Is lithium a Neuroprotective agent? Psychol Med.Feb.2014


Different lines of evidence ( animal studies, tissue culture, brain imaging) suggest that Lithium has neuroprotective effects.Lithium treatment is associated with larger grey matter volume. Is the observed   increase in brain volume  a direct neurochemical effect of Li or an indirect effect secondary to treatment response?  If it is indeed a primary neuroprotective agent, many other disorders may benefit  from lithium.

A group of researchers  (International Group for the Study of Lithium- Treated Patients),   Hajek et al, prospectively followed patients with BD (minimum of 10 years of illness and at least five episodes) on  long-term ongoing Li treatment (minimum of 2 years) and a similar group with no/minimal lifetime Li exposure. The third group was an age and sex-matched control group. Patients who had more than one course of ECT,co-morbid Axis I or II psychiatric disorders;  active substance abuse, etc were excluded. 19 non-Li, 37 Li-treated Bipolar patients and 50 controls were recruited from 4 countries.  Because hippocampal volume changes are the most consistent reported brain change in bipolar disorder, researchers  chose to measure this in the above three groups.Illness course and treatment response to Li was recorded using the National Institute of Mental Health Life-Chart Method.


Li and non Li Bipolar groups were similar in most illness variables. Overall duration of illness (time since the first episode) were longer in the Li  group. Non lithium treated group had significantly smaller hippocampal volumes relative to controls  and also relative to the Li-treated BD participants.This pattern was seen in all study sites.The Li-treated participants had comparable hippocampal volumes to control subjects. 


Can the observed difference be due to  fundamental difference between lithium responders and non responders rather than due to Lithium?  69% of patients continued to experience episodes of illness while on Li , so this may not be the case.  More possible explanation is lithium itself is responsible for the volume changes.

Limitations : Hippocampal volumes were not measured prospectively . Given that long duration of li exposure (11 yrs average), prospective design may not be feasible at all. Both groups  had other medications effects of which ( i.e. neuroprotection) we don’t know. However,exclusion of participants treated with antipsychotics or anticonvulsants did not alter results. Sample selected was more homogenous one ( through exclusion criteria) and generalisabilty is limited to routine clinic samples.

Conclusion: Lithium has neuroprotecive effects in BPD and  is independent of long terms treatment response.

Comment: Studies have indicated that Lithium can reduce the generally elevated risk of neurodegenerative disorders among patients with BD.Lithium might also  have a role in pre symptomatic stages ofAlzheimer’s dementia. Lithium’s possible role in neuropsychiatric disorders is an interesting development at a time when prescription rates of Lithium is declining in affective disorders due to various reasons.

Summary of the article:

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

Hajek T, Bauer M, Simhandl C, Rybakowski J, O’Donovan C, Pfennig A, König B, Suwalska A, Yucel K, Uher R, Young LT, Macqueen G, Alda M.

Psychol Med. 2014 Feb;44(3):507-17.




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