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Principal Clinical Disorders and Problems

10. SCHIZOPHRENIA A N D SCHIZOAFFECTIVE DISORDERS

Herbert T. Nagamto, M.D

1. Define schizophrenia. Schizophrenia is a complex illness or group of disorders characterized by hallucinations, delusions, behavioral disturbances, disrupted social functioning, and associated symptoms in what is usually an otherwise clear sensorium.

2. What are the symptoms of schizophrenia?

Schizophrenia involves at least a 6-month period of continuous signs of the illness. Active symptoms may include: Delusions, which are false beliefs that (1) persist despite what most people would accept as evidence to the contrary and (2) are not shared by others in the same culture or subculture. Hallucinations,which are perceptions that appear to be real when no such stimulus is actually present. Hallucinations may involve any of the five normal senses, but in schizophrenia they are usually auditory. Disorganized speech. Grossly disorganized or catatonic behavior. Catatonia, a syndrome characterized by stupor with rigidity or flexibility of the musculature, may alternate with periods of overactivity. Negative symptoms, such as ( 1 ) affective flattening or decreased emotional reactivity; (2) alogia or poverty of speech; (3) avolition or lack of purposeful action. Usually work performance, social relations, and self-care decrease below the highest previous levels.

3. What are some additional clinical features? Prodromal or residual phases may include social isolation or withdrawal, peculiar behavior,
digressive overelaborate speech, odd beliefs such as ideas of reference (thinking that others words, actions, or expressions are in reference to oneself when this is not the case) or magical thinking, unusual perceptual experiences, or marked lack of initiative, interests, or energy. Age of onset is usually during adolescence or early adulthood. The course is highly variable, but generally involves significant functional impairment. Violent acts sometimes receive significant attention. While it has been generally accepted that violent acts are no more frequent in schizophrenic patients than in the general population, recent epidemiologic data have shown a link between mental illness and violence. The percentage of violence in the U.S. attributed to schizophrenic patients, however, is minimal-and much less than that due to alcohol abuse. Some schizophrenic patients have various somatic complaints as part of their illness, but they also may be medically ill and not complain or incorporate symptoms into their delusional system. Life expectancy is reduced by death from suicide and other causes. Approximately 40% of schizophrenics attempt suicide at some point in their lifetime, and 10-20% succeed.
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4. How common is schizophrenia? The lifetime incidence of schizophrenia is approximately 1%.This figure is remarkably stable across racial, cultural, and national lines. 5. What medical conditions may induce psychosis and be mistaken for acute schizophrenia? Psychosis, which is characterized by a disturbance in or loss of contact with reality, may include symptoms of schizophrenia, including delusions, hallucinations, bizarre behavior, ideas of reference, paranoia (irrational suspiciousness or false beliefs of persecution), disorganized speech, and illogical thinking. A number of medical conditions can induce psychosis: Substance abuse and drug toxicity (see Question 6) Space-occupying central nervous system lesions-tumor (especially limbic and pituitary), aneurysm, abscess Head trauma Infections-encephalitis, abscess, neurosyphilis Endocrine disease-thyroid, Cushings, Addisons, pituitary, parathyroid Systemic lupus erythematosus and multiple sclerosis Cerebrovascular disease Huntingtons disease Parkinsons disease Migraine headache and temporal arteritis Pellagra and pernicious anemia Porphyria Withdrawal states, including alcohol and benzodiazepines Delirium and dementia Sensory deprivation or overstimulation states can induce psychosis, such as psychosis induced in the intensive care unit
6. Which street drugs and prescription medications may induce psychosis? Street drugs Prescription drugs Cocaine Metronidazole and other antibiotics Antidepressants Phencyclidine L-dopa Lysergic acid diethylBromocriptine amide (LSD) Amantadine Mescaline Ephedrine Psilocybin Phenylpropanolamine Marijuana Idomethacin and other nonsteroidal antiinflammatory agents Morning glory seeds Cimetidine and other antihistamines Alcohol Disulfiram Carbamazepine and other anticonvulsants Digoxin, propranolol, and other cardiac medications Thyroid hormones Various medications with strong anticholinergic effects Note that routine urine toxicology screens usually monitor for only a limited number of substances.

7. Which tests should a screening medical work-up of psychosis include? Complete blood count Serum electrolytes, glucose, blood urea nitrogen, creatinine, calcium, and phosphate Liver function tests Thyroid function tests VDRL or RPR, HIV antibody test in high-risk patients* Electrocardiogram Urinalysis and urine toxicology screen

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Chest x-ray Sleep-deprived EEG Head CT or MRI scan Blood levels of therapeutic medications, when appropriate Lumbar puncture, when appropriate * VDRL = Venereal Disease Research Laboratory test, RPR = rapid plasmin reagin test, HIV = human immunodeficiency virus.

8. How is schizophrenia differentiated from manic-depressive illness and other psychiatric conditions? The differential diagnosis of schizophrenia and other psychiatric conditions that may manifest psychotic symptoms is difficult and best done from a longitudinal perspective on the course of the illness. Such a differential is crucial, because effective treatments vary depending on the conditions. In affective disorders (manic depressive illness and major depression), the duration of psychotic symptoms is relatively brief in relation to the affective symptoms. Schizophreniformdisorder, by definition, involves the symptoms of schizophrenia with a duration of less than 6 months. Patients with obsessive-compulsivedisorder may have beliefs that border on delusions but generally recognize that their symptoms are at least somewhat irrational. Brief reactive psychoses may be seen in patients with borderline or other personality disorders as well as dissociative disorders. Posttraumatic stress disorder may involve visual, auditory, tactile, and olfactory hallucinations during flashbacks. Beliefs or experiences should not be considered delusional or psychotic if they are in the context of a persons religion or culture. 9. What causes schizophrenia? This question thus far has eluded an answer. A number of factors, however, have been implicated in the pathogenesis of schizophrenia, which often is conceptualized as a group of disorders with common symptoms.
Factors Implicated in the Etiology o f Schizophrenia

Genetic factors (see Question 10) Brain structural changes Neurochemical changes Neurophysiologicalchanges

Endocrine factors Viral and immune factors

Brain structural studies have failed to find a pathognomonic lesion in schizophrenia, but have consistently found a number of abnormalities. CT, MRI, and postmortem studies have found changes in frontal, temporal, limbic, and basal ganglia areas, as well as in brain symmetry, in schizophrenic patients. Some of these findings have been corroborated by changes in regional cerebral blood flow, functional MRI, and positron emission tomographic (PET) studies. Multiple neurochemical changes also have been implicated in schizophrenia. It has been long noted that an excess in dopaminergic activity in the central nervous system is central to the development of schizophrenic symptoms. Compelling data also implicate norepinephrine, serotonin, and cholinergic (muscarinic and nicotinic), glutamatergic, GABAergic, and neuropeptide systems. Neurophysiological changes have been shown through various neuropsychologic and physiologic measures. Schizophrenic patients have shown abnormal informational processing on such measures as the Continuous Performance Test. They also have shown abnormal sensory processing on skin conductance habituation, backward masking, smooth pursuit eye movements, prepulse inhibition of acoustic startle, and evoked potentials, such as P300, P I , mismatched negativity, and failure to decrement the P50 auditory response in a conditioning-testing paradigm. Endocrine factors have long been suspected. Females tend to develop schizophrenia later and often have less severe symptoms than males. In males, the onset of schizophrenia typically is during puberty. Changes in prolactin, melatonin, and thyroid function have been found in schizophrenia.

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Viral and immune factors also have been implicated. Although the search for a causative virus in schizophrenia has thus far been unfruitful, various factors point to this possibility. For example, a number of immune changes have been found, including IgA, IgG, and IgM. Furthermore, a larger than expected number of schizophrenic patients are born in late winter and early spring, leading to the hypothesis that perinatal viral infections may be involved in causing schizophrenia. Psychosocial factors are no longer felt to be causative in schizophrenia but clearly play a role in the course of the illness.
10. What is the role of genetics in schizophrenia? Genetic factors play a significant role, but are not sufficient alone to account for the development of schizophrenia. Compelling data have come from family studies. In the general population, the lifetime risk of developing schizophrenia is approximately 1%. A child born with one schizophrenic parent has about a 14% chance of developing schizophrenia. The risk rises to approximately 25% if both parents are schizophrenic. Another approach has looked at siblings with varying degrees of genetic similarity. Nontwin siblings of a schizophrenic patient have about an 8% chance of developing schizophrenia. For nonidentical (dizygotic) twins, if one twin is schizophrenic, approximately 10% of the other twins develop schizophrenia. This risk, or concordance rate, rises to 40-50% in identical (monozygotic) twins. Genetic linkage studies to date have implicated chromosomes 5, 6, 8, 10, 13, and 15 in schizophrenia. Although such data support a strong role for genetics in the etiology of schizophrenia, they also clearly show that other factors play a significant role in determining who does and does not develop schizophrenia.

11. What are the treatments for schizophrenia? Antipsychotic medications are the cornerstone of the treatment of schizophrenia (see Chapter 48). Inpatient treatment in a therapeutic milieu may be crucial in the early and acute phases. Residential treatment settings, group homes, and day hospital programs may help patients to remain outside the hospital. Supportive individual and group psychotherapy can help patients to understand and come to terms with their illness and need for treatment, to identify factors that influence symptoms, and to develop strategies to deal more effectively with the illness. Family therapy sessions also may help families of schizophrenic patients to understand the illness and to help the patient. Families may have a negative impact if they are high in expressed emotion, hypercritical, or overtly hostile toward the patient. Schizophrenic patients often have extremely poor social skills. Social skills training has been shown to be highly effective in helping to improve quality of life. Vocational rehabilitationhelps some stabilized patients to return to more productive roles in society.

12. List the positive prognostic signs in schizophrenia.

Improved prognosis in schizophrenia is associated with: Good premorbid functioning, late onset, female gender, clear precipitating events, acute onset. Mood disturbances, brief active phase, good interepisode functioning, marriage, decreased residual symptoms, fewer chronic negative symptoms. Decreased structural brain abnormalities, normal neurologic functioning. Family history positive for mood disorder, negative for schizophrenia. 13. What is schizoaffective disorder? Schizoaffective disorder has been defined in numerous ways, but essentially it is an illness that combines symptoms of schizophrenia with a major affective disorder, i.e., major depression or manic-depressive illness.

14. How is schizoaffective disorder different from schizophrenia or manic-depressive illness? Mood disturbance is common in all phases of schizophrenia, and psychotic symptoms are common during acute phases of manic-depressive illness (bipolar affective disorder). Accurate diagnosis often requires a clear longitudinal history of symptoms. In schizophrenia, the total duration of

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affective symptoms is brief relative to the total duration of the illness. In manic-depressive illness, delusions and hallucinations primarily occur during periods of mood instability. A DSM-IV diagnosis of schizoaffective disorder requires an uninterrupted period of illness during which there is either a major depressive, manic, or mixed (manic and depressive) episode that is concurrent with active symptoms of schizophrenia. In addition, during the same period of illness, there are delusions or hallucinations for at least 2 weeks in the absence of prominent mood symptoms, and mood episode symptoms are present for a substantial portion of the active and residual phases of the illness. It is important to make as clear a diagnosis as possible, as the cornerstone of treatment for schizophrenia is antipsychotic medications, whereas mood stabilizers and antidepressants are crucial in treating affective disorders.

15. Does significant depression rule out schizophrenia? Although the diagnosis of schizophrenia emphasizes that psychotic symptoms predominate over mood symptoms, schizophrenic patients may suffer significant depression, which strongly contributes to their increased suicide risk. Increased suicide risk may extend even after an episode of depression resolves, and may result from the patients inability to come to terms with the debilitating effects of schizophrenia. Pharmacologic treatment of depression in schizophrenia is somewhat controversial, because antidepressants apparently reduce the efficacy of antipsychotic medications in acutely ill schizophrenic patients. On the other hand, adjunctive antidepressant medications have been shown to be effective in the acute maintenance treatment of depression in schizophrenic and schizoaffective patients.
BIBLIOGRAPHY
1. Adler LE, et al: Schizophrenia, sensory gating, and nicotinic receptors. Schizophr Bull 24:189-202, 1998. 2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC, American Psychiatric Association, 1994. 3. Buckley PF (ed): Schizophrenia. Psychiatr Clin North Am 21(1), 1998. 4. DeLisi LE (ed): Depression in Schizophrenia. Washington, DC, American Psychiatric Press, 1990. 5. Hales RE, Yudofksy SC, Talbott JA (eds): The American Psychiatric Press Textbook of Psychiatry, 3rd ed. Washington DC, American Psychiatric Press, 1999. 6. Kaplan HI, Sadock BJ (eds): Comprehensive Textbook of Psychiatry, 6th ed. Baltimore, Williams & Wilkins, 1995. I. Tamminga CA (ed): Schizophrenia in a Molecular Age. Ann Rev Psychiatry 18(4), 1999. 8. Yudofsky SC, Hales RE (eds): The American Psychiatric Press Textbook of Neuropsychiatry, 3rd ed. Washington DC, American Psychiatric Press, 1997.

1 1 . PARANOID DISORDERS
Theo C. Manschreck, M.D.
1. What are paranoid disorders? The term paranoid disorders refers to a variety of conditions characterized by delusions and related behavior. One of the earliest described of these disorders was paranoia, now called delusional disorder, which is of unknown cause. The cardinal psychopathologic feature is the delusion. Paranoia actually is uncommon; other forms are seen frequently. There are two broad categories of paranoid disorders: disorders with known causes (medical and substance disorders) and idiopathic disorders, which include delusional disorder, paranoid personality disorder, shared psychotic disorder, atypical psychosis (psychotic disorders not otherwise specified), schizophrenia and schizophreniform disorder, mood (psychotic forms of mania and depression) disorder, and schizoaffective disorder.