Subtypes

Five subtypes of schizophrenia have been described based predominantly on clinical presentation: paranoid,
disorganized, catatonic, undi􀏱erentiated, and residual. DSM-5 no longer uses these subtypes but they are
listed in the 10th revision of the International Statistical Classi􀏧cation of Diseases and Related Health Problems
(ICD-10). They are included in this text because the authors believe them to be of clinical signi􀏱cance and they
are still used by most clinicians in the United States and around the world to describe the phenomenology of
schizophrenia.
Paranoid Type. The paranoid type of schizophrenia is characterized by preoccupation with one or more
delusions or frequent auditory hallucinations. Classically, the paranoid type of schizophrenia is characterized
mainly by the presence of delusions of persecution or grandeur (Fig. 7.1-4). Patients with paranoid
schizophrenia usually have their first episode of illness at an older age than do patients with catatonic or
disorganized schizophrenia. Patients in whom schizophrenia occurs in the late 20s or 30s have usually
established a social life that may help them through their illness, and the ego resources of paranoid patients
tend to be greater than those of patients with catatonic and disorganized schizophrenia. Patients with the
paranoid type of schizophrenia show less regression of their mental faculties, emotional responses, and
behavior than do patients with other types of schizophrenia. FIGURE 7.1-4 This patient had an arti􀏱cial eye
that he believed had special powers when removed from the socket. (Courtesy of Emil Kraepelin, M.D.)
Patients with paranoid schizophrenia are typically tense, suspicious, guarded, reserved, and sometimes hostile
or aggressive, but they can occasionally conduct themselves adequately in social situations. Their intelligence
in areas not invaded by their psychosis tends to remain intact.
Schizophrenia
Schizophrenia is a disease with an increased familial incidence. It is characterized by delusions, hallucinations,
socially inacceptable behavior and/or inadequate associations (socalled positive symptoms). Lack of motivation
and of emotion also frequently occur (socalled negative symptoms). In some patients the positive symptoms
predominate (type I), in others the negative ones (type II).

In schizophrenia there is reduced blood flow and glucose uptake especially in the prefrontal cortex and, in
type II patients, also a decrease in the number of neurons (reduction in the amount of gray matter). In
addition, abnormal migration of neurons during brain development is of pathophysiological significance (!A2).

Atrophy of the spiny dendrites of pyramidal cells has been found in the prefrontal cortex and the cingulate
gyrus. The spiny dendrites contain glutamatergic synapses; their glutamatergic transmission is thus disturbed
(!A1). In addition, in the affected areas the formation of GABA and/or the number of GABAergic neurons
seems to be reduced, so that inhibition of pyramidal cells is reduced.

Special pathophysiological signficance is ascribed to dopamine: excessive availability of dopamine or

dopamine agonists can produce symptoms of schizophrenia, and inhibitors of D2 dopamine receptors have
been successfully used in the treatment of schizophrenia (see below). On the other hand, a reduction in D2
receptors has been found in the prefrontal cortex (!A1), and a reduction of D1 and D2 receptors correlates
with negative symptoms of schizophrenia, such as lack of emotions. It is possible that the reduction in
dopamine receptors is the result of an increased dopamine release and in itself has no pathogenetic effect.

Dopamine serves as a transmitter in several pathways (!B):

! Dopaminergic pathways to the limbic (mesolimbic) system; and
! to the cortex (mesocortical system) are probably essential in the development of schizophrenia.
! In the tubuloinfundibular system dopamine controls the release of hypophyseal hormones (especially
inhibition of prolactin release; !p. 260ff.).
! It controls motor activity in the nigrostriatal system (!p. 312ff.).

Release and action of dopamine are increased by several substances that promote the development of
schizophrenia (!A3, left). Thus, the dopaminergic treatment of Parkinson’s disease can lead to symptoms of
schizophrenia, which in turn can limit the treatment of Parkinson’s disease:
! L-dopa leads to an increased formation and release of dopamine.
! Monoamine oxidase inhibitors (MAO inhibitors) inhibit the breakdown of dopamine and thus increase its
availability for release in the synaptic cleft.
! Cocaine stimulates dopamine release in the synaptic cleft, too.
! Amphetamine inhibits dopamine uptake in presynaptic nerve endings and thus at the
same time raises the transmitter concentration in the synaptic cleft.

Conversely, antidopaminergic substances can improve schizophrenia (!A3, right):

! Some substances (e.g., phenothiazines, haloperidol) displace dopamine from receptors and
thus have an antidopaminergic action.
! Inhibition of the uptake of dopamine in the synaptic vesicle, for example, by reserpine, ultimately impairs the
release of the transmitter in the synaptic cleft. However, reserpine is at present not used therapeutically.

The long-term use of dopamine antagonists in a patient with schizophrenia can lead to “tardive dyskinesia” as
a result of their action on the striatum (!p. 314). This complication can limit the treatment of schizophrenia. It
is possible that serotonin also plays a role in producing schizophrenic symptoms. Excessive serotonin action
can cause hallucinations, and many antipsychotic drugs block 5-HT2 A receptors (!A1).