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

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
Literature review current through: Apr 2022. | This topic last updated: Mar 24, 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.

(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".)

(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, 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 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 side effects of an antipsychotic medication.

Deficit schizophrenia — While not a recognized American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 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].

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", 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 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 — 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

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

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 [74], clustered in families [75], 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 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 [76].

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 [77].

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-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) [78]. 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".)

Postschizophrenic 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.

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".)

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 – 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

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
  2. Murray CJL, Lopez AD. The Global Burden of Disease, Harvard University Press, Cambridge, MA 1996. p.21.
  3. Carpenter WT Jr, Strauss JS, Bartko JJ. The diagnosis and understanding of schizophrenia. Part I. Use of signs and symptoms for the identification of schizophrenic patients. Schizophr Bull 1974; :37.
  4. Bartko JJ, Strauss JS, Carpenter WT Jr. The diagnosis and understanding of schizophrenia. Part II. Expanded perspectives for describing and comparing schizophrenic patients. Schizophr Bull 1974; :50.
  5. Strauss JS, Carpenter WT Jr, Bartko JJ. The diagnosis and understanding of schizophrenia. Part III. Speculations on the processes that underlie schizophrenic symptoms and signs. Schizophr Bull 1974; :61.
  6. Thomas P, Mathur P, Gottesman II, et al. Correlates of hallucinations in schizophrenia: A cross-cultural evaluation. Schizophr Res 2007; 92:41.
  7. Andreasen NC, Flaum M. Schizophrenia: the characteristic symptoms. Schizophr Bull 1991; 17:27.
  8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, American Psychiatric Association, Washington DC 2000.
  9. Cermolacce M, Sass L, Parnas J. What is bizarre in bizarre delusions? A critical review. Schizophr Bull 2010; 36:667.
  10. Andreasen NC, Olsen S. Negative v positive schizophrenia. Definition and validation. Arch Gen Psychiatry 1982; 39:789.
  11. Strauss GP, Horan WP, Kirkpatrick B, et al. Deconstructing negative symptoms of schizophrenia: avolition-apathy and diminished expression clusters predict clinical presentation and functional outcome. J Psychiatr Res 2013; 47:783.
  12. Blanchard JJ, Cohen AS. The structure of negative symptoms within schizophrenia: implications for assessment. Schizophr Bull 2006; 32:238.
  13. Buchanan RW, Kreyenbuhl J, Kelly DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull 2010; 36:71.
  14. Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull 2006; 32:214.
  15. Kirkpatrick B, Kopelowicz A, Buchanan RW, Carpenter WT Jr. Assessing the efficacy of treatments for the deficit syndrome of schizophrenia. Neuropsychopharmacology 2000; 22:303.
  16. Strauss GP, Harrow M, Grossman LS, Rosen C. Periods of recovery in deficit syndrome schizophrenia: a 20-year multi-follow-up longitudinal study. Schizophr Bull 2010; 36:788.
  17. Fenton WS, McGlashan TH. Antecedents, symptom progression, and long-term outcome of the deficit syndrome in schizophrenia. Am J Psychiatry 1994; 151:351.
  18. Kirkpatrick B, Buchanan RW, Ross DE, Carpenter WT Jr. A separate disease within the syndrome of schizophrenia. Arch Gen Psychiatry 2001; 58:165.
  19. Kirkpatrick B, Amador XF, Flaum M, et al. The deficit syndrome in the DSM-IV Field Trial: I. Alcohol and other drug abuse. Schizophr Res 1996; 20:69.
  20. Kirkpatrick B, Buchanan RW, Breier A, Carpenter WT Jr. Depressive symptoms and the deficit syndrome of schizophrenia. J Nerv Ment Dis 1994; 182:452.
  21. Nuechterlein KH, Barch DM, Gold JM, et al. Identification of separable cognitive factors in schizophrenia. Schizophr Res 2004; 72:29.
  22. Gold JM, Hahn B, Strauss GP, Waltz JA. Turning it upside down: areas of preserved cognitive function in schizophrenia. Neuropsychol Rev 2009; 19:294.
  23. Dickinson D, Iannone VN, Wilk CM, Gold JM. General and specific cognitive deficits in schizophrenia. Biol Psychiatry 2004; 55:826.
  24. Kraus MS, Keefe RS. Cognition as an outcome measure in schizophrenia. Br J Psychiatry Suppl 2007; 50:s46.
  25. Wilk CM, Gold JM, McMahon RP, et al. No, it is not possible to be schizophrenic yet neuropsychologically normal. Neuropsychology 2005; 19:778.
  26. Palmer BW, Heaton RK, Paulsen JS, et al. Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology 1997; 11:437.
  27. Bora E, Murray RM. Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis? Schizophr Bull 2014; 40:744.
  28. Bilder RM, Goldman RS, Robinson D, et al. Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry 2000; 157:549.
  29. Snitz BE, Macdonald AW 3rd, Carter CS. Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophr Bull 2006; 32:179.
  30. Goldberg TE, Ragland JD, Torrey EF, et al. Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Arch Gen Psychiatry 1990; 47:1066.
  31. Saeedi H, Remington G, Christensen BK. Impact of haloperidol, a dopamine D2 antagonist, on cognition and mood. Schizophr Res 2006; 85:222.
  32. Moore AR, O'Keeffe ST. Drug-induced cognitive impairment in the elderly. Drugs Aging 1999; 15:15.
  33. Kraepelin E. Dementia Praecox and Paraphrenia, Krieger, New York 1971.
  34. Torrey EF. Studies of individuals with schizophrenia never treated with antipsychotic medications: a review. Schizophr Res 2002; 58:101.
  35. Stroup TS, Olfson M, Huang C, et al. Age-Specific Prevalence and Incidence of Dementia Diagnoses Among Older US Adults With Schizophrenia. JAMA Psychiatry 2021; 78:632.
  36. Dickerson FB, Sommerville J, Origoni AE, et al. Experiences of stigma among outpatients with schizophrenia. Schizophr Bull 2002; 28:143.
  37. Drapalski AL, Lucksted A, Perrin PB, et al. A model of internalized stigma and its effects on people with mental illness. Psychiatr Serv 2013; 64:264.
  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 schizophrenia. Psychiatry Res 2010; 180:10.
  40. Yanos PT, Lucksted A, Drapalski AL, et al. Interventions targeting mental health self-stigma: A review and comparison. Psychiatr Rehabil J 2015; 38:171.
  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. Schizophr Bull 2005; 31:962.
  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 schizophrenia. Am J Psychiatry 1999; 156:1349.
  45. Hennekens CH, Hennekens AR, Hollar D, Casey DE. Schizophrenia and increased risks of cardiovascular disease. Am Heart J 2005; 150:1115.
  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 Psychiatry 2015; 72:1172.
  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 Psychopharmacol 2005; 19:56.
  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 2003; 160:2202.
  54. Harding CM, Brooks GW, Ashikaga T, et al. The Vermont longitudinal study of persons with severe mental illness, I: Methodology, study sample, and overall status 32 years later. Am J Psychiatry 1987; 144:718.
  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 Psychiatry 2001; 178:506.
  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.
  59. Dixon LB, Dickerson F, Bellack AS, et al. The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements. Schizophr Bull 2010; 36:48.
  60. Kane JM, Robinson DG, Schooler NR, et al. Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program. Am J Psychiatry 2016; 173:362.
  61. Martland N, Martland R, Cullen AE, Bhattacharyya S. Are adult stressful life events associated with psychotic relapse? A 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 Psychiatry 2021; 78:876.
  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 Psychiatry 2002; 24:412.
  66. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003; 60:82.
  67. Taipale H, Tanskanen A, Mehtälä J, et al. 20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). World Psychiatry 2020; 19:61.
  68. Fischer BA, Carpenter WT. Remission. In: Clinical Handbook of Schizophrenia, Mueser KT, Jeste DV (Eds), Guilford Publications, New York 2008. p.559.
  69. Andreasen NC, Carpenter WT Jr, Kane JM, et al. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 2005; 162:441.
  70. Bellack AS. Scientific and consumer models of recovery in schizophrenia: concordance, contrasts, and implications. Schizophr Bull 2006; 32:432.
  71. Schneider K. Clinical Psychopathology, Grune & Stratton, New York 1959.
  72. Rosen C, Grossman LS, Harrow M, et al. Diagnostic and prognostic significance of Schneiderian first-rank symptoms: a 20-year longitudinal study of schizophrenia and bipolar disorder. Compr Psychiatry 2011; 52:126.
  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.
  74. Kendler KS, Gruenberg AM, Tsuang MT. Subtype stability in schizophrenia. Am J Psychiatry 1985; 142:827.
  75. Kendler KS, Gruenberg AM, Tsuang MT. A family study of the subtypes of schizophrenia. Am J Psychiatry 1988; 145:57.
  76. Malaspina D, Owen MJ, Heckers S, et al. Schizoaffective Disorder in the DSM-5. Schizophr Res 2013; 150:21.
  77. Debbané M, Eliez S, Badoud D, et al. Developing psychosis and its risk states through the lens of schizotypy. Schizophr Bull 2015; 41 Suppl 2:S396.
  78. World Health Organization. Schizophrenia, schizotypal and delusional disorders. International Statistical Classification of Disease and Related Health Problems. Tenth Revision. Version:2015. http://apps.who.int/classifications/icd10/browse/2015/en#/F20-F29.
Topic 6962 Version 44.0

References