Discovery Guides Areas


Tracking down the Footprints of Bipolar Disorder
(Released June 2005)

  by Jennifer A. Phillips  


Key Citations

Web Sites




Adrenaline: Also called EPINEPHRINE, this is the "fight or flight hormone", accelerating the heartbeat, suppressing appetite, increasing alertness, creating excitement, anxiety, or fear depending on the cognitive mood. It also accelerates the breakdown of proteins in the body. Stimulants such as caffeine, nicotine from cigarettes, chili peppers, cocaine, etc. all raise adrenaline levels. Too much stimulation tends to exhaust adrenaline levels. The adrenaline-noradrenaline system works in tandem with thyroid hormone to control heart rate, blood pressure, subjective energy levels, and so on.

Bipolar disorder: Also known as manic-depression. Comprehensive information can be found here: NIMH. People so affected experience stronger mood swings than normal. The most extreme mood swings, whether mania or depression can cause psychosis, possibly due to flooding of the brain with excessive neurotransmitters. This seems to damage the brain. Bipolar disease is classified in two types. Bipolar disorder I with psychosis often resembles schizophrenia. Bipolar II is most commonly diagnosed as major or unipolar depression, often inappropriately treated with SSRIs which can trigger mild to serious mania. SSRIs are also not recommended for childhood depression. A way to determine the best drugs to treat bipolar depression is needed sorely as depression is more frequent and crippling, if less drastic than mania, for bipolar patients.

Brunner Syndrome: also known as MAO-A deficiency, this rare disease is well-studied. The deficient MAO-A (monoamine oxidase A) fails to mop up neurotransmitters after use. People with Brunner's syndrome are mildly mentally retarded, have extremely dangerous behavior swings in response to mood changes. It is very rare, causes mild mental retardation, and is X-linked. A related gene is under study for its role in stress and bipolar disorder—OMIM: Brunner Syndrome.

Canine Genome Information can be found at FHCRC Dog Genome. The goal is to map all the genes in the dog, also studying their arrangement relative to the human genome. If a gene is located in the dog genome we will be able to know where to look for it in the human genome also.

Deep Alpha Waves: These waves detected on an EEG have a frequency of 8-13 times per second. They reflect an awake, relaxed state, and have high amplitude (peaks), showing a lot of neurons are firing together.

Disruption of hormones: Thousands of plant compounds and chemical compounds activate the body similarly to hormones, and can disrupt the endocrine system (hormonal balance). Estrogen disruptors are particularly well studied. Isoflavones in soy stimulate one type of estrogen receptor, helping (in moderate doses) to reduce risk of breast cancer. In excessive doses, it can make the body shut down estrogen production and cause various health problems; in men it causes sperm problems. Corn, wheat, and peas have some natural estrogen disruptors, but pesticides have stronger effects. Caffeine stimulates adrenaline, and PCBs and dioxin disrupt thyroid hormones. All those factors differ from individual to individual.

DNA Methylation: A chemical process that adds a methyl group to DNA , rendering the genes coded or controlled by that stretch of DNA unusable, since proteins cannot bind to the DNA at the proper spots to begin gene expression.

Part of the Limbic system (emotional system), it controls spatial memory and association of smell & emotion with memory

Facultative hyperthyroidism: Hyperthyroidism that is triggered in periods of stress, and then returns to normal levels. It occurs in PTSD or under stress, and is not a normal stress response. It can lead to autoimmune thyroid disease or permanent hyperthyroidism. See Hot Topic: Thyroid Hormone Disorders.

functional Magnetic Resonance Imaging (fMRI): A new form of Magnetic resonance imaging (MRI) that allows brain function to be studied. For more information: BipolarWeb FMRI reference

Gene Expression: When a gene is actively copied by mRNA ("turned on") to be used for making protein, RNA or other active molecules.

Lyme disease: Caused by infection with Borrelia burburgdorferi, it can cause chronic illness with multiple, varying symptoms. It is transmitted by deer ticks and is a hazard in the United States. Laboratory tests for Borrelia, and in fact most intracellular parasites, are not very accurate, so this is an under-diagnosed disease, since it depends mainly on clinical evaluation and the patient recalling any tick bites in the past few years. A vaccine is under development. An overview can be found at: (BipolarWeb folder:

Monoamine Oxidase (MAO): This is a term for two related genes. MAO-A is implicated in Brunner syndrome. High levels of MAO-B, the other gene, seem to cause depression, and MAO inhibitors have been used for decades, in spite of their side effects. Interestingly, MAO is also active in the gut. People with low levels of MAO-A or those taking MAO inhibitors must avoid high levels of tyramine (an amino acid), such as cheese, fermented or spoiled food, etc, or risk migraines, high blood pressure, or other health effects. (See Foods to avoid with MAOIs)

Reticular formation: A network of neurons throughout the brain that keep a person awake. Damage to this causes a disorder called narcolepsy in which a person falls asleep suddenly during the daytime and cannot resist the sleep. For some people, excitement can cause a narcoleptic attack. Dogs have recently been used as an animal model for locating the narcoleptic gene. (Narcolepsy in Dogs)

Neurotransmitters: Molecules exchanged between neural cells as a form of communication and simulation. This includes ions (e.g. calcium, sodium), monoamines (e.g. serotonin, dopamine) and even basic nutrients such as glucose.

Olfactory bulb: The smell organ in the nose, it is also a direct extension of the brain, in fact it grows directly from the limbic system (the part of the brain that helps deal with emotion).
olfactory bulb & neurons

Omega-3 fatty acids: Essential fatty acids found in fish, flaxseed oil, canola, and olive oil; they are greatly lacking in the American diet since most livestock are fed grains which are high in Omega-6s, and Americans do not eat enough from other sources. They are essential to proper cell membranes, and deficiencies in Omega-3s are associated with depression, increased insulin resistance, heart disease, and many other lifestyle diseases.

Post-traumatic stress syndrome: PTSD, once known as "shell shock," it affects survivors of war, physical disasters, or abuse. Why some are more prone than other is unknown. There may be a genetic basis. The feeling of loss of control and unpredictability of repeated trauma is a large factor; it is well known that a lost sense of control increases stress hormones considerably. PTSD causes long-term hormone changes which may include hyperthyroidism, or future hypothyroidism, flashbacks as simple sensations bring back powerful memories, depression, anger, sleep disturbances, and dissociation from daily life activities.

Protein Kinase C (PKC): A family of a few different proteins that catalyze the phosphorylation of tyrosine residues in proteins, effectively activating some and inactivating others. In this paper, "an increase in PKC" specifically means an increase not just in PKCa, but also the PKC?, PKC? isoforms. All three PKCs require calcium for activation, and PKCa plays a role in controlling infection by intracellular parasites such as Legionella pneumophila.

SSRI: Serotonin reuptake inhibitors, a class of drugs that have the effect of preventing the brain from removing serotonin after use. This elevates serotonin levels in the brain. Its use is oftentimes inappropriate for bipolar disorder since the serotonin levels are not necessarily low. Many people taking it for undiagnosed bipolar depression go into mild or severe mania. Children taking SSRIs have had extreme behavior disturbances. Serotonin is related to and synthesized on the same biochemical pathway as melantonin & adrenaline.

Unipolar depression: Biologically different from bipolar depression, as it is chronic and lacks the risk of mania, although it can be just as crippling. It has been localized to hyperactivity in a frontal lobe, and a recent paper links major depression with the failure to dampen down a "fear learning" circuit once it is activated.
Major depression may be runaway grief: A part of the right frontal lobe is hyperactive in major depression

Wolfram Syndrome: A rare disorder causing deaf-blindness and/or diabetes, it is traced to the Wolframin gene, and both affected patients and carriers have a higher incidence of bipolar-like psychiatric disorders—OMIM: Wolfram Syndrome.