10. Schizophrenia and Achizoaffective Disorders

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I l l Principal Clinical Disorders and Problems

10. SCHIZOPH RENIA A N D SCHIZOAFFECTIVEDISORDERS

Herbert T. Nagamto, M.D

1. Define schizophrenia.Schizoph renia is a complex illness or group of d isorders characterized by hallucinations, d elu-

sions, behavioral disturbances, disrupted social functioning, and associated symptoms in what isusually an otherwise clear sensorium.

2. What are the symptoms of schizophrenia?Schizophrenia involves at least a 6-month periodof continuous signs of the illness. Active

symptoms m ay include:Delusions, which a re 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 m ay involve anyof the five norm al senses, but in schizophrenia they a reusu-

ally auditory.Disorganized speech.Grossly disorganized or catatonic behavior. Catatonia, a syndrom e 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 em otion al reactivity;(2)

alogia or poverty of speech;(3) avolition or lack of purposeful action. Usually work perform ance,social relations, and self-care decrease below the highes t previous levels.

3. What are some additional clinical features?Prodromal or residual phases may include social isolation o r 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) o r magical thinking,un-usual perceptual experiences, or marked lackof initiative, interests, or energy.

Age of onset is usually during adolescence or early adulthood. The cou rseis highly variable,but generally involves significant functional impairment.

Violent acts som etimes receive significant attention. While it has been generally accepted thatviolent acts are no more frequent in schizophrenic patients than in the general population, recent epi-demiologic data have shown a link between mental illness and violence. The percentage of violencein the U.S. attributed to schizophrenic patients, however, is minimal-and much less than that due toalcohol abuse.

Som e schizophrenic patients have varioussomatic complaints as part of their illness, but theyalso may be medically ill and not complainor incorporate symptoms into their delusional system .

Life expectancy is reduced by death from suicide and other causes. App roximately40 ofschizophrenics attempt suicide at some point in their lifetime, and10-20 succeed.

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52 Schizophrenia and Schizoaffective Disorders

4. How common is schizophrenia?

across racial, cultural, and national lines.The lifetime incidence of schizophrenia is approximately1 . This figure is remarkably stable

5. What medical conditions may induce psychosis and be mistaken for acute schizophrenia?Psychosis, which is characterized by a disturbance in or loss of con tact with reality, may includesymptoms of schizophrenia, including delusions, hallucinations, b izarre behavior, ideasof reference,paranoia (irrational suspiciousness or false beliefs of persecution), disorganized speech, and illogicalthinking. A num ber of m edical conditions can induce psychosis:

Substance abuse and d rug toxicity ( see Question6Spac e-occ upy ing centra l nerv ous system lesions-tumor (espe cially limb ic and pituitary),

Head traumaInfections-encep halitis, abscess, neurosyphilis

Endo crine disease-thyroid, Cush ings, Addisons, pituitary, parathyroidSystemic lupus erythematosu s and m ultiple sclerosisCerebrovascular diseaseHuntingtons diseaseParkinsons diseaseMigraine head ache an d temp oral arteritisPellagra and pernicious anem iaPorphyriaWithdrawal states, including alcoho l and benzodiazepinesDelirium and dem entiaSensory deprivation or overstimulation states can induce p sychosis, such as psychosis induced

aneurysm, abscess

in the intensive care unit

6. Which street drugs and prescription medications may induce psychosis?Street drugs Prescription drugsCocaine Metronidazole and other antibioticsPhencyclidineLysergic acid diethyl-

MescalinePsilocybinMarijuanaMorning glory seedsAlcohol

amide (LSD)

AntidepressantsL-dopaBromocriptineAmantadineEphedrinePheny propanolamineIdom ethacin and other nonsteroidal antiinflammatory ag entsCim etidine and other antihistaminesDisulfiramCarbam azepine and other anticonvulsantsDigox in, propranolol, and other cardiac medicationsThyroid horm onesVarious 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 countSerum electrolytes, glucose, blood urea nitrogen, creatinine, calcium, and pho sphateLiver function testsThyroid function testsVDRL or RPR, HIV antibody test in high-risk patients*ElectrocardiogramUrinalysis and urine toxicology screen


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Schizophren ia an d Schizoaffective Disorders 53

Chest x-raySleep-deprived EEGHead CT or MR I scanBlood levels of therapeutic medications, when appropriate

Lum bar puncture, when appropriateVDRL = 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 psychiatricconditions?

Th e differential diagnosis of schizophrenia and other psychiatric conditions that may manifestpsychotic sy mp toms is difficult and best do ne from a long itudinal perspective o n the course of theillness. 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 psychoticsymptoms is relatively brief in relation to the affective symp toms.Schizophreniform disorder, bydefinition, involves the sympto ms of sch izophrenia with a duration of less than6 months. Patientswith obsessive-compulsive disorder may have beliefs that border on delusions but generally recog-nize that their symptoms are at least somewhat irrational.Brief reactive psychoses may be seen inpatients with borderline or other personality disorders as well as dissociative disorders.Post-traumatic stress disorder may involve visual, auditory, tactile, and olfactory hallucinations duringflashbacks. Beliefs or experiences should not be considered delusional or psychotic if theyare in thecontext of a persons religion or culture.

9. What causes schizophrenia?Th is question th us far has eluded a n answer. A number of factors, however, have been impli-

cated in the pathogenesis of schizophrenia, which often is conceptualized as a group of disorderswith common symptoms.

Factors Implicated in the Etiology of Schizophrenia

Genetic factors (see Question10)Brain structural changesNeurochemical changesNeurophysiological changes

Endocrine factorsViral and immune factors

Brain structural studies have failed to find a pathognomonic lesion in schizophrenia, but haveconsistently found a number of abnormalities. CT, MRI, and postmortem studies have found changesin frontal, temporal, limbic, and basal ganglia areas, as well as in brain symmetry, in schizophrenicpatients. So me of these findings have been corroborated by changes in regional cerebral blood flow,functional M RI, and positron emission tomographic (PET ) studies.

Multiple neurochemical changes also have been implicated in schizophrenia. It has been lon gnoted that an excess in dopaminergic activity in the central nervous system is central to the develop-ment of schizophrenic sym ptoms. Comp elling d ata also implicate norepinephrine, serotonin, andcholinergic (muscarinic and nicotinic), glutamatergic, GABAergic, and neuropeptide systems.

Neurophysiological changes have been shown through various neuropsychologic and physio-logic measures.

Schizophrenic patients have shown abnorm al informational processing on such measures asthe Continuous Performance T est. They also have shown abnormal sensory processing on skin con-ductance habituation, backward masking, sm ooth pursuit eye movements, prepulse in hibition ofacou stic startle, an d evoked potentials, such as P300,P I , mismatched negativity, and failure todecrement the P50 auditory response in a cond itioning-testing paradigm.

Endocrine factors have long been suspected. Fem ales tend to develop schizophrenia later andoften have less severe symptoms than males. In m ales, the onset of schizophrenia typically is duringpuberty. Chan ges in prolactin, m elatonin, and thyroid function have been found in schizophrenia.


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54 Schizophrenia and Schizoaffective Disorders

Viral and immune factors also have been imp licated. Although the search for a causative virusin schizophrenia has thus far been u nfruitful, various fa ctors point to this possibility. For exam ple, anumber of imm une changes have been found, including IgA , IgG, and Ig M . Furthermore, a largerthan expected num ber of schizophren ic patients are born in late winter and early spring, leading to

the hypothesis that perinatal viral infections m ay be involved in causing schizophrenia.Psychosocial factors are no lon ger felt to be causative in sch izophrenia but clearly play a rolein the courseof 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 develop-

ment of schizophrenia. Compelling data have come from family studies. In the general population,the lifetime risk of developing schizophrenia is approximately1 . child born with one schizo-phrenic parent has about a 14 chance of developing schizophrenia. The risk rises to approximately25 if both parents are schizophrenic. Ano ther approach has looked at siblings with varying degreesof genetic similarity. Nontwin siblings of a schizophren ic patient have about an8 chance of devel-oping schizophrenia. For n onidentical (dizygotic) twins, if o ne twin is schizophrenic, approximately10 of the other twins develop schizophrenia. Th is risk, or conco rdan ce rate, rises to40-50 inidentical (mono zygotic) twins.

Genetic linkage studies to date have implicated chrom osom es5 6, 8, 10, 13, and 15 in schizo-phrenia. Although such data support a strong role for genetics in the etiology o f schizophrenia, theyalso clearly show that other factors play a significant role in determining who d oes and d oes not de-velop schizophrenia.

11. What are the treatments for schizophrenia?Antipsychotic medications are the cornerstone of the treatment of sch izophrenia (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 ho spital programs may h elp patients to remainoutside the hospital. Supportiveindividual and group psychotherapy can help patients to under-stand and com e to terms w ith their illness an d need fo r treatment,to identify factors that influencesymptoms, and to develop strategies to deal mo re effectively with the illness.Family therapy ses-sions also may help families of schizophrenic patients to understand the illness andto help the pa-tient. Families may have a negative impact if they are high in expressed emotion, hypercritical, orovertly 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 rehabilitation helps som e stabilized patients to return to more produc tive roles in society.

12. List the positive prognostic signs in schizophrenia.Improved prognosis in schizophren ia is associated with:

Good prem orbid functioning, late onset, fem ale gender, clear precipitating events, acute onset.Mood disturb ance s, brief active phase, good interep isode functioning, m arriage, decreased

Decreased structural brain abn ormalities, normal neurologic functioning.Family history p ositive for m ood d isorder, negative for schizophrenia.

residual symptom s, fewer chronic negative sym ptoms.

13. What is schizoaffective disorder?

Schizoaffective disorder has been defined in n um erous w ays, but essentially it is an illness thatcomb ines symp toms of schizophrenia with a m ajor affective disorder, i .e., m ajor depression ormanic-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

comm on during acute phases of manic-depressive illness (bipolar affective disorder). Accurate diag-nosis often requires a clear longitudinal historyof sym ptom s. In schizophrenia, the total duration of


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10. Schizophrenia and Achizoaffective Disorders