What chemicals regulate emotions? What chemical imbalance occurs in depression?

Literally thousands of different chemicals participate in brain function and fall into different groups based on their chemical structure, mechanism of action, psychotropic effects, from where they originally come, or disease process they are designed to treat. The chemicals affecting emotional states in the brain consist of three broad types of compounds: neurotransmitters, which are chemically derived from single amino acids, the core constituents of proteins; neuropathies, small links of amino acids that together form a protein with psychoactive effects; and hormones, chemicals made in different regions throughout the body that are released into the bloodstream and have psychoactive effects.

Hundreds of different neurotransmitters exist in the brain, and they fall in different groups as well based on their chemical structure. The biogenic amines[1] are the most understood group of neurotransmitters and include dopamine, serotonin, and norepinephrine. Each biogenic amine is made within a small region of the brain, but axons from the neurons in those areas of the brain disseminate these neurotransmitters widely throughout the brain. All three of the noted biogenic amines are involved in the regulation of mood. Dopamine, for example, is implicated in the brain's natural reward system and therefore is seen as pleasure generating. Norepinephrine[2] is linked to the hormone epinephrine, also known as adrenaline. Adrenaline has become associated with all risk-taking activities that cause a "rush." Serotonin[3] traditionally was linked to activities involving sleep, appetite, and sexual function, better known in psychiatry as vegetative activities, but more recently has been implicated in control of mood and anxiety.

A large body of evidence supports the roles of dopamine, serotonin, and norepinephrine in mood regulation, although ongoing research is investigating the role of various other neurotransmitters in depression as well. Where does the evidence come from? Basically, the evidence stems from three sources: primarily from our understanding of the biologic and clinical effects of various psychoactive agents on the brain, secondarily from postmortem human studies, and finally from experimentation with animal models. Some of the evidence includes the following:

• Depletion of serotonin (by other medications such as certain antihypertensive) can precipitate depression.

• Patients who have successfully committed suicide by violent means have evidence of reduced serotonin levels in the central nervous system[4] based on postmortem analyses.

• Antidepressant medications increase the functional capacity of dopamine, serotonin, and norepinephrine to varying degrees in the brain.

• Successfully treated depression with an antidepressant can be reversed by blocking transport of the amino acid tryptophan[5] that is used to make serotonin.

• Nearly all effective antidepressant medications affect receptors for dopamine, norepinephrine, and serotonin in the brains of animal models.

A balance exists between the various chemicals involved in the regulation of signals that effect mood, and therefore depression can be viewed simply as a chemical imbalance.

In depression, the biogenic amines are believed to be insufficient in quantity within the synaptic cleft, and thus proper communication to the receiving neuron does not occur. Medications used as treatment for depression typically improve the signals between nerves by directly increasing the amount of dopamine, serotonin, or norepinephrine activity in the synaptic clefts between nerves. This can be done by blocking either the destruction of the neurotransmitter or the reuptake of the neurotransmitter. There is, however, a secondary effect. Increasing the amount of neurotransmitter in the synaptic cleft affects both the amount of other neurotransmitters and the numbers of receptors available to receive these neurotransmitters. If one thinks of the body as continually adjusting itself to maintain a proper balance, the increase in the amount of neurotransmitter causes a compensatory decrease in the number of receptors to balance out the relationship between the two. This is known in neuroscience as down-regulation. Down-regulation can take approximately 4 to 6 weeks to occur, which is one theory as to the reason that it may take 4 to 6 weeks for an antidepressant to have its full effect. A balance exists between the various chemicals involved in the regulation of signals that effect mood, and therefore depression can be viewed simply as a chemical imbalance. Balance is therefore restored through the use of medications that either block destruction of the chemicals or block the reuptake of those chemicals. Monoamine oxidize inhibitors (MAOIs) are a class of medications that block the destruction of the chemicals. Other antidepressants, including the commonly used serotonin reuptake inhibitors, block the return or transport of serotonin or norepinephrine into the sending neuron so that more of the neurotransmitter remains in the cleft. Some studies have demonstrated evidence of similar brain changes in response to interventions other than medications, such as from psychotherapy, as well. It is important to keep in mind that it is not clear at present whether the "chemical imbalance" is the cause or result of depression because the two appear simultaneously. Therefore the fact that depression can improve with therapy and medication is not surprising, and the term "chemical imbalance" does not argue for one approach over another.

  • [1] a group of compounds in the nervous system that participate in the regulation of brain activity, including dopamine, serotonin, and norepinephrine.
  • [2] a neurotransmitter that is involved in the regulation of mood, arousal, and memory.
  • [3] a neurotransmitter found in the brain and throughout the body. Serotonin is involved in mood regulation, anxiety, pain perception, appetite, sleep, sexual behavior, and impulsive behavior.
  • [4] nerve cells and their support cells in the brain and spinal cord.
  • [5] 1 of the 20 amino acids that constitute the building blocks of proteins in the body. Tryptophan is the building block for serotonin.
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