Episode 82: The Science & Treatment Of Bipolar Disorder | Huberman Lab

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Key Takeaways

  • Manic episodes are the defining criteria of bipolar disorder AKA bipolar depression – not all people with bipolar disorder experience deep depression
  • Types of bipolar disorder: (1) Bipolar I – characterized by an extended period of mania (elevated mood, impulse, distractibility, etc.) – the mania is extreme and noticeable to people around; (2) Bipolar II – characterized by swings of hypomania (lessened intensity of mania or shorter duration of mania) and depressive episodes
  • Bipolar I presents itself more overtly because of bouts of mania; Bipolar II can duck under the radar because of the intense depressive state and hypomania which might look more normal compared to a depressive state
  • Heritability of bipolar disorder among the general population is 85% – if someone has bipolar disorder, it’s likely they inherited a gene, set of genes, or susceptibility in genes to influences that can trigger bipolar disorder
  • Major neurological deficits in people with bipolar disorder: (1) lack of internal awareness (interoception); (2) top-down control on overall levels of energy (reduction in connectivity between parietal region and limbic system)
  • Treatment approaches need to be comprehensive and in combination – for example, lithium + talk therapy
  • “It’s naïve and in fact, wrong, to say that lifestyle interventions alone are going to prevent especially extreme forms of mania and depression.” – Dr. Andrew Huberman

Introduction

Dr. Andrew Huberman, Ph.D. is a Professor of Neurobiology and Ophthalmology at Stanford University School of Medicine. His lab focuses on neural regeneration, neuroplasticity, and brain states such as stress, focus, fear, and optimal performance.

In this episode of the Huberman Lab podcast, Andrew Huberman explains the biology, symptoms, causes, and types of bipolar disorder. He discusses mechanisms and neuroplasticity as they relate to how the brain normally regulates mood, energy, and perceptions. He outlines treatment options including lithium, ketamine, different talk therapies, electroconvulsive therapy, transcranial magnetic stimulation, and nutraceuticals.

Host: Andrew Huberman (@hubermanlab)

Background On Bipolar Disorder

  • Bipolar disorder AKA bipolar depression – but note, not all people with bipolar disorder experience deep depression  
  • Prevalence: 1% of the population has bipolar disorder
  • People with bipolar disorder have a 20-30% greater incidence of suicide
  • The typical age of onset is 20-25 years old – the earlier the onset, the more the disorder will be a “stable” feature of personality
  • Psychiatrists have a tough job diagnosing bipolar because they only see a snapshot of someone and have to eliminate other conditions and diagnose through talk – the person could be on day 1 or day 7 of a manic episode
  • Bipolar I: characterized by an extended period of mania (elevated mood, impulse, distractibility, etc.) – the mania is extreme and noticeable to people around
    • Diagnostic criteria: manic mode for 7 days or more; 3 or more of the following symptoms – (1) distractibility; (2) impulsivity; (3) words or actions of grandiosity; (4) flight of ideas (stream of consciousness discussion); (5) agitation; (6) no sleep (literally none or minimal); (7) rapid-fire speech
  • People with Bipolar I disorder spend about 50% of the time symptom-free; about 40% of the time in a majorly depressed state; and about 10% in a manic state
  • Bipolar II: characterized by swings of hypomania (lessened intensity of mania or shorter duration of mania) and depressive episodes
    • Diagnostic criteria: manic mode for 4 days or less; 3 or more of the following symptoms – (1) distractibility; (2) impulsivity; (3) words or actions of grandiosity; (4) flight of ideas (stream of consciousness discussion); (5) agitation; (6) no sleep (literally none or minimal); (7) rapid-fire speech
  • People with Bipolar II disorder spend about 45% of the time symptom-free; about 45% of the time in a majorly depressed state; and about 4-5% in a hypomanic state
  • Bipolar can present very different from person to person – could be rapid cycling or longer cycling and take many forms therein
  • People with bipolar disorder tend to spend immense amounts of money they don’t have during manic episodes, which contributes to severe financial stress and lower lows in depression
  • Certain occupations have a higher prevalence of bipolar disorder than others – for example, writers, poets

Neuroscience Of Bipolar Disorder

  • People with bipolar disorder experience atrophy or removal of connections over time that cause individuals to be very bad at registering internal state (interoception)
  • People have hyperactivity early in the disorder which leads to overuse/toxicity and hypoactivity in those circuits over time
  • The lack of interoception becomes key in intervention since the person can’t accurately describe how long they’ve been feeling a certain way – people around notice bipolar more than the person experiencing
  • People with bipolar disorder have reductions in connectivity between the parietal brain region and limbic system – the parietal exerts less suppression of elements of the limbic system so the limbic system is revving higher and/or longer

Emotional, Occupational, & Educational Burden Of Bipolar Disorder

  • Global burden: years lost in normal life due to disability
  • Having bipolar disorder is among the top 10 disabilities leading to a global burden among all categories
  • Heritability of depression: 20-45% chance a pair of twins will both have a major depressive disorder (in other words, it’s not all genes and there is strong environmental influence)
  • Heritability of bipolar disorder: 40-70% chance a pair of twins will both have bipolar disorder (in other words, higher heritability of bipolar disorder)
  • Heritability of bipolar disorder among the general population is 85% – if someone has bipolar disorder, it’s likely they inherited a gene, set of genes, or susceptibility in genes to influences that can trigger bipolar disorder
  • Extreme highs and lows impact life in substantial ways

Bipolar Disorder Vs Borderline Personality Disorder

  • Borderline personality disorder can have periods of mania or hypomania but there’s usually an environmental trigger for manic episodes– bipolar disorder does not have an external stimulus or trigger for mania
  • Defining characteristic of borderline personality disorder:  splitting – enjoying spending time with someone then switching to feeling like that person is against them or attacking them
  • People with borderline personality disorder experience some sort of external trigger or someone behaving a certain way that shifts multiple personality disorder from one mode to the other
  • Borderline personality disorder will be covered in depth on a future podcast

Neuroplasticity As It Relates To Bipolar Disorder

  • Homeostatic neuroplasticity: regulations in neural circuits over time that lead to homeostatic balance of circuit without long fluctuations or imbalances – circuits can become more or less excitable by the availability of neurotransmitters in the synapse
  • Drugs used to treat depression or bipolar disorder, etc. work by changing the availability of neurotransmitters in the synapse (SSRIs don’t directly increase serotonin)
  • MAO-inhibitors inhibit the enzyme and prevent the breakdown of neurotransmitters

Treatments: Lithium & Ketamine

  • Discovery of lithium as a treatment for bipolar disorder: discovered in the 1940s when physician injected guinea pigs and noticed they calmed down (the story is much more interesting – link to full study & Ted Talk below)
  • Cons of lithium: lithium can be highly toxic – regular bloodwork must be done  
  • Lithium can’t be patented because it’s naturally occurring so there are no huge profits for pharmaceutical companies
  • There is research pointing to the idea that lithium increases brain-derived neurotropic factor (BDNF) which permits neuroplasticity
  • Pros of lithium: potent anti-inflammatory and can suppress inflammation in neural tissues in the brain, neuroprotection (prevents neurons from dying)
  • Lithium reduces manic episodes through neural protection and diminishes activity in circuits
  • Ketamine is an effective treatment for major depression and major depressive episodes in people who suffer from bipolar disorder
  • Effects of ketamine are potent but transient – treatment must be done repeatedly
  • Lithium and ketamine exert effects through homeostatic neuroplasticity

Drug Therapy Vs Talk Therapy

  • “Without question drug therapies are going to be most effective when done in combination with talk therapies.” – Dr. Andrew Huberman
  • Talk therapy alone is rarely, if ever, effective in the treatment of the bipolar disorder (applies to both bipolar I and bipolar II)
  • Cognitive behavioral therapy is the best form of therapy for bipolar disorder – exposes the patient to triggers that would exacerbate bipolar disorder (e.g., stress)
  • Family-focused therapy: involves other family members who are close enough to the patient to speak to behavior; this also helps families learn to predict episodes
  • Interpersonal and social rhythm therapy: expansion of family-focused therapy and considers social interactions in personal life, workplace, etc.
  • Electric shock therapy: in a controlled setting of the hospital for treatment-resistant patients; induces a global seizure in the brain and nervous system which induces flow of neurotransmitters and allows neuroplasticity to take place (cons: associated memory loss, high cost, invasive)
  • Transcranial magnetic stimulation: non-invasive procedure; cap is placed on head and practitioner strategically targets magnetic fields and reduces the activity of certain circuits (still an early technique)
  • Psilocybin: being explored for the treatment of major depression; however, no controlled clinical trials for a manic component of bipolar disorder
  • Cannabis does not seem to have therapeutic effects for depressive or manic states of bipolar disorder – but – may help with sleep

Naturopathic Methods & Supplements To Consider

  • Of course, ample sunlight & optimizing sleep is critical for better health overall to support the psyche and nervous system
  • Inositol (and lithium) change how readily things float around the cell membrane
  • Myo-inositol at 18g daily for one month has had outcomes similar to pharmaceutical antianxiety and antidepressants; it also has positive effects on sleep quality and the ability to fall back asleep if woken up
  • Omega-3 fatty acids can be incorporated into pathways or cell membranes, changing the way they work
  • The data supporting omega-3 supplementation (in combination with medication) for the management of bipolar symptoms are mixed – but it appears doses need to be quite high and likely more helpful for depression than mania
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Notes By Maryann

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