What is the position of Neurotransmitter Theories in Bipolar Disorder?
Many current theories regarding the cause of bipolar disorder focus on the relationship between interacting neurotransmitter systems, particularly those involving norepinephrine, dopamine, and serotonin. When reading the following discussion of neurotransmitter theories, as well as the information about the treatment of bipolar disorder presented in the next unit, keep in mind that different agents used to treat bipolar disorder may affect the balance of these systems in different ways.
The catecholamine hypothesis, proposed in the 1960s, suggests that depression is associated with a decrease in one or more catecholamines, while mania results from an excess of these neurotransmitters. The theory initially focused on norepinephrine, partly because one class of drugs that is effective in depression, tricyclic antidepressants (TCAs), is known to increase norepinephrine in the synapse.
What is the role of Dopamine in Bipolar Disorder?
Many studies have suggested that dopamine may play a role in the manic symptoms of bipolar disorder. For example, excess L-dopa (which is synthesized in the body into dopamine) may produce hypomania in people with bipolar disorder. Moreover, amphetamines (which promote the release of dopamine and inhibit its removal from synapses) can precipitate hypomania or mania in people with bipolar disorder and can induce a hypomanic state in normal people. Also, antipsychotic drugs that block dopamine receptors are effective in treating severe mania.
Some researchers theorize that abnormal dopamine levels may trigger the hyperactivity and psychosis seen in severe mania, while abnormal norepinephrine levels may trigger euphoria and grandiosity.
Serotonin appears to play an inhibitory role in some areas of the brain. For example, normal levels of serotonin act to inhibit the activity of some neurons, leading to inhibition of certain behaviors. Conversely, low levels of serotonin can lead to activation (or disinhibition) of a variety of behaviors. According to one theory, a defect in the inhibitory effects of serotonin (particularly affecting its role in inhibiting norepinephrine and dopamine systems) could lead to wide swings between depression and mania. Thus, increasing serotonin activity (thereby increasing its inhibitory effects) could improve symptoms of bipolar disorder.
Neurons that secrete gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, inhibit dopamine- and possibly norepinephrine-secreting neurons. Moreover, drugs that reduce mania (e.g., lithium, benzodiazepines, and the anticonvulsant agents valproate and carbamazepine) enhance the function of GABA-secreting neurons. This suggests that a GABA deficiency may be involved in the pathogenesis of manic symptoms.
Other theories regarding the etiology of bipolar disorder include:
- sensitization and kindling theories - recurrent mood episodes are believed to result from sensitization and kindling following an initial episode
- electrolyte and membrane theories - defects in tiny channels in the neuronal membrane can affect whether a neuron "decides" to fire and activate other neurons
- neuroendocrine theories - abnormal levels of hormones that are regulated by the neuroendocrine system (e.g., cortisol) may be involved in the etiology of depressive disorders
- circadian rhythms - abnormalities in areas of the brain that control circadian rhythms could play a role in triggering mood disturbances
- seasonal patterns - seasonal changes, such as light and temperature variations, can trigger mood shifts; seasonal findings related to bipolar disorder include:
- depressive episodes tend to peak during the spring and autumn
- manic episodes often peak in the summer months
- some people experience recurring depression in the winter and hypomania in the summer
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