Clinical:Schizophrenia

Signs and Symptoms

Schizophrenia usually presents with a mix of positive, negative, cognitive and affective symptoms. Positive symptoms include the classic psychotic symptoms of delusions and hallucinations. Delusions are fixed AND false beliefs; the most common delusions are persecutory delusions, other types being religious, infidelity, and grandiosity. Hallucinations may came in any sensory modality, however the most commonly seen in schizophrenia are auditory hallucinations, usually in the form of voices talking to the patient in derogatory terms.Negative symptoms include: blunted affect, alogia, asociality, anhedonia, poverty of speech, and avolition-apathy ^[1]. These negative symptoms may be primary or secondary.

Diagnosis

Diagnostic Criteria from the American Psychiatric Association DSM IV TR

The diagnostic criteria for schizophrenia according to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) ^[2] are:

At least 2 of the following symptoms:

1. delusions
2. hallucinations
3. disorganized speech
4. disorganized or catatonic behavior
5. negative symptoms

Only 1 symptom is required if the delusions are bizarre or if auditory hallucinations occur in which the voices comment in an ongoing manner on the person's behavior, or if 2 or more voices are talking with each other. The patient must experience at least 1 month of symptoms (or less if successfully treated) during a 6-month period, and social or occupational deterioration problems occur over a significant amount of time. These problems must not be caused by another condition for the diagnosis of schizophrenia to be made.

Schizophrenia subtypes according to the DSM-IV

Paranoid Type

A type of Schizophrenia in which the following criteria are met:

1. Preoccupation with one or more delusions or frequent auditory hallucinations.
2. None of the following is prominent: disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect.

Catatonic Type

A type of Schizophrenia in which the clinical picture is dominated by at least two of the following:

1. motor immobility as evidenced by catalepsy (including waxy flexibility) or stupor
2. excessive motor activity (that is apparently purposeless and not influenced by external stimuli)
3. extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism
4. peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing
5. echolalia or echopraxia

Disorganized Type

A type of Schizophrenia in which the following criteria are met:

1. All of the following are prominent:
   1. disorganized speech
   2. disorganized behavior
   3. flat or inappropriate affect
2. The criteria are not met for Catatonic Type.

Undifferentiated Type

A type of Schizophrenia in which symptoms that meet Criterion A are present, but the criteria are not met for the Paranoid, Disorganized, or Catatonic Type.

Residual Type

A type of Schizophrenia in which the following criteria are met:

1. Absence of prominent delusions, hallucinations, disorganized speech, and grossly disorganized or catatonic behavior.
2. There is continuing evidence of the disturbance, as indicated by the presence of negative symptoms or two or more symptoms listed in Criterion A for Schizophrenia, present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).

Diagnostic Criteria Based on the WHO ICD 10

The World Health Organization publishes the ICD, currently in its 10th edition, where schizophrenia received the code F20, along with other psychotic disorders such as schizotypal - which is classified as a personality disorder in the DSM IV - and delusional disorders (F20-F29)

F20 Schizophrenia

The schizophrenic disorders are characterized in general by fundamental and characteristic distortions of thinking and perception, and affects that are inappropriate or blunted. Clear consciousness and intellectual capacity are usually maintained although certain cognitive deficits may evolve in the course of time. The most important psychopathological phenomena include thought echo; thought insertion or withdrawal; thought broadcasting; delusional perception and delusions of control; influence or passivity; hallucinatory voices commenting or discussing the patient in the third person; thought disorders and negative symptoms. The course of schizophrenic disorders can be either continuous, or episodic with progressive or stable deficit, or there can be one or more episodes with complete or incomplete remission. The diagnosis of schizophrenia should not be made in the presence of extensive depressive or manic symptoms unless it is clear that schizophrenic symptoms antedate the affective disturbance. Nor should schizophrenia be diagnosed in the presence of overt brain disease or during states of drug intoxication or withdrawal. Similar disorders developing in the presence of epilepsy or other brain disease should be classified under F06.2, and those induced by psychoactive substances under F10-F19 with common fourth character .5.

Excludes: schizophrenia: · acute (undifferentiated) ( F23.2 ) · cyclic ( F25.2 ) schizophrenic reaction ( F23.2 ) schizotypal disorder ( F21 )

F20.0 Paranoid schizophrenia

Paranoid schizophrenia is dominated by relatively stable, often paranoid delusions, usually accompanied by hallucinations, particularly of the auditory variety, and perceptual disturbances. Disturbances of affect, volition and speech, and catatonic symptoms, are either absent or relatively inconspicuous. Paraphrenic schizophrenia Excludes: involutional paranoid state ( F22.8 ) paranoia ( F22.0 )

F20.1 Hebephrenic schizophrenia

A form of schizophrenia in which affective changes are prominent, delusions and hallucinations fleeting and fragmentary, behaviour irresponsible and unpredictable, and mannerisms common. The mood is shallow and inappropriate, thought is disorganized, and speech is incoherent. There is a tendency to social isolation. Usually the prognosis is poor because of the rapid development of "negative" symptoms, particularly flattening of affect and loss of volition. Hebephrenia should normally be diagnosed only in adolescents or young adults. Disorganized schizophrenia Hebephrenia

F20.2 Catatonic schizophrenia

Catatonic schizophrenia is dominated by prominent psychomotor disturbances that may alternate between extremes such as hyperkinesis and stupor, or automatic obedience and negativism. Constrained attitudes and postures may be maintained for long periods. Episodes of violent excitement may be a striking feature of the condition. The catatonic phenomena may be combined with a dream-like (oneiroid) state with vivid scenic hallucinations. Catatonic stupor Schizophrenic: · catalepsy · catatonia · flexibilitas cerea

F20.3 Undifferentiated schizophrenia

Psychotic conditions meeting the general diagnostic criteria for schizophrenia but not conforming to any of the subtypes in F20.0-F20.2, or exhibiting the features of more than one of them without a clear predominance of a particular set of diagnostic characteristics. Atypical schizophrenia Excludes: acute schizophrenia-like psychotic disorder ( F23.2 ) chronic undifferentiated schizophrenia ( F20.5 ) post-schizophrenic depression ( F20.4 )

F20.4 Post-schizophrenic depression

A depressive episode, which may be prolonged, arising in the aftermath of a schizophrenic illness. Some schizophrenic symptoms, either "positive" or "negative", must still be present but they no longer dominate the clinical picture. These depressive states are associated with an increased risk of suicide. If the patient no longer has any schizophrenic symptoms, a depressive episode should be diagnosed (F32.-). If schizophrenic symptoms are still florid and prominent, the diagnosis should remain that of the appropriate schizophrenic subtype (F20.0-F20.3).

F20.5 Residual schizophrenia

A chronic stage in the development of a schizophrenic illness in which there has been a clear progression from an early stage to a later stage characterized by long- term, though not necessarily irreversible, "negative" symptoms, e.g. psychomotor slowing; underactivity; blunting of affect; passivity and lack of initiative; poverty of quantity or content of speech; poor nonverbal communication by facial expression, eye contact, voice modulation and posture; poor self-care and social performance. Chronic undifferentiated schizophrenia Restzustand (schizophrenic) Schizophrenic residual state

F20.6 Simple schizophrenia

A disorder in which there is an insidious but progressive development of oddities of conduct, inability to meet the demands of society, and decline in total performance. The characteristic negative features of residual schizophrenia (e.g. blunting of affect and loss of volition) develop without being preceded by any overt psychotic symptoms.

F20.8 Other schizophrenia

Cenesthopathic schizophrenia Schizophreniform: · disorder NOS · psychosis NOS Excludes: brief schizophreniform disorders ( F23.2 )

F20.9 Schizophrenia, unspecified

Differential Diagnosis

Persons presenting with psychotic symptoms can have a variety of psychiatric and medical conditions, including:

Psychiatric Disorders

1. Schizophreniform disorder
2. Schizoaffective disorder
3. Delusional disorder
4. Depressive disorder with psychotic symptoms
5. Bipolar disorder

Medical Disorders

1. Systemic lupus erythematosus
2. Brain tumors
3. Wilson disease
4. Huntington disease
5. Neurosyphilis
6. Vitamin B-12 and thiamine deficiency
7. Paraneoplastic disorders
8. Dementia with Lewy bodies

Exams and tests

There are no specific laboratory examinations to rule in schizophrenia, however lab tests can be used to rule out secondary causes of psychosis.

History

Eugen Bleuler (1857-1939). Source: Courtesy of the National Library of Medicine

The term schizophrenia was coined by the Swiss psychiatrist Eugen Bleuler to express the breakdown between thought, emotions and behavior observed in patients with the condition. Schizophrenia then replaced the term Dementia praecox previously proposed by the German psychiatrist Emil Kraepelin to unify the descriptions of Paranoia, Hebephrenia, and Catatonia. That term Dementia praecox had been previously used by the French psychiatrist Benedict Morel in the mid 1800's.

Emil Kraepelin (1856-1926). Source: Courtesy of the National Library of Medicine

Etymology

From the Greek roots schizo meaning splitting and phrenia meaning mind or personality.

Risk factors

Risk factors for schizophrenia include ^[3]:

Season-of-birth: higher risk in winter born in Northern hemisphere

Birth complications: higher risk

Parental age: higher risk with advanced paternal age.

Cannabis use: higher risk

Infections and the immune system disorders: a number of auto-immune conditions may present with psychosis

Urban residency: higher risk compared to rural settings.

Migration: higher risk among migrants when compared to native born individuals.

Epidemiology

The epidemiology of schizophrenia has been extensively described, however there are discrepancy among estimates due to methodological problems such as (1) definition of diagnostic criteria, (2) use of lay interviewers, (3) generalizability of community samples, (4) biased clinical samples, and (5) use of structures interviews. A review of current prevalence and incidence estimates is provided below. A summary of the issues regarding methodological issues in schizophrenia can be found here.

Prevalence

Prevalence. The point prevalence of schizophrenia is the proportion of the population at a point in time that has the disorder. The point prevalence of schizophrenia is about five per thousand in the population. The estimate depends on the age distribution of the population– if persons too young to be at risk are included in the denominator, for example, the estimates will be lower. Table 1 presents findings from areas in which credible estimates of both prevalence and incidence are available. The range in prevalence in Table 1 is from 2.7/1000 to 8.3/1000, and this range would not be much affected if several dozen other studies, available from prior reviews, were included. Lifetime prevalence has been estimated by surveys with examinations by medically trained persons, with resulting estimates not too different. A recent review of the prevalence of schizophrenia can be found here.

Incidence

Contrary to widely cited claims of similar incidence across cultures and regions, recent estimates seem to indicate significant variance in the global incidence of schizophrenia, with a median value (10%–90% quantile) of 15.2 (7.7–43.0) per 100,000. A systematic review on the incidence of schizophrenia can be found here here.

Treatment

The treatment of schizophrenia may be better understood in terms of phases: acute psychotic episode, treatment of co-occurring conditions, relapse prevention and maintenance ^[4]. In all phases anti-psychotics are the keystone of treatment. Supportive psychotherapy, family psychoeducation and vocational rehabilitations are important components of treatment. The treatment of Schizophrenia should include a combination of medication and psychotherapy. The Texas Algorithm for Schizophrenia can be found here and the American Psychiatric Association Practice Guidelines here.

Medications

First Generation Antipsychotics

First Generation Antipsychotics (FGA) are usually divided into high and low potency drugs. Low potency FGAs tend to be more sedating with less potential for extra-pyramidal side effects (EPS), while high potency FGAs have less sedation and more EPS potential. Among the low potency FGAs one finds: thioridazine (Mellaril) and chlorpromazine (Thorazine), examples of high potency FDAs include haloperidol (Haldol) and fluphenazine (Prolixin). Most FGA tend to lead to weight gain, with a notable exception: molindone. PORT recommended antipsychotic dosage range for the treatment of schizophrenia.

Second Generation Antipsychotics

Over the last decade a new generation of antipsychotics has entered the market and rapidly become the main treatment options for schizophrenia. They are, on order of appearance on the market:

Risperidone

The main commercial name: Risperdal. Produced by Janssen Pharmaceuticals. Part of Johnson & Johnson.

Initial dosage: 1 mg hs; Maintenance: 2-8 mg hs.

Most clinically significant side effects: Orthostatic hypotension and reflex tachycardia, insomnia, and agitation.

Long terms side effects: weight gain and prolactin elevation.

Olanzepine

Commercial name: Zyprexa. Produced by Lilly.

Initial dosage: 5-10 mg QD, usually at bedtime; Maintenance: 10-20 mg QHS.

Most clinically significant side effects: drowsiness, dry mouth, akathisia and sedation.

Long terms side effects: weight gain and lipid and glucose metabolism alterations.

Quetiapine

Commercial name: Seroquel. Produced by Astra Zeneca.

Initial dosage: 50 mg QHS; Maintenance: 400-800 mg QD. Max: 1200 mg QD.

Most clinically significant side effects: Orthostatic hypotension, sedation.

Long terms side effects: weight gain and lipid and glucose metabolism alterations.

Ziprazodone

Commercial name: Geodon. Produced by Pfizer.

Initial dosage: 20 mg BID; Maintenance: 80 mg BID.

Most clinically significant side effects: QTc prologation.

Aripiprazole

Commercial name: Abilify. Produced by Bristol-Meyers BMS.

Initial dosage: 10-15 mg qAM; Maintenance: 10-30 mg per day.

Most clinically significant side effects: headache, nausea and vomiting, usually resolving in a week.

Paloperidone

Commercial name: Invega. Other Janssen product - a metabolite of risperidone.

Initial dosage: 6 mg/day. Can be given once a day.

Long terms side effects: weight gain and prolactin elevation. Similar to risperidone.

Psychosocial treament

A number of psychosocial strategies will be helpful in treating patients with schizophrenia, including:

Individual psychotherapy

Family therapy

Group therapy

Social skills training

Vocational therapy

Case management

Clinical Trials

There are hundreds of active clinical treatment trials for schizophrenia in the United States. A complete list can be found here: clinicaltrials

References

1. ↑ Blanchard JJ, Cohen AS. The structure of negative symptoms within schizophrenia: implications for assessment.Schizophr Bull. 2006 Apr;32(2):238-45.
2. ↑ American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) 2000
3. ↑ Messias EL, Chen CY, Eaton WW. Epidemiology of schizophrenia: review of findings and myths. Psychiatr Clin North Am. 2007 Sep;30(3):323-38. Review.
4. ↑ Lehman AF, Kreyenbuhl J, Buchanan RW, Dickerson FB, Dixon LB, Goldberg R, Green-Paden LD, Tenhula WN, Boerescu D, Tek C, Sandson N, Steinwachs DM. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2003. Schizophr Bull. 2004;30(2):193-217