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Increased hippocampal size after lithium treatment in bipolars

December 11, 2009


Q: What is bipolar disorder?

Bipolar disorder, also known as manic-depressive illness, is a brain disorder that causes unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks.Bipolar disorder often develops in a person’s late teens or early adult years. At least half of all cases start before age 25. For more information please check the booklet on bipolar disorders prepared by National Institute of Mental Health.

Q: Why would a researcher be interested studying hippocampus in bipolar disorder?

Hippocampus has a role in cognitive proccesses such as memory, attention and emotional regulation dysfunctions of which are seen in patients with bipolar disorder.

Q: Is there a change in the size of hippocampus in bipolars?

No. Although researchers have found smaller hippocampi (plural for hippocampus) on both sides, left and right in patients with major depression, there is a tendency to believe that hippocampus size is similar to that of healthy normal controls in patients with bipolar disorder.On the other hand, with a relatively more sophisticated approach to structural analysis, three-dimensional mapping Bearden et al (2008) observed reduction in the subregions of the hippocampus in unmedicated bipolar patients, and they suggested a possible neural correlate for memory deficits frequently reported in this illness. Conventional structural MRI measurements might not be specific enough to detect any changes in hippocampal size in bipolars, compared to more sophisticated analysis detecting changes in a more detailed way at the subregional level.

Q: What is the treatment protocol for bipolar disorders?

Mood stabilizing medications are usually the first choice to treat bipolar disorder. In general, people with bipolar disorder continue treatment with mood stabilizers for years. Except for lithium, many of these medications are anti-convulsants. Anticonvulsant medications are usually used to treat seizures, but they also help control moods.

Atypical antipsychotic medications are sometimes used to treat symptoms of bipolar disorder.Antidepressant medications are sometimes used to treat symptoms of depression in bipolar disorder.

Lithium (sometimes known as Eskalith or Lithobid) was the fi rst mood-stabilizing medication approved by the U.S. Food and Drug Administration (FDA) in the 1970s for treatment of mania. It is often very effective in controlling symptoms of mania and preventing the recurrence of manic and depressive episodes.

Q: What was your approach in your hippocampal volume studies in bipolar disorder?

Most previous magnetic resonance imaging (MRI) studies of patients with bipolar disorder report similar hippocampus volumes across patients and controls, but because patients studied were heterogeneous with respect to course of illness variables and medication status, the conclusions of these studies remain equivocal. During my post-doctoral fellowship under the supervision of Dr.Glenda MacQueen who is now the head of Department of Psychiatry, University of Calgary we worked on a series of brains which have been collected since late 90s. This was a precious set, as there were patients who have started medication just only entrance to the study (unmedicated group), as well as patients who were medicated for a long period of time.

Q: What you have found in your studies about the size of hippocampus in patients with bipolar disorder?

We have used the structural MRI approach to investigate hippocampus in patients with bipolar disorder.

We have published our results in two papers; one showing short-term effects of lithium (1 to 8 weeks) on the hippocampal volumes of patients with bipolar disorder, another one showing the long-term effects (2 to 4 years). We did not find change in size of the hippocampi in patients who did not receive any type of medication in their lifetime or received for a very short period of time prior to their MRI scan (n=9) compared to those of healthy controls (n=30). We found increased hippocampal volume in patients who were on lithium (n=12) compared to those of controls. 12 patients who were on lithium were followed up for 2-4 years, and we also observed increase in the hippocampus size on both left and right sides.

Q: What are the clinical implications of your studies?

It is hard to come up with functional implications, as the cognitive performance of individuals are heterogeneous and not necessarily there would be a linear relationship between anatomy and function.

We,however, found preliminary evidence between increase in hippocampal size and improvement in verbal memory in bipolar patients.

Lithium might have a protective effect on a possible damage in the hippocampus as stated by a bulk of animal studies.

Q: What have the others found on the effects of lithium on the hippocampal size in patients with bipolar disorder?

Our studies were the first ones where we examined the effect of treatment with lithium on hippocampus size with a systematic approach.

Sax et al (1999) found no differences in hippocampal volumes between medicated and unmedicated patients with bipolar disorder.

No change in hippocampal volume was apparent in patients treated with lithium when compared to patients treated with medication other than lithium (Chen et al, 2004) or drug-free patients (Brambilla et al,2003).

Beyer et al (2004) found a correlation between Li use and an increase in hippocampal sizes in an older patient population.

Velakoulis et al (2006) found no change in hippocampal volumes of patients experiencing their first episode of mood-related psychosis; excluding those patients using lithium from the data did not change this pattern.

Foland et al (2008) reported increased volumes of the amygdala and hippocampus in bipolar patients treated with lithium compared with patients who were not taking lithium.

Bearden et al (2008) reported increased total hippocampal volume in lithium-treated bipolar patients compared with healthy controls and unmedicated bipolar patients.

An interview with me at Connections- St.Joseph’s Hamilton Healthcare’s NewsLetter

4 Comments leave one →
  1. November 10, 2009 12:09 am

    I look forward to this post! My understanding is that people with bipolar experience ongoing shrinking of the hippocampus, and that Lithium actually restores it. Or is this incorrect?

  2. November 11, 2009 3:04 am

    Hi there,
    The short answer to that question of your is : No. For a longer answer; I am planning to write the rest of the posts here till the end of this month. Thanks for your interest.

  3. December 13, 2009 10:59 am


    This was a very informative piece. I have great interest in this area. I look forward to more information relating to this topic.

    See you in class!



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