Шизофренія

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 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.

1. 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

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.

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.

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.

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.

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).

1. 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

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:

• Brief psychotic disorder

• Delusional disorder

• Schizoaffective disorder

• Schizophreniform disorder

• Schizotypal personality disorder

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.

1. 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

1. 1. RAISE: Recovery After an Initial Schizophrenia Episode—A Research Project of the National Institute of Mental Health (NIMH). Accessed 1/14/22.

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.

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.

1. 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. 2. Wang SM, Han C, Lee SJ: Investigational dopamine antagonists for the treatment of schizophrenia. Expert Opin Investig Drugs 26(6):687-698, 2017.  doi: 10.1080/13543784.2017.1323870