Schizophrenia
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More Specific Terms
- catatonic schizophrenia (includes periodic catatonia)
- disorganized (hebephrenic) schizophrenia
- late-onset schizophrenia
- paranoid schizophrenia
- residual schizophrenia
- schizoaffective disorder
- schizophreniform disorder
- undifferentiated schizophrenia
Etiology
- specific etiology unknown
- dopamine hypothesis
- hypoactive dorsolateral prefrontal cortex ( DLPFC)
- hyperactive limbic system dopaminergic neurons
- adolescence triggers onset of symptoms secondary to the need to use DLPFC dopaminergic neurons as higher cognitive functions develop
- pharmacologic precipitants:
Epidemiology
- 1% per lifetime
- men & women equally affected
- late onset (age > 45) women > men [4]
- average age of onset: late teens to early adulthood
- worldwide distribution with similar prevalence
- higher social class at birth associated with increased risk [6]
Pathology
-
- hypoactive dopaminergic neurons secondary to problems in migration of neural tissue during development
- thought to account for chronic phase (negative symptoms) of schizophrenia
- alterations of mGluR3 receptors in the DLPFC might have a role in the pathogenesis of schizophrenia; schizophrenia subjects had lower mGluR3 than controls & had higher levels of glutamate carboxypeptidase-2, an enzyme that metabolizes N-acetylaspartylglutamate, the only known specific endogenous agonist of mGluR3 [10]
- compensatory response to hypoactive DLPFC dopaminergic neurons
- thought to account for active phase (positive symptoms) of schizophrenia
- adolescence triggers onset of symptoms secondary to the need to use DLPFC dopaminergic neurons as higher cognitive functions develop
Genetics
- often family history
- schizophrenia susceptibility
- chromosomal translocation t(9;14)(q34;q13) involving NPAS3 is found in a family with schizophrenia
- chromosomal translocation t(1;11)(q42.1;q14.3) involving DISC1 segregates with schizophrenia & related psychiatric disorders in a large Scottish family
- overexpression of RIC3 in brains from patients with bipolar disease or schizophrenia
- human endogenous retrovirus HERV-W antigenemia more common in patients than controls [9]
- other implicated genes DAOA, MICB, C6orf217, MAP6, CPLX2
Clinical-manifestations
- active phase (positive symptoms)
- present for at least 1 month
- hallucinations: usually auditory hallucinations
- delusions
- chronic phase (negative symptoms)
- present for at least 6 months
- cataplexy
- flat affect
- poverty of speech, alogia
- lack of initiative
- isolation
- social withdrawal
- poor job performance, avolition
- poor hygiene
- unusual perceptions
- no mood symptoms: depression or mania
- functional impairment
- suicidal attempts in 50%; 10% are successful
- mental status
- usually alert & oriented without fluctuations in level of consciousness
- motor activity variable
- agitation
- psychomotor retardation
- memory often impaired (less so in late onset form) [4]
Laboratory
- mental status exam
- test of exclusion
Diagnostic-procedures
- EEG: frequently left sided abnormalities (non-specific)
Radiology
- CT of head: ventricular enlargement 10-50% (non-specific)
- PET scan: decreased frontal lobe metabolism
- MRI may show periventricular hyperintensities (late onset) [4]
Complications
- increased risk of mortality
- largely due to
- possible a result of
- lifestyle of the mentally ill
- adverse effects of medications [13]
- accelerated aging suggested [14]
Differential-diagnosis
- substance abuse
- schizophreniform disorder (symptoms < 6 months)
- psychosis (symptoms < 1 month, > 1 day)
- schizoaffective disorder
- mood disorder with psychotic symptoms
- psychosis brief compared with mood symptoms
- delusional disorder: delusion without other symptoms of schizophrenia
- personality disorder
- paranoid
- borderline
- schizoid
- schizotypal
- Huntington's diesase
- Wilson's disease
- temporal lobe epilepsy
- heavy metal poisoning
- Werneke- Korsakoff syndrome
- HIV
- syphilis
- herpes encephalitis [12]
Management
-
- combined dopamine & serotonin receptor blockade
- fewer extrapyramidal symptoms than other antipsychotic agents
- clozapine ( Clozaril) reduces mortality [11]
- risperidone ( Risperdal) [5]
- olanzapine [12]
- high potency antipsychotic agents
- dopamine D2 receptor antagonist
- pharmaceutical agents
- dosage: 5-30 mg
- extrapyramidal side effects
- preferred agents during pregnancy
- low potency antipsychotic agents
- dopamine D2 receptor antagonist
- pharmaceutical agents
- dosage: 300-1000 mg
- anticholinergic side effects
- 2/3 of patients relapse within 6 months after discontinuation of antipsychotic medication
- muscarinic receptor agonist xanomeline may be of benefit [8]
- patient education
- Alliance for the Mentally ill (800) 950-NAMI
- group therapy
More General Terms
Internet Database
OMIM: 181510
OMIM: 181500
OMIM: 600511
OMIM: 600850
OMIM: 603013
OMIM: 603175
OMIM: 603176
OMIM: 603206
OMIM: 603342
OMIM: 604906
OMIM: 600850
References
- Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
- Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1145-1147
- Prescriber's Letter 7(11):65 2000
- UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- Journal Watch 22(4):32, 2002 Csernansky JG et al A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 346:16, 2002 PMID: [1]
- Journal Watch 22(4):32, 2002 Mulvany F et al Effect of social class at birth on risk and presentation of schizophrenia: case-control study. BMJ 323:1398, 2001 PMID: &dopt=Abstract
- Lieberman JA et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005 Sep 22; 353:1209-23. PMID: [2]
- Shekhar A et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry 2008 Aug; 165:1033. PMID: [3]
- Perron H et al, Endogenous retrovirus type W GAG and envelope protein antigenemia in serum of schizophrenic patients. Biol Psychiatry 2008, 64:1019 PMID: [4]
- Torry EF and Yolen RH The past is the future. Biol Psychiatry 2008, 64:1017 PMID: [5] - Ghose S et al Differential expression of metabotropic glutamate receptors 2 and 3 in schizophrenia: A mechanism for antipsychotic drug action? Am J Psychiatry 2009 Jun 1; [e-pub ahead of print]. <PubMed> PMID: [6] <Internet> [7]
- Tiihonen J et al. 11-year follow-up of mortality in patients with schizophrenia: A population-based cohort study (FIN11 study). Lancet 2009 Jul 11 <PubMed> PMID: [8] <Internet> [9]
- Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
- Hoang U et al. Mortality after hospital discharge for people with schizophrenia or bipolar disorder: Retrospective study of linked English hospital episode statistics, 1999-2006. BMJ 2011 Sep 13; 343:d5422 PMID: [10]
- Fernandez-Egea E et al. Testosterone in newly diagnosed, antipsychotic-naive men with nonaffective psychosis: A test of the accelerated aging hypothesis. Psychosom Med 2011 Oct; 73:643. PMID: [11]
- Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
- Schizophrenia: NIH Institute and Center Resources [12]
- National Guideline Clearinghouse
- Schizophrenia. Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care. ngc-guideline: [13]
- Clinical practice guideline for schizophrenia and incipient psychotic disorder. Catalan Agency for Health Information, Assessment and Quality ngc-guideline: [14]
