Abstract
Background: Recent preclinical studies have shown that lithium (Li) robustly increases
the levels of the major neuroprotective protein, bcl-2, in rat brain and in cells
of human neuronal origin. These effects are accompanied by striking neuroprotective
effects in vitro and in the rodent central nervous system in vivo. We have undertaken
the present study to determine if lithium exerts neurotrophic/neuroprotective effects
in the human brain in vivo.
Methods: Using quantitative proton magnetic resonance spectroscopy, N-acetyl-aspartate (NAA) levels (a putative marker of neuronal viability and function)
were investigated longitudinally in 21 adult subjects (12 medication-free bipolar
affective disorder patients and 9 healthy volunteers). Regional brain NAA levels were
measured at baseline and following 4 weeks of lithium (administered in a blinded manner).
Results: A significant increase in total brain NAA concentration was documented (p < .0217). NAA concentration increased in all brain regions investigated, including
the frontal, temporal, parietal, and occipital lobes.
Conclusions: This study demonstrates for the first time that Li administration at
therapeutic doses increases brain NAA concentration. These findings provide intriguing
indirect support for the contention that chronic lithium increases neuronal viability/function
in the human brain, and suggests that some of Li’s long-term beneficial effects may
be mediated by neurotrophic/neuroprotective events.
Keywords
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Article info
Publication history
Accepted:
December 31,
1999
Received in revised form:
December 28,
1999
Received:
July 13,
1999
Identification
Copyright
© 2000 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
