Lithium Demonstrates Neuroprotective Effects

MIAMI — Treatment with lithium is associated with increased hippocampal volume in patients with bipolar disorder, even if those patients have severe, highly recurrent illness.

The finding provides more evidence that lithium has neuroprotective effects and may be more widely useful in patients with neurodegenerative disorders, researchers said here in an oral session at the 10th International Conference on Bipolar Disorders (ICBD).

"We see pronounced structural brain changes in patients with bipolar disorder who have been ill for a long time, unless they have been treated with lithium," lead author Tomas Hajek, MD, from Dalhousie University, Halifax, Nova Scotia, Canada, told Medscape Medical News.

"Patients who are not treated with lithium have smaller hippocampal volumes compared with those who are treated with lithium. Even if the patients have been ill for years, have had many episodes, and have spent months or years in those episodes, if they are treated with lithium, their brains are comparable to those of healthy controls," Dr. Hajek said.

Unresolved Question

Neuroimaging studies have shown an association between lithium treatment and brain structure in humans, "but without further clinical research, the potential neuroprotective effects of lithium remain of little practical benefits to our patients," he said.

"A critical question that has been unresolved is whether the action of lithium on brain structure represents direct neurochemical effects or indirect effects that are secondary to treatment response," Dr. Hajek said.

In the current study, which was done in partnership with the International Group for the Study of Lithium-treated Patients (IGSLi), Dr. Hajek and his colleagues obtained 1.5T magnetic resonance imaging data from 37 patients with bipolar disorder who had undergone at least 2 years of lithium treatment (the lithium group), 19 patients with bipolar disorder who had undergone less than 3 months of lifetime lithium exposure more than 2 years ago (the non-lithium group), and 50 healthy control participants.

All bipolar disease patients were prospectively followed and had at least 10 years of illness and 5 episodes of mania.

The researchers found that the non-lithium group had smaller hippocampal volumes than control participants or the patients in the lithium group (F = 4.97, df = 2;102, P = .009).

Yet, patients treated with lithium spent more than 3 times longer in a mood episode when on mood stabilizers than the non-lithium group (t = 2.00, df = 51, P = .05).

Even when lithium-treated patients were having an episode while on lithium, their hippocampal volumes were comparable to that of healthy control participants, and they were significantly larger than those of the non-lithium patients (t = 2.62, df = 43, P = .006).

Lithium May Have Other Uses

"The effects of lithium seem independent from treatment response, so even those patients who did not have a full clinical response still showed the beneficial effect on their brains," Dr. Hajek said.

"If the effects of lithium on the brain were simply to prevent mood problems, then it could not be used in other patient populations. But if these effects are independent, then perhaps we can use lithium in other neurodegenerative disorders. This study is proof of the concept that lithium could be used elsewhere in neuropsychiatry or neurology."

For example, glycogen synthase kinase-3 beta, which is the main tau kinase in the human brain and is involved in several neurogenetic illnesses, is directly inhibited by lithium, Dr. Hajek said.

"The findings from Dr. Hajek's study are all preliminary, but it gives us at least a good idea that lithium has indeed, in humans, a neuroprotective effect," Michael Bauer, MD, PhD, president of IGSLi, Dresden, Germany, told Medscape Medical News.

"This is why we do not see in the clinic many bipolar patients who are on lithium developing dementia. Very few people on long-term lithium develop Alzheimer's disease, and this study provides us with at least some preliminary clinical data of the neuroprotective effects of lithium," Dr. Bauer said.

Dr. Hajek and Dr. Bauer report no relevant financial relationships.

10th International Conference on Bipolar Disorders (ICBD). Abstract 38. Presented June 15, 2013.

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Cite this: Lithium Demonstrates Neuroprotective Effects - Medscape - Jun 21, 2013.