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Schizophrenia in adults: Clinical manifestations, course, assessment, and diagnosis

Authors: Bernard A Fischer, MD, Robert W Buchanan, MD


Section Editor: Stephen Marder, MD
Deputy Editor: Richard Hermann, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Jan 26, 2018.

INTRODUCTION — Schizophrenia is a psychiatric disorder involving chronic or recurrent psychosis. It is commonly


associated with impairments in social and occupational functioning [1]. It is among the most disabling and economically
catastrophic medical disorders, ranked by the World Health Organization as one of the top ten illnesses contributing to the
global burden of disease [2].

Characteristics of schizophrenia typically include positive symptoms, such as hallucinations or delusions, disorganized speech;
negative symptoms, such as a flat affect or poverty of speech; and impairments in cognition, including attention, memory and
executive functions. A diagnosis of schizophrenia is based on the presence of such symptoms, coupled with social or
occupational dysfunction, for at least six months in the absence of another diagnosis that would better account for the
presentation.

This topic discusses clinical manifestations, assessment, diagnosis, and course of schizophrenia. The epidemiology and
pathogenesis of schizophrenia are discussed separately. Anxiety, depression, and substance abuse in schizophrenia are
discussed separately. The treatments for schizophrenia are discussed separately, as are other psychotic disorders.
Schizophrenia in children is also reviewed separately. (See "Schizophrenia in adults: Epidemiology and pathogenesis" and
"Depression in schizophrenia" and "Anxiety in schizophrenia" and "Pharmacotherapy for schizophrenia: Acute and
maintenance phase treatment" and "Pharmacotherapy for schizophrenia: Side effect management" and "Co-occurring
schizophrenia and substance use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment and
diagnosis" and "Psychosocial interventions for schizophrenia" and "Schizophrenia in children and adolescents: Epidemiology,
pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Pharmacotherapy and psychosocial
interventions for schizophrenia in children and adolescents".)

CLINICAL MANIFESTATIONS — Schizophrenia is a syndrome. People with schizophrenia generally present with several
symptom domains (ie, areas of distinct psychopathology):

● Positive symptoms

● Negative symptoms

● Cognitive impairment

● Mood and anxiety symptoms

Positive symptoms — This group of symptoms includes the reality distortion symptoms of hallucinations and delusions, as
well as disorganized thoughts and behavior [3-5].

Hallucinations — Hallucinations are defined as the perception of a sensory process in the absence of an external source.
They can be auditory, visual, somatic, olfactory, or gustatory.

● Auditory hallucinations are the most common form of hallucination, with prevalence estimates between 40 and 80 percent
in people with schizophrenia [6,7]. Although auditory hallucinations are frequently voices, they can also take the form of
other sounds such as music, body noises, or machinery. Some people with schizophrenia describe the sounds as coming
from inside their head, whereas others can point to a specific external location from which they emanate. Auditory
hallucinations are often the manifestation of the illness most responsive to antipsychotic medication. Many people with
schizophrenia report antipsychotics “turn down the volume” of these hallucinations such that they can cope with them
better.

● Visual hallucinations are often unformed, such as glowing orbs or flashes of color. However, some people with
schizophrenia describe fully formed human figures, faces, or body parts.
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● Somatic hallucinations can include feelings of being touched, of sexual intercourse, or of pain.

● Olfactory and gustatory hallucinations have not been systematically studied, but occasional patients will report a strange
taste or smell.

Delusions — Delusions, defined as a fixed (ie, resistant to change, even in the face of overwhelming contradictory
evidence), false belief, are present in approximately 80 percent of people with schizophrenia [7]. Because insight into their
illness may be impaired, people with schizophrenia often have delusional explanations for their hallucinations. Delusions are
broadly categorized as bizarre or non-bizarre although the distinction is less important in the current diagnostic rubric.

● Bizarre delusions are clearly implausible, ie, they have no possibility of being true (eg, contradict the laws of physics).
Their content is not understandable [8]. Basic concepts may be described in an unusual way, eg, how the person
experiences time, space, the self, or causality [9]. An example of a bizarre delusion is the belief that aliens have cloned a
perfect body for the patient, but he must find a way to take off his head so that his spirit can flow into the new body.

● A non-bizarre delusion is one that while not true is understandable and has the possibility of being true. An example is
that the IRS is after the patient for not paying taxes.

The content of delusions can often be categorized as ideas of reference, grandiose, paranoid, nihilistic, and erotomanic.

● Ideas/delusions of reference are beliefs that random or neutral events are not random or neutral, but include the individual
in a special way. Common ideas of reference include believing that occurrences on the television or radio (certain words
said or songs played) are meant to deliver a special message to the individual.

● Grandiose delusions form around the belief that the person has some special significance or power.

● Paranoid delusions are clinically important, because they may prevent the individual from cooperating with evaluation or
treatment, and because they may increase the likelihood of problems, such as homelessness, as the person goes “off the
grid.”

● Nihilistic delusions are uncommon, bizarre beliefs that one is dead or one’s body is breaking down or that one does not
exist.

● In erotomanic delusions, the person erroneously believes that he/she has a special relationship with someone. These
delusions can lead to legal problems, such as restraining orders and trespass charges.

Disorganization — Schizophrenia is a thought disorder. People with schizophrenia typically display some disorganization
in behavior and/or thinking. Disorganized behaviors are directly observed while disorganized thoughts must be inferred from
the speech of the person. Disjointed, disconnected speech patterns reflect a disruption in the organization of person’s
thoughts. The most commonly observed forms of abnormal speech are tangentiality and circumstantiality, while more severe
thought disorder includes derailment, neologisms, and word salad. The symptoms of disorganization are independent of the
severity of hallucinations or [10].

● Tangential speech – The person gets increasingly further off the topic without appropriately answering a question.

● Circumstantial speech – The person will eventually answer a question, but in a markedly roundabout manner.

● Derailment – The person suddenly switches topic without any logic or segue.

● Neologisms – The creation of new, idiosyncratic words.

● Word salad – Words are thrown together without any sensible meaning.

Negative symptoms — While positive symptoms represent an exaggeration of normal processes, negative symptoms are
conceptualized as an absence or diminution of normal processes. Negative symptoms may be primary or secondary.

Primary, enduring negative symptoms represent a core feature of schizophrenia; they are also referred to as deficit symptoms.
Examples of negative symptoms include decreased expressiveness, apathy, flat affect, and a lack of energy. Independent of
the primary/secondary distinction, negative symptoms appear to cluster into two components: a diminished expression
symptom cluster and an avolition-apathy cluster [11,12]. The recognition of the existence of these two clusters may facilitate
the delineation of the pathophysiology of this illness component and lead to the development of novel therapeutics. A table
lists negative symptoms (table 1).

Primary negative symptoms are very resistant to treatment [13-15] and closely related to functional outcome [16,17]. The
severity of negative symptoms is independent of the reality distortion positive symptoms (ie, hallucinations and delusions) [18].

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A person may simultaneously have deficit symptoms and be quite psychotic, or have deficit symptoms in the absence of
positive symptoms.

Alternatively, negative symptoms may be secondary to other manifestations of the illness or its treatment. As examples,
paranoia may lead to social isolation, and depression may lead to anergy. An unchanging facial expression may be due to
extrapyramidal side effects of an antipsychotic medication.

Deficit schizophrenia — While not a recognized DSM-5 subtype of schizophrenia, people with schizophrenia who have
prominent negative (or deficit) symptoms appear to represent a distinct subgroup [18]. People with deficit schizophrenia are
less likely to have delusions with high emotional content (eg, jealous delusions), to have a depressive disorder, or to have a
substance use disorder compared with nondeficit schizophrenia [17,19,20]. People categorized as deficit are least likely to
show improvement and recovery over the course of the illness. (See "Schizophrenia in adults: Epidemiology and
pathogenesis", section on 'Deficit schizophrenia'.)

Cognitive impairment — Areas of cognition that seem to be the most affected in schizophrenia are described below [21]. It is
not known whether these areas reflect multiple unique impairments, or a generalized impairment that affects multiple areas of
cognition [22,23].

● Processing speed

● Attention

● Working memory

● Verbal learning and memory

● Visual learning and memory

● Reasoning/executive functioning

● Verbal comprehension

● Social cognition

These impairments are reflected in the performance on neuropsychological tests among people with schizophrenia. On
average, the neuropsychological test performance of someone with schizophrenia is one to two standard deviations lower than
the performance of healthy controls [22,24]. If an individual tests within the normal range on any given neuropsychological
battery, then his or her pre-morbid performance was very likely to have been above average. People with schizophrenia who
appear to lack cognitive impairment, when matched to healthy controls on age, education, and intelligence quotient (IQ), may
actually show a unique pattern of performance impairments in memory and processing speed [25,26].

Cognitive impairments usually precede the onset of positive symptoms [27]. Impairment in the performance of cognitive tasks
in people with first-episode schizophrenia is usually of a similar magnitude as that seen in people with multiple episodes [28].
The same pattern of cognitive impairment is observed in the family members of people with schizophrenia, though the
magnitude of impairment is less [29]. In a study of monozygotic twins discordant for the disorder, affected twins performed
worse on tests of memory and vigilance than the unaffected siblings [30].

Although antipsychotic and anticholinergic medications can impair cognition [31,32], reports of memory disturbances in
schizophrenia frequently predate the advent of pharmacologic treatment [33]. The same pattern of cognitive dysfunction in
people with schizophrenia is seen in both treated groups and those who have never been exposed to antipsychotics [34].

Mood and anxiety symptoms — Mood and anxiety symptoms are common in schizophrenia; mood and anxiety disorders
appear to occur at a higher rate than in the general population. The epidemiology, clinical manifestations, diagnosis, and
treatment of mood and anxiety symptoms in schizophrenia are discussed separately. (See "Depression in schizophrenia" and
"Anxiety in schizophrenia".)

Stigma — In the course of assessment and ongoing clinical care, the clinician can be an important source of compassion and
education for the patient and family. Along with treatment for symptoms and medication side effects, the patient may need help
coping with disabilities, associated losses, and the stigma associated with the diagnosis of schizophrenia. The experience of
stigmatizing attitudes towards people with schizophrenia is common [35] and may be internalized, leading to “self-stigma” [36].
Internalized stigma can be as damaging as the direct effects of the illness. In a five-month longitudinal study of 78 people with
schizophrenia, internalized stigma was associated with poorer response to vocational rehabilitation [37]. A discriminant
function analysis of 105 people with schizophrenia found that self-stigma was a predictor of decreased treatment adherence
[38,39].

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Associated physical manifestations — There are several physical manifestations associated with schizophrenia, including
neurological disturbances, catatonia, and metabolic disturbances.

Neurological disturbances — Neurological “soft signs” involve subtle impairments of sensory integration, motor
coordination, and sequencing [40]. Examples of neurological soft signs are right-left confusion, agraphesthesia (the inability to
recognize letters or numbers traced on the skin, usually on the palm of the hand), and astereognosia (the inability to identify
familiar objects by touch alone). These neurological soft signs are observed in schizophrenia, are relatively stable, and are
largely unrelated to medication [40-43].

Research findings have linked certain symptom domains to neurological signs, ie, sensory integration problems have been
correlated with deficit symptoms, disorganization, and cognitive impairment, while impaired sequencing of complex motor
behaviors has been correlated with disorganization [42,43].

Most neurological disturbances readily observed in people with schizophrenia are likely medication-induced. Antipsychotic
dopamine blockade can cause extrapyramidal symptoms (EPS), such as tremor and bradykinesia, acute dystonias, akathisia
(a subjective sense of restlessness or actual restlessness), or tardive (meaning ‘late’) dyskinesia (which includes abnormal
peri-oral and other movements). However, descriptions of movement disorders including signs of pseudoparkinsonism,
choreiform movements, and myoclonic jerking are common in the descriptions of schizophrenia that predate the development
of antipsychotics [34]. (See "First-generation antipsychotic medications: Pharmacology, administration, and comparative side
effects" and "Second-generation antipsychotic medications: Pharmacology, administration, and side effects" and "Tardive
dyskinesia: Etiology and epidemiology" and "Pharmacotherapy for schizophrenia: Side effect management".)

Catatonia — Catatonia can present in schizophrenia as either extreme negativism, eg, motiveless motor resistance to
instruction or attempts to move the person or mutism, or catatonic excitement, eg, excessive, purposeless motor activity.
Catatonia is reviewed in more detail separately (See "Catatonia in adults: Epidemiology, clinical features, assessment, and
diagnosis".)

Metabolic disturbances — Schizophrenia is associated with diabetes, hyperlipidemia, and hypertension. Although many
antipsychotic medications cause metabolic disturbances, including weight gain and diabetes, people with schizophrenia often
have other risk factors for these conditions, including a sedentary lifestyle and smoking. The life expectancy of people with
schizophrenia is reduced by more than a decade compared with the general population. This excess medical mortality is
largely mediated by heart disease [44]. (See "Pharmacotherapy for schizophrenia: Side effect management".)

Schizophrenia, independent of treatment with antipsychotic medication, is associated with altered glucose homeostasis,
indicating an increased risk of diabetes. A meta-analysis examined 16 case-control studies of glucose homeostasis in 731
antipsychotic-naive individuals with first-episode schizophrenia compared with 614 healthy controls [45]. Higher levels of
fasting plasma glucose (Hedges g = 0.20; 95% CI 0.02-0.38) and fasting plasma insulin (0.41; 95% CI 0.09-0.72) were seen
as well as lower glucose tolerance (0.61; 95% CI 0.16-1.05) and greater insulin resistance (0.35; 95% CI 0.14-0.55) in people
with schizophrenia compared with controls. Hemoglobin A1c levels did not differ between the two groups.

There is also evidence from the pre-antipsychotic era and insulin coma treatments that schizophrenia itself is associated with
insulin resistance [46].

COURSE — Although earlier descriptions of schizophrenia suggested that the course was quite poor, the course actually
shows considerable heterogeneity. One of the first and most influential longitudinal studies of the course of schizophrenia
described eight course types, which differ in several ways [47]:

● Onset – Abrupt versus insidious

● Symptom presentation – Continuous versus intermittent

● Outcome – Poor versus non-poor

Most people with schizophrenia in the study had an acute onset, intermittent symptoms, and later had no or only mild
symptoms. Only about 20 percent had the stereotypical insidious onset, continuous symptoms, and poor outcome. In a re-
examination of these data, participants were re-diagnosed with more stringent DSM-IV and ICD criteria, and the results among
those retaining a schizophrenia diagnosis were largely unchanged from the original course observations [48].

Other influential longitudinal studies of schizophrenia demonstrate that the course of schizophrenia is not uniform and that
there are subsets of individuals with fairly good outcome [49-51]. A 15- to 25-year follow-up of 644 participants with
schizophrenia who participated in World Health Organization studies (including the International Pilot Study of Schizophrenia
and the Determinants of Outcome of Severe Mental Disorders study) found that about half had favorable outcomes (minimal or
no symptoms, employment, Global Assessment of Functioning (GAF) scores greater than 60) [51,52].

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In general, people with the deficit form of schizophrenia seem to have a more consistently poor prognosis compared with their
nondeficit peers [16,17].

Earlier in the illness, functional recovery is rarer. In a medication algorithm study, only about 14 percent of 118 people with a
first episode of schizophrenia or schizoaffective disorder met recovery criteria for two or more years during the first five years
of the illness [53]. Recovery in this study was defined as no more than mild psychotic symptoms, no more than moderate
negative symptoms, adequate role function (student, employment, homemaker), attention to hygiene, and independence in
daily chores.

Timely, intensive treatment can impact functional recovery early in the illness. As an example, a clinical trial randomized 34
community mental health centers in 21 US states to offer people with newly-diagnosed, nonaffective psychosis either standard
care (181 patients) or a program of intensive treatment (computerized, algorithm-assisted medication management; family
psychoeducation; resiliency-focused individual psychotherapy; and supported education/employment; 223 patients) [54]. After
two years, people receiving the intensive intervention had greater improvement in quality of life, more involvement in
school/work, and less psychopathology. Rates of hospitalization did not differ between groups.

The DSM-5 has several specifiers that can be applied to describe the course of illness after one year following the patient’s
diagnosis [1]. (See 'Specifiers for schizophrenia in DSM-5' below.)

Remission of schizophrenia refers to a state in which the individual has no symptoms, or minimal symptoms that do not
interfere with behavior, for a period of at least six months [55,56].

Over the past decade, consumer advocacy has drawn attention to the concept of recovery from schizophrenia. The model of
recovery that has emerged differs from a strictly clinical model of recovery (eg, no or mild symptoms, restored functioning).
The consumer-driven model is a blend of function, life-satisfaction, and independence. Despite scientific efforts to capture this
outcome, there are no currently accepted scales to measure recovery [57].

ASSESSMENT — The differential diagnosis of psychosis, and the medical workup to identify/exclude psychoses secondary to
medical conditions, are described separately. (See "Clinical manifestations, differential diagnosis, and initial management of
psychosis in adults".)

The diagnosis of schizophrenia is often one of exclusion. No symptom or group of symptoms is pathognomonic for
schizophrenia; however, there are specific hallucinations and delusions that are characteristic of the illness, known as “first-
rank symptoms” [58] (table 2). Although upwards of 85 percent of people with schizophrenia endorse these symptoms, up to
25 percent of manic bipolar patients endorse first-rank symptoms in cross-sectional studies [7], and about 45 percent endorse
these symptoms in longitudinal studies [59], which suggests that these symptoms are not specific to schizophrenia [59,60].
There are no laboratory or physical examination findings or other biomarkers that are useful in making the diagnosis.

The patient assessment is based on the diagnostic interview supplemented by collateral information. Family members or
caregivers are often a good source of information about a patient’s clinical presentation outside the office or hospital. Medical
records, especially from the initial presentation of the illness and most recent hospitalization, can give additional information.

Working with patients who are uncooperative, whether from paranoia or for other reasons, can be challenging. Even if a
person denies hearing voices, it is sometimes observed that he or she seems to be responding to internal stimulation (by
smiling inappropriately, looking in the direction from where they hear a voice, or seeming distracted during an interview).
Although there are other reasons a person might act this way, and diagnosis should not be based solely on these
observations, the behaviors of a person may provide useful information as to their ongoing internal experiences.

The severity of symptoms should be assessed in each domain affected by the illness, ie, psychosis/thought disorder, negative
symptoms, cognitive impairment, mood/anxiety.

Assessment of someone with schizophrenia should include evaluations of health, including cholesterol, blood glucose, weight
and BMI, prolactin, evaluation of motor disturbances, and a urine drug screen.

DIAGNOSIS — The diagnosis of schizophrenia requires the presence of “characteristic symptoms” of the disorder (delusions,
hallucinations, disorganized speech or behavior, and/or negative symptoms) coupled with social and/or occupational
dysfunction for at least six months in the absence of another diagnosis that would better account for the presentation.

DSM-5 diagnostic criteria for schizophrenia are described in more detail below [1].

● A. Two or more of the characteristic symptoms below are present for a significant portion of time during a one-month
period (or less if successfully treated):

• 1. Delusions

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• 2. Hallucinations

• 3. Disorganized speech (eg, frequent derailment or incoherence)

• 4. Grossly disorganized or catatonic behavior

• 5. Negative symptoms, ie, affective flattening, alogia, or avolition

● B. For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as
work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset. When the onset is in
childhood or adolescence: failure to achieve expected level of interpersonal, academic, or occupational achievement.

● C. Continuous signs of the disturbance persist for at least six months. The six-month period must include at least one
month of symptoms (or less if successfully treated) that meet Criterion A (ie, active-phase symptoms) and may include
periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may
be manifested by only negative symptoms or two or more symptoms listed in Criterion A that present in an attenuated
form (eg, odd beliefs, unusual perceptual experiences).

● D. Schizoaffective disorder and mood disorder with psychotic features have been ruled out because either: (1) no major
depressive, manic, or mixed episodes have occurred concurrently with the active-phase symptoms; or (2) if mood
episodes have occurred during active-phase symptoms, their total duration has been brief relative to the duration of the
active and residual periods.

● E. The disturbance is not due to the direct physiological effects of a substance (eg, a drug of abuse or medication) or a
general medical condition.

● F. If the patient has a history of autistic disorder or another pervasive developmental disorder, the additional diagnosis of
schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if
successfully treated).

Specifiers for schizophrenia in DSM-5 — The following course specifiers can be applied only after at least 1 year has
elapsed since the initial onset of the disorder.

Specify if:

● First episode, currently in acute episode

● First episode, currently in partial remission

● First episode, currently in full remission

● Multiple episodes, currently in acute episode

● Multiple episodes, currently in partial remission

● Multiple episodes, currently in full remission

● Continuous

● Unspecified

Specify if: with catatonia

Specify current severity: Each of the following symptoms may be rated for its highest severity in the last seven days. A five-
point scale is used: from 0 (not present) to 4 (present and severe).

● Delusions

● Hallucinations

● Disorganized speech

● Abnormal psychomotor behavior

● Negative symptoms

Changes to the diagnostic criteria for schizophrenia from DSM-IV to DSM-5 included [1]:

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● At least two of the five A-criteria symptoms must be present, and at least one must be delusions, hallucinations, or
disorganized speech in DSM-5. One symptom was sufficient in certain circumstances in DSM-IV.

● A specifier to document the presence of catatonia was added in DSM-5; the DSM-IV specifier, with prominent negative
symptoms, was omitted from DSM-5. (See "Catatonia in adults: Epidemiology, clinical features, assessment, and
diagnosis".)

● DSM-5 included new specifiers for rating the severity of A-criteria symptoms and for describing the patient’s course of
illness.

● DSM-5 excluded the five subtypes of schizophrenia that were included in previous versions of the manual. There was little
evidence that these subtypes were stable [61], clustered in families [62], or provided clinical utility beyond a description of
the patient’s presentation at the time of diagnosis.

Differential diagnosis — In the differential diagnosis of schizophrenia, the most common psychiatric disorders include
schizophreniform disorder, schizoaffective disorder, bipolar disorder, and major depression with psychotic features, and
substance-induced psychotic disorders. Characteristics of psychiatric disorders informing the differential diagnosis of
schizophrenia are described below. An algorithm describes the differential diagnosis of delusions (algorithm 1).

● In schizophreniform disorder all the criteria for schizophrenia are met, but the total duration of the disorder is less than
six months.

● Schizoaffective disorder, bipolar disorder, and major depression with psychotic features all differ from
schizophrenia in that there is a prominent mood component to the patient’s presentation. (See "Unipolar major depression
with psychotic features: Epidemiology, clinical features, assessment, and diagnosis" and "Bipolar disorder in adults:
Clinical features".)

● Schizoaffective disorder is essentially schizophrenia with manic episodes or a significant depressive component. The
validity and reliability of schizoaffective disorder remains unresolved [63].

● The difference between mood disorders with psychosis and schizoaffective disorder is the timing of symptoms.

In schizoaffective disorder, psychosis can and does occur in the absence of a mood episode.

In psychotic mood disorders the psychosis is only observed in the presence of a mood episode. (See "Unipolar major
depression with psychotic features: Epidemiology, clinical features, assessment, and diagnosis".)

● In substance-induced psychotic disorders the symptoms are a manifestation of intoxication or acute withdrawal and do
not persist after the individual is sober.

● Psychosis due to a general medical condition should be ruled out. Conditions, such as previous CVA or TBI, Wilson’s
disease, porphyria, syphilis infection, and others, can present with psychotic symptoms.

● Delusional disorder is present if the individual has a delusion, but criteria from schizophrenia have never been met. An
exception to this is that the person may have olfactory or tactile hallucinations consistent with the delusion, but not
auditory hallucinations.

● Schizotypal personality disorder is a long-standing pattern of odd or eccentric beliefs and/or perceptual disturbances
that do not rise to the level of delusions or hallucinations. People with this presentation may eventually transition to a
psychotic disorder, but many do not [64].

● Schizoid personality disorder is a long-standing pattern of little interest in social relationships or intimacy. There is
overlap with the negative symptoms seen in schizoid personality disorder and schizophrenia, but schizoid personality
disorder does not present with psychosis.

● Pervasive developmental disorders may present with psychosis or negative symptoms. An additional diagnosis of
schizophrenia should only be made in a patient with autism if psychotic symptoms last more than one month.

The diagnoses of schizophreniform disorder, schizophrenia, schizoaffective disorder, schizotypal personality disorder, and
schizoid personality disorder are described collectively as ‘schizophrenia spectrum’ disorders. Although most researchers
believe schizophrenia is likely a syndrome of distinct disease entities, the concept of schizophrenia spectrum disorders is
useful for epidemiological research.

In many cases, repeated assessment longitudinally is necessary to definitively diagnose a patient presenting with a
schizophrenia spectrum disorder.

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ICD-10 diagnosis – The World Health Organization’s International Statistical Classification of Disease and Related Health
Problems, 10th Revision (ICD-10) is primarily a coding source text and not a diagnostic manual, ie, there is minimal guidance
on making a diagnosis [65]. Psychiatric diseases are listed with a short, prototypical description. The schizophrenia section
describes first-rank and negative symptoms as characteristic and includes information on the variable course that can be seen
in the illness.

ICD-10 includes the following subtypes of schizophrenia, many of which are similar to the subtypes found in DSM-IV, but no
longer present in DSM-5:

● Paranoid – Prominent delusions and hallucinations with little disturbance in affect or speech.

● Hebephrenic – Similar to the DSM-IV disorganized schizophrenia, “affective changes are prominent… mood is shallow
and inappropriate… should normally only be diagnosed in adolescents and young adults.”

● Catatonic. (See "Catatonia in adults: Epidemiology, clinical features, assessment, and diagnosis".)

● Post-schizophrenic depression – Although listed with the subtypes of the illness, this diagnosis refers to a period of
depressed mood occurring after the resolution of an acute psychotic exacerbation in someone with schizophrenia.

● Residual – Described as a “chronic stage… in which there has been a clear progression from an early stage to a later
stage characterized by long-term… negative symptoms.”

● Simple – The picture of residual schizophrenia without having previously experienced any explicit psychosis.

● Undifferentiated – Schizophrenia that does not fit a subtype.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the
Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they
answer the four or five key questions a patient might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your
patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the
keyword(s) of interest.)

● Basics topics (see "Patient education: Schizophrenia (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Clinical manifestations of schizophrenia include positive and negative symptoms, cognitive impairment, and mood or
anxiety symptoms. Positive symptoms include hallucinations, delusions, and disorganization. (See 'Positive symptoms'
above.)

• Hallucinations are defined as the perception of a sensory process in the absence of an external source. They can be
auditory, visual, somatic, olfactory, or gustatory.

• Delusions are defined as a fixed, false belief. They can be bizarre or non-bizarre. Their content can often be
categorized as grandiose, paranoid, nihilistic, or erotomanic.

• Disorganization can typically be seen in both behavior and speech. The most commonly observed forms of abnormal
speech are tangentiality and circumstantiality, while more severe thought disorder includes derailment, neologisms,
and word salad.

● Primary, enduring negative symptoms represent a core feature of schizophrenia; they are also referred to as deficit
symptoms. Examples of negative symptoms include a flat affect, poverty of speech, and a lack of interest or energy. A
table lists other negative symptoms (table 1). Secondary negative symptoms can be caused by antipsychotic medications.
(See 'Negative symptoms' above.)

● Physical manifestations of schizophrenia include neurological “soft signs,” catatonia, and metabolic disturbances.
Metabolic abnormalities and movement disorders can be caused by schizophrenia itself as well as by antipsychotic
medications. (See 'Associated physical manifestations' above.)

● The diagnosis of schizophrenia (table 3) requires the presence of two of the five characteristic symptoms below coupled
with social and/or occupational dysfunction for at least six months, and the absence of another diagnosis that would better

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account for the presentation (such as drug use, certain medical conditions, or psychotic mood disorders). (See 'Diagnosis'
above.)

• Delusions

• Hallucinations

• Disorganized speech

• Disorganized or catatonic behavior

• Negative symptoms

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GRAPHICS

Negative symptoms in schizophrenia

Negative symptom
Negative symptom As manifested by:
cluster

Diminished expression Affective flattening Unchanging facial expression

Little spontaneous movement

Little use of expressive gestures

Poor eye contact

Affective non-responsivity

Lack of vocal inflections

Alogia Poverty of speech

Thought blocking

Increased latency of response

Avolition-apathy Apathy Poor grooming and hygiene

Failure of appropriate role responsibilities

Anergy

Asociality/anhedonia Failure to engage with peers socially

No interest in stimulating activities

Little interest in sex

Little to no intimacy with others

Modified with permission from: Andreasen NC. Negative symptoms in schizophrenia: Definition and reliability. Arch Gen Psychiatry 1982;
39:784. Copyright © 1982 American Medical Association. All rights reserved.

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First-rank symptoms in schizophrenia

1. Audible thoughts - hearing one's thoughts spoken aloud

2. Somatic passivity - the feeling of being touched or strange unexplained sexual sensations

3. Thought insertion - the feeling an external force is putting thoughts into one's mind

4. Thought withdrawal - thoughts are withdrawn

5. Thought broadcasting - the feeling people can read one's mind

6. Made feelings - the feeling an external force is making you experience something

7. Made impulses - the feeling an external force is making you want something

8. Made volition - the feeling an external force is making you act a certain way

9. Voices arguing/discussing (often referring to the patient as "he" or "she")

10. Voices commenting - voices narrate one's actions as if giving a running commentary

11. Delusional percepts - a physical sensation (such as seeing or feeling something) that is interpreted as a very special event has
happened and something important is realized

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Differential diagnosis of delusions

Adapted from: American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th Ed: DSM-5. Washington, D.C.:
American Psychiatric Association, 2013.

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DSM-5 diagnostic criteria for schizophrenia

A. Two (or more) of the following, each present for a significant portion of time during a one-month period (or less if successfully
treated). At least one of these must be (1), (2), or (3):

1) Delusions.

2) Hallucinations.

3) Disorganized speech (eg, frequent derailment or incoherence).

4) Grossly disorganized or catatonic behavior.

5) Negative symptoms (ie, diminished emotional expression or avolition).

B. For a significant portion of the time since the onset of the disturbance, level of functioning in one or more major areas, such as work,
interpersonal relations, or self-care, is markedly below the level achieved prior to the onset (or when the onset is in childhood or
adolescence, there is failure to achieve expected level of interpersonal, academic, or occupational functioning).

C. Continuous signs of the disturbance persist for at least 6 months. This six-month period must include at least 1 month of symptoms
(or less if successfully treated) that meet Criterion A (ie, active-phase symptoms) and may include periods of prodromal or residual
symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or
by two or more symptoms listed in Criterion A present in an attenuated form (eg, odd beliefs, unusual perceptual experiences).

D. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either 1) no major
depressive or manic episodes have occurred concurrently with the active-phase symptoms, or 2) if mood episodes have occurred during
active-phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness.

E. The disturbance is not attributable to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or another
medical condition.

F. If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of
schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are
also present for at least one month (or less if successfully treated).

Specify if:

The following course specifiers are only to be used after a 1-year duration of the disorder and if they are not in contradiction to the
diagnostic course criteria.

First episode, currently in acute episode: First manifestation of the disorder meeting the defining diagnostic symptom and
time criteria. An acute episode is a time period in which the symptom criteria are fulfilled.

First episode, currently in partial remission: Partial remission is a period of time during which an improvement after a
previous episode is maintained and in which the defining criteria of the disorder are only partially fulfilled.

First episode, currently in full remission: Full remission is a period of time after a previous episode during which no disorder-
specific symptoms are present.

Multiple episodes, currently in acute episode: Multiple episodes may be determined after a minimum of two episodes (ie,
after a first episode, a remission and a minimum of one relapse).

Multiple episodes, currently in partial remission.

Multiple episodes, currently in full remission.

Continuous: Symptoms fulfilling the diagnostic symptom criteria of the disorder are remaining for the majority of the illness
course, with subthreshold symptom periods being very brief relative to the overall course.

Unspecified.

Specify if:

With catatonia

Specify current severity:

Severity is rated by a quantitative assessment of the primary symptoms of psychosis, including delusions, hallucinations,
disorganized speech, abnormal psychomotor behavior, and negative symptoms. Each of these symptoms may be rated for its current
severity (most severe in the last seven days) on a 5-point scale ranging from 0 (not present) to 4 (present and severe).

NOTE: Diagnosis of schizophrenia can be made without using this severity specifier.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright © 2013). American
Psychiatric Association. All Rights Reserved.

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Contributor Disclosures
Bernard A Fischer, MD Nothing to disclose Robert W Buchanan, MD Nothing to disclose Stephen Marder,
MD Grant/Research/Clinical Trial Support: Forum; Neurocrine [schizophrenia and tardive dyskinesia]. Consultant/Advisory
Boards: Takeda, Gideon Richter, Boeringer-Ingleheim, Otsuka; Allergan; Teva [schizophrenia (brexpiprazole,
cariprazine)]. Richard Hermann, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multi-level review process, and through requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

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