1. ¹Department of Psychiatry, Charité, Campus Benjamin Franklin, Berlin, Germany
2. ²Physikalisch-Technische Bundesanstalt, Berlin, Germany
3. ³Department of Radiology and Nuclear Medicine, Charité, Campus Benjamin Franklin, Berlin, Germany
4. ⁴Department of Radiology, University of Louisville Hospital, Louisville, KY, USA

Correspondence: Dr M Colla, Department of Psychiatry, Charité, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany. E-mail: michael.colla@charite.de

⁵These authors contributed equally to this work.

Received 9 July 2007; Revised 3 October 2007; Accepted 4 December 2007; Published online 18 March 2008.

Abstract

While an excess of glucocorticoids is associated with hippocampal pathology in mood disorders, lithium exerts robust neuroprotective and neurotrophic effects. Here, 21 stably remitted bipolar I patients who had been on chronic lithium maintenance therapy, on average, for more than a decade, and 19 carefully matched healthy controls were studied using 3 T ¹H-magnetic resonance spectroscopy of left and right hippocampus. Salivary cortisol samples were obtained to assess activity of the hypothalamus–pituitary–adrenal system. Absolute concentrations of N-acetylaspartate (NAA), choline-containing compounds and total creatine were similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate concentrations were significantly increased as an effect of patient status (patients>controls) and laterality (left hippocampus>right hippocampus). Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across groups and within the patient group, diurnal saliva cortisol levels showed a significant inverse relationship with both Glu and NAA. Taken together, these results add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.