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, where they originally came from, or disease
process that 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; neuropeptides, 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 blood stream 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 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 is linked to the hormone epinephrine, also
known as adrenaline. Adrenaline has become associated with all
risk-taking activities that cause a "rush." Serotonin 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.
Three neurotransmitters (or chemicals) with a large body of evidence
supporting their roles in mood regulation are dopamine, serotonin, and
norepinephrine, 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 biological 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
antihypertensives) can precipitate depression.
• Patients who have successfully committed suicide by violent means have
evidence for reduced serotonin levels in the central nervous system based
on post-mortem 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 used to make serotonin.
• Nearly all effective antidepressant medications affect receptors for
dopamine, norepinephrine, and serotonin in the brains of animal models.
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 as well as the numbers of receptors available
to receive these neurotransmitters. If one thinks of the body as
continually adjusting itself in order to maintain a proper balance, the
increase in the amount of neurotransmitter causes a compensatory decrease
in the number of receptors in order 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 oxidase 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 as 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.
