A Cause Of Bipolar Disorder Is Discovered Thanks To Lithium

Although Bipolar disorder affects between 1% and 3% of the population, the great variability of its possible causes means that its nature remains relatively unknown. Something similar happened until recently with lithium, the drug of choice in the treatment of this disorder, which has been used for decades without its mechanism of action being known.

A study by Evan Snyder, Brian Tobe and other authors recently published in the journal Proceedings of the National Academy of Sciences has provided fundamental keys about the mechanism of action of lithium and the cause of cases of bipolar disorder that improve with this drug. Specifically, they have detected alterations in the CRMP2 protein.

Characteristics of Bipolar Disorder

Bipolar disorder is characterized by the appearance of periods of weeks to months in which the mood is pathologically low (depression), along with others in which energy levels increase significantly and a feeling of emotional euphoria (mania) predominates.

Both manic and depressive episodes significantly interfere with a person’s normal functioning; In fact, this disorder constitutes the sixth most common cause of disability in the world population.

Specifically, the diagnosis of bipolar disorder is associated with a marked increased risk of suicide and self-harm. This is one of the reasons why it is customary to treat with powerful medications; If these do not work, electroconvulsive therapy may even be applied.

The causes of this disorder

The appearance of bipolar disorder has been related to a large number of different causes. It is believed that Genetic inheritance explains 70% of the risk of developing this alterationapproximately.

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However, the specific causal genes are not clear, since they seem to vary depending on the case; The dominant hypothesis defends that there are multiple genes involved.

Furthermore, the finding of structural and functional alterations in regions such as the lateral ventricles, basal ganglia and amygdala suggests that anatomical and physiological factors also play a relevant causal role.

On the other hand, not all people with a biological predisposition to bipolar disorder develop it. For this to happen psychosocial stress is often necessary, especially during the early stages of life; The fact that 30-50% of affected people report having suffered abuse or trauma in childhood is striking.

What is lithium?

Lithium is a chemical element of the metal family. It is the solid element, and therefore also the lightest metal of all. At a pharmacological level, lithium salts are used to regulate mood in the treatment of bipolar disorder and other similar psychological problems, such as schizoaffective disorder or cyclical depression.

Among other effects, lithium reduces the risk of suicide in people with these disorders. Although it is the medication of choice to treat bipolar disorder, lithium is only effective in about a third of affected people.

Furthermore, since the therapeutic dose is very close to the toxic dose, lithium carries risks and causes relevant secondary symptoms and adverse reactions, such as emotional dullness, weight gain, muscle tremors, nausea or the onset of diabetes insipidus and hypothyroidism.

Lithium began to be used as a psychotropic drug about 60 years ago. Yes ok its effectiveness in treating symptoms of bipolar disorder (as we have seen, in a third of cases) has been widely demonstrated in this time, until very recently the cause of these effects, that is, their mechanism of action, was not known.

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The mechanism of action of lithium

The research team led by Evan Snyder analyzed the brain cells of people with bipolar disorder, distinguishing between those that responded well to lithium and those that did not. Specifically, they used artificial stem cells to study the path of lithium once it has been introduced into the body.

Snyder and his collaborators found that in cases of bipolar disorder that benefit from treatment with lithium, the CRMP2 protein, which regulates the central nervous system. It appears that the activity of CRMP2 is altered, since it is much lower in these patients than in those who do not respond adequately to lithium.

This finding indicates that there are different variants of bipolar disorder, which reinforces the dominant theory that it is a polygenic disorder (that is, not determined by a single gene).

The discovery of the mechanism of action of lithium can promote the development of more effective drugs and with fewer side effects, since it allows research efforts to be focused on the most relevant biological processes.

Likewise, the study by Snyder’s team suggests that the identification of the causes of bipolar disorder in each specific case should be considered a determining aspect in choosing the most appropriate pharmacological treatment for the person.