Schizophrenia is characterized by psychosis (loss of contact with reality), hallucinations (false perceptions), delusions (false beliefs), disorganized speech and behavior, flattened affect (restricted range of emotions), cognitive deficits (impaired reasoning and problem solving), and occupational and social dysfunction. The cause is unknown, but evidence for genetic and environmental components is strong. Symptoms usually begin in adolescence or early adulthood. One or more episodes of symptoms must last ≥ 6 months before the diagnosis is made. Treatment consists of drug therapy, cognitive therapy, and psychosocial rehabilitation. Early detection and early treatment improve long-term functioning.
(See also Introduction to Schizophrenia and Related Disorders.)
Psychosis refers to symptoms such as delusions, hallucinations, disorganized thinking and speech, and bizarre and inappropriate motor behavior (including catatonia) that indicate loss of contact with reality.
Worldwide, the prevalence of schizophrenia is about 1%. The rate is comparable among men and women and relatively constant cross-culturally. Urban living, poverty, childhood trauma, neglect, and prenatal infections are risk factors, and there is a genetic predisposition. The condition starts in late adolescence and lasts a lifetime, typically with poor psychosocial function throughout.
The average age at onset is early to mid 20s in women and somewhat earlier in men; about 40% of males have their first episode before age 20. Onset is rare in childhood; early-adolescent onset or late-life onset (when it is sometimes called paraphrenia) may occur.
Etiology of Schizophrenia
Although its specific causes and mechanisms are unknown, schizophrenia has a biologic basis, as evidenced by
Alterations in brain structure (eg, enlarged cerebral ventricles, thinning of the cortex, decreased size of the anterior hippocampus and other brain regions)
Recently demonstrated genetic risk factors (1)
Some experts suggest that schizophrenia occurs more frequently in people with neurodevelopmental vulnerabilities and that the onset, remission, and recurrence of symptoms are the result of interactions between these enduring vulnerabilities and environmental stressors.
Neurodevelopmental vulnerability
Although schizophrenia rarely manifests in early childhood, childhood factors influence disease onset in adulthood. These factors include
Genetic predisposition
Intrauterine, birth, or postnatal complications
Viral central nervous system infections
Childhood trauma and neglect
Although many people with schizophrenia do not have a family history, genetic factors are strongly implicated. People who have a 1st-degree relative with schizophrenia have about a 10 to 12% risk of developing the disorder, compared with a 1% risk among the general population. Monozygotic twins have a concordance of about 45%.
Maternal exposure to famine and influenza during the 2nd trimester of pregnancy, birth weight < 2500 g, Rh incompatibility during a 2nd pregnancy, and hypoxia increase risk.
Neurobiologic and neuropsychiatric tests suggest that aberrant smooth-pursuit eye tracking, impaired cognition and attention, and deficient sensory gating occur more commonly among patients with schizophrenia than among the general population. These findings also can occur among 1st-degree relatives of people with schizophrenia, and indeed in patients with many other psychotic disorders, and may represent an inherited component of vulnerability. The commonality of these findings across psychotic disorders suggests that our conventional diagnostic categories do not reflect underlying biologic distinctions among psychoses (1).
Environmental stressors
Environmental stressors can trigger the emergence or recurrence of psychotic symptoms in vulnerable people. Stressors may be primarily pharmacologic (eg, substance use, especially marijuana) or social (eg, becoming unemployed or impoverished, leaving home for college, breaking off a romantic relationship, joining the Armed Forces). There is emerging evidence that environmental events can initiate epigenetic changes that could influence gene transcription and disease onset.
Protective factors that may mitigate the effect of stress on symptom formation or exacerbation include strong psychosocial support, well-developed coping skills, and antipsychotic drugs.
Etiology reference
1. Schizophrenia Working Group of the Psychiatric Genomics Consortium: Biological insights from 108 schizophrenia-associated genetic loci. Nature 511(7510):421-427, 2014. doi: 10.1038/nature13595
Symptoms and Signs of Schizophrenia
Schizophrenia is a chronic illness that may progress through several phases, although duration and patterns of phases can vary. Patients with schizophrenia tend to have had psychotic symptoms an average of 8 to 15 months before presenting for medical care, but the disorder is now often recognized earlier in its course.
Symptoms of schizophrenia typically impair the ability to perform complex and difficult cognitive and motor functions; thus, symptoms often markedly interfere with work, social relationships, and self-care. Unemployment, isolation, deteriorated relationships, and diminished quality of life are common outcomes.
Phases of schizophrenia
In the prodromal phase, individuals may show no symptoms or may have impaired social competence, mild cognitive disorganization or perceptual distortion, a diminished capacity to experience pleasure (anhedonia), and other general coping deficiencies. Such traits may be mild and recognized only in retrospect or may be more noticeable, with impairment of social, academic, and vocational functioning.
In the advanced prodromal phase, subclinical symptoms may emerge; they include withdrawal or isolation, irritability, suspiciousness, unusual thoughts, perceptual distortions, and disorganization (1). Onset of overt schizophrenia (delusions and hallucinations) may be sudden (over days or weeks) or slow and insidious (over years). But, even in an advanced prodromal phase, only a fraction (< 40%) tend to convert to full schizophrenia.
In the early psychosis phase, symptoms are active and often at their worst.
In the middle phase, symptomatic periods may be episodic (with identifiable exacerbations and remissions) or continuous; functional deficits tend to worsen.
In the late illness phase, the illness pattern may become established but there is considerable variability; disability may stabilize, worsen, or even diminish.
Symptom categories in schizophrenia
Generally, symptoms are categorized as
Positive: Hallucinations and delusions
Negative: Diminution or loss of normal functions and affect
Disorganized: Thought disorder and bizarre behavior
Cognitive: Deficits in memory, information processing and problem solving
Patients may have symptoms from one or all categories.
Positive symptoms can be further categorized as
Delusions
Hallucinations
Delusions are erroneous beliefs that are maintained despite clear contradictory evidence. There are several types of delusions:
Persecutory delusions: Patients believe they are being tormented, followed, tricked, or spied on.
Delusions of reference: Patients believe that passages from books, newspapers, song lyrics, or other environmental cues are directed at them.
Delusions of thought withdrawal or thought insertion: Patients believe that others can read their mind, that their thoughts are being transmitted to others, or that thoughts and impulses are being imposed on them by outside forces
Delusions in schizophrenia tend to be bizarre—ie, clearly implausible and not derived from ordinary life experiences (eg, believing that someone removed their internal organs without leaving a scar).
Hallucinations are sensory perceptions that are not perceived by anyone else. They may be auditory, visual, olfactory, gustatory, or tactile, but auditory hallucinations are the most common. Patients may hear voices commenting on their behavior, conversing with one another, or making critical and abusive comments. Delusions and hallucinations may be extremely vexing to patients.
Negative (deficit) symptoms include
Blunted affect: The patient’s face appears immobile, with poor eye contact and lack of expressiveness.
Poverty of speech: The patient speaks little and gives terse replies to questions, creating the impression of inner emptiness
Anhedonia: There is a lack of interest in activities and increased purposeless activity.
Asociality: There is a lack of interest in relationships.
Negative symptoms often lead to poor motivation and a diminished sense of purpose and goals.
Disorganized symptoms, which can be considered a type of positive symptom, involve
Thought disorders
Bizarre behaviors
Thinking is disorganized, with rambling, non–goal-directed speech that shifts from one topic to another. Speech can range from mildly disorganized to incoherent and incomprehensible. Bizarre behavior may include childlike silliness, agitation, and inappropriate appearance, hygiene, or conduct. Catatonia is an extreme example of bizarre behavior, which can include maintaining a rigid posture and resisting efforts to be moved or engaging in purposeless and unstimulated motor activity.
Cognitive deficits include impairment in the following:
Attention
Processing speed
Working and declarative memory
Abstract thinking
Problem solving
Understanding of social interactions
The patient’s thinking may be inflexible, and the ability to problem solve, understand the viewpoints of other people, and learn from experience may be diminished. Severity of cognitive impairment is a major determinant of overall disability.
Subtypes of schizophrenia
Some experts classify schizophrenia into deficit and nondeficit subtypes based on the presence and severity of negative symptoms, such as blunted affect, lack of motivation, and diminished sense of purpose.
Patients with the deficit subtype have prominent negative symptoms unaccounted for by other factors (eg, depression, anxiety, an understimulating environment, drug adverse effects).
Those with the nondeficit subtype may have delusions, hallucinations, and thought disorders but are relatively free of negative symptoms.
The previously recognized subtypes of schizophrenia (paranoid, disorganized, catatonic, residual, undifferentiated) have not proved valid or reliable and are no longer used.
Suicide
About 5 to 6% of patients with schizophrenia commit suicide, and about 20% attempt it; many more have significant suicidal ideation. Suicide is the major cause of premature death among people with schizophrenia and explains, in part, why on average the disorder reduces life span by 10 years.
Risk may be especially high for young men with schizophrenia and a substance use disorder. Risk is also increased in patients who have depressive symptoms or feelings of hopelessness, who are unemployed, or who have just had a psychotic episode or been discharged from the hospital.
Patients who have late onset and good premorbid functioning—the very patients with the best prognosis for recovery—are also at the greatest risk of suicide. Because these patients retain the capacity for grief and anguish, they may be more prone to act in despair based on a realistic recognition of the effect of their disorder.
Violence
Schizophrenia is a surprisingly modest risk factor for violent behavior. Threats of violence and aggressive outbursts are more common than seriously dangerous behavior. Indeed, people with schizophrenia are overall less violent than people without schizophrenia.
Patients more likely to engage in significant violence include those with substance use disorders, persecutory delusions, or command hallucinations and those who do not take their prescribed drugs. A very few severely depressed, isolated, paranoid patients attack or murder someone whom they perceive as the single source of their difficulties (eg, an authority, a celebrity, their spouse).
Symptoms reference
1. Tsuang MT, Van Os J, Tandon R, et al: Attenuated psychosis syndrome in DSM-5. Schizophr Res 150(1):31–35, 2013. doi: 10.1016/j.schres.2013.05.004
Diagnosis of Schizophrenia
Clinical criteria (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5])
Combination of history, symptoms, and signs
The earlier the diagnosis is made and treated, the better the outcome.
No definitive test for schizophrenia exists. Diagnosis is based on a comprehensive assessment of history, symptoms, and signs. Information from collateral sources, such as family members, friends, teachers, and coworkers, is often important.
According to the DSM-5, the diagnosis of schizophrenia requires both of the following:
≥ 2 characteristic symptoms (delusions, hallucinations, disorganized speech, disorganized behavior, negative symptoms) for a significant portion of a 6-month period (symptoms must include at least one of the first 3)
Prodromal or attenuated signs of illness with social, occupational, or self-care impairments evident for a 6-month period that includes 1 month of active symptoms
Differential diagnosis
Psychosis due to other medical disorders or to substance use disorders must be ruled out by history and examination that includes laboratory tests and neuroimaging (Medical Assessment of the Patient With Mental Symptoms). Although some patients with schizophrenia have structural brain abnormalities present on imaging, these abnormalities are insufficiently specific to have diagnostic value.
Other mental disorders with similar symptoms include several that are related to schizophrenia:
In addition, mood disorders can cause psychosis in some people.
Neuropsychologic tests, brain imaging, electroencephalogram, and other tests of brain function (eg, eye-tracking) do not help to distinguish among major psychotic disorders. However, early research (1) suggests that results of such tests can be used to group patients into 3 distinct psychosis biotypes that do not correspond to current clinical diagnostic categories.
Certain personality disorders (especially schizotypal) cause symptoms similar to those of schizophrenia, although they are usually milder and do not involve psychosis.
Diagnosis reference
1.Clementz BA, Sweeney JA, Hamm JP, et al: Identification of distinct psychosis biotypes using brain-based biomarkers. Am J Psychiatry 173(4): 373-384, 2016. doi: 10.1176/appi.ajp.2015.14091200
Prognosis for Schizophrenia
Studies derived from the RAISE (Recovery After an Initial Schizophrenia Episode) initiative have shown that the earlier treatment is started and the more intensive it is, the better the outcome (1).
During the first 5 years after onset of symptoms, functioning may deteriorate and social and work skills may decline, with progressive neglect of self-care. Negative symptoms may increase in severity, and cognitive functioning may decline. Thereafter, the level of disability tends to plateau. Some evidence suggests that severity of illness may lessen in later life, particularly among women. Spontaneous movement disorders may develop in patients who have severe negative symptoms and cognitive dysfunction, even when antipsychotics are not used.
Schizophrenia can occur with other mental disorders. When associated with significant obsessive-compulsive symptoms, prognosis is particularly poor; with symptoms of borderline personality disorder, prognosis is better. About 80% of people with schizophrenia experience one or more episodes of major depression at some time in their life.
For the first year after diagnosis, prognosis is closely related to adherence to prescribed psychoactive drugs and avoiding recreational drug use.
Overall, one third of patients achieve significant and lasting improvement; one third improve somewhat but have intermittent relapses and residual disability; and one third remain severely incapacitated. Only about 15% of all patients fully return to their pre-illness level of functioning.
Factors associated with a good prognosis include
Good premorbid functioning (eg, good student, strong work history)
Late and/or sudden onset of illness
Family history of mood disorders other than schizophrenia
Minimal cognitive impairment
Few negative symptoms
Shorter duration of untreated psychosis
Factors associated with a poor prognosis include
Young age at onset
Poor premorbid functioning
Family history of schizophrenia
Many negative symptoms
Longer duration of untreated psychosis
Men have poorer outcomes than women; women respond better to treatment with antipsychotic drugs.
Substance use is a significant problem in many people with schizophrenia. There is evidence that use of marijuana or hallucinogens is highly disruptive for patients with schizophrenia and should be strongly discouraged and treated aggressively if present. Comorbid substance use is a significant predictor of poor outcome and may lead to drug nonadherence, repeated relapse, frequent rehospitalization, declining function, and loss of social support, including homelessness.
Prognosis reference
1. RAISE: Recovery After an Initial Schizophrenia Episode—A Research Project of the National Institute of Mental Health (NIMH). Accessed 1/14/22.
Treatment of Schizophrenia
Rehabilitation, including cognitive remediation, community-based training, and support services
Psychotherapy, oriented toward resilience training
The time between onset of psychotic symptoms and first treatment correlates with the rapidity of initial treatment response and quality of treatment response. When treated early, patients respond more quickly and fully. Without ongoing use of antipsychotics after an initial episode, 70 to 80% of patients have a subsequent episode within 12 months. Continuous use of antipsychotics can reduce the 1-year relapse rate to about 30% or lower with long-acting drugs. Drug treatment is continued for at least 1 to 2 years after a first episode. If patients have been ill longer, it is given for many years.
Early detection and multifaceted treatment has transformed care of patients with psychotic disorders like schizophrenia. Coordinated specialty care, which includes resilience training, personal and family therapy, addressing cognitive dysfunction, and supported employment, is an important contribution to psychosocial recovery.
General goals for schizophrenia treatment are to
Reduce the severity of psychotic symptoms
Preserve psychosocial function
Prevent recurrences of symptomatic episodes and associated deterioration of functioning
Reduce use of recreational drugs
Antipsychotics, rehabilitation with community support services, and psychotherapy are the major components of treatment. Because schizophrenia is a long-term and recurrent illness, teaching patients illness self-management skills is a significant overall goal. Providing information about the disorder (psychoeducation) to parents of younger patients can reduce the relapse rate (1, 2). (See also the American Psychiatric Association’s Practice Guideline for the Treatment of Patients With Schizophrenia, 3rd Edition.)
Antipsychotic drugs are divided into first-generation antipsychotics (FGAs) and 2nd-generation antipsychotics (SGAs) based on their specific neurotransmitter receptor affinity and activity. SGAs may offer some advantages, both in terms of modestly greater efficacy (although recent evidence casts doubt on SGAs' advantage as a class) and reduced likelihood of an involuntary movement disorder and related adverse effects. However, risk of metabolic syndromelong QT syndrome
Rehabilitation and community support services
Psychosocial skill training and vocational rehabilitation programs help many patients work, shop, and care for themselves; manage a household; get along with others; and work with mental health care practitioners.
Supported employment, in which patients are placed in a competitive work setting and provided with an on-site job coach to promote adaptation to work, may be particularly valuable. In time, the job coach acts only as a backup for problem solving or for communication with employers.
Support services enable many patients with schizophrenia to reside in the community. Although most can live independently, some require supervised apartments where a staff member is present to ensure drug adherence. Programs provide a graded level of supervision in different residential settings, ranging from 24-hour support to periodic home visits. These programs help promote patient autonomy while providing sufficient care to minimize the likelihood of relapse and need for inpatient hospitalization. Assertive community treatment programs provide services in the patient’s home or other residence and are based on high staff-to-patient ratios; treatment teams directly provide all or nearly all required treatment services.
Hospitalization or crisis care in a hospital alternative may be required during severe relapses, and involuntary hospitalization may be necessary if patients pose a danger to themselves or others. Despite the best rehabilitation and community support services, a small percentage of patients, particularly those with severe cognitive deficits and those poorly responsive to drug therapy, require long-term institutional or other supportive care.
Cognitive remediation therapy helps some patients. This therapy is designed to improve neurocognitive function (eg, attention, working memory, executive functioning) and to help patients learn or relearn how to do tasks. This therapy may enable patients to function better.
Psychotherapy
The goal of psychotherapy in schizophrenia is to develop a collaborative relationship between the patients, family members, and physician so that patients can learn to manage their illness, take drugs as prescribed, and handle stress more effectively.
Although individual psychotherapy plus drug therapy is a common approach, few empirical guidelines are available. Psychotherapy that begins by addressing the patient’s basic social service needs, provides support and education regarding the nature of the illness, promotes adaptive activities, and is based on empathy and a sound dynamic understanding of schizophrenia is likely to be most effective. Many patients need empathic psychologic support to adapt to what is often a lifelong illness that can substantially limit functioning.
In addition to individual psychotherapy, there has been significant development of cognitive behavioral therapy for schizophrenia. For example, this therapy, done in an individual or a group setting, can focus on ways to diminish delusional thoughts.
For patients who live with their families, psychoeducational family interventions can reduce the rate of relapse. Support and advocacy groups, such as the National Alliance on Mental Illness, are often helpful to families.
General treatment references
1. Correll CU, Rubio JM, Inczedy-Farkas G, et al: Efficacy of 42 pharmacologic cotreatment strategies added to antipsychotic monotherapy in schizophrenia: Systematic overview and quality appraisal of the meta-analytic evidence. JAMA Psychiatry 74(7):675-684, 2017. doi: 10.1001/jamapsychiatry.2017.0624
2. Wang SM, Han C, Lee SJExpert Opin Investig Drugs 26(6):687-698, 2017. doi: 10.1080/13543784.2017.1323870
Key Points
Schizophrenia is characterized by psychosis, hallucinations, delusions, disorganized speech and behavior, flattened affect, cognitive deficits, and occupational and social dysfunction.
Suicide is the most common cause of premature death.
Threats of violence and minor aggressive outbursts are more common than seriously dangerous behavior, but such behavior may be more common in people with paranoid psychosis who abuse drugs.
Treat with antipsychotic drugs early, basing selection primarily on adverse effect profile, required route of administration, and the patient’s previous response to the drug.
Psychotherapy helps patients understand and manage their illness, take drugs as prescribed, and handle stress more effectively.
With treatment, one third of patients achieve significant and lasting improvement; one third improve somewhat but have intermittent relapses and residual disability; and one third are severely incapacitated.
More Information
The following are some English-language resources that may be useful. Please note that The Manual is not responsible for the content of these resources.
American Psychiatric Association (APA), Clinical Practice Guidelines for Schizophrenia, 3rd Edition: Practice guidelines include information on the social determinants of mental health and on effectively using technology (including social media, telepsychiatry, and mental health apps) to provide optimal patient care.
National Alliance on Mental Illness (NAMI), Schizophrenia: NAMI promotes ongoing awareness of schizophrenia, as well as educational and advocacy initiatives to support those who have it, and crisis-response services (including a HelpLine) to assist those in need.
