eMedicine Specialties > Emergency Medicine > Psychosocial

Schizophrenia

Author: Paul S Gerstein, MD, Attending Physician, Baystate Mary Lane Hospital Emergency Department
Contributor Information and Disclosures

Updated: Jun 1, 2009

Introduction

Background

Commonly known as insanity or madness, schizophrenia is a chronic psychotic disorder with onset typically occurring in adolescence or young adulthood. Schizophrenia results in fluctuating, gradually deteriorating, or relatively stable disturbances in thinking, behavior, and perception. Severity can range from mild and subtle with very good adaptation to everyday life, to severely disabling requiring constant supervision in a restricted environment. The illness is marked by the presence of "positive" symptoms, such as delusions, hallucinations, and disorganized speech and behavior, and "negative" symptoms, such as poverty of speech, flattened affect, social withdrawal, and avolition.

To satisfy the diagnostic requirements of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), the syndrome must continue for at least 6 months, with at least 1 month of active symptoms present much of the time, and must result in significant impairment of occupational and social functioning.

Other schizophrenia-related disorders may have a less severe, less global, or more transient course but can share strong familial associations with schizophrenia. Certain psychotic disorders such as bipolar disorder in a manic phase and delusive disorder share some of the positive symptoms of schizophrenia but can have distinctly different courses and prognosis. Easily confused with schizophrenia in their acute presentations, time is required to observe for differences between these disorders in order to make a secure diagnosis unless the patient's past psychiatric history is already known. Autistic disorders, as well, share superficial similarities to schizophrenia and can be easily misdiagnosed in the acute setting.

It is essential in the emergency department not to confuse the thought and behavioral disturbances of organically based acute delirium with any of the psychotic disorders. The avoidance of this confusion is the primary reason for "medical clearance" examinations and drugs-of-abuse screening.

Because of the variability of symptom expression, diagnostic requirements of chronicity, and lack of pathognomonic features, an ED diagnosis of schizophrenia should be provisional at best. As a diagnosis-by-exclusion, schizophrenia must be distinguished from the numerous psychiatric and organic disorders that also can lead to psychotic disturbances in thinking and behavior (see Delirium, Dementia, and Amnesia).

For additional reading, see Schizophrenia.

Pathophysiology

Schizophrenia currently is conceptualized as a broad syndrome expressed by a heterogeneous group of brain disorders rather than as a single disease entity. In addition, schizophrenia is viewed as the most severe end of a spectrum of schizophrenia-related disorders. Although placed in the category of "functional" psychiatric disorders, schizophrenia is associated primarily with abnormalities of brain neurochemistry, neuroanatomy, and development.

Genetics and intrauterine events likely play the major etiologic role in schizophrenia, with psychosocial stressors serving as precipitating or exacerbating factors. This view is a move away from the psychodynamic theories of the mid-twentieth century and a return to some of the earliest conceptions of the disease.

This modern biopsychiatric model has a firm foundation in twin concordance studies and research into the actions of antipsychotic medications on the dopamine systems, and, more recently, serotonin, glutamate, and muscarine systems in the brain. As a result, antipsychotic medications are now the primary treatment for schizophrenia, with counseling and behavioral therapies playing supportive, but secondary, roles.

The dopamine hypothesis suggests that the hallmark neurochemical disturbance is an overactivity of the dopamine system in the brain, particularly that involving the D2 receptors, which are blocked by all antipsychotic drugs (with the possible exception of the newest atypical antipsychotic drugs). Dopamine overactivity is thought to cause the positive symptoms of the disease.

Diminished activity in the prefrontal cortex (ie, hypofrontality) related to serotonin transmission is associated with the negative symptoms. The efficacy of the new atypical antipsychotics in reversing negative symptoms may be owing to their blockage of specific serotonin receptors. 

Glutamatergic and, most recently, muscarinic systems have been shown in some studies to be related to both positive and negative schizophrenia symptoms. Modulation of these systems is at the forefront of research on schizophrenia medication treatment.

Frequency

United States

The approximate lifetime incidence is 1% or 3 million individuals. In 1990, direct and indirect costs were estimated to be $33 billion, accounting for 2.5% of the healthcare dollar. Patients with schizophrenia occupy as many as 25% of all hospital beds at any given time.

International

A remarkably constant 1% worldwide lifetime incidence exists across all cultural, geographic, and socioeconomic boundaries.

Mortality/Morbidity

Schizophrenia in its full expression is usually a devastating disorder and has a profound impact on family, social, and occupational life. According to Kaplan, "To patients, schizophrenia threatens the loss of what almost everyone takes for granted: selfhood, the ontological sense of being someone and something. Only when that sense is missing is its importance, its survival value, and its function of endorsing people as sentient creatures, appreciated."¹

To underscore the profound impact of this illness, an editorial in the journal Science described schizophrenia as the worst disease affecting mankind (not excepting AIDS) for the following reasons:

• Lost productivity in the United States costs an estimated $20 billion per year.
• The completed suicide rate is 10%.
• Premature death may result from poor health maintenance, substance abuse, poverty, and homelessness.

Total economic burden of schizophrenia in the United States was estimated at $62.7 billion in 2002.²  

Sex

The lifetime risk is equal for both sexes, but onset is earlier and outcome is poorer in males than in females.

• Females have a better response than males to antipsychotic medications.
• Monozygotic twin concordance rates are higher for females than for males.

Age

The peak onset is age 18-25 years for males and age 26-45 years for females.

• Disease onset before puberty is rare.
• Disease onset in persons older than 45 years is uncommon.
• An individual's symptoms may improve gradually when they are middle aged and older. Rarely, full spontaneous recovery occurs after many years of chronic illness.

Clinical

History

The onset is insidious in approximately one half of all patients. The prodromal phase can begin years before the full-blown syndrome and is characterized by losses of functioning in home, society, and occupation (eg, poor school or work performance, deterioration of hygiene and appearance, decreasing emotional connections with others, behaviors that are odd for the individual in the past).

A gradual onset indicates a more severe and prolonged course of illness.

An abrupt onset of hallucinations and delusional, bizarre, or disorganized thinking in patients who previously functioned normally may result in a better intermediate and long-term outcome. Such patients arriving in a psychotic crisis that requires immediate management may not have been diagnosed with psychiatric illness previously. They often present diagnostic dilemmas involving organic versus psychiatric etiology and primary psychotic versus affective disorder diagnosis. Treatment may be complicated further by the presence of alcohol or drug intoxication.

Often, the history obtained in the ED relates to a complication of treatment (medication adverse effects) or crisis arising from socioeconomic factors secondary to schizophrenia (eg, poverty, homelessness, social isolation, failure of support systems).

While the primary diagnosis of schizophrenia rarely is made in the ED, several historical features can be helpful to distinguish the illness from the many medical and psychiatric conditions that can mimic it.

• Two or more of the following must have been present over the prior month for a significant period (unless treated with medication):
  • Delusions - Bizarre or illogical false beliefs, which often have a paranoid, grandiose, persecutory, or religious flavor; false interpretation of normal perceptions
  • Hallucinations - Typically auditory (visual or tactile strongly suggest organic etiology), often involving malevolent or taunting voices commenting on the patient's actions or character, often with sexual flavor; giving commands (ie, command hallucinations); 2 or more voices discussing or arguing with each other; audible thoughts; thought withdrawal (feeling that thoughts are being removed from head), thought broadcasting, or thought interference by outside agent
  • Disorganized speech - Tangential, incoherent, rambling speech; neologisms (new word creation); loosening of associations
  • Behavior - Grossly disorganized or catatonic
  • Negative symptoms - Poverty of speech (ie, alogia), emotional and/or social withdrawal, blunting of affect, avolition
• Loss of a previously held level of occupational, social, or self-care functioning must have occurred since the onset of illness.
• Presence of an affective disorder (eg, major depression, bipolar disorder, schizoaffective disorder) must be excluded; these conditions can be mistaken for schizophrenia and have very different prognoses and therapies. Additionally, an organic etiology (eg, drug intoxication, medical illness) must be ruled out.
• A problem with antipsychotic medications commonly is the chief complaint.
  • Acute dystonia (muscle rigidity and spasm), oculogyric crisis (bizarre and frightening upward gaze paralysis and contortion of facial and neck musculature), akathisia (dysphoric sense of motor restlessness)
  • Parkinsonian symptoms of stiffness, resting tremor, difficulty with gait, and feeling slowed-down
  • Orthostatic hypotension caused by alpha-adrenergic blockade
  • Dry mouth, fatigue, sedation, visual disturbance, inhibited urination, and sexual dysfunction, which can be adverse reactions to antipsychotic medication or to anticholinergic drugs taken for prophylaxis of dystonia
• Obtain the following information when an acutely psychotic patient presents to the ED.
  • Potential danger the patient presents to self or others
    • A paranoid schizophrenic, in response to delusions and command hallucinations, can be extremely dangerous and unpredictable.
    • Find out about threats made to others, expressions of suicidal intent, and possession of weapons at home or on the person.
  • Prior medical and psychiatric records, including past hospitalizations and medication therapy
  • Baseline level of functioning
  • Current or recent substance abuse
  • Current use of prescribed, over-the-counter (OTC), and herbal medications
  • Compliance with current psychiatric medications

Physical

Depending on the reason for ED presentation, the patient with schizophrenia may present wildly agitated, combative, withdrawn, or severely catatonic. Conversely, they may appear rational, cooperative, and well controlled (perhaps only with some blunting of affect). They also could be subtly odd, unkempt, or frankly bizarre in manner, dress, and/or affect.

• Perform a general physical examination on all patients, with attention to vital signs, pupillary findings, hydration status, and mental status.
• A comprehensive physical examination and laboratory evaluation is required when an organic etiology or drug intoxication may be related to mental status changes (see Delirium, Dementia, and Amnesia).
  • Pay particular attention to fever, tachycardia (in association with rigidity, can be a sign of neuroleptic malignant syndrome), heatstroke (antipsychotics inhibit sweating), and other medical illness.
  • Look for signs of dystonia, akathisia, tremor, and muscle rigidity.
  • Tardive dyskinesia is a common and often irreversible sequela of long-term (and sometimes brief) antipsychotic use. It involves uncontrollable tongue thrusting, lip smacking, and facial grimacing.
• Mental status testing should typically reveal clear sensorium and orientation to person, place, and time. Assess attention, language, memory, constructions, and executive functions. Absence of clear sensorium and/or orientation may indicate the presence of acute delirium, a medical condition.

Causes

• The causes of schizophrenia are multifactorial, including genetically inherited brain abnormalities and/or embryonic developmental insult, perhaps in concert with psychosocial stressors.
  • Hallucinogenic or sympathomimetic drug abuse is a frequent precipitating or contributing factor. Marijuana use in teenagers has been statistically associated with a higher risk of chronic psychosis.
  • Psychosocial stressors often interact with the etiology and expression of the disorder.
  • The final common pathway of these various factors is sustained hyperactivity of dopamine neurotransmission in the brain in association with decreased frontal lobe functioning, likely involving serotonin-mediated neurons.
  • "Hypofrontality" (flat affect and other negative symptoms is thought to be secondary to overactivity of specific serotonin subreceptors possibly in concert with dopamine overactivity. Specific serotonin receptors may also be involved with hallucinations and delusions (Note: LSD and other psychotomimetics act upon brain serotonin receptors.). The newer atypical antipsychotic medications, especially clozapine, affect both dopaminergic and serotonergic transmission and improve both positive (dopamine and, possibly, serotonin) and negative (serotonin) symptoms. Older antipsychotic medications (haloperidol and others) do not affect serotonin and fail to improve negative symptoms.
• In a retrospective study of the medical records of 87,907 people born in Jerusalem, Israel, it was found that older men were more likely than younger men to father children who later developed schizophrenia. The study concluded that 26.6% of cases were related to the father's age, whereas the mother's age was unrelated to schizophrenia risk.³ Other studies show increased risk of autism as well (father's age 35 years old and older).
  • Men aged 45-49 years were twice as likely as men younger than 25 years to father children who developed schizophrenia.
  • Men older than 50 years were 3 times as likely as men younger than 25 years to father children who developed schizophrenia.
  • These findings support the remarkably persistent 1% incidence of schizophrenia worldwide, in spite of the reduced reproduction rate of individuals with schizophrenia (lowered mating secondary to social deficits resulting from the illness). Apparently, fresh genetic mutations in aging sperm replenish schizophrenia genes in the population, allowing incidence to remain stable.
• Findings from twin concordance, adoption, and family tree studies suggest a strong genetic contribution independent of environmental or child-rearing factors.
  • Monozygotic twins are 65% concordant, and dizygotic twins are 12% concordant.
  • The risk of occurrence is 5-10% in persons who have 1 parent with schizophrenia and 46% or more in persons who have 2 parents with schizophrenia.
  • Among second-degree relatives, the risk of any schizophrenia spectrum disorder is twice that of the general population.
• Other factors supporting the fundamental role of brain abnormalities include the following:
  • Preponderance of winter and early spring births (60%) suggesting that intrauterine insult may be of viral etiology (unproven)
  • High prevalence of ventricular enlargement and other neuroanatomical abnormalities on imaging and postmortem examination
  • Impaired smooth eye-tracking in most patients
• Factors supporting neurochemical theories include the following:
  • Paranoid psychosis resulting from prolonged amphetamine or cocaine abuse is often indistinguishable from schizophrenia. This lends support to the dopamine hypothesis.
  • Lysergic acid diethylamide (LSD) and cannabis, particularly with long-term abuse, may precipitate persistent psychotic states that can be indistinguishable from schizophrenia. Acutely, LSD is a serotonin receptor agonist and can cause hallucinations distinct from schizophrenia—predominantly visual rather than auditory.
  • Phencyclidine (PCP) and ketamine produce a wide range of schizophrenia-like symptoms supporting the hypoglutamatergic hypothesis of schizophrenia. Both drugs are NMDA/glutamate receptor antagonists. Although current antipsychotic medications do not significantly affect the brain's glutamate system, intensive research is ongoing to develop medications that will directly target these receptors.
• According to the stress-diathesis model, inherited vulnerability combined with stressful circumstances results in development of overt schizophrenia.

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