Page 360 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Depression
Depression is a disease with an increased fa- Serotonin (5-hydroxytryptamine [5-HT]) is
milial incidence. It can alternate with manic formed in neurons of the raphe nuclei that
phases (bipolar disorder) or can occur in isola- project to the spinal cord, cerebellum, thala-
tion (unipolar disorder). mus, hypothalamus, basal ganglia, the limbic
Pathophysiologically, depression is thought system, and cerebral cortex (→ B).
Systems to be connected with decreased (relative or ab- (→ B1) favors development of depression, for
A reduced availability or action of serotonin
solute) availability of norepinephrine and/or
example
serotonin in the brain.
! by inhibiting synthesis from tryptophan
Norepinephrine is formed in neurons of the
Neuromuscular and Sensory ons from the tegmentum predominantly con- ! by inhibiting uptake in presynaptic stores
(e.g., chlorophenylalanine);
locus ceruleus and the tegmentum (→ A). Ax-
(e.g., reserpine);
nect with the hypothalamus, anterior pitui-
! due to increased consumption of serotonin
tary, brain stem, and spinal cord. Fibers from
the locus ceruleus project to spinal cord, hypo-
through formation of inactive melatonin
(when dark, in the pineal gland).
thalamus, thalamus, limbic system, and cor-
An antidepressive effect has been observed
tex.
The release and action of norepinephrine at
when serotonin action or stimulation of the
B2):
of substances, leading to depression (→ A1):
! Availability of tryptophan can be increased
! The synthesis of norepinephrine from tyro-
10 the nerve endings can be reduced by a number serotonin receptors has been increased (→
sine via DOPA can be reduced by enzyme in-
by administering glucose. Glucose promotes
hibitors (e.g., methyltyrosine). insulin release, and the antiproteolytic and
! The uptake of norepinephrine in presynaptic protein synthesis-stimulating effect of insulin
stores can be inhibited (e.g., by reserpine). leads to a reduction of amino acid concentra-
! Norepinephrine can be replaced at the post- tion in blood. Some amino acids competitively
synaptic receptors (e.g., phenoxybenzamine, inhibit tryptophan uptake across the blood–
phentolamine). brain barrier. Loss of this inhibition would
The synaptic norepinephrine concentration raise tryptophan uptake in the brain.
and action can, however, also be increased, an ! Tricyclic antidepressants (e.g., imipramine,
effect which is in part utilized in the drug fluoxetine) inhibit the re-uptake of serotonin
treatment of depression (→ A2). in presynaptic stores and in this manner also
! Inhibitors of monoamine oxidase A (MAO- increase its synaptic concentration.
A), which is specific to norepinephrine (and ! MAO-A inhibitors (see above) raise the
serotonin) (e.g., tranylcypromine, moclobe- availability of serotonin by inhibiting its break-
mide), can delay the breakdown of norepi- down.
nephrine in the presynaptic endings and thus ! Exposure to light inhibits the conversion of
increase its availability. serotonin to melatonin. Because of the short
! Inhibitory substances of catechol-ortho- and relatively dark days, depression is particu-
methyl-transferase ([COMT] e.g., tropolone) larly frequent in northern countries during the
delay the breakdown of norepinephrine. winter months. Conversely, depression can
! Amphetamines increase synaptic concen- sometimes be succesfully treated by exposing
tration of norepinephrine, dopamine, and patients to bright light (phototherapy).
serotonin by inhibiting transport of the trans- ! Agonists (e.g., lysergic acid diethylamide
mitter. [LSD]) can directly stimulate serotonin recep-
! Desipramine inhibits re-uptake, and thus tors.
similarly increases the synaptic norepineph- ! Lithium probably exerts its antidepressive
rine concentration. effect by influencing intracellular signal trans-
! The receptors can be stimulated by agonists mission (→ p. 6).
350 (e.g., clonidine).
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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