Recommendations
Key Recommendations
The diagnosis is challenging, as there are no pathognomonic features and no confirmatory laboratory tests. A family history of schizophrenia is an important risk factor. Diagnosis is based on diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders [DSM-5-TR] or International Classification of Diseases [ICD-11]), with tests performed to rule out other possible causes as indicated.
Early detection and treatment are important, as they reduce the duration of psychosis and may predict favorable outcomes, although some studies fail to support this observation.[53][54][55][56][57][58][59][60]
Identifying patients at risk for schizophrenia
The period of time leading to the first full-blown episode of psychosis is characterized by nonspecific symptoms sometimes described as the prodrome or the at-risk for psychosis period.[61][62] The onset of psychosis may be preceded by a variable period (weeks to years) of early warning signs such as suspiciousness about others, trouble concentrating, spending more time alone than usual, a decline in self-care, or a significant drop in school or job performance. The prodrome typically occurs 1 to 2 years before the appearance of psychotic symptoms. Similar symptoms and behaviors may be seen in avoidant, schizoid, and schizotypal personality disorders too. In time, these symptoms can lead to anxiety and depression.
Initial assessment
Patients presenting for the first episode of psychosis are typically young adults, referred by a family member or friend.
The symptoms that patients experience can be divided into four domains:
Positive symptoms
Negative symptoms
Cognitive impairment
Affective disturbance.
Mild "soft" neurologic signs (e.g., rigidity, gait imbalance, tremor) may also be present.[63][64]
A comprehensive assessment is warranted to determine the correct diagnosis. The assessment is based on a clinical interview, observations and reports of the patient's behaviors, and information from people in close contact with the patient. It is also important to assess the patient's level of functioning and available social support.[65] Assessment of a patient presenting with a possible psychotic disorder should include:[65]
Ascertaining the reason the individual is presenting for evaluation; determining their goals and preferences for treatment
An assessment of tobacco use and drug abuse
An assessment of physical health
An assessment of psychosocial and cultural factors
A mental status examination, including cognitive assessment
A review of psychiatric symptoms and trauma history; a psychiatric treatment history
An assessment of risk of suicide and aggressive behaviors.
Laboratory tests and neuroimaging should be used to rule out other etiologies (e.g., drug use or a general medical condition).[66] See the Tests section, below.
If the diagnosis has previously been established and the patient presents with an acute psychotic episode, the assessment should also include a careful review of the patient's disease course and treatment history. Previous medication trials should be reviewed, and the possibility of nonadherence with medication should be considered. Other factors that may have precipitated an acute psychotic episode, such as drug use or comorbid medical conditions, should be assessed.
Positive symptoms
Positive symptoms include hallucinations, delusions, and disorganized thought processes.
Hallucinations
Hallucinations are perception-like experiences that occur without an external stimulus. They are vivid and clear, with the full force and impact of normal perceptions, and not under voluntary control.[1]
Assessment should address the type and content of hallucinations. Hallucinations can occur in any sense - touch, smell, taste, or vision - but auditory hallucinations are the most common (usually “hearing voices”).[67]
Auditory hallucinations may be perceived as either inside or outside the patient's brain; they are usually described as command, derogatory, conversing, and/or running commentaries. The patient usually has concerns about these experiences, and patients tend to be very illustrative when discussing them if asked in a nonjudgmental way. One can also note internal preoccupation, reflected by prolonged time elapsing between queries and answers. The patient may be responding to internal stimuli, which may delay responses. The patient may even respond verbally to such stimuli, giving the clinician a clear clue that hallucinations are present. Visual, olfactory, and gustatory hallucinations also occur but are less common.[1]
Tactile hallucinations (i.e., electrical pulses, crawling sensation) rarely present in schizophrenia and should prompt suspicion of drug-induced psychosis. Rarely, the patient might report cenesthetic hallucinations, described as unfounded, somatic sensations, such as a burning sensation in the brain, cutting pain in bone marrow, or a pushing feeling in the blood vessels.
Delusions
Delusions refer to fixed beliefs that are not reality based and cannot be explained as part of the patient's cultural background.[1] They are not amenable to change in light of conflicting evidence.[1]
Common types of delusions include persecutory, grandiose, nihilistic, or religious.[1] Other types of delusions include thought control delusions, such as thought insertion (false beliefs that someone is putting thoughts in the patient's brain) or thought withdrawal delusions (beliefs that someone is stealing thoughts from the patient's brain). Thought broadcasting refers to a belief that the patient's thoughts are being broadcast out loud and can be perceived by others. Delusions of reference refer to the belief that common events or coincidences refer to the patient directly (e.g., personal messages from television and newspapers; two strangers who start talking "on purpose" when the patient passes them).
Delusions commonly present at the onset of illness. Delusions typically change theme during the prodromal and early phase of the disease; over time, delusions tend to become crystallized.
Identifying delusions may be more challenging than identifying hallucinations, because the patient's beliefs are embedded into real-life situations and may form part of the patient’s cultural norms. Patients consider the delusions as real, and in time develop very elaborate connections. If indicated, psychosis should be assessed through interpreters or in a second or third language to avoid the misunderstanding of unfamiliar metaphors as delusions.[1]
Other positive symptoms
Additional positive symptoms that should be assessed during the initial interview include:
Bizarre or disorganized behavior.
Incongruent affect: this refers to disconnect between thought and speech content.
Pressured speech: this refers to rushed intense speech.
Distractible speech: this refers to an inability to maintain attention. The patient shifts from one topic to another with minimal provocation or is distracted too frequently by unimportant or irrelevant external stimuli.
Tangentiality: this refers to an inability to stay on topic, jumping from one subject to another with minimal connection.
Circumstantiality: this refers to an inability to give a concise answer due to over-inclusion of unnecessary details.
Looseness of association (derailment): this refers to the complete incoherence that occurs when tangentiality is extreme.
Verbigeration: a repetition of words in the absence of stimuli.
Perseveration: a repetition of the same response (e.g., word or phrase) to different stimuli.
Word salad: a speech form in which no connection between words is found.
Derealization: this refers to an altered perception of the external world as strange or unreal. A patient might report feeling "as if in a movie." If this symptom is prominent, other pathologies should be considered.
Déjà-vu: a paramnesia in which patients experience the feeling that they are seeing something that they have seen before. If this symptom is prominent, other pathologies should be considered.
Catatonic excitement: an overall increase in purposeless and excessive motor activity without obvious cause.
Negative symptoms
Negative symptoms refer to deficits in motivation, increased social isolation, and decreased emotional expression; they have been shown to correlate inversely with the overall functioning and quality of life of patients with schizophrenia.[1]
Specific negative symptoms include:[1]
Asocial behavior: a loss of drive for social interactions
Affective blunting: diminished or absent ability to express emotions and feelings
Anhedonia: decreased ability to experience pleasure
Alogia: quantitative and qualitative decrease in speech
Avolition: decreased motivation to self-initiate purposeful activities (e.g., the patient may sit for long periods of time and show little interest in participating in work or social activities).
Negative symptoms can occur any time during the course of the illness and may be worsened by acute psychosis, depression, and drug-related adverse effects.[68]
Cognitive symptoms
Schizophrenia affects all cognitive domains, including attention, language, memory, executive function, and processing speed.[1]
Executive function describes the set of higher-level cognitive processes that are utilized for control and coordination of cognitive and behavioral abilities. Examples include: the ability to start and stop actions, anticipate outcomes, adapt to new situations, and plan future behaviors in novel scenarios. Abstract thinking is often considered a part of executive functioning.
Cognitive symptoms are typically the first to appear and are predominant features during the prodromal period. Some people with schizophrenia show social cognition deficits; they may not be able to infer the intentions of other people, and may misinterpret social cues.[1] Cognitive deficits in schizophrenia are common and are strongly linked to vocational and functional impairments.[1]
Some patients with psychosis may lack insight or awareness of their disorder (i.e., anosognosia). This symptom is the most common predictor of nonadherence to treatment, and it predicts higher relapse rates, increased number of involuntary treatments, poorer psychosocial functioning, aggression, and an unfavorable course.[1]
Affective symptoms
Patients may display:[1]
Inappropriate affect (e.g., laughing in the absence of an appropriate stimulus)
A dysphoric mood state that can take the form of depression, anxiety, or anger
Disturbed sleep patterns (e.g., daytime sleeping, nighttime activity)
Food refusal or a lack of interest in eating.
Affective disorders are common and may appear during the at-risk or prodromal period. Affective blunting, a primary negative symptom, needs to be differentiated from depression. Patients may also present with mood elation. Anxiety can occur at any time during the acute or chronic phases of schizophrenia.
Although affective symptoms may occur as part of schizophrenia, comorbid conditions (including drug use or toxins) should be considered as differentials. If affective symptoms occur before the appearance of psychotic symptoms or persist after psychotic symptoms subside, an affective disorder with psychosis, schizoaffective disorder, or an anxiety disorder should be ruled out. See Differentials.
Suicidal ideation is one of the most dangerous complications of schizophrenia.[69] The risk of suicide is highest at the onset of the illness. Approximately 20% of patients with schizophrenia attempt suicide at least once, and many more have significant suicidal ideation.[1] Approximately 5% to 6% of patients with schizophrenia die by suicide.[70][71][72]
Catatonia
Catatonic symptoms represent a state of extreme loss or excess of motor activity. The following catatonic symptoms are sometimes observed in patients with schizophrenia:[1]
Stupor: a decreased response to surroundings, immobility, and mutism; the most severe type of catatonia
Rigidity: immobility and resistance to movement
Negativism: refusal of all instructions
Excitement: an overall increase in purposeless and excessive motor activity without obvious cause (this could be considered a positive symptom)
Stereotypies: stilted goal-directed behaviors that manifest as uniformly repetitive movements
Parakinesias: grimacing, twitching, and jerking
Echopraxia: repetition of movement seen in others
Automatic obedience: automatic execution of directions
Waxy flexibility: ability to maintain imposed positions for long periods of time.
Examination: neurologic and physical
Neurologic examination usually does not reveal gross deficits but might be significant for "soft" neurologic signs, which are found in over half of people with schizophrenia.[73][74] These include motor coordination deficits, a smooth pursuit eye movement deficit, a sensory integration deficit, and right-left disorientation.[1] Although the clinical value of these findings is limited, there is some evidence that their presence may be associated with a worse prognosis.[75][76] One study suggests the presence of primary motor coordination dysfunction at initial presentation may be associated with a more severe nonremitting course.[77]
Patients with schizophrenia may present with somatization symptoms.[1] Somatization results from psychological stress that is subconsciously expressed somatically and is represented by physical symptoms that are persistent and can affect any organ system. Common examples include pain, gastrointestinal symptoms, and "pseudoneurologic" symptoms (symptoms arising from any neurologic impairment for which there is no medical explanation).
Cultural considerations
When interpreting symptoms, cultural and socioeconomic factors should be considered, particularly when the patient and the clinician do not share a cultural and/or socioeconomic background.[1][65]
Ideas that appear to be delusional in one cultural context (e.g., evil eye, causing illness through curses, influences of spirits) may be commonly held in others. Visual or auditory hallucinations with a religious content (e.g., hearing God’s voice) may be an expected component of some religious experiences. If the assessment is conducted in a language that is different from the patient’s primary language, care must be taken to ensure that alogia (paucity of speech) is not related to linguistic barriers. In certain cultures, distress might take the form of hallucinations or pseudo-hallucinations and overvalued ideas; although presentation may be clinically similar to true psychosis, these manifestations might be a product of the patient’s cultural or social group.[65]
Misdiagnosis of schizophrenia in patients with other psychiatric disorders is more likely to occur in certain racial groups (e.g., particularly African Americans in the US). This may be attributable to clinical bias, racism, or discrimination leading to misinterpretation of symptoms.[65]
Diagnostic criteria
Once the assessment of the patient is complete, a diagnosis of schizophrenia can be made if diagnostic criteria are met. The most widely used criteria in the US are those from the DSM; according to the fifth edition (DSM-5-TR), a schizophrenia diagnosis requires the following:[1]
Two or more of the following symptoms are present: delusions, hallucinations, disorganized speech (e.g., frequent derailment or incoherence), grossly disorganized/catatonic behavior, or negative symptoms (i.e., diminished emotional expression or avolition). At least one of the symptoms needs to be delusion, hallucination, or disorganized speech.
Continuous signs of the disturbance for a period of at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet criterion A (active-phase symptoms) and may include periods of prodromal or residual symptoms.
Functional decline for a significant portion of the time since the onset of the disturbance.
Symptoms do not occur concomitantly with drug use or with another medical condition.
Some specialists will instead use the World Health Organization (WHO) ICD-11 criteria for diagnosis of schizophrenia.[78] Symptoms may be identified by the individual’s report or through observation by the clinician or other informants. ICD-11 criteria state a diagnosis of schizophrenia can be made if symptoms (e.g., persistent delusions, persistent hallucinations, disorganized thinking) are present most of the time for a period of 1 month or more.
Tests
Although test results do not inform the diagnosis of schizophrenia, investigations should be performed to rule out other etiologies as indicated.
Drug intoxications can lead to psychosis in their own right or can exacerbate underlying psychotic illnesses. A drug toxicology screen is therefore recommended if clinically indicated in any patient presenting with a psychotic episode.[65]
STI testing is indicated for all patients at risk of STIs; syphilis and HIV, in particular, can cause psychiatric symptoms. In addition, HIV infection is more common in people with schizophrenia.[79][80]
A magnetic resonance imaging (MRI) or computed tomographic (CT) scan of the head may be indicated on the basis of neurologic examination or history; MRI is preferred of the two modalities.[65] Brain imaging may demonstrate stroke or other mass lesions or the basal ganglia changes of Huntington disease.[65] Factors that suggest a possible need for brain imaging include focal neurologic signs, new onset of seizures, later age at symptom onset, symptoms suggestive of intracranial pathology (e.g., chronic or severe headaches, nausea, vomiting), and symptoms suggestive of autoimmune encephalitis (e.g., rapid progression of working memory deficits over less than 3 months; decreased or altered level of consciousness, lethargy, or personality change).[65]
A complete blood count including absolute neutrophil count (ANC) should be performed to screen for anemia.[65] Fatigue and depression are associated with anemia and can mimic negative symptoms of schizophrenia. Volume abnormalities in red blood cells may suggest vitamin deficiencies or increased alcohol intake.
Other blood tests that should be performed at initial or baseline assessment include:[65]
Blood chemistries (electrolytes, renal function tests, liver function tests, thyroid-stimulating hormone)
A pregnancy test for women of childbearing age
Fasting blood glucose, and lipid panel (alongside screening for diabetes risk factors)
Prolactin, to screen for hyperprolactinemia, if indicated on the basis of clinical history.
Patients should also be assessed for metabolic syndrome, which is defined by the presence of at least three of the following five risk factors: elevated waist circumference; elevated triglycerides; reduced high-density lipoprotein (HDL) cholesterol (HDL-C); elevated blood pressure; and elevated fasting glucose.[65]
Chromosomal testing may be indicated on the basis of physical exam or history, including developmental history.[65] Factors that may suggest a possible need for chromosomal testing (e.g., to identify abnormalities such as 22q11.2 deletion syndrome) include mild dysmorphic features, hypernasal speech, developmental delays, intellectual impairments, learning difficulties, and congenital heart defects.[65]
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