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Bipolar Disorders

The brain is the most complex and least understood organ in the body.

[B]rain scans can show where abnormal activity is occurring, or whether the brain is structured differently than usual.

Along with the hormone melatonin, several neurotransmitters appear to be involved in bipolar disorders....

Some types of seizures are hard to recognize....

Physical activity, exercise, diet, vitamins, and herbal supplements can also affect these neurotransmitters.

Gender can influence medical diagnosis....

What Causes Bipolar Disorders?

The following excerpt is taken from Chapter 1 of Bipolar Disorders: A Guide to Helping Children and Adolescents by Mitzi Walsh, copyright 2000 by O'Reilly & Associates, Inc. For book orders/information, call (800) 998-9938. Permission is granted to print and distribute this excerpt for noncommercial use as long as the above source is included. The information in this article is meant to educate and should not be used as an alternative for professional medical care.

Bipolar disorders are caused by differences in how a person's brain and nervous system regulate basic behaviors.

The human nervous system is an amazing organic machine, creating and reacting to a complex stew of chemical, electrical, and magnetic impulses. It's constantly humming away, taking in information from all of our senses and reacting to it in ways that control every bodily activity, from basic breathing and circulation on up.

A single misstep in one of these processes can set a chain of events in motion that leads to a neurological event, such as a memory lapse, a seizure, or a manic episode. If such missteps occur constantly, the person has a neurological disorder.

Circadian rhythms

The nervous systems of people with bipolar disorders frequently make specific types of regulatory errors. Many of them involve the body's internal clock, which controls the phenomena known as circadian rhythms. These are the regular rhythmic changes in waking and sleeping, waxing and waning activity levels, even sensations of hunger or thirst and their satisfaction. The chemical clock that governs these rhythms is located in a part of the hypothalamus gland called the suprachiasmatic nucleus, which (among other things) regulates the pineal gland's secretion of the hormone melatonin.

You've probably heard about melatonin supplements sold as a cure for insomnia. Indeed, this hormone is the body's own shut-down mechanism, and production of it usually kicks in as dusk begins. The suprachiasmatic nucleus sets itself based on the past several days' pattern of light and dark, slowly adjusting itself in pace with the seasons. It does seem important for people to be exposed to at least some strong, direct light (sunlight or artificial) around mid-day, and for the overall patterns of dark and light to change slowly and naturally. People with bipolar disorders appear to have more difficulty in regulating this system. It's a chicken-and-egg situation: the rhythms are disordered, so sleep, waking, and other patterns are disturbed. As insomnia, oversleeping, changes in eating habits, and higher or lower activity levels set in, the clock gets harder to reset, and the person becomes more and more ill.1

The production of the neurotransmitter serotonin is also affected by a reduced amount of light in the environment. Neurotransmitters are hormone-like chemicals that send signals to all parts of the nervous system. Serotonin affects mood, appetite, and much more. In people with bipolar disorders, serotonin and other neurotransmitters may be created in the wrong amounts, absorbed by the wrong parts of the brain or other sites, or refused admittance at sites that should accept them.

With each regulatory error, the person's symptoms become more noticeable, and more serious. It's like a snowball rolling downhill: eventually the circadian rhythms and other regulatory systems are completely off track, resulting in extreme mood swings, and bringing on depression, mania, or other abnormal states of mind. The affected person may start to have noticeable errors in thinking. He may even hear sounds or voices that aren't there, feel that he's being watched, or think that he is a special person with a great mission to accomplish.

The nervous system's disordered condition will eventually show up outwardly as well. Movements may become rapid or very slow, jerky or super-precise. The tone and pace of speech may change. For example, speedy, disjointed speech is associated with mania.

What is it about people with bipolar disorders that permits this devastating chain reaction to occur? As of this writing, no one can point to a specific gene or brain difference with certainty, but bipolar disorders are probably caused by a complicated mix of inherited genetic differences, differences in brain structure and chemistry, unusual electrical or magnetic activity in the brain, and environmental factors.

Genetic differences

There is currently no doubt that bipolar disorders run in families. Several studies have made the genetic links clear, even though the exact mechanism isn't understood.2 As with other psychiatric disorders known to have genetic underpinnings, the inheritance pattern of bipolar disorders probably involves a complex interaction of several different genes.
My husband was the only one who was skipped on the paternal side from getting bipolar disorder. He has seen his sister and many uncles, etc., die as a result of this illness, and his dad is still alive with it. --Lynn, mother of 11-year-old Michael (diagnosed BPI, mixed states with psychosis)
Clues are emerging. One of the most interesting is the link between bipolar disorder and velo-cardio-facial syndrome (VCFS), as reported by a team headed by psychiatric researcher Dr. Demetri Papolos. VCFS is a fairly common set of physical abnormalities that includes a characteristically long face with a large nose, small ears with a folded portion, narrow "squinty" eyes, and a relatively expressionless mouth. People with VCFS have very nasal vocal tone, may be born with a cleft palate, have heart problems, and have learning disabilities. A deletion on chromosome 22 causes VCFS.3

Other researchers have proposed possible chromosomal differences on chromosomes 5, 12, 18, 21, and the X chromosome in people with bipolar disorders.

Brain differences

A deletion on chromosome 22 is probably at least part of the problem, likely leading to structural differences in the developing brain. There may also be differences in how the eyes (which are a sense organ tightly bound to the brain) absorb light.

The brain is the most complex and least understood organ in the body. It is the focal point of the central nervous system, which also includes the nerves of the spine. The central nervous system receives, processes, and sends billions of signals every day by way of chemicals and electrical impulses. Scientists are only starting to identify how these chemicals and power surges work, and what we know right now is woefully inadequate for helping when these processes go awry.

The brain is mostly made up of two kinds of cells. The first kind, neurons, do the hard work of transmitting all that information. The second kind, glial cells, are twice as numerous as neurons. Glial cells have the less glamorous jobs of making sure the neurons have enough nutrients and other chemicals, repairing the brain if it is injured, and confronting bacteria that try to attack the brain.

These cells combine to form a vastly intricate architecture. The brain is made up of several complex parts, all of which work together to control body functions, produce thought and emotion, and store and retrieve memories. Researchers are not absolutely sure which parts of the central nervous system are affected by bipolar disorders, although a clearer picture is emerging every year thanks to brain-imaging technologies. These include computer tomography (CAT), magnetic resonance imagery (MRI), and single photon emission computed tomography (SPECT or neuroSPECT) scans.

Although they can't be used to diagnose bipolar disorders just yet, brain scans can show where abnormal activity is occurring, or whether the brain is structured differently than usual. The Bipolar Disorders Clinic at Stanford University has been at the forefront of brain imaging research, and its preliminary findings implicate differences in the prefrontal and anterior paralimbic areas of the brain, including the almond-shaped portion called the amygdala.4

Prefrontal areas have also been found to be different in patients with ADHD. Other specific differences found in ADHD via MRI scans are significant loss of normal right/left asymmetry in the caudate nucleus, smaller right globus, smaller right anterior frontal region, smaller cerebellum, and reversal of normal lateral ventricular asymmetry, among others.5

The amygdala is one of several small structures deep within the brain that are called the basal ganglia. These structures are involved with governing automatic movements and behaviors, and are connected to the hypothalamus gland by nerve fibers. The basal ganglia are part of the brain's inhibitory system, and when they're not working properly, compulsive movements (tics), compulsive or obsessive thoughts and behaviors, and disinhibition can occur. There is a higher prevalence of bipolar disorder among people diagnosed with Tourette syndrome, a neurological disorder known to involve differences in the basal ganglia.6

More bipolar-specific findings from brain scans include an enlarged caudate nucleus, and white matter hyperintensities ("white spots" of unknown origin that show up on the scans).7 Imaging studies are not in total agreement, and the number of studies done is still fairly small. No one is sure what these brain differences really mean, nor are they leading medicine in new diagnostic or treatment directions as yet.

Neurotransmitters: The brain's telephone system

Neurons are the brain's internal communication centers, but they don't trade messages directly. Neurons have a central cell body with long "arms" called axons, and smaller tentacle-like structures called dendrites. Inside a neuron, all the messages are sent via electrical impulses. Where two neurons meet to swap information, however, there's a small space between them called the synaptic cleft. Electrical impulses have to be translated into neurotransmitters, chemicals that cross the synaptic cleft and are then retranslated into electrical signals on the other side.

The structure of a neuron
The structure of a neuron

Neurotransmitters crossing the synaptic cleft
Neurotransmitters crossing the synaptic cleft

There are many different neurotransmitters and related hormones running around in the human brain, the central nervous system, and the gastrointestinal system. They're all site-specific chemicals that can be absorbed only by certain cells, and only at certain spots. This ensures that the right kinds of messages get through. They are also used and absorbed differently in various areas of the body, and sometimes turned into other kinds of chemicals.

Along with the hormone melatonin, several neurotransmitters appear to be involved in bipolar disorders, including:

  • Serotonin. Also called 5-hydroxytryptamine or 5-HT, Serotonin controls sleep, mood, some types of sensory perception, body-temperature regulation, and appetite. It affects the rate at which hormones are released, and has something to do with inflammation.

  • Dopamine. Sometimes abbreviated as DA, this neurotransmitter helps control body movements and thought patterns, and also regulates how hormones are released.

  • Norepinephrine. Used by both the central nervous system and the peripheral sympathetic nervous system (the nerves that communicate with the rest of the body), it governs arousal, the "fight or flight" response, anxiety, and memory.
Medications that change how much of certain hormones and neurotransmitters are produced, or how these chemicals are absorbed in the brain, produce changes in symptoms--that's one of the clues that have let researchers know which chemicals have something to do with various health conditions. These medicines don't cure the underlying disorder, but in some people they can create major improvements in behavior and emotional stability. It's a bit like taking the hormone insulin for diabetes: you're still a diabetic, and you still must watch your diet, but the insulin injections help you control the illness and prevent its most debilitating effects.

Physical activity, exercise, diet, vitamins, and herbal supplements can also affect these neurotransmitters. That's one of the reasons parents and professionals should be as careful about choosing alternative treatments as they would be about prescription drugs.

There is even some evidence that positive or negative life experiences, including talk therapy and behavior modification, can help make actual neurological change over a period of time. Therapy is definitely very helpful for learning to handle the negative aspects that can occur with these disorders, from embarrassing public behavior to difficulties in personal relationships. A good relationship with a therapist is often the key to ensuring that patients keep on their medication and maintain a healthy lifestyle.

Electrical miswiring

The brain's electrical system is intimately intertwined with its chemical messaging system. Problems can occur during the electrical side of the communication process when uncontrolled surges of electricity, called seizures, take place inside the brain. Seizure disorders (epilepsy) are somewhat more common in people with bipolar disorders. That's a clue that abnormal electrical activity may sometimes be involved in causing mood swings, or may happen as a result of mood swings.

Some types of seizures are hard to recognize, even with sophisticated equipment. For example, some doctors believe that the inexplicable temper tantrums and rages characteristic of children and some adults with bipolar disorders may be related to seizures occurring deep within the brain. Others suspect that an increase in a phenomenon called kindling--sort of an electrical "blip" in brain activity that can be caused by environmental triggers--may be at fault. In people with epilepsy, the kindling process leads to a seizure, while in those with migraine, kindling precedes a migraine headache or other symptom. Perhaps in some people with bipolar disorders, the result of kindling is behavioral or psychiatric disturbances. No one really knows just yet.

If epileptic seizures are suspected, neurologists usually rely on evidence gathered via an electroencephalogram (EEG). Unfortunately, EEG equipment is not sensitive enough to detect all types of seizures in all parts of the brain.

Immune-system impairment

It's not a totally mainstream idea, but some scientists theorize that bipolar disorders may include an immune system problem. There's a certain amount of good sense to this idea, since the immune system is tightly bound to the endocrine (hormonal) system. In addition, people with known immune disorders, such as lupus, often experience mood swings.

Interestingly, lithium, the most popular medication for bipolar disorders, also seems to have some antiviral effects. There hasn't been enough research done on this angle yet, but for at least some patients, immune-system problems could be a cause or a side effect of manic-depressive illness.

Other factors in bipolar disorders

Gender can influence medical diagnosis more than one might expect. Women are diagnosed more often with depressive disorders in general, although childhood bipolar diagnoses are balanced fairly evenly between males and females. There is some evidence that childhood bipolar disorder is diagnosed more commonly among males.8 Other studies have found more diagnoses of adolescent bipolar disorder among females.9

It seems likely that women and girls are sometimes misdiagnosed as bipolar due to problems that are actually caused by hormonal cycles--although men, too, can have hormonal disorders that cause mood swings. Culture has an impact as well: the bias and stress experienced by women and girls in a sexist culture can produce emotional problems, and normal behavior for a particular girl or woman can be "pathologized" when seen through certain cultural lenses. A female with a tempestuous, artistic, assertive, even aggressive temperament might be called mentally ill in a culture that does not value these attributes in females. Girls and women may also seek medical help more often than males with similar symptoms.

Bipolar women do seem to be more prone to rapid cycling than male patients, and to have more depressed and mixed moods. Hormonal activity definitely plays a role in how and when bipolar illness expresses itself, particularly right after pregnancy.10

Males can also be affected by gender bias. A man or boy with undiagnosed bipolar disorder may come to the attention of the criminal justice system before he sees a mental health professional. He may find himself with a police record rather than a treatment plan, simply because moody, unpredictable, aggressive behavior in males is generally seen as a personal problem, not a medical one. Statistically, males with bipolar disorder are more likely to get involved in potentially criminal, aggressive, assaultive, or risky behavior than females. This may be because males often have greater access to tools that make such behavior more dangerous, such as weapons and fast cars. There may also be more cultural acceptance of aggressive, risky, and even assaultive behavior among males, leading to missed diagnosis, and missed opportunities for intervention. Even though females are more likely to attempt suicide, males are more likely to actually kill themselves.

Other cultural issues, including race, religion, economic status, and nationality, can have an impact on diagnosis as well. Psychiatric professionals, school officials, and families all carry some cultural baggage, ranging from assumptions about what is proper behavior to stereotypes about the behavior of other cultural or racial groups. These ideas can play a role in who gets diagnosed, how they are treated, and what resources are made available.

Although bipolar disorders run in families, there is no evidence that any ethnic group is immune, nor is there evidence that members of any particular group have a far higher chance of developing bipolar disorder. Characteristics that often accompany these disorders, such as the ability to hyperfocus, enhanced creativity, and (within bounds) aggressiveness, are so valuable that despite the disorder's down side, individuals with bipolar disorders have been desirable as mates, and so are found in every community.

And as parents and professionals dealing with childhood bipolar disorders, it's those good characteristics that we must keep in mind. It's not right to think of everything about bipolar disorders as bad, nor should we try to turn youth with these challenges into carbon copies of their peers. Along with their illness they have often received special gifts, and these gifts can actually help them overcome their difficulties. Whether it's a creative streak, an ability to produce massive amounts of work in short bursts, or simply the wacky sense of humor and gift of gab that characterize many people with bipolar disorder, we need to recognize and build upon what's special and wonderful in these individuals. Then they can not only achieve mental health, but reach their full creative potential as individuals.


  1. Ellen Leibenluft, MD, "Circadian Rhythms Factor in Rapid-Cycling Bipolar Disorder," Psychiatric Times 8, no. 5 (May 1996).

  2. J. Rice et al., "The Familial Transmission of Bipolar Illness," Archives of General Psychiatry 44 (1987): 441-447, and M. Strober, "Relevance of Early Age-of-Onset in Genetic Studies of Bipolar Affective Disorder," Journal of the American Academy of Child and Adolescent Psychiatry 31 (1992): 606-10.

  3. D. F. Papolos, MD, et al., "Bipolar Spectrum Disorders in Patients Diagnosed with Velo-Cardio-Facial Syndrome." American Journal of Psychiatry 153 (1996): 1541-47.

  4. Arline Kaplan, "Imaging Studies Provide Insights into Neurobiology of Bipolar Disorders," Bipolar Disorders Letter (February 1998).

  5. Judith L. Rapoport, MD, et al., "Quantitative Brain Magnetic Resonance Imaging in Attention-Deficit Hyperactivity Disorder," Archives of General Psychiatry 53 (1996): 607-16.

  6. J. Kerbeshian, L. Burd, and M. G. Klug, "Comorbid Tourette's Disorder and Bipolar Disorder: An Etiologic Perspective," American Journal of Psychiatry 152, no. 11 (November 1995): 1646-51.

  7. E. H. Aylward et al., "Basal Ganglia Volumes and White Matter Hyperintensities in Bipolar Disorder," American Journal of Psychiatry 151 (1994): 687-63.

  8. Elizabeth Costello, "Child Psychiatric Disorders and Their Correlates: A Primary Care Pediatric Sample," Journal of the American Academy of Child and Adolescent Psychiatry 28 (1989): 851-55.

  9. Anne Brown, "Mood Disorders in Children and Adolescents," NARSAD Research Newsletter (Winter 1996).

  10. Jennifer Ianthe Downey, MD, "Recognizing the Range of Mood Disorders in Women," Medscape Women's Health 1, no. 8 (1996).

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