Schizophrenia in Adults - Clinical Manifestations, Course, Assessment, and Diagnosis - UpToDate

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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: Michael Friedman, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2022. | This topic last updated: Sep 29, 2022.
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 10 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.
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● (See "Psychosis in adults: Epidemiology, clinical manifestations, and diagnostic evaluation".)

● (See "Schizophrenia in adults: Epidemiology and pathogenesis".)
● (See "Depression in schizophrenia".)
● (See "Anxiety in schizophrenia".)
● (See "Schizophrenia in adults: Maintenance therapy and side effect management".)
● (See "Co-occurring schizophrenia and substance use disorder: Epidemiology, pathogenesis, clinical manifestations, course,
assessment and diagnosis".)
● (See "Psychosocial interventions for schizophrenia in adults".)
● (See "Schizophrenia in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, course, assessment,
and diagnosis".)
● (See "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.
● 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 nonbizarre 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 nonbizarre 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 beliefs that are defined in the American Psychiatric Association’s Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) as the conviction that a major catastrophe
will occur. However, other definitions of nihilistic delusions include the delusional belief of being dead, decomposed or
annihilated, having lost one's own internal organs or even not existing entirely as a human being.
● In erotomanic delusions, the person erroneously believes that they have 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 delusions [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].
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 symptoms of an antipsychotic medication.
Deficit schizophrenia — While not a recognized DSM-5-TR subtype of schizophrenia, people with schizophrenia who have
prominent negative (or deficit) symptoms as a primary manifestation of the illness (eg, not akinesia due to antipsychotic-related
parkinsonism or social isolation secondary to paranoia), 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 their premorbid 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].
Older individuals with schizophrenia have an increased risk of receiving a diagnosis of dementia [35]. In a retrospective study
using United States Medicare data, over 74,000 individuals with a diagnosis of schizophrenia were compared with 7.9 million
individuals without serious mental illness [35]. At 66 years of age, the prevalence of dementia diagnosis in individuals with
schizophrenia was greater than in the comparator group (28 versus 1 percent). At 80 years of age, the prevalence was 70 versus
11 percent, respectively. While the cause of the increased rate of dementia among these individuals is not fully understood, the
association of schizophrenia with other risk factors for dementia, such as cardiovascular disease, hyperlipidemia, smoking, and
substance use may play a role. Additionally, the role of decreased cognitive reserve and the use of psychotropic medications
may be contributory.
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 [36] and may be internalized, leading to “self-stigma”
[37]. 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 [38]. A discriminant
function analysis of 105 people with schizophrenia found that self-stigma was a predictor of decreased treatment adherence
[39,40].
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 [41]. 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 [41-44].
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 [43,44].
Most neurological disturbances readily observed in people with schizophrenia are likely medication-induced. Antipsychotic
dopamine blockade can cause extrapyramidal symptoms, 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".)
● (See "Second-generation antipsychotic medications: Pharmacology, administration, and side effects".)
● (See "Tardive dyskinesia: Etiology, risk factors, clinical features, and diagnosis", section on 'Clinical spectrum'.)
● (See "Schizophrenia in adults: Maintenance therapy and side effect management", section on '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 [45]. (See "Schizophrenia in adults: Maintenance therapy and side effect management", section on
'Metabolic dysregulation'.)
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 [46]. 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 [47].
COMORBID GENERAL MEDICAL DISORDERS
People diagnosed with schizophrenia are at increased risk of developing several co-occurring medical conditions. In a Danish
national registry study, investigators compared people carrying a diagnosis of schizophrenia with age- and sex-matched
controls who did not have a diagnosis of schizophrenia (sample sizes not reported) [48]. People with schizophrenia had an
increased risk for circulatory, endocrine, gastrointestinal, hematological, pulmonary, and urogenital disorders (hazard ratios
ranging from approximately 1.2 to 1.7). In other studies, schizophrenia has been prominently associated with greater rates of
cardiovascular disease, dyslipidemia, dementia [35], and type 2 diabetes compared with the general population, with a resulting
decrease in average lifespan of up to 20 years [49,50]. Although some diabetes risk is attributable to medications, increased
rates of diabetes and insulin resistance in people with schizophrenia predate antipsychotics, and may also be related to shared
genetics, lifestyle, and/or diet [47,51].
COURSE OF ILLNESS
Heterogeneity — 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 described eight course types, which
differ in several ways [52]:
● Onset – Abrupt versus insidious

● Symptom presentation – Continuous versus intermittent
● Outcome – Poor versus nonpoor
Most people with schizophrenia in the study had an acute onset, intermittent symptoms, and later had no or only mild
symptoms. Only approximately 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 Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (DSM-IV) and International Classification of Diseases (ICD) criteria, and the results among those
retaining a schizophrenia diagnosis were largely unchanged from the original course observations [53].
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 [54-56]. 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 approximately half had favorable outcomes
(minimal or no symptoms, employment, Global Assessment of Functioning scores greater than 60) [56,57].
Though the course of schizophrenia may be heterogenous, functional recovery tends to be less common earlier in the illness. In
a medication algorithm study, only approximately 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 [58]. 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.
Factors influencing course — The course of illness is affected by numerous factors, including early intervention and utilization
of a multidisciplinary care approach, symptom types, level of stressors, socioeconomic factors, and effectiveness and adherence
to medication regimen.
Early intervention and multidisciplinary treatment — Timely, intensive treatment can positively impact psychosocial
functioning early in the illness. Treatment programs offering multicomponent interventions have been associated with lower
rehospitalization rates, lower core illness symptoms, and improved interpersonal and everyday living skills in patients
recovering from first episode of psychosis [59,60].
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Comprehensive review of pharmacologic and psychosocial management of patients with schizophrenia is discussed elsewhere.
(See "Schizophrenia in adults: Maintenance therapy and side effect management", section on 'Multidisciplinary care' and
"Psychosocial interventions for schizophrenia in adults", section on 'Multimodal interventions'.)
Stressors — External stressors may have an impact on the course of schizophrenia. A systematic review of observational and
retrospective studies suggested that stressful events such as trauma, bereavement, financial problems, and interpersonal
conflict are associated with relapse of psychosis [61].
Deficit schizophrenia — Persons with the deficit form of schizophrenia (eg, with primary and enduring negative symptoms)
seem to have a more consistently poor prognosis compared with their nondeficit peers [16,17]. (See "Schizophrenia in adults:
Epidemiology and pathogenesis", section on 'Deficit schizophrenia'.)
Effects of adherence to medication — Effectiveness of medications and assessment and treatment of nonadherence to

medications are discussed in detail elsewhere. (See "Psychosis in adults: Initial management", section on 'Antipsychotic therapy'
and "Schizophrenia in adults: Maintenance therapy and side effect management", section on 'Nonadherence'.)
Suicide — The rate of suicide among people with schizophrenia is much higher than in the general population. In a
retrospective study including over 668,000 individuals with schizophrenia using United States Medicare data, the rate of suicide
was found to be over four times higher than the general population (standardized mortality ratio 4.5, 95% CI 4.4-4.7) [62]. The
rate of suicide was highest in the youngest age group (18 to 34 years; standardized mortality ratio 10.2, 95% CI 9.3-11.2) and
declined with age (≥65 years; standardized mortality ratio 1.5, 95% CI 1.3-1.8). Approximately 5 percent of people with
schizophrenia commit suicide over their lifetime [63]. Among all completed suicides, approximately 10 percent occur in people
with schizophrenia [64,65].
However, treatment can decrease the risk of suicide. In a two-year randomized trial that compared clozapine with olanzapine in
patients with schizophrenia and schizoaffective disorder (n = 980), fewer suicide attempts occurred with clozapine (34 versus 55)
[66]. (See "Guidelines for prescribing clozapine in schizophrenia".)
In addition, treatment with antipsychotic medication may decrease the long-term risk of suicide mortality. A national registry
study identified patients with schizophrenia (n >60,000) who were followed for a median of 14 years, and compared the rate of
suicide during periods of antipsychotic use with the rate during periods of nonuse [67]. After adjusting for some potential
confounding factors (eg, age, duration of illness, and comorbidities), the analyses found that fewer suicide deaths occurred
during antipsychotic use than during nonuse (adjusted hazard ratio 0.5, 95% CI 0.4-0.6). The analyses also found that the
cumulative all-cause mortality rates were lower during antipsychotic use than nonuse (26 versus 46 percent). However, not
every antipsychotic was associated with a similar reduction in mortality.
Remission and recovery — Remission of schizophrenia refers to a state in which the individual has no symptoms, or minimal
symptoms which do not interfere with behavior, for a period of at least six months [68,69].
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 accepted scales to measure recovery [70].
ASSESSMENT
The differential diagnosis of psychosis, and the medical workup to identify/exclude psychoses secondary to medical conditions,
are described separately. (See "Psychosis in adults: Epidemiology, clinical manifestations, and diagnostic evaluation".)
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” ( table 2) [71]. 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 approximately 45 percent
endorse these symptoms in longitudinal studies [72], which suggests that these symptoms are not specific to schizophrenia
[72,73]. 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 they seem 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-TR 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
• 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-TR — The following course specifiers can be applied only after at least one 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
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 psychosis ( 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 [74].
● 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 cerebrovascular
accident or traumatic brain injury, Wilson 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 [75].
● 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.
ICD-11 diagnosis — The World Health Organization’s International Statistical Classification of Disease and Related Health
Problems, 11th Revision (ICD-11) is primarily a coding source text and not a diagnostic manual (ie, there is minimal guidance on
making a diagnosis) [76]. Psychiatric diseases are listed with a short, prototypical description. The schizophrenia or other
psychotic disorders section includes schizophrenia, schizoaffective disorder, schizotypal disorder, acute and transient psychotic
disorder, delusional disorder, symptomatic manifestations of primary psychotic disorders, substance-induced psychotic
disorder, and schizophrenia or other primary psychotic disorder, unspecified.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided
separately. (See "Society guideline links: Psychotic disorders".)
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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 – Clinical manifestations of schizophrenia include positive and negative symptoms, cognitive
impairment, and mood or anxiety symptoms. (See 'Clinical manifestations' above.)
• Positive 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. (See 'Hallucinations' above.)
- Delusions are defined as a fixed, false belief. They can be bizarre or nonbizarre. Their content can often be
categorized as grandiose, paranoid, nihilistic, or erotomanic. (See 'Delusions' above.)
- 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. (See 'Disorganization' above.)
• Negative symptoms – Primary, enduring negative symptoms (ie, deficit symptoms) represent a core feature of
schizophrenia. Examples of negative symptoms include a flat affect, poverty of speech, and a lack of interest or
motivation. A table lists other negative symptoms ( table 1). Secondary negative symptoms can be caused by
antipsychotic medications. (See 'Negative symptoms' above.)
• Cognitive impairment – Areas of cognitive impairment that seem to be the most affected in schizophrenia include
processing speed, attention, working memory, executive functioning, and social cognition. (See 'Cognitive impairment'
above.)
• 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. (See 'Mood and anxiety symptoms' above.)
● Physical manifestations – 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.)
● Course – The course of schizophrenia shows considerable heterogeneity. The course may be affected by early intervention
and utilization of a multidisciplinary care approach, symptom types, level of stressors, socioeconomic factors, and
effectiveness and adherence to medication regimen.
● Suicide – The rate of suicide among people with schizophrenia is much higher than in the general population. (See
'Suicide' above.)
● Diagnosis – 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 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
Use of UpToDate is subject to the Terms of Use.
REFERENCES
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24. Kraus MS, Keefe RS. Cognition as an outcome measure in schizophrenia. Br J Psychiatry Suppl 2007; 50:s46.
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27. Bora E, Murray RM. Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the
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35. Stroup TS, Olfson M, Huang C, et al. Age-Specific Prevalence and Incidence of Dementia Diagnoses Among Older US Adults
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36. Dickerson FB, Sommerville J, Origoni AE, et al. Experiences of stigma among outpatients with schizophrenia. Schizophr Bull
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37. Drapalski AL, Lucksted A, Perrin PB, et al. A model of internalized stigma and its effects on people with mental illness.
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38. Yanos PT, Lysaker PH, Roe D. Internalized stigma as a barrier to improvement in vocational functioning among people with
schizophrenia-spectrum disorders. Psychiatry Res 2010; 178:211.
39. Tsang HW, Fung KM, Chung RC. Self-stigma and stages of change as predictors of treatment adherence of individuals with
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40. Yanos PT, Lucksted A, Drapalski AL, et al. Interventions targeting mental health self-stigma: A review and comparison.
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41. Heinrichs DW, Buchanan RW. Significance and meaning of neurological signs in schizophrenia. Am J Psychiatry 1988;
145:11.
42. Bombin I, Arango C, Buchanan RW. Significance and meaning of neurological signs in schizophrenia: two decades later.
43. Arango C, Kirkpatrick B, Buchanan RW. Neurological signs and the heterogeneity of schizophrenia. Am J Psychiatry 2000;
157:560.
44. Arango C, Bartko JJ, Gold JM, Buchanan RW. Prediction of neuropsychological performance by neurological signs in
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45. Hennekens CH, Hennekens AR, Hollar D, Casey DE. Schizophrenia and increased risks of cardiovascular disease. Am Heart J
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46. Pillinger T, Beck K, Gobjila C, et al. Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and
Meta-analysis. JAMA Psychiatry 2017; 74:261.
47. Kohen D. Diabetes mellitus and schizophrenia: historical perspective. Br J Psychiatry Suppl 2004; 47:S64.
48. Momen NC, Plana-Ripoll O, Agerbo E, et al. Association between Mental Disorders and Subsequent Medical Conditions. N
Engl J Med 2020; 382:1721.
49. Olfson M, Gerhard T, Huang C, et al. Premature Mortality Among Adults With Schizophrenia in the United States. JAMA
50. Hoffman RP. The Complex Inter-Relationship Between Diabetes and Schizophrenia. Curr Diabetes Rev 2017; 13:528.
51. Holt RI, Bushe C, Citrome L. Diabetes and schizophrenia 2005: are we any closer to understanding the link? J
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52. Blueler M. The Schizophrenic Disorders: Long-Term Patient and Family Studies, Yale University Press, London 1978.
53. Modestin J, Huber A, Satirli E, et al. Long-term course of schizophrenic illness: Bleuler's study reconsidered. Am J Psychiatry
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54. Harding CM, Brooks GW, Ashikaga T, et al. The Vermont longitudinal study of persons with severe mental illness, I:
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55. Harding CM, Brooks GW, Ashikaga T, et al. The Vermont longitudinal study of persons with severe mental illness, II: Long-
term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. Am J Psychiatry 1987; 144:727.
56. Recovery from Schizophrenia: An International Perspective; A Report from the WHO Collaborative Project, The International
Study of Schizophrenia, Hopper K, Harrison G, Janca A, Sartorius N (Eds), Oxford University Press, New York 2007.
57. Harrison G, Hopper K, Craig T, et al. Recovery from psychotic illness: a 15- and 25-year international follow-up study. Br J
58. Robinson DG, Woerner MG, McMeniman M, et al. Symptomatic and functional recovery from a first episode of
schizophrenia or schizoaffective disorder. Am J Psychiatry 2004; 161:473.
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Outcomes From the NIMH RAISE Early Treatment Program. Am J Psychiatry 2016; 173:362.
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systematic review of 23 studies. Psychol Med 2020; 50:2302.
62. Olfson M, Stroup TS, Huang C, et al. Suicide Risk in Medicare Patients With Schizophrenia Across the Life Span. JAMA
63. Hor K, Taylor M. Suicide and schizophrenia: a systematic review of rates and risk factors. J Psychopharmacol 2010; 24:81.
64. Arsenault-Lapierre G, Kim C, Turecki G. Psychiatric diagnoses in 3275 suicides: a meta-analysis. BMC Psychiatry 2004; 4:37.
65. Suominen K, Isometsä E, Heilä H, et al. General hospital suicides--a psychological autopsy study in Finland. Gen Hosp
66. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention
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73. Thorup A, Petersen L, Jeppesen P, Nordentoft M. Frequency and predictive values of first rank symptoms at baseline among
362 young adult patients with first-episode schizophrenia Results from the Danish OPUS study. Schizophr Res 2007; 97:60.
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2015; 41 Suppl 2:S396.
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Topic 6962 Version 46.0
GRAPHICS
Negative symptoms in schizophrenia
Negative symptom cluster Negative symptom As manifested by:
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.
Graphic 81542 Version 13.0
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
Algorithm on the diagnostic differentiation of psychosis*
* Presence of psychosis (defined as the presence of delusions, hallucinations, disorganized speech or behavior, or impaired reality
testing) meets all four of the following criteria:
Not due to an underlying medical condition.
Not due to medication or other substance.
Not culturally sanctioned.
Not a pervasive pattern of distrust, suspiciousness, or perceptual disturbances or behavior eccentricities beginning in early
adulthood and present in a variety of contexts.
¶ Symptoms: Prodromal, residual, and attenuated psychotic symptoms count towards the duration of psychotic symptomatology.
Δ Or ≥1 psychotic symptom if negative symptoms are present.
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.
Contributor Disclosures
Bernard A Fischer, MD No relevant financial relationship(s) with ineligible companies to disclose. Robert W Buchanan, MD No relevant
financial relationship(s) with ineligible companies to disclose. Stephen Marder, MD Grant/Research/Clinical Trial Support: Boeringer-
Ingleheim [Psychosis/schizophrenia]. Consultant/Advisory Boards: Bioexcel [Psychosis/schizophrenia]; Biogen [Psychosis/schizophrenia];
Boeringer-Ingleheim [Psychosis/schizophrenia]; Merck [Psychosis]; Otsuka [Psychosis/schizophrenia]; Sunovion [Psychosis/schizophrenia]. All
of the relevant financial relationships listed have been mitigated. Michael Friedman, MD No relevant financial relationship(s) with ineligible
companies 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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Schizophrenia in adults: Clinical manifestations, course, assessment, and

● (See "Psychosis in adults: Epidemiology, clinical manifestations, and diagnostic evaluation".)

● Neologisms – The creation of new, idiosyncratic words.

COMORBID GENERAL MEDICAL DISORDERS

● Onset – Abrupt versus insidious

Effects of adherence to medication — Effectiveness of medications and assessment and treatment of nonadherence to

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

• 4. Grossly disorganized or catatonic behavior

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

● First episode, currently in acute episode

● First episode, currently in full remission

Specify if: with catatonia

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

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

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Terms of Use.

Negative symptoms in schizophrenia

Negative symptom cluster Negative symptom As manifested by:

Diminished expression Affective flattening Unchanging facial expression

Little spontaneous movement

Little use of expressive gestures

Poor eye contact

Lack of vocal inflections

Alogia Poverty of speech

Increased latency of response

Avolition-apathy Apathy Poor grooming and hygiene

Failure of appropriate role responsibilities

Asociality/anhedonia Failure to engage with peers socially

No interest in stimulating activities

Little interest in sex

Little to no intimacy with others

Graphic 81542 Version 13.0

First-rank symptoms in schizophrenia

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

4. Thought withdrawal - thoughts are withdrawn

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

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

Graphic 76914 Version 1.0

Algorithm on the diagnostic differentiation of psychosis*

Δ Or ≥1 psychotic symptom if negative symptoms are present.

Graphic 131414 Version 2.0

DSM-5 diagnostic criteria for schizophrenia

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

4) Grossly disorganized or catatonic behavior.

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

Multiple episodes, currently in partial remission.

Multiple episodes, currently in full remission.

Specify current severity:

Graphic 54426 Version 12.0

Conflict of interest policy

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