Psychological Medicine

Original Articles

Hippocampal function in schizophrenia and bipolar disorder

J. Halla1 c1, H. C. Whalleya1, K. Marwicka1, J. McKirdya1, J. Sussmanna1, L. Romaniuka1, E. C. Johnstonea1, H. I. Wana2, A. M. McIntosha1 and S. M. Lawriea1

a1 Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK

a2 Clinical Translational Medicine, Wyeth Research, Collegeville, PA, USA


Background 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.

Method 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.

Results 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.

Conclusions 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.

(Received January 29 2009)

(Revised July 01 2009)

(Accepted July 07 2009)

(Online publication September 07 2009)


c1 Address for correspondence: Dr J. Hall, Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK. (Email: