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Neurochemistry and Endocrinology in Bipolar Disorder

Rashmi Nemade, Ph.D. & Mark Dombeck, Ph.D.

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. 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 synaptic junction and the next cell receives the signal by catching the messenger chemical as it floats across the synapse in a receptor structure. 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.

brain and neuronsImportantly, 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 mechanism for allowing neurons to communicate with one another, neurotransmitters literally enable the brain to function. There are millions and millions of individual synapses in the brain. The neurotransmitter traffic and activity occurring inside those synapses is constant and complicated.

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

Measuring neurotransmitters, their chemical variants, locations, and their effects constitute a large area of study in bipolar research. It is known that these chemicals are in some way unbalanced in the bipolar brain compared to normal brain. For example, GABA is observed to be lower in the blood and spinal fluid of bipolar patients, while oxytocin-active neurons are increased in bipolar patients, but the relevancy of these findings to overall brain functioning in bipolar and normal individuals 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, but the importance of neurochemicals in creating bipolar disease is indisputable

Bipolar Disorder and Endocrinology

Just as the brain relies on neurochemical messengers for communication, the rest of the body, including the brain depends, in some part, on the endocrine system. The endocrine system uses hormones as chemical messengers. Hormones circulate from one organ to another through the bloodstream. The target or destination organ interprets the hormonal signals sent by the sending organ and acts on them accordingly. Endocrinology is the branch of medicine dealing with the endocrine system and its specific hormones. The endocrine and nervous systems are linked by the hypothalamus (a centrally located 'switching station' within the brain). The hypothalamus is an exceptionally complex region. with multiple components that control many different body functions, including the regulation of blood pressure, hunger immune responses, body temperature, and maternal behavior, just to name a few. Of particular note with regard to bipolar conditions is the fact that the hypothalamus coordinates circadian and seasonal body rhythms (See our section below on Body Rhythms for more information).

The thyroid, an endocrine organ located in the neck which produces thyroid hormone, has been the focus of much mood disorder research. Depression is frequently associated with low levels of thyroid hormone, a condition known as Hypothyroidism, while mood elevation is often associated with high levels of thyroid hormone (Hyperthyroidism). Treating hypothyroidism by supplementing or replacing thyroid hormone (in the form of Synthroid, for instance) sometimes helps alleviate depression. Similarly, reducing levels of high thyroid hormone with lithium may ease manic symptoms. Given that up to half of patients with 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 dysregulated 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, and there is little information regarding their possible role in causing or maintaining bipolar symptoms.

Because of the connections between the nervous and endocrine systems, (e.g., hypothalamic involvement in mood determination, and the effects of thyroid and ovarian hormonal imbalances on mood) it is thought that endocrine dysfunction is a potential cause of bipolar disorders. Though this may not be a surprising conclusion, it is nevertheless a difficult one to establish scientifically. It has proven difficult to determine whether endocrine dysfunction is a cause of bipolar disorder or an effect.