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)
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
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
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
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
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
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
“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
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