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Mental Health
4 Min Read
Last Updated: 12.06.23

The Science & Treatment of Bipolar Disorder

Huberman explains bipolar disorder, its biology, symptoms, causes, and types. Discusses neuroplasticity, mood regulation, and contrasts with bipolar biology. Outlines brain mechanisms, treatments (lithium, ketamine, therapies, ECT, TMS, nutraceuticals). Relevant for those with bipolar disorder and those interested in brain function.

Key Takeaways

High level takeaways from the episode.

The prominent markers of bipolar disorder include:

  • Manic episodes
  • Displaying elevated mood and expansive thoughts all day, every day
  • Distractibility and trouble holding attention
  • Impulsivity

The prominent markers of bipolar disorder include:

  • Grandiosity (i.e., delusions of grandeur)
  • Agitation, that is difficulty staying still or sitting down
  • Lack of sleep, either little or none, often going a week or more with limited sleep
  • Fast speech, with no opportunity for conversation or rapport
  • Hopelessness and a lack of optimism for the future

Bipolar disorder (BD), often called bipolar depression, is a severe psychological condition that consists of two components, Bipolar 1 (BP‑I) and Bipolar 2 (BP-​​II). The leading theory underpinning the condition is that an individual inherits a susceptibility to BD, which then becomes triggered by environmental factors.

Bipolar disorder can be difficult to detect and often goes undiagnosed, as other conditions can cause similar bouts of manic state, and in some cases, can present identical symptoms. These include, for example, traumatic brain injury, seizure, prescription drugs, illicit drugs such as amphetamine and cocaine, and corticosteroids that are often prescribed for immune conditions.

For someone to be diagnosed they must meet these criteria:

  • Present at least three symptoms for a minimum of seven days
  • The symptoms must not be better explained by something else going on in a person’s life or their immediate medical history

Bipolar disorder’s inheritability is 85%, meaning that certain individuals have a gene or a set of genes that create a susceptibility for the condition to present itself.

Usually begins to display itself when an individual reaches their early twenties. The earlier the onset on the condition, the higher likelihood that it will become a stable feature of that individual’s psychology.

There is no single gene or identified gene cluster that determines where this susceptibility is inherited from. The disorder is predominantly triggered by environmental factors.

Bipolar Disorder‑1

  • Bipolar Disorder 1 (BP‑I) is characterised by: 
    • extended period of mania
    • elevated mood and energy
    • distractibility
  • BP‑I is very noticeable and very extreme. An individual experiencing it may not recognize it, but it’s highly recognizable to others.

BP‑1 vs BP‑2

  • It is a common misconception that BD is always accompanied by severe depression. In fact, people with BP‑I do not suffer from such deep depressive states in comparison to those with BP-II.

BP‑1, on average

  • ~50% of life symptom-free
  • ~32% of life suffering from major depression /​​ severe challenges
  • ~15% of life in a manic state

BP‑2, on average

  • ~45% of life symptom-free
  • ~50% of life suffering from major depression /​​ severe challenges
  • ~4–5% of life in a manic state

People with BP-​​II experience four days or less of mania or hypomania, compared to a minimum of seven days in BP‑I individuals.

People with bipolar disorder have hyperactivity — an increased level of certain circuits in the brain. This generally manifests in their early twenties, but can be earlier.

The overuse of certain circuits can lead to a diminishing or even death of those brain circuits. This hyperactivity then leads to hypoactivity, after the death of neural circuits. This makes bipolar disorder an extremely complex condition to treat.

People suffering from bipolar disorder have progressively diminished levels of interoception. This atrophy of neural circuits for interoception is emerging as one of the defining of neural circuit characteristics of bipolar disorder, explaining symptoms such as rapid speech and a lack of sleep or appetite.

Bipolar disorder is a time sensitive condition and once it has been properly diagnosed, it is important to begin treatments as early as possible to prevent some of the longer lasting changes in brain circuitry.

It is highly recommended that sufferers implement a protocol that combines drug treatments, talk therapy, lifestyle interventions and supplements.

Bipolar Disorder

  • Affects 1% of the population
  • Higher risk of suicide (20–30% greater incidence)
  • Typical age of onset: 20–25 years old
  • Two types: Bipolar I and Bipolar II

Bipolar 1

  • Characterized by extended periods of mania (elevated mood, energy, distractibility, impulsivity)
  • Manic episodes last for 7 days or more

Bipolar 1

  • Diagnosis requires at least three of the following symptoms: 
    • Distractibility
    • Impulsivity
    • Grandiosity
    • Flight of ideas (rapid, disorganized thoughts)
    • Increased goal-​​directed activity
    • Decreased need for sleep
    • Excessive involvement in pleasurable activities with potential for negative consequences

Manic episodes: grandiosity, flight of ideas, agitation, no sleep, rapid pressured speech

To be diagnosed with a manic episode, at least three symptoms must be present for at least seven days

Bipolar II

  • Characterized by the presence of both manic episodes (mania) and depressive episodes
  • Often diagnosed on the basis of manic episodes lasting four days or less
  • Associated with drops into depressive episodes
  • Hypomania: a somewhat suppressed level of mania, can be due to the duration or intensity of mania

Bipolar disorder can vary tremendously between individuals

  • Some may experience very high highs and very low lows, while others may rapidly cycle between mania and depression
  • It is important to erase the idea that manic bipolar disorder is a simple sine wave, cycling up and down between mania and depression
  • Bipolar 1: manic episodes lasting 7 days or more
  • Bipolar 2: hypomanic episodes lasting 4 days or less

Bipolar 1:

  • 50% of time symptom-free
  • 32% of time depressed
  • 15% of time in manic or mixed manic state

Bipolar 2:

  • 50% of time in a depressed state
  • 45% of time symptom-free
  • 4–5% of time in hypomanic state

Bipolar disorder is one of the highest risk factors for global burden (years lost in engaging in normal life due to disability)

Proper treatment is crucial to reduce the impact of bipolar disorder on life trajectory

Heritability of bipolar disorder is 85%

  • Higher genetic component than major depression
  • No single gene or gene cluster identified for bipolar disorder
  • Genetic susceptibility to environmental influences can trigger bipolar disorder

If a family member has bipolar disorder, be on the lookout for symptoms in yourself and other family members

Lithium treatment for Bipolar

  • Still used with success in many patients with bipolar disorder
  • Requires careful monitoring of blood levels due to toxicity
  • Not all patients respond to lithium treatment
  • Possibility for better treatments with fewer side effects

Urgent need for new and better treatments for bipolar disorder. Understanding lithium’s mechanisms can lead to new discoveries:

  • Increases BDNF (brain-​​derived neurotrophic factor)
  • Potent anti-​​inflammatory
    • Suppresses inflammation in neural tissues and the brain
  • Neuroprotective
    • Prevents neurons from dying under certain conditions
    • Protects against excitotoxicity (hyperactivity of certain brain areas killing off neurons)

People with bipolar disorder have atrophy or removal of certain neural connections over time

  • Leads to diminished interoception (registering one’s own internal state)

Hyperactivity of certain neural circuits early in the disease

  • Leads to excitotoxicity and atrophy of circuits responsible for interoception

People with bipolar disorder have reduced internal awareness due to disrupted neural structures like the insula

  • Top-​​down control over limbic system is also disrupted in bipolar disorder

Homeostatic Plasticity

  • A form of neuroplasticity that balances neural circuit activity
  • If a neural circuit is overactive, changes occur at the cellular level to reduce activity
  • If a neural circuit is underactive, changes occur to increase activity
  • Involves the addition or removal of receptors in the postsynaptic neuron

Lithium and ketamine seem to exert their actions through effects on homeostatic neuroplasticity

  • Lithium reduces excitability of neurons over time, making them less excitable
  • Ketamine increases the number of receptors in postsynaptic neurons, leading to greater excitability and electrical activity within neural circuits

Ketamine: effective treatment for major depression and depressive episodes in bipolar disorder

  • Effects are potent but transient, requiring repeated treatments

Lithium: reduces manic episodes and intensity of manic symptoms in bipolar disorder

  • Protects neural circuits from dying away due to overactivity and excitotoxicity
  • Reduces the number of receptors in certain elements within circuits, leading to less excitability and preventing excitotoxicity

Drug therapies are most effective when combined with talk therapies

  • Talk therapy alone is rarely effective for bipolar disorder

Cognitive Behavioral Therapy (CBT) is the most popular and effective talk therapy for bipolar disorder

  • Progressive exposure to triggers or conditions that exacerbate bipolar disorder in a controlled clinical setting

Family Focused Therapy

  • Involves family members in the treatment process, helping patients navigate and predict conditions that can trigger bipolar episodes

Interpersonal and Social Rhythm Therapy

  • Focuses on establishing and maintaining regular daily routines and social rhythms to stabilize mood and prevent relapse

Repetitive Transcranial Magnetic Stimulation (rTMS)

  • Non-​​invasive technique to reduce activity in specific neural circuits
  • Effective in increasing neuroplasticity and reducing depressive episodes
  • Early technique with limited availability

Ketamine Therapy

  • Primarily targets depressive aspects of bipolar disorder

Cannabis is not effective for treating manic or depressive phases of bipolar disorder

Sleep, exercise, nutrition, social interactions, and sunlight can support the nervous system and psyche of someone with bipolar disorder

  • These factors have a modulatory effect, indirectly shifting the likelihood or intensity of an episode
  • However, most people with bipolar disorder will still need drug therapy intervention

Inositol and omega‑3 fatty acids have shown potential in adjusting symptoms of bipolar disorder

People with bipolar disorder should consider a combination of drug treatments, talk therapy, lifestyle interventions, and supplement-​​based treatments (such as omega‑3 supplementation) to manage their illness

Certain aspects of mania are associated with creativity

  • Occupations with higher incidence of bipolar depression: poetry, fiction writing, art, nonfiction writing, music composition, theater
  • Important to distinguish between emotional states and full-​​blown bipolar disorder
  • Be cautious when labeling people as “bipolar” or “OCD” without understanding the severity of these psychiatric conditions


Science-​​based tools and supplements that push the needle.

Drug Therapies + Talk Therapies for Bipolar


SSRIs for Bipolar


Monoamine Oxidase Inhibitors (MAO Inhibitors) for Bipolar


Cognitive Behavioral Therapy for Bipolar


Electroconvulsive Therapy (ECT) for Bipolar


Repetitive Transcranial Magnetic Stimulation (rTMS/​​TMS) for Bipolar


Lithium for Bipolar


Psilocybin for Bipolar


Myo-​​Inositol for Bipolar


Omega‑3 Fatty Acids for Bipolar


Ketamine for Bipolar



We recommend using this distillation as a supplemental resource to the source material.

  • The Science & Treatment of Bipolar Disorder

    Huberman Lab #82

    Huberman explores bipolar disorder’s biology, symptoms, causes, types, and treatments. Covers neuroplasticity, mood regulation, and brain mechanisms. Relevant for understanding bipolar and brain function.

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