Lithium

Lithium is mainly used for the treatment of bipolar disorder, which is a mental health condition characterized by periods of lowered mood and depression; as well as periods of heightened mood and mania. Although the mechanism of action is not well understood, lithium acts as a mood stabilizer, that can smooth out the highs and lows they experience.

Alright, almost everyone has ups and downs throughout their life. They can feel happy on a sunny day or a bit down when it’s raining outside. They might also have some extreme highs, like when they meet the love of their life, and they might even have some pretty serious lows after losing a job or a person they were close to.

However, in bipolar disorder, which used to be called manic depression, the individual has dramatic shifts in emotions, mood, and energy levels, involving extreme lows and extreme highs. These shifts usually happen over several days or weeks.

The low moods are identical to those in major depressive disorder, also known as unipolar depression. Individuals with this feel hopeless and discouraged; have a lack of energy and mental focus; and have physical symptoms, like eating and sleeping too much or too little. But along with these lows, they have periods of high moods as well, which are called manic episodes or hypomanic episodes, depending on their level of severity. In a manic state, people feel energetic; overly happy and optimistic; or even euphoric with really high self-esteem.

And on the surface, these might seem like very positive characteristics, but when an individual is in a full manic episode, these symptoms can reach a dangerous extreme. Patients experiencing mania can behave recklessly, they can have pressured speech, where they talk constantly at a rapid-fire pace, or they might have racing thoughts, and feel as if they don’t need sleep. Manic episodes also include delusions of grandeur, for example they might believe that they are on a personal mission from God, or that they have supernatural powers.

Now, the exact underlying cause of bipolar disorder isn’t known, but it’s thought that both genetic and environmental factors play a part. Even though there’s no cure for bipolar disorder, identifying and treating individuals is really important, since there’s a real danger that the person could harm themselves or die by suicide.

One of the oldest treatments for bipolar disorder is also one of the most effective treatments, and that’s lithium! It can be used as maintenance therapy to decrease the frequency and the magnitude of the ups and downs. Lithium can also be used in the treatment of acute manic episodes, although the treatment of choice is antipsychotics. Apart from the treatment of bipolar disorder, lithium is also indicated for unipolar depression that doesn’t respond to antidepressants.

Okay, but the exact mechanism by which lithium acts still remains a mystery. It’s thought that lithium regulates the release of neurotransmitters, which are signaling molecules in the brain, like serotonin, that regulate a lot of brain functions, like a person’s mood. Neurotransmitters are released by one neuron, the presynaptic neuron, and received by receptors on the postsynaptic neuron.

Okay, let’s zoom into a presynaptic neuron. Inositol is a cyclic sugar alcohol that is abundant in neurons and is the structural basis of some super important molecules. Inositol is first phosphorylated to phosphatidylinositol, or PI, which is then phosphorylated again to phosphatidylinositol 4-phosphate, or PIP, and a third time to form phosphatidylinositol 4,5 bisphosphate, or PIP2. Next, a membrane bound enzyme called phospholipase C, or PLC, splits PIP2 into inositol trisphosphate, or IP3, and diacylglycerol, or DAG.