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Neuroprotective effect of lithium on hippocampal volumes in bipolar disorder independent of long-term treatment response

Published online by Cambridge University Press:  31 May 2013

T. Hajek ,
M. Bauer ,
C. Simhandl ,
J. Rybakowski ,
C. O'Donovan ,
A. Pfennig ,
B. König ,
A. Suwalska ,
K. Yucel  and
R. Uher
...Show all authors
T. Hajek*
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada Prague Psychiatric Center, Department of Psychiatry and Medical Psychology, 3rd School of Medicine, Charles University, Prague, Czech Republic
M. Bauer
Affiliation:
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
C. Simhandl
Affiliation:
Psychiatrische Abteilung, Krankenhaus Neunkirchen, Austria
J. Rybakowski
Affiliation:
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poland
C. O'Donovan
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada
A. Pfennig
Affiliation:
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
B. König
Affiliation:
Psychiatrische Abteilung, Krankenhaus Neunkirchen, Austria
A. Suwalska
Affiliation:
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poland
K. Yucel
Affiliation:
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
R. Uher
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada
L. T. Young
Affiliation:
Department of Psychiatry, University of Toronto, ON, Canada
G. MacQueen
Affiliation:
Department of Psychiatry, University of Calgary, AB, Canada
M. Alda
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada Prague Psychiatric Center, Department of Psychiatry and Medical Psychology, 3rd School of Medicine, Charles University, Prague, Czech Republic
*
*Address for correspondence: T. Hajek, M.D., Ph.D., Department of Psychiatry, Dalhousie University, QEII HSC, Abbie J. Lane Bldg, Room 3093, 5909 Veteran's Memorial Lane, Halifax, NS B3H 2E2, Canada. (Email: [email protected])
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Abstract

Background

Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD).

Method

To address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts.

Results

The non-Li group had smaller hippocampal volumes than the controls or the Li group (F2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t51 = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t43 = 2.62, corrected p = 0.02).

Conclusions

Our findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.

Keywords

Hippocampuslithiummood stabilizationMRIneuroprotection
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 3 , February 2014 , pp. 507 - 517
Copyright
Copyright © Cambridge University Press 2013 

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