Bipolar Disorder on the Knife’s Edge of Emotion

When I cook pasta, I need to ask my wife to taste it for doneness. She tastes it and invariably advises “30 more seconds,” which might seem minor but is actually critical. Too little cooking time results in tough, chalky pasta that fails to twirl on a fork. Too much cook time and it becomes gummy and gross. To get it al dente (Italian for “to the tooth”) and perfect, I have to balance heat, saltiness, pasta thickness, and my own lack of skill (I have to ask her every time. Every. Time.) The way our brain determines mood is much more complex, but there are similar problems if things swing too far one way or the other. Bipolar disorder is a good example of what happens when you don’t have a professional chef wife helping regulate things.

Bipolar disorder is a common condition, affecting around 1 in 25 people.^[1] Even though it is a leading cause of disability worldwide, the condition is often initially misdiagnosed.^[1,2] On top of this, bipolar disorder is heavily stigmatized, and many sufferers are unaware they have the disorder. Seventy percent of cases have an onset between the ages of 15 and 24.^[2] The risks of developing a psychological disorder like bipolar disorder are complex and hard to boil down. This is because the brain is a complex spaghetti of neurons sprinkled with neurochemicals, proteins, support cells, immune cells, and more. Research shows that bipolar disorder is caused by a complex interaction of:^[2,3]

• Genetics
  • Bipolar disorder runs in families
• Epigenetics
  • Changes to gene expression
• Environmental effects
  • Childhood circumstances, stress, employment, etc.
• Brain chemicals
  • The balance of signaling and regulatory molecules, proteins, immune cells, etc., in the brain

Bipolar disorder also tends to be present with other medical conditions, including heart disease, high blood pressure, obesity, metabolic syndrome, diabetes, anxiety, and substance abuse disorders.^[1]

For some people, an unfortunate combination of risks can spill over into bipolar disorder. Bipolar disorder is defined by cyclic swings of mood, from episodes of manic mood elevation to debilitating depression.^[1] These are two sides of the same corzetti with drastically different flavors. The range of possible moods are:^[1,2]

• Manic episode
  • Increased energy and activity that causes impairment, including risky behavior and not sleeping
• Subsyndromal hypomanic
  • Increased energy and activity without impairing everyday activities
• Cycling/mixed
  • Manic-like and depressive symptoms occurring in rapid succession or simultaneously (e.g. sleepless, impulsive, and distressed)
• Euthymia
  • Relatively stable, the person’s baseline
• Subsyndromal depressive
  • Depressive symptoms without impairing everyday activities
• Major depressive episode (MDE)
  • An intense period of at least two weeks with sadness, despair, and/or loss of interest in once-enjoyable activities, with other symptoms.

The “dominant pole” of bipolar disorder is depression, with significantly more time spent in depressive episodes than in elevated states.^[1,4] Major depressive episodes are the primary cause of suffering (morbidity), and depression can be treatment-resistant and occasionally fatal.^[4] Bipolar disorder holds the highest suicide risk of any major psychological disorder, up to 60 times that of the general population.^[5] Both manic episodes and major depressive episodes can be medical emergencies and may require hospitalization. People experiencing an episode should talk to a qualified medical professional. 

Bipolar disorder is a psychological disorder linked to physical changes in the body and brain. Scientists do not fully understand the underlying processes, but just like the risk factors, it is an interaction between genetic, epigenetic, environmental, and neurochemical factors.^[2] Researchers have found some links between bipolar disorder and increased epigenetic aging, inflammation, and mitochondrial dysfunction outside of the brain, and definite changes to connections, signaling molecules, and regulatory chemicals inside the brain.^[2,3] These changes inside the brain mix together into changes with the brain’s reward system.

The brain’s reward system motivates us to do things and is critical for our mood and function in the world.^[6] Brain chemicals like dopamine and serotonin are released after rewarding experiences like eating, sex, and drug use.^[6] These are the major brain chemicals targeted by bipolar medications.^[6] Medications for acute manic episodes generally aim to lower reward chemical concentrations, and those prescribed for major depressive episodes aim to raise chemical levels.^[1] This has resulted in several medications approved for acute mania, but can be problematic when applied to major depressive disorder, as cooking too hot can be addictive and dangerous. Using general antidepressants for bipolar depression is controversial, as there is no conclusive evidence of their efficacy, and there is a chance of triggering a manic episode.^[4] There are some bipolar-specific medications that target depression, though a significant number of people have major depressive episodes that are resistant to treatment, necessitating new targets.^[7] An exciting area of research for bipolar disorder is to regulate the body’s own release of reward neurochemicals.^[7,6] This includes new medications that target brain receptors that are suspected to be responsible for bipolar disorder. The thinking is that by changing the body’s own dopamine release systems, medications may be able to avoid addictive and mania-inducing effects while raising the mood back to a stable euthymic state.^[7] Bipolar disorder might be a disease on the knife’s edge between mania and depression, but clinical trials are hoping to take this disease to the tooth.

Creative Director Benton Lowey-Ball, MWC, BS, BFA

References:

[1] Miller S, Dell'Osso B, Ketter TA. The prevalence and burden of bipolar depression. Journal of affective disorders. 2014 Dec 1;169:S3-11. https://doi.org/10.1016/S0165-0327(14)70003-5

[2] Jain A, Mitra P. Bipolar disorder. In: StatPears [Internet]. StatPearls Publishing; Updated February 20, 2023. Accessed February 17, 2026. https://www.ncbi.nlm.nih.gov/books/NBK558998/

[3] Scaini G, Valvassori SS, Diaz AP, Lima CN, Benevenuto D, Fries GR, Quevedo J. Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings. Brazilian Journal of Psychiatry. 2020 Apr 3;42(5):536-51. https://doi.org/10.1590/1516-4446-2019-0732

[4] Frye MA, Prieto ML, Bobo WV, Kung S, Veldic M, Alarcon RD, Moore KM, Choi DS, Biernacka JM, Tye SJ. Current landscape, unmet needs, and future directions for treatment of bipolar depression. Journal of Affective Disorders. 2014 Dec 1;169:S17-23. https://doi.org/10.1016/S0165-0327(14)70005-9

[5] Costa LDS, Alencar ÁP, Neto PJN, dos Santos MD, da Silva CGL, Pinheiro SDFL, Teixeira Silveira R, Bianco BAV, Pinheiro Júnior RF, de Lima MAP, Reis AOA. Risk factors for suicide in bipolar disorder: a systematic review. Journal of affective disorders. 2015 Jan 1;170:237-54. http://dx.doi.org/10.1016/j.jad.2014.09.003

[6] Bruijnzeel AW. kappa-Opioid receptor signaling and brain reward function. Brain research reviews. 2009 Dec 11;62(1):127-46. https://doi.org/10.1016/j.brainresrev.2009.09.008

[7] Jacobson ML, Browne CA, Lucki I. Kappa opioid receptor antagonists as potential therapeutics for stress-related disorders. Annual review of pharmacology and toxicology. 2020 Jan 6;60(1):615-36. https://doi.org/10.1146/annurev-pharmtox-010919-023317