Define: Manic Depressive Brain Chemistry and the Neurotransmitters Involved in Bipolar Disorder

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In the United States, about 2.6 percent of adults, or 5.7 million people, have bipolar disorder, according to the National Institute of Mental Health (NIMH). People who are manic depressive experience both depression and mania. When depressed, bipolar disorder patients experience a low mood, feelings of hopelessness and a decreased interest in activities.

When manic, bipolar disorder patients feel euphoric, have little need for sleep and participate in risky behaviors. What mood the patient has predominantly depends on the type of bipolar disorder. For example, a patient with bipolar disorder I has mainly manic symptoms with periods of depression, while a patient with bipolar disorder II has mainly depressive symptoms with periods of hypomania. But why do bipolar disorder patients have these mood changes? It may have to do with their brain chemistry. Several studies have investigated manic depressive brain chemistry and the differences in neurotransmitters. Let’s define manic depressive brain chemistry.


A catecholamine, dopamine is linked to the reward system and movement. In bipolar disorder patients who exhibit psychotic symptoms, such as hallucinations and delusions, there is a larger density of D2 receptors, a type of dopamine receptor, in the caudate nucleus, note Soares and Mann.

Medications that affect dopamine levels may trigger symptoms in bipolar disorder patients. Ackenheil reports that when bipolar disorder patients took cocaine, which inhibits the uptake of dopamine, they experienced manic symptoms. Some patients also had a triggering of manic symptoms when they took L-dopa, a precursor to dopamine. While an increase in dopamine causes the manic symptoms, a decrease in the neurotransmitter causes the depressive symptoms. For example, when depressed, many patients have a decrease in motivation, suggesting a decrease in dopamine. Ackenheil adds that treatment-resistant depression may result from a dopaminergic system dysfunction.


Another neurotransmitter that may be altered in the brain of a bipolar disorder patient is norepinephrine, also called noradrenaline. Also a catecholamine, norepinephrine forms from dopamine through the enzyme dopamine β-hydroxylase. Depressive symptoms may result from deficits in the functioning of the noradrenergic system, according to Ackenheil. Manji et al. add that when analyzing the brains of deceased bipolar disorder patients, higher rate of use of norepinephrine is noticed in the thalamic and cortical areas of the brain. Manic bipolar disorder patients have larger concentrations of norepinephrine and 3-methoxy-4-hydroxyphenylglycol, a metabolite of norepinephrine, according to the Lundbeck Institute.


Some of the behavioral problems that arise in bipolar disorder patients may result from abnormalities with serotonin. The neurotransmitter is involved in mood, sleep, eating and arousal. Low serotonin levels in a manic depressive’s brain may account for the changes in sleep and suicidal thoughts, notes Ackenheil. The Lundbeck Institute points out that bipolar disorder patients who are aggressive or have attempted suicide have a decreased concentration of 5-hydroxyindoleacetic, a metabolite of serotonin.


The neurotransmitter acetylcholine may also play a role in bipolar disorder. The Lundbeck Institute notes that bipolar disorder patients have lower levels of choline in their erythrocytes, or red blood cells. The enzyme choline acetyltransferase takes choline and Acetyl CoA to form acetylcholine.


NIMH: The Numbers Count: Mental Disorders in America

Soares, J.C. And Mann, J.J. (1997) The Functional Neuroanatomy of Mood Disorders. Journal of Psychiatric Research., 31(4) pp. 393-432

Ackenheil, M. (2001). Neurotransmitters and signal transduction processes in bipolar affective disorders: a synopsis. Journal of Affective Disorders, 62(1-2) pp.101-111

Manji, H.K., Quiroz, J.A., Payne, J.L., Singh, J., Lopes, B.P., Viegas, J.S. and Zarate. C.A. (2003). The underlying neurobiology of bipolar disorder. World Psychiatry, 2(3) pp.136-146

Lundbeck Institute: Bipolar Disorder – Aetiology