Page 362 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Schizophrenia
Schizophrenia is a disease with an increased (especially inhibition of prolactin release;
familial incidence. It is characterized by delu- → p. 260ff.).
sions, hallucinations, socially inacceptable be- ! It controls motor activity in the nigrostriatal
havior and/or inadequate associations (so- system (→ p. 312ff.).
called positive symptoms). Lack of motivation Release and action of dopamine are in-
Systems and of emotion also frequently occur (so- creased by several substances that promote
called negative symptoms). In some patients
the development of schizophrenia (→ A3,
the positive symptoms predominate (type I),
left). Thus, the dopaminergic treatment of Par-
kinson’s disease can lead to symptoms of
in others the negative ones (type II).
Neuromuscular and Sensory flow and glucose uptake especially in the pre- treatment of Parkinson’s disease:
schizophrenia, which in turn can limit the
In schizophrenia there is reduced blood
! L-dopa leads to an increased formation and
frontal cortex and, in type II patients, also a de-
release of dopamine.
crease in the number of neurons (reduction in
the amount of gray matter). In addition, ab-
! Monoamine oxidase inhibitors (MAO inhibi-
tors) inhibit the breakdown of dopamine and
normal migration of neurons during brain de-
thus increase its availability for release in the
velopment is of pathophysiological signifi-
synaptic cleft.
cance (→ A2).
Atrophy of the spiny dendrites of pyramidal
synaptic cleft, too.
! Amphetamine inhibits dopamine uptake in
and the cingulate gyrus. The spiny dendrites
10 cells has been found in the prefrontal cortex ! Cocaine stimulates dopamine release in the
presynaptic nerve endings and thus at the
contain glutamatergic synapses; their gluta-
matergic transmission is thus disturbed same time raises the transmitter concentra-
(→ A1). In addition, in the affected areas the tion in the synaptic cleft.
formation of GABA and/or the number of Conversely, antidopaminergic substances
GABAergic neurons seems to be reduced, so can improve schizophrenia (→ A3, right):
that inhibition of pyramidal cells is reduced. ! Some substances (e.g., phenothiazines, hal-
Special pathophysiological signficance is operidol) displace dopamine from receptors and
ascribed to dopamine: excessive availability thus have an antidopaminergic action.
of dopamine or dopamine agonists can pro- ! Inhibition of the uptake of dopamine in the
duce symptoms of schizophrenia, and inhibi- synaptic vesicle, for example, by reserpine, ul-
tors of D 2 dopamine receptors have been suc- timately impairs the release of the transmitter
cessfully used in the treatment of schizophre- in the synaptic cleft. However, reserpine is at
nia (see below). On the other hand, a reduction present not used therapeutically.
in D 2 receptors has been found in the prefron- The long-term use of dopamine antagonists
in a patient with schizophrenia can lead to
tal cortex (→ A1), and a reduction of D 1 and D 2
receptors correlates with negative symptoms “tardive dyskinesia” as a result of their action
of schizophrenia, such as lack of emotions. It on the striatum (→ p. 314). This complication
is possible that the reduction in dopamine re- can limit the treatment of schizophrenia.
ceptors is the result of an increased dopamine It is possible that serotonin also plays a role
release and in itself has no pathogenetic effect. in producing schizophrenic symptoms. Exces-
Dopamine serves as a transmitter in several sive serotonin action can cause hallucinations,
pathways (→ B): and many antipsychotic drugs block 5-HT 2 A re-
! Dopaminergic pathways to the limbic (me- ceptors (→ A1).
solimbic) system; and
! to the cortex (mesocortical system) are prob-
ably essential in the development of schizo-
phrenia.
! In the tubuloinfundibular system dopamine
352 controls the release of hypophyseal hormones
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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