, Brammer, MJ, Williams, SC, Simmons, A, Giles, N, Lloyd, AJ, Harrison, CL, Seal, M, Murray, RM, Ferrier, IN, Young, AH, Curtis, VA (2004). A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction. Bipolar Disorders 6, 550564.
Nelson, HE, Willison, JR (1991). The Revised National Adult Reading Test – Test Manual. NFER-Nelson: Windsor, UK.
Ongur, D, Cullen, TJ, Wolf, DH, Rohan, M, Barreira, P, Zalesak, M, Heckers, S (2006). The neural basis of relational memory deficits in schizophrenia. Archives of General Psychiatry 63, 356365.
Phillips, ML, Vieta, E (2007). Identifying functional neuroimaging biomarkers of bipolar disorder: toward DSM-V. Schizophrenia Bulletin 33, 893904.
Sperling, R, Chua, E, Cocchiarella, A, Rand-Giovannetti, E, Poldrack, R, Schacter, DL, Albert, M (2003). Putting names to faces: successful encoding of associative memories activates the anterior hippocampal formation. NeuroImage 20, 14001410.
Strakowski, SM, DelBello, MP, Adler, CM (2004). The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Molecular Psychiatry 10, 105116.
Summerfield, C, Greene, M, Wager, T, Egner, T, Hirsch, J, Mangels, J (2006). Neocortical connectivity during episodic memory formation. PLoS Biology 4, e128.
Toulopoulou, T, Rabe-Hesketh, S, King, H, Murray, RM, Morris, RG (2003). Episodic memory in schizophrenic patients and their relatives. Schizophrenia Research 63, 261271.
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273289.
Vargha-Khadem, F, Gadian, DG, Watkins, KE, Connelly, A, Van Paesschen, W, Mishkin, M (1997). Differential effects of early hippocampal pathology on episodic and semantic memory. Science 277, 376380.
Woods, SW (2003). Chlorpromazine equivalent doses of the newer atypical antipsychotics. Journal of Clinical Psychiatry 64, 663667.
Wright, IC, Rabe-Hesketh, S, Woodruff, PWR, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 1625.
Young, RC, Biggs, JT, Ziegler, VE, Meyer, DA (1978). A rating scale for mania: reliability, validity and sensitivity. British Journal of Psychiatry 133, 429435.
Zeineh, MM, Engel, SA, Thompson, PM, Bookheimer, SY (2003). Dynamics of the hippocampus during encoding and retrieval of face–name pairs. Science 299, 577580.


Type Description Title
Supplementary materials

Hall supplementary material

 Word (159 KB)
159 KB


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