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Schizophrenia

Synonyms: dementia praecox, auditory hallucinations, impaired information processing

Background: Schizophrenia is a chronic debilitating psychiatric disorder. It is not well

understood and probably consists of several separate illnesses. Symptoms include
disturbances in thoughts (or cognitions), affects, and perceptions and difficulties in
relationships with others. The hallmark symptom of schizophrenia is the experience of
auditory hallucinations. However, impaired information processing is probably the most
harmful symptom. Patients with schizophrenia have lower rates of employment, marriage,
and independent living than other people.

Pathophysiology: The causes of schizophrenia are not known. However, at least 2

groups of risk factors, genetic and perinatal, are widely thought to exist. A genetic factor
probably does exist because the risk of schizophrenia is elevated in biological relatives of
patients who are schizophrenic but not in adopted relatives. The risk of schizophrenia in
first-degree relatives of people with schizophrenia is 10%. If both parents are
schizophrenic, the risk of schizophrenia in their child is 40%. Concordance for
schizophrenia is about 10% for dizygotic twins and 40-50% for monozygotic twins.

Much research concerning the association of pregnancy and birth complications with
schizophrenia has been conducted. Women who are malnourished or who have certain
viral illnesses during their pregnancy may be at greater risk of giving birth to children who
later develop schizophrenia. Children born to Dutch mothers who were malnourished
during World War II have a high incidence of schizophrenia. The 1957 influenza A2
epidemic in Helsinki resulted in an increase in schizophrenia in the offspring of women
who developed this flu during their second trimester. Obstetric complications may be
associated with a higher incidence of schizophrenia. Children born in the winter months
may be at greater risk for developing schizophrenia. These perinatal risk factors suggest
that schizophrenia is a neurodevelopmental disorder, although the exact nature is far from
understood. Interest has also focused on the various connections within the brain rather
than localization in one part of the brain. Indeed, neuropsychological studies show
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impaired information processing in patients with schizophrenia, and MRI studies show
anatomic abnormalities in a network of neocortical and limbic regions and interconnecting
white matter tracts.

The prevalence of schizophrenia is approximately 1% worldwide. Reported values range

between 0.11 and 0.70 per 1000. The most recent studies indicate that the incidence of
schizophrenia may have declined during the past 10-20 years. Problems with sampling
and changes in diagnostic criteria may account for the decreased incidence.

Cost. In the United States the most recent cost estimated for direct treatment is 17.3
billion annually; for indirect treatment, the estimated cost is 15.2 billion annually.

Mortality/Morbidity: People with schizophrenia have a 10% lifetime risk of suicide.

Race: No known racial differences exist in the prevalence of schizophrenia. Some

research indicates that schizophrenia is diagnosed more frequently in black people than in
white people.

Sex: The prevalence of schizophrenia is the same in men and women. The onset of
schizophrenia is later and the symptomatology is less severe in women than in men. This
may be because of the antidopaminergic influence of estrogen.

Age: The onset usually occurs in adolescence, and symptoms remit somewhat in older
patients. Most of the deterioration that occurs in patients with schizophrenia occurs in the
first 5-10 years of the illness and is usually followed by decades of relative stability,
although a return to baseline is unusual.

The patient is usually someone who was unexceptional in his or her childhood who began
to experience a change in personality and a decrease in academic, social, and
interpersonal functioning during mid-to-late adolescence. In retrospect, family members
may describe the person with schizophrenia as an individual who was physically clumsy
and emotionally aloof during childhood. Usually, about a year passes between the onset
of these vague symptoms and the first visit to a psychiatrist.

The symptoms of schizophrenia may be divided into the 3 following domains:

◊ Positive symptoms are those that are added to the presentation such as
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hallucinations, which are usually auditory; delusions; catatonia, agitation and

disorganized speech and behavior.
◊ Negative symptoms are those patient characteristics that appear missing from the
presentation. They may include a decrease in emotional range, affective
flattening, apathy, poverty of speech, loss of interests, loss of drive, social
withdrawal, anhedonia.
◊ Cognitive symptoms include deficits in attention, memory, and executive
functions such as the ability to organize and abstract.

Symptoms usually follow a waxing and waning course.

◊ The patient's pattern of symptoms may change over years.

◊ Positive symptoms respond fairly well to antipsychotic medication, but the other
symptoms are quite persistent.
◊ Full recovery is uncommon, especially if the illness has been present for years.
The course is usually worse if comorbid substance abuse exists.
◊ Patients who are schizophrenic may show a repertoire of strange poorly
understood behaviors that are rarely observed in others. These include water
drinking to the point of intoxication, staring at oneself in the mirror, hoarding
useless objects, self-mutilation, and a disturbed wake-sleep cycle.

Some patients who are schizophrenic may be violent.

◊ Because the violence may be unpredictable and bizarre, these events are often
highly publicized.
◊ Violence may be associated with command hallucinations and is often associated
with substance abuse.
◊ Most patients who are schizophrenic are not violent and are usually afraid of
others rather than threatening to others.

Findings on a general physical examination are usually without abnormality and are not
contributory. This examination is necessary to rule out other illnesses. A neurological
examination is important to evaluate the patient for movement disorders, particularly those
that might indicate Wilson disease or Huntington disease, or disorders that are present
before the initiation of antipsychotic medications.
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A schizophrenic person may be dressed oddly and pay insufficient attention to personal
hygiene. This person may be unduly suspicious of the examiner and endorse a variety of
odd beliefs or delusions. A schizophrenic person often has a flat affect. The person may
admit to hallucinations or attend to auditory or visual stimuli not apparent to the examiner.
The person may show thought blocking in which long pauses are made before answers to
questions or odd pauses occur in the middle of answers. Conversation and initiation of
speech may be limited. Schizophrenic patients often demonstrate their difficulty in abstract
thinking by not being able to understand common proverbs. Alternatively, the patient may
produce an esoteric or intriguing interpretation that turns out to be idiosyncratic and
meaningless on further investigation. The patient often shows poor attention, disorganized
thinking, and stereotyped or perseverative thinking. The patient may make odd
movements. Often, the person has no insight into his or her problems (anosognosia).
Orientation is usually intact. No pathognomonic signs or symptoms of schizophrenia exist.
The illness has a variety of symptoms, including disorders of thinking, perception,
emotional well-being, and interaction with others. According to the American Psychiatric
Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the patient
must have experienced at least 2 of the following symptoms for most of 1 month:

A.

1. delusions
2. hallucinations
3. disorganized speech
4. grossly disorganized or catatonic behavior
5. Negative symptoms.

Only 1 of these is required if definitions are bizarre or if hallucinations consist of a voice

keeping up a running commentary on the person*s behavior or thoughts, or if there are
two or more voices conversing with each other.

B. Marked social or occupational dysfunction.

C. Duration of at least 6 month of persistent symptoms such as attenuated forms of group
A symptoms or negative symptoms. At least 1 month of this must include a group A
symptoms.
D. Symptoms of schizoaffective and mood disorder are ruled out.
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E. Substance abuse and medical conditions are ruled out as etiological.

The diagnostic criteria of DSM-IV represent a departure from trends established by the
DSM-III in that they are less concerning symptoms of schizophrenia and oriented more the
course of the disorder. Current criteria for the diagnosis of schizophrenia require that
some symptoms be present for at least 6 months with significant disturbance for at least 1
month of that time. The actual course varies widely among individuals. The newer criteria
are more inclusive. The International Pilot Study of Schizophrenia, a World Health
Organization study, attempted to discover reliable methods of diagnosing schizophrenia
across different cultures and national boundaries.

Characteristic features.

Clinical expression of schizophrenia varies according to diagnostic criteria used to define

the population and, to some extent, the etiologic models of the clinical or researcher.
Symptoms of schizophrenia may change and become less severe over the course of the
illness. Symptoms usually include descriptions in areas of psychological and social
functioning. They are: form of thought, content of thought, perceptual disorders, affect,
sense of self, volitional symptoms, relationship to the external world, motor activity and
social behavior.

A. Form of thought refers to the structure of thought as experienced by patients and

displayed through verbal communication. Disturbances in the form of thought are
defined as formal thought disorder, which may manifest in the following ways:
loosening of associations, poverty of content and speech and thought bloking.

1. Loosening of associations is observed in speech when connections

among the patient*s ideas are absent or obscure. Listeners may fell as if
understanding of the patients* thought had been suddenly lost. Examples of loosening
of associations are listed below.
◊ Word use may be highly idiosyncratic and individualized. Words
may be created (neologism) or selected by patients using their own internal
logic and special symbolism.
◊ Abnormal concept formation is a perceptual defect in which patients
are unable to exclude irrelevant or competing ideas from their consciousness;
thinking becomes over inclusive. Extraneous items and details that have
specific meaning to patients are incorporated into the patients* communication
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but are difficult for listeners to follow.
◊ Logic in schizophrenia may follow a primitive pattern. Illogical
reasoning, exclusion of important information from the reasoning process, and
frank distortion of logical connections occurs in schizophrenic patients.
Patients assume the existence of causal connections when others perceive no
such connections. Patients may treat symbols as if they were actual objects or
may inappropriately substitute them for other logical elements.
◊ Concreteness may substitute for abstraction. The ability to form
abstract ideas may be severely impaired. The ability to discern abstractions
within ideas may become limited, and concrete interpretations of abstract
ideas may become predominant. The ability to understand metaphors and
similes may be lost.
◊ Language structural problems are seen in schizophrenia, but many
of these problems are rare. However, unusual, stilted language is common.
Examples include: neologism, verbigeration (the persistent repetition of words
or phrases), echolalia (a repetition of the words of examiner, which is seen in
severely disorganized psychotic states), mutism (a functional inhibition of
speech and vocalization, which is seen in a variety of nonpsychotic and
psychotic illnesses), word “salad” (a complete lack of language, which is seen
in patients with psychosis and several very specific central nervous system
lesions).
2. Poverty of content and speech is seen in several of the schizophrenic
spectrum disorders. Speech may be complex, concrete, or limited in overall
productivity, but it generally lacks specific information content.
3. Thought blocking is an internal interruption in patients” speech and flow of
thought. It may appear that a hallucination may interrupt patients, although they may
not be able to identify the interruption.

B. Content of thought refers to the most characteristic feature of schizophrenia,

delusions, which are defined as fixed, false beliefs. Delusions cannot be changed
by reasoning and are inconsistent with the beliefs of the patients* cultural group. In
some cases delusions may be so individualistic that no cultural connections can be
made. Delusions may be relatively circumscribed or may pervade all aspects of
patients* life and thinking. In some cases delusions may appear relatively trivial to
patients, but, more commonly, they become an organizing force in patients* lives.
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Delusions may be simple in their organization or highly complex and systematized.
Sexual, religious and philosophical content of delusions are common. They may
be: Delusions of persecution, delusions of reference, delusions of influence,
thought broadcasting, grandiose delusions, somatic delusions and others.
C. Perceptual disorders include a variety of distortions of sensory experiences and
their interpretation. Recent data suggest that a fundamental perceptual defect in
schizophrenia is the inability to habituate and suppress extraneous environmental
stimuli or internal thought processes. However, it must be emphasized that no
perceptual disturbance is pathognomonic of schizophrenia. Perceptual distortions
may occur in healthy people as well as in patients with mood disorders or organic
mental syndromes.

Perceptual disorders include hallucinations and illusions. For example, hallucinations may
be auditory, visual, tactile, gustatory, olfactory or somatic.

D. Affect is defined as the observable manifestations of mood and emotion. Affective

findings in patients with schizophrenia may be, in some cases, unreliable due to the
parkinsonian effects of the neuroleptic drugs and to cultural differences in body
language. Affective disturbances in schizophrenia include blunted affect, flat affect,
and inappropriative affect.
E. Sense of self is the perception of one’s individuality, separateness from others,
and continuity in space and time. The erosion of the sense of self may lead to the
delusions of reference and influence found in schizophrenia.
◊ In normal individuals, a solid sense of self is thought to be the basis of
good self-esteem and an ability of the individual to weather losses,
disappointments, and slights from others.
◊ In schizophrenia, as well as in other conditions, a disrupted sense of self
may manifest as:
• loss of self-esteem
• confusion about sexual identity
• an inability to separate oneself from events in the environment (i.e.,
feeling that one’s thoughts have harmed another person)
• projection of one’s own fears or suspicions onto others
• experiencing the self and others as dichotomous opposites (i.e., all
good or all bad) with little integration of the opposing features
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F. Volitional symptoms are among the most persistent and intractable features of
schizophrenia. Difficulties initiating and maintaining purposeful and goal-directed
activity and interest in the environment may account for the difficulties many patients
with schizophrenia experience in maintaining stable work and living situations.

◊ Interest in the environment may be difficult to generate and maintain for

schizophrenic patients. This difficulty may be related to ambivalence or to an
inability to generate interest internally. It may result from conflicting wishes or
desires.
◊ Initiative, or the ability to begin a goal-directed activity, is often lacking in
advanced cases of schizophrenia. Patients may experience difficulty finding
housing, financial support, and other needs as a consequence of this
symptom. They also may be unable to initiate spontaneous movement without
direction from others.
◊ Drive is the ability to pursue a goal-directed activity after in has been started.
Difficulties in maintaining goal-directed behavior appear to be common in,
although not unique to, schizophrenia. These difficulties may be a result of the
cognitive symptoms experienced by these patients or the inability to sustain
thoughts amid the perceptual and cognitive disturbances of schizophrenia.
◊ Ambition may be preserved in the absence of drive and initiative, as in
patients whose grandiose wishes are to be film or music stars, or it may be
absent. Unrealistic ambitions combined with the patient’s delusions may be an
organizing principle for complex dysfunctional patterns of behavior.

G. Relationship to the external world may change. Patients with schizophrenia tend
to become increasingly preoccupied with internal events and decreasingly influenced
by external events. Preoccupation with delusional and hallucinatory symptoms and
difficulty in communicating with others may lead to withdrawal from the world, which in
its extreme form is called autism.

H. Motor activity may change. Some alterations in motor activity and behavior may be
associated with the pharmacologic treatment of schizophrenia. Acathisia,
bradykinesia, and tardive dyskinesia are commonly associated with the effects of
neuroleptic medications rather than with schizophrenia.

Also motor activity changes may include catatonic stupor and catatonic excitement.
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Catatonic stupor is a state of dramatic motor inactivity. Patients may be unable to

initiate eating, drinking, or elimination.

Catatonic excitement, a hypermetabolic state, is a psychiatric emergency. A patient’s

activity and speech may be excessive, driven, and purposeless. Patients in this state
may be violent.

Echopraxia is the behavior equivalent of echolalia. Patients involuntary mimic the

movements of another person.

I. Social behavior may be impaired. In early and severe cases of schizophrenia,

patients may display a loss of the social skills, body language, and empathic abilities
that permit successful interaction with others and pursuit of social and vocational
functioning. Frequently, normal individuals perceive schizophrenic persons as bizarre,
hostile, or socially inept. Impairment of social skills, disturbances of thought,
perception, speech, and behavior, or long-term institutionalization can result in
schizophrenic patients who are severely socially debilitated and who may live on the
fringe of society as severely dysfunctional “street people”. In the past, these same
individuals may have been long-term institutionalized patients.

In all of the following subtypes of schizophrenia, the diagnostic criteria for schizophrenia
must be met first, particularly criterion A symptoms:

Paranoid type

A. Preoccupation with one or more delusions or frequent auditory hallucinations.

B. Does not have prominent disorganized speech, disorganized behavior, flat or
inappropriate affect, or catatonic behavior.

Disorganized type

B. All of the following are prominent:

1. Disorganized speech
2. Disorganized behavior
3. Flat or inappropriate affect
C. Does not meet criteria for catatonic type
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Catatonic type

A. Motoric immobility as evidenced by catalepsy or stupor

B. Excessive motor activity (apparently purposeless and not influenced by external
stimuli)
C. Extreme negativism or mutism
D. Peculiarities of voluntary movement such as posturing, stereotyped movements,
prominent mannerism, or prominent grimacing.
E. Echolalia or achopraxia

Undifferentiated type

Symptoms of schizophrenia criterion A are present, but the criteria are not met for
paranoid, catatonic or disorganized types.

Residual type

A. Criterion A for schizophrenia is no longer met, and criteria for other subtypes of
schizophrenia are not met.
B. Evidence of the disturbance (evidenced by negative symptoms or 2 or more
criterion A symptoms) is present in an attenuated form.

Medical Care: The use of antipsychotic medications, also known as neuroleptic

medication or major tranquilizers, is the mainstay of treatment for schizophrenia. These
medications have repeatedly been shown to diminish the positive symptoms of
schizophrenia and prevent relapses. Approximately 80% of patients who are
schizophrenic relapse within one year if antipsychotic medications are stopped, while only
20% relapse if treated. Novel antipsychotic medications are associated with fewer
extrapyramidal adverse effects, are preferred by patients, and are probably more effective
in treating the negative symptoms and cognitive impairment of schizophrenia than are the
conventional antipsychotic agents. Movement disorders should alert the physician to the
possibility of Wilson or Huntington disease. Some patients with schizophrenia have motor
disturbances, such as stereotypic movements or mannerisms, before they are exposed to
antipsychotic agents. The following adverse effects are those typically associated with
conventional antipsychotic agents. Akathisia (25-75%) is a subjective sense of inner
restlessness, mental unease, irritability, and dysphoria. Dystonia is the occurrence of
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painful and frightening muscle cramps that usually occur within 12-48 hours of the
beginning of treatment or an increase in dose. This typically occurs in young muscular
men in the head and neck, but it may extend to the trunk and limbs. Hyperprolactinemia is
associated with galactorrhea, amenorrhea, gynecomastia, impotence, and osteoporosis.
Patients with neuroleptic malignant syndrome present with hyperthermia, muscular rigidity,
altered mental state, and autonomic instability. Laboratory findings include increased
creatine kinase and myoglobinuria. Acute renal failure may be present. A significant
mortality rate exists. Rare reports of clozapine-associated neuroleptic malignant syndrome
have been made. Parkinsonism (50%) presents with tremor, bradykinesia, akinesia, and,
sometimes, rigidity or bradyphrenia. This occurs particularly in women and elderly
patients. Tardive dyskinesia. The incidence of tardive dyskinesia (TD) is as high as 70% in
elderly patients. It presents as involuntary and repetitive (but not rhythmic) movements of
the mouth and face. Chewing, sucking, grimacing, or pouting movements of the facial
muscles may occur. People may rock back and forth or tap their feet. Occasionally,
diaphragmatic dyskinesia exists, which leads to loud and irregular gasping. The patient is
often not aware of these movements. Orthostatic hypotension can be problematic at the
beginning of therapy, with dose increases, and in elderly patients. This is related to
alpha1-blockade and is particularly severe with risperidone and clozapine. Weight gain
may occur with all agents but is particularly troublesome with clozapine and olanzapine.
Some approaches to the problem of weight gain include educational programs on nutrition
and exercise, cognitive behavioral therapy, or the addition of other medications, such as
amantadine or nizatidine. The efficacy of adding medications has not yet been
established.

Diet: No particular diet is recommended. However, many psychotropic medications are

associated with weight gain, so nutritional counseling may be helpful.

Activity: Because many psychotropic medications are associated with weight gain,
persons with schizophrenia should be encouraged to be as physically active as possible.

Most patients with schizophrenia smoke. This may be a result of previous conventional
antipsychotic treatment because nicotine may ameliorate some of the adverse effects of
these drugs. Smoking may also be related to the boredom associated with
hospitalizations, the peer pressure from other patients to smoke, or the boredom
associated with unemployment. In any case, the health risks from smoking are well
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known, and patients who are schizophrenic should be encouraged to stop smoking.

All medications should be used in lower doses with children and elderly patients and with
great caution in women who are pregnant or breastfeeding.

Clozapine is the oldest atypical antipsychotic agent. It is often referred to as the criterion
standard because it is probably the most effective antipsychotic agent. It is associated
with about a 1% risk of agranulocytosis, so patients must have weekly white blood cell
count monitoring for the first 6 months (the period of greatest risk) and then monitoring
every 2 weeks. Clozapine is also associated with anticholinergic adverse effects, sedation,
and drooling. However, approximately one third of patients who have not responded to
conventional antipsychotic agents do better on clozapine. Violence, substance abuse,
smoking, and suicidality are diminished with the use of clozapine. Haloperidol (Haldol) --
Drug of choice for patients with acute psychosis when no contraindications exist.

Olanzapine (Zyprexa)

Risperidone (Risperdal)

Further Inpatient Care:

• Inpatient hospitalizations are usually very brief and are for the purposes of
stabilization rather than treatment.

Further Outpatient Care:

• The bulk of care for patients with schizophrenia occurs in an outpatient setting. This
probably is best performed with a team. Suggested members of the team include a
psychopharmacologist, counselor or therapist, social worker, nurse, vocational
counselor, and case manager.

• In the United States, many people with schizophrenia do not live with their families.
They do not always have the skills needed for independent living, so a system of
alternative housing arrangements has emerged. At their most basic, these systems
may consist of boarding houses or single-room occupancy (SRO) hotels with no
supervision. Many organizations, often state-supported, provide communal-living
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settings with 24-hour supervision in halfway houses. In some Veterans

Administration (VA) facilities, family care homes exist. Therapeutic halfway houses
in which independence and social skills training are encouraged also exist.

• One form of case management known as assertive case treatment is typically used
for patients who have had multiple inpatient hospitalizations. The treatment
involves active outreach to patients. Case managers usually have a fairly small
outpatient load of about 10 patients and are able to go into the community to work
with their clients. The managers coordinate and integrate care. This kind of
treatment is very expensive but may be associated with a better clinical and social
outcome.

• Alcohol and drug abuse are common. Of patients with schizophrenia, 20-70% have
a comorbid substance abuse problem. Comorbid substance abuse, particularly
common in younger men, is associated with increased hostility, crime, violence,
suicidality, noncompliance with medication, homelessness, poor nutrition, and
poverty. The deleterious effects of substance abuse cannot be overestimated.
Schizophrenic patients who also abuse substances may fare better in dual
diagnosis treatment programs, in which principles from both mental health and
chemical dependency fields can be integrated.

• Noncompliance with medication is difficult to estimate and is one of the reasons for
the use of intramuscular preparations of antipsychotic medications.

• Many patients with schizophrenia report symptoms of depression. Considerable

uncertainty exists as to whether depression is part of schizophrenia, a reaction to
the illness, or a complication of treatment. This is a particularly important problem
because of the high rate of suicide in patients with schizophrenia. The research
evidence for the utility of antidepressant agents in schizophrenia is mixed. Further
complicating the situation are the findings that all antipsychotic agents may have
antidepressant properties.

Prognosis:

• The prognosis is guarded.

• Patients with schizophrenia have a 10% risk of suicide.

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• Full recovery is unusual.

• Early onset of illness, family history of schizophrenia, and prominent negative

symptoms are suggestive of poor prognosis. Paradoxically, a history of substance
use may also be associated with better prognosis. However, suicide may be more
common in more intact patients.