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Neurochemistry and Endocrinology in Bipolar Disorder

Rashmi Nemade, Ph.D. & Mark Dombeck, Ph.D., edited by Kathryn Patricelli, MA

Bipolar Disorder and Neurochemistry

The brain uses a number of chemicals as messengers to communicate with other parts of the brain and nervous system. These chemical messengers, known as neurotransmitters, are essential to all of the brain's functions. Since they are messengers, they typically come from one place and go to another to deliver their messages. Where one neuron or nerve cell ends, another one begins.

brain and neurons In between two linked neurons is a tiny space or gap called a synapse. In a simple scenario, one cell sends a neurotransmitter message across this gap and the next cell receives the signal by catching the messenger chemical as it floats across the gap. The receiving neuron's capture of the neurotransmitter chemicals alerts it that a message has been sent, and this neuron in turn sends a new message off to additional neurons that it is connected to, and so on down the line.

Neurons cannot communicate with each other except by means of this synaptic chemical message. The brain would cease to function in an instant if chemical messengers were somehow removed. By providing a way for allowing neurons to communicate with one another, neurotransmitters literally allow the brain to function. There are millions and millions of individual synapses, or gaps, in the brain. The neurotransmitter traffic and activity happening inside those gaps is constant and complicated.

There are many different kinds of neurotransmitter chemicals in the brain. The neurotransmitters that are suspected to be involved in bipolar disorder include dopamine, norepinephrine, serotonin, GABA (gamma-aminobutyrate), glutamate, and acetylcholine. Researchers also believe that another class of neurotransmitter chemicals known as neuropeptides (including endorphins, somatostatin, vasopressin, and oxytocin) play an important role in both normal brains and those brains with bipolar disorder.

Measuring neurotransmitters, their chemical variations, locations, and their effects is a large area of study in bipolar research. It is known that these chemicals are in some way unbalanced in the brain of a person with bipolar disorder compared to the brain of someone without the condition. For example, GABA is observed to be lower in the blood and spinal fluid of patients with bipolar disorder, while oxytocin-active neurons are increased in those with bipolar disorder. However, the role of these findings to overall brain functioning is not yet understood. Whether the presence, absence, or change in these chemicals is a cause or outcome of bipolar disorder remains to be determined. The importance of neurochemicals in creating bipolar disease cannot be denied.

Bipolar Disorder and Endocrinology

Neurotransmitters are not the only important chemical messengers in the body. The body also uses hormones as chemical messengers. Produced in the endocrine system, hormones circulate from one organ to another through the bloodstream. Receiving organs in the body interpret hormonal signals and respond to their messages.

The endocrine and nervous systems are linked by the hypothalamus. This is a centrally located 'switching station' within the brain. The hypothalamus is an exceptionally complex brain region. It controls many different body functions such as blood pressure, appetite, immune responses, body temperature, maternal behavior, and body rhythms dealing with circadian and seasonal rhythms. This coordination of circadian and seasonal body rhythms is particularly important when discussing bipolar disorder. (See our section below on Body Rhythms for more information).

The thyroid is an endocrine organ located in the neck that produces thyroid hormone. It has been the focus of much mood disorder research. Depression is frequently associated with low levels of thyroid hormone, a condition known as Hypothyroidism. Mood elevation is often associated with high levels of thyroid hormone (Hyperthyroidism). Treating hypothyroidism by supplementing or replacing thyroid hormone may sometimes alleviate depression. Similarly, reducing levels of high thyroid hormone with lithium may ease manic symptoms. Given that up to half of patients with a rapid cycling form of bipolar disease also have hypothyroidism, the involvement of the thyroid gland in producing or enabling bipolar disorders for some patients is a strong possibility.

Another component of the endocrine system which is known to cause mood fluctuations when not being regulated correctly is the reproductive system. As reproductive hormones are known to affect mood, most prominently in women, the source of this effect is thought to be the ovaries which secrete estrogen and testosterone. Although the role sex hormones play in mood conditions are well documented (See our earlier discussion concerning PMDD), exactly how these hormones affect mood is unclear. There is little information available currently regarding their possible role in causing or maintaining bipolar symptoms.

Because of the connections between the nervous and endocrine systems, it is thought that endocrine dysfunction is a potential cause of bipolar disorders. Though this may not be a surprising conclusion, it is a difficult one to establish scientifically. It has proven difficult to determine whether endocrine dysfunction is a cause of bipolar disorder or an effect of the condition being present.