The Science & Treatment of Bipolar Disorder

KEYPOINTS

• 01

  Bipolar disorder is rare, often starts in the early 20s, and is dangerous

  About 1% of people have it, compared with 10–17% who have major depression. It typically begins between ages 20 and 25, and an earlier first episode makes it more likely to be a lasting feature. Huberman cites a 20–30% higher incidence of suicide than in the general population. It also ranks among the top contributors to 'global burden', meaning years of normal life lost to disability.

• 02

  Bipolar 1 is defined by mania lasting seven days or more

  A psychiatrist looks for at least three of seven symptom categories, present all day, every day, for a week or longer. These include extreme distractibility, impulsivity (one person's ex-spouse bought 10+ air fryers; others book 12 international trips in an afternoon), grandiosity held as genuine belief, flight of ideas, a reduced need for sleep that doesn't bother the person, and rapid 'machine-gun' pressured speech. The person often can't see the shift, but others can.

• 03

  Other causes of mania must be ruled out first

  Traumatic brain injury, seizures, amphetamine or cocaine use, and prescribed corticosteroids can all produce identical-looking mania. Diagnosis is hard because the clinician gets a single snapshot, through conversation, of someone who may be on day one or day six of an episode, or using drugs as part of their impulsivity. There is no blood test.

• 04

  Bipolar 2 involves shorter, milder hypomania and more depression

  Hypomanic episodes last about four days or less and are less intense. The pattern is not a neat sine wave: some people swing high to low, others rapid-cycle (for example three days manic, three normal, three depressed), and some go manic and then back to baseline without depression.

• 05

  Bipolar disorder is highly heritable, but not a single-gene condition

  Heritability is about 85%, which means a susceptibility, usually across sets of genes, that interacts with environmental factors such as early life stress and trauma. Anyone with a twin, sibling, parent, or even a cousin or uncle with bipolar 1 should watch for signs in themselves and their family.

• 06

  Borderline personality disorder differs in its triggers

  Borderline personality disorder can produce manic-looking spending, promiscuity or flights of ideas, but these episodes almost always have an external trigger. Bipolar episodes of mania or major depression arise without any trigger, although life stress can worsen symptoms.

• 07

  Lithium reaches patients slowly because it can't be patented

  Lithium is element three of the periodic table and cheap, so drug companies had little incentive to produce it. The US FDA approved it for mania only in 1970, 21 years after Cade's paper. It works for many but not all patients, has real toxicity, and needs careful blood-level monitoring, especially in the first three months.

• 08

  Lithium and ketamine act on homeostatic plasticity in opposite directions

  Homeostatic plasticity keeps circuits from being too active or too quiet for too long. Citing a Neuron review, 'Targeting Homeostatic Plasticity for the Treatment of Mood Disorders', Huberman explains that lithium lowers the excitability of postsynaptic neurons, while ketamine increases receptor numbers and excitability. Ketamine is effective for major depressive episodes, including in bipolar disorder, but its effects are transient and must be repeated. Lithium also raises BDNF, which permits rather than directs plasticity.

• 09

  Weaker parietal–limbic connectivity may underlie poor interoception

  Imaging of people at high risk for, or diagnosed with, bipolar disorder shows reduced connectivity between parietal regions and the limbic system. The parietal lobe then exerts less top-down control over the limbic system. Over time people become poor at interoception, the sensing of their own emotional and bodily states.

• 10

  Talk therapies reduce harm alongside medication

  Cognitive behavioural therapy has the most evidence, partly because it has been studied longest, and can sometimes let drugs work at lower doses. Family-focused therapy uses relatives as early-warning observers of sleep and eating changes. Interpersonal and social rhythm therapy addresses relationships, work and school. The goal throughout is harm reduction, because manic spending, promiscuity and broken relationships deepen the depressions that follow.