The Science & Treatment of Bipolar Disorder | Huberman Lab Essentials
In a Nutshell
Bipolar disorder (BP1 and BP2) involves severe manic and depressive episodes driven by neural circuit hyperactivity and atrophy of interoceptive circuits, with a 20-30x elevated suicide risk. Lithium remains the primary treatment by suppressing inflammation and protecting neurons, while combining it with CBT, interpersonal therapy, and lifestyle interventions is far more effective than any single approach. High-dose omega-3s (9.6 g/day) show some benefit as an adjunct, and creativity is statistically linked to manic traits, especially in eminent poets, writers, and artists.
These notes were generated by AI and may contain inaccuracies.
Bipolar disorder, often called bipolar depression, involves massive shifts in energy, perception, and mood that are all maladaptive. These shifts can cause tremendous damage to the person suffering from the condition and to people in their lives. People suffering from bipolar disorder are at 20 to 30 times greater risk of suicide.
Bipolar disorder impacts about 1% of people. The typical age of onset is anywhere from 20 to 25 years old, although it can be much earlier.
There are two kinds of bipolar disorder: bipolar 1 and bipolar 2. Bipolar 1 is characterized by a fairly extended period of mania. Mania is a period of very elevated mood, energy, distractibility, impulsivity, and other symptoms.
A key clinical criterion for bipolar 1 is that a person display manic episodes for 7 days or more. A psychiatrist evaluates whether the person has at least three of the following symptoms:
- Distractibility: people talk about one topic then switch rapidly, and are prone to any stimulus within the room
- Impulsivity: relates to actions, such as fidgeting then trying to leave the room
- Grandiosity: actual beliefs about their grandiose position or potential in the world
- Flight of ideas: talking extensively about one thing then switching to another
- Agitation: feeling extremely physically agitated with shaking and moving about, difficulty sitting still or acting calm
- No sleep or very minimal sleep: people can go 7 days or more with zero sleep and are not troubled by it
- Rapid pressured speech: speech comes at the listener with no room for conversation
To be diagnosed in a manic episode, a person needs to present at least three symptoms for at least 7 days.
Bipolar 2 (BP2) is characterized most often by the presence of both manic episodes and depressive episodes, or hypomania. Bipolar 2 is often diagnosed on the basis of manic episodes lasting 4 days or even less. These episodes involve increased energy, goal-directed activity, irritability, euphoria, and reduced sleep, but are not quite as intense as bipolar 1.
Bipolar 2 is often associated with drops into depressive episodes. One person might go from very high highs lasting 7 days or more to very low lows with bouts of major depression lasting 2 weeks or more. Others are rapid cycling with patterns such as 3 days manic, 3 days normal, 3 days manic, then 3 days depression.
Manic bipolar disorder does not follow a simple sine wave pattern cycling between mania and depression. The very manic to deep bouts of depression pattern is easier to recognize because of the extremes of those highs and lows.
John Cade was an Australian psychiatrist and soldier who became a prisoner of war from 1942 until 1945 after the fall of Singapore to Japan. During imprisonment, he observed fellow inmates going through wild vacillations in mood and energy from manic to depressed or normal episodes.
Cade hypothesized that there was some build-up of a chemical in these people's brains that they would urinate out, and that urinating it out would allow them to be more relaxed. After release in 1945, he began experiments taking urine from manic and non-manic patients and injecting it into guinea pigs.
Cade found that urine from manic patients seemed more toxic to guinea pigs. He identified two toxic substances in urine: urea and uric acid. Urea levels were the same in manic and non-manic patients, so he focused on uric acid.
To put uric acid into solution for injection, Cade used lithium to assist in dilution, creating lithium urate. He found that lithium urate calmed down guinea pigs injected with toxic urea, and lithium alone had a generally calming effect.
Cade moved quickly from the animal model to human patients, injecting or providing lithium orally, and found a profound and positive effect in reducing symptoms of mania. He published results in a paper entitled "Lithium Salts in the Treatment of Psychotic Excitement" on September 3rd, 1949 in the Medical Journal of Australia.
Lithium has toxicity, so blood levels must be monitored extremely carefully. It is not something people can take at a given dose with every patient responding the same. There is significant oversight and blood tests required, especially in the first 3 months of treatment.
Lithium suppresses inflammation, including in neural tissues and the brain. It is neuroprotective, allowing neurons to better handle stress such as excitotoxicity. In bipolar disorder, hyperactivity of certain brain areas can kill off neurons through chemicals like calcium and the neurotransmitter glutamate.
Exteroception is attention to things happening beyond the skin. Interoception is perception of things happening internally. People with bipolar disorder, especially into the second and third decade of the condition, seem to have progressively diminished levels of interoception. This makes it difficult to register excessive talking, lack of sleep for days, or not eating for long periods.
Atrophy of neural circuits for interoception is emerging as one of the defining neural circuit characteristics of bipolar disorder. People with bipolar depression likely have hyperactivity in certain brain circuits early in the disease, which typically sets in around the early 20s. This hyperactivity leads to excitotoxicity of neural circuits responsible for interoception. Lithium appears to protect against atrophy of those circuits.
Drug therapies are most effective when combined with talk therapies. Talk therapy on its own is rarely if ever effective for bipolar depression or bipolar disorder, whether BP1 or BP2.
Cognitive behavioral therapy seems to be the most effective talk therapy based on statistics and papers, and has been explored the most. It involves progressive exposure of the patient in a controlled clinical setting to triggers or conditions that would exacerbate bipolar disorder.
Interpersonal and social rhythm therapy focuses on how people relate to others in their life, workplace, school, and family. It is an expansion on family focused therapy. An emerging theme in psychiatry is to incorporate more social and interpersonal aspects rather than viewing the patient only as one biological system.
Electric shock therapy, or electroconvulsive therapy (ECT), shows great promise and in some cases great outcomes for bipolar disorder. It is generally used for treatment-resistant depression where people have no positive response to drug therapies. ECT does not target the manic aspects of bipolar disorder.
Negatives of ECT include that it is invasive, requires hospital visits and often inpatient care afterward, is high cost especially without insurance, requires anesthesia, and is often associated with some memory loss. These factors often rule out ECT for most patients, making it a late-stage or last-resort treatment.
It is not wise to rely purely on talk therapy or natural approaches to treat bipolar disorder given the intensity of the disorder and high suicide risk. It is a chemical and neural circuit disruption that needs to be dealt with through appropriate chemistry and prescription drug approaches from a board-certified psychiatrist.
Lifestyle interventions that support people with bipolar disorder include better sleep, adequate exercise, proper nutrition, quality healthy social interactions, regular sunlight during the day, and avoiding bright light at night. These support the nervous system and psyche of anybody.
Two supplement-based approaches have shown some promise: inositol and omega-3 fatty acids. Inositol is taken for various reasons; 900 mg of myo-inositol every third night can improve sleep and has an anti-anxiety effect during the day.
Omega-3 fatty acids from fish oil, particularly EPA and DHA, have been explored at high dosages. One study showed that 9.6 g of fish oil per day for 4 months greatly reduced symptoms of bipolar depression compared to a control group receiving olive oil. This double-blind study involved 30 subjects, males and females, ages 18 to 64.
Supplementing with high-dose omega-3s does seem to be beneficial for a good number of people with bipolar disorder. However, it should not be viewed as the only treatment approach for bipolar disorder. It is hard to imagine a scenario in which just talk therapy and fish oil and lifestyle interventions are going to completely suppress or treat bipolar disorder. People with bipolar disorder really need to consider the full picture of treatments, the drug treatments, the talk therapy treatments, and lifestyle treatments, and nutraceutical or supplement-based treatments such as omega-3 supplementation, as a full and necessary picture for dealing with their illness.
When we think of a disorder, we think of something that is really detrimental to us, something that really impairs our ability to function in work, in school, in relationships, and really starts to pull down our health status in a variety of ways. Bipolar disorder meets those criteria.
However, there is this idea that things like bipolar disorder, even things like schizophrenia in some cases, are responsible for some of the creative aspects or the creative works that have been observed and carried out by human beings for many centuries. There are good data to support the fact that certain aspects of mania are associated with creativity.
There are data pointing to the fact that certain individuals of certain occupations tend to be more creative and that creativity is associated with higher levels or incidents of bipolar depression and maybe even other forms of depression. This is a study looking at mood disorders in eminent individuals, meaning people that are not just good at what they do, but are exceptional at what they do. The study explored the percentage of people in given professions with either depression or mania.
This was a data set gleaned from more than a thousand 20th century Westerners based on their biographies that were reviewed by other people. It is an indirect measurement compiled from self-reports or from reads of self-reports. The study explored a number of different professions including the military, professional athletes, natural scientists, social scientists, people who occupied positions in public office, musical performers, artists, non-fiction writers, poetry, and others.
Those in the military and those who are professional athletes or had jobs in the social or natural sciences had a lower percentage of those that had depression or mania. In some cases, like those who were professional athletes, there was no incidence of mania, at least in this data set.
At the opposite extreme, those that were poets, so these are eminent individuals, people that were exceptional poets, exceptional fiction writers, exceptional artists, or non-fiction writers, had much higher rates. Especially for the poets, as many as 90% of these very successful poets had either depression or mania.
Creative occupations including poetry, fiction, art, non-fiction writing, music composition, and theater showed much higher incidence of things like mania. For the people in theater, the actors, even though the overall occurrence of depression and mania is lower than that in poets, the fraction of those individuals that have mania is exceedingly high. About 30% of those that they looked at who are actors have manic episodes or have full-blown mania.
These data are interesting because up until now the discussion has focused on bipolar disorder and other mood disorders for their maladaptive effects, and they are extremely maladaptive with much higher incidence of suicide. However, it would be wrong to say that certain aspects of manic episodes do not lend themselves well to creativity, or that certain aspects of major depression do not lend themselves well to creativity, or to the performing arts, or to poetry.
Bipolar disorder is an extremely serious condition. If you suspect that you have bipolar disorder or you know somebody who does, please make sure that you or they talk to a qualified health professional.
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