The Science & Treatment of Bipolar Disorder

This solo episode explains what bipolar disorder is, distinguishing bipolar 1 (extended manic episodes of seven days or more) from bipolar 2 (shorter or milder hypomania, often with major depression). Huberman covers diagnostic criteria, prevalence, the very high heritability (85%), and how it differs from borderline personality disorder. He tells the remarkable story of how Australian physician John Cade discovered lithium as a treatment using guinea pigs and urine experiments, then explains the neural circuit and homeostatic plasticity mechanisms behind lithium, ketamine, and other treatments. He reviews talk therapies, ECT, TMS, and supplement approaches like inositol and omega-3s, and closes on the correlation between mania and creativity.

• Not everyone with bipolar disorder cycles into depression; many bipolar 1 patients have manic episodes then simply return to baseline.
  00:14:30
• People with diagnosed bipolar 1 spend roughly 50% of their lives symptom-free, which makes diagnosis very difficult.
  00:33:55
• Bipolar disorder is about 85% heritable, far higher than major depression, despite affecting only 1% of people.
  00:44:19
• Lithium was discovered as a treatment before the underlying biology of bipolar disorder was understood, via Cade's guinea pig and urine experiments.
  00:54:46
• Because lithium is a naturally occurring element it cannot be patented, so the FDA did not approve it for bipolar use until 1970, 21 years after Cade's paper.
  01:03:35
• Lithium and ketamine act on opposite ends of homeostatic plasticity: lithium reduces neuronal excitability, ketamine increases it.
  01:30:35
• Most psychiatrists say talk therapy alone is rarely effective for bipolar disorder; drug therapy is almost always necessary.
  01:36:47
• As many as 90% of eminent poets had either depression or mania, revealing a strong correlation between creativity and mood disorders.
  02:10:14

• People suffering from bipolar disorder are at 20 to 30 times greater risk of suicide.
  00:01:02
• People in a manic episode can go seven days or more with zero sleep and not be troubled by it.
  00:23:24
• A diagnosis of mania requires at least three of: distractibility, impulsivity, grandiosity, flight of ideas, agitation, no sleep, rapid pressured speech.
  00:19:13
• Bipolar disorder differs from borderline personality disorder mainly because bipolar episodes need no external trigger.
  00:47:32
• Lithium increases BDNF, is anti-inflammatory, and is neuroprotective against excitotoxicity.
  01:06:42
• People with bipolar disorder progressively lose interoception, the ability to register their own internal emotional and bodily states.
  01:10:47
• Ketamine is an NMDA receptor antagonist and is FDA-approved for major depression, but its effects are transient.
  01:30:35
• Huberman personally takes 900 mg of myo-inositol every third night to improve sleep depth and quality.
  01:54:33
• A 1999 study found 9.6 grams of fish oil per day over four months greatly reduced bipolar depression symptoms versus an olive oil control.
  02:01:20
• Psilocybin shows promising results for major depression in trials at Johns Hopkins but has not been tested for the mania of bipolar disorder.
  01:48:22