II. Epidemiology
-
Prevalence: 0.3 to 0.7% worldwide across all ethnicities, nationalities (up to 1% in U.S.)
- Most common Psychotic Disorder
- However, in U.S., black patients are disproportionately diagnosed over non-hispanic whites
- Gara (2012) Arch Gen Psychiatry 69(6): 593-600 [PubMed]
- Gender: Equal among men and women
- Men present ages 18 to 25 years old
- Women present age 25 to mid-30s and also after age 40 years old
- Children rarely present age <15 years (but case reports in children as young as 5 years old)
- Age
- Age onset in transition from Adolescence to Adulthood
- Men present earlier than women (see above)
- First attack usually occurs before 40 years old (although some women may present later)
III. Pathophysiology
- Polygenic Threshold Model
- Combination of genetic predisposition and environmental factors
- Heredity Concordance
- Monozygotic twins: 69%
- Dizygotic: 13%
- Schizoid Personality Disorder
- Associated with Schizophrenia (RR=50)
- Protective factors in the family environment
- Uncommon criticism
- Straightforward communication
- Altered Neurotransmission
- Glutamate, Serotonin and Dopamine have altered activity in the Hippocampus, Midbrain, corpus striatum and prefrontal cortex
- Increased and dysregulated Dopamine exacerbates positive symptoms (Antipsychotics primarily reduce Dopamine)
- Other factors
- Inflammatory Cytokines
- Endocrine, Physical associations are only coincidental
- Neurohumoral: Super sensitive receptors
- Neurophysiologic: Spiking or slow waves at Hippocampus
IV. Risk Factors
-
Family History or Genetic Risk Factors (most significant risk)
- However, most patients with Schizophrenia have no Family History
- Schizophrenia confers an increased risk of mental illness to family members
- Increased risk includes Schizophrenia, schizoaffective disorder, Bipolar Disorder, Major Depression
- Monozygotic twin: 50% lifetime Incidence
- Dizygotic twin: 17% lifetime Incidence
- First degree relative: 6-17% lifetime Incidence
- Lewis (2000) Neuron 28:325-34 [PubMed]
- Environmental Risk Factors
- Obstetric complications (e.g. neonatal hypoxic events)
- Maternal or early childhood infections (e.g. Toxoplasmosis, Rubella, HSV 2, Influenza)
- Maternal or early childhood nutritional deficiency (e.g. Folic Acid Deficiency, Iron Deficiency, Vitamin D Deficiency)
- Early childhood CNS Infection
- Advanced paternal age (over 55 years old)
- Childhood Trauma
- Marijuana (or Cannabis) use
- Excess Stimulation of Cannabinoid Receptor 1 may trigger increased Dopamine release
- Risk increases with degree of consumption
- Arseneault (2002) BMJ 325(7374): 1212-3 [PubMed]
- Marconi (2016) Schizophr Bull 42(5): 1262-9 [PubMed]
V. Types
- See Psychosis Types
VI. History
VII. Symptoms: Phases
- Premorbid Phase
- Typically asymptomatic
- Prodromal phase
- Social withdrawal
- Loss of interest in school or work
- Hygiene and grooming deteriorate
- Angry outbursts
- Unusual behavior
- Syndromic Phase
- Chronic or Residual Phase
- Variable depending on Medication Compliance and social support
VIII. Signs
- See Psychosis Exam
IX. Labs
- See Psychosis Labs
- Indicated to exclude other causes in the Psychosis Differential Diagnosis
X. Differential Diagnosis
XI. Diagnosis
- See Schizophrenia Diagnosis
- Schizophrenia is a clinical diagnosis
- Lab and imaging are solely indicated to exclude other possible causes in the differential diagnosis
- Schizophrenia has no specific lab or imaging findings
XII. Associated Conditions
- Anxiety Disorder
- Panic Disorder
- Postraumatic Stress Disorder
- Obsessive Compulsive Disorder
XIII. Management: General
- See Psychosis for acute management
- See Neuroleptic Medications
- Urgent psychiatry referral
- Admission to a controlled setting is preferred for acute Psychosis
- Medication initiation
- Patients should be offered medication management at the time of initial diagnosis
- In the primary care setting, consult with a psychiatrist if considering the start of an Antipsychotic
- Medication adverse effects and monitoring requirements should be discussed prior to starting Antipsychotics
- Do not use a loading dose of Antipsychotics
- Response to first 2-4 weeks of therapy is predictive of longterm response
- Maximal effect may not be evident for months after initiating therapy
- Medications help patients return to baseline functioning (esp. social), quality of life and prevent longterm Disability
- Schizophrenia medication management is intended for lifelong, continuous use
- Relapse and decompensation occurs when medications are stopped
- Adjunctive therapy (improves quality of life, relapse rates, Medication Compliance)
- Cognitive Behavioral Therapy for Psychosis should be offered to patients with Schizophrenia
- Acceptance and Mindfulness-based therapy
- Meta-cognitive therapy
- Positive psychology interventions
- Cognitive remediation training
- Decreases positive symptoms
- Improves concentration, memory and problem solving
- Other measures
- Family interventions
- Social skill training
- Electroconvulsive Therapy
- Weekly telephone-based care management
- Decreases rehospitalization rates
- Cognitive Behavioral Therapy for Psychosis should be offered to patients with Schizophrenia
XIV. Management: Pitfalls
-
Atypical Antipsychotics offer no significant effectiveness benefit over first generation agents
- Select agents based on which adverse effects are expected to be least tolerated
- First generation agents cause Extrapyramidal Side Effects most significantly
- Second generation agents (atypicals) cause weight gain and metabolic changes most significantly
- Manage metabolic adverse effects including weight gain (e.g. Metformin, Topiramate)
- Monitor and manage Tardive Dyskinesia
- Patients stop their medications frequently
- Patients who stopped meds within 18 months: 74%
- Relapse is very high risk after stopping medications (within 1-2 years)
- Lieberman (2005) New Engl J Med 353:1209-23 [PubMed]
- Delay in treatment significantly worsens prognosis
- Best outcomes are with early diagnosis
- Wyatt (1997) Psychol Med 27:261-8 [PubMed]
- Monotherapy with a single Antipsychotic may be preferred
- However more than 50% of Schizophrenia patients may be on more than one Antipsychotic
- Consider adjunctive use of Antidepressants or mood stabilizers where appropriate
- Consider switching to a different Antipsychotic after an adequate duration and dose
- Consider Clozapine in treatment resistant Schizophrenia (review Clozapine adverse effects)
- Consider long-acting injectables when Medication Compliance is low
- If a second Antipsychotic is required, consider an agent that balances the adverse effects of the first
- Barbui (2009) Schizophr Bull 35(2):458-68 [PubMed]
XV. Prognosis
- High risk of Suicide
- Lifetime risk: 5-10% (13 fold higher than the general population)
- Increased risk with Auditory Hallucinations, Delusions, Substance Abuse or prior Suicide attempt
- Higher rate of overall mortality
- Death rates are 2-4 fold higher than the general population
- Cardiovascular disease (RR 2-3, premature and accelerated) is the most common cause of death in Schizophrenia
- Increased risks of cardiovascular disease, respiratory disease, stroke, cancer and Venous Thromboembolism
- Encourage Tobacco Cessation
XVI. References
- (2000) DSM IV, American Psychiatric Association, p. 297-343
- (2013) DSM V, American Psychiatric Association, p. 99
- Arnold (2024) Am Fam Physician 109(5): 482-3 [PubMed]
- Crawford (2022) Am Fam Physician 106(4): 388-96 [PubMed]
- Freedman (2003) N Engl J Med 349:1738-49 [PubMed]
- Holder (2014) Am Fam Physician 90(11): 775-82 [PubMed]
- Lewis (2000) Neuron 28:325-34 [PubMed]
- Schultz (2007) Am Fam Physician 75:1821-9 [PubMed]
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Related Studies
Definition (MSH) | A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior. |
Definition (MEDLINEPLUS) |
Schizophrenia is a serious brain illness. People who have it may hear voices that aren't there. They may think other people are trying to hurt them. Sometimes they don't make sense when they talk. The disorder makes it hard for them to keep a job or take care of themselves. Symptoms of schizophrenia usually start between ages 16 and 30. Men often develop symptoms at a younger age than women. People usually do not get schizophrenia after age 45. There are three types of symptoms:
No one is sure what causes schizophrenia. Your genes, environment, and brain chemistry may play a role. There is no cure. Medicine can help control many of the symptoms. You may need to try different medicines to see which works best. You should stay on your medicine for as long as your doctor recommends. Additional treatments can help you deal with your illness from day to day. These include therapy, family education, rehabilitation, and skills training. NIH: National Institute of Mental Health |
Definition (NCI_NCI-GLOSS) | A group of severe mental disorders in which a person has trouble telling the difference between real and unreal experiences, thinking logically, having normal emotional responses to others, and behaving normally in social situations. Symptoms include seeing, hearing, feeling things that are not there, having false ideas about what is taking place or who one is, nonsense speech, unusual behavior, lack of emotion, and social withdrawal. |
Definition (NCI) | A major psychotic disorder characterized by abnormalities in the perception or expression of reality. It affects the cognitive and psychomotor functions. Common clinical signs and symptoms include delusions, hallucinations, disorganized thinking, and retreat from reality. |
Definition (CSP) | class of psychoses with disturbance mainly of cognition (content and form of thought, perception, sense of self versus external world, volition) and psychomotor function, rather than affect. |
Concepts | Mental or Behavioral Dysfunction (T048) |
MSH | D012559 |
ICD9 | 295.90, 295.9, 295 |
ICD10 | F20 , F20.9 |
SnomedCT | 192327003, 191579000, 191528006, 154870000, 58214004, 191526005 |
LNC | MTHU020814, LA10584-3 |
English | Schizophrenias, Disorder, Schizophrenic, Disorders, Schizophrenic, Schizophrenic Disorder, Schizophrenic Disorders, Unspecified schizophrenia, Dementia praecox, Schizophrenia NOS, Schizophrenia, unspecified, Unspecified schizophrenia, unspecified state, [X]Schizophrenia, unspecified, SCHIZOPHRENIA, SCZD, Schizophrenia, SCHIZOPHRENIC DIS, dementia praecox, schizophrenia, unspecified schizophrenia, schizophrenia (diagnosis), Dementia Praecox, Schizophrenia NOS-unspec, Schizophrenia [Disease/Finding], disorder schizophrenic, schizophrenia types, schizophrenia disorder, schizophrenic disorders, disorder schizophrenia, disorders schizophrenic, schizophrenias, disorders schizophrenia, disorders schizophrenics, schizophrenia type, schizophrenic disorder, type schizophrenia, Unspecified schizophrenia, unspecified, [X]Schizophrenia, unspecified (disorder), Unspecified schizophrenia (disorder), Schizophrenia NOS (disorder), schizophrenia disorders (diagnosis), schizophrenia disorders, -- Schizophrenia, Schizophrenic disorders, Schizophrenia (disorder), Schizophrenic disorders (disorder), praecox; dementia, Schizophrenia, NOS |
Dutch | schizofrenie NAO, dementia praecox, niet-gespecificeerde schizofrenie, niet-gespecificeerde schizofrenie, niet-gespecificeerde toestand, schizofrene stoornissen, praecox; dementie, Schizofrenie, niet gespecificeerd, schizofrenie, Schizofrene stoornissen, Schizofrenie |
French | Schizophrénie SAI, Schizophrénie non précisée, état non précisé, Démence précoce, Schizophrénie non précisée, Schizophrénie, Troubles schizophréniques |
German | Schizophrenie NNB, schizophrene Erkrankungen, unspezifische Schizophrenie,unspezifischer Zustand, unspezifische Schizophrenie, Dementia praecox, Schizophrenie, nicht naeher bezeichnet, Schizophrenie, Schizophrene Störungen |
Italian | Schizofrenia non specificata, Demenza precoce, Schizofrenia NAS, Schizofrenia non specificata, stato non specificato, Disturbi schizofrenici, Schizofrenia |
Portuguese | Esquizofrenia NE, estado NE, Perturbações esquizofrénicas, Demência precoce, Esquizofrenia NE, Demência Precoce, Esquizofrenia, Transtornos Esquizofrênicos |
Spanish | Esquizofrenia no especificada, estado no especificado, Demencia precoz, Trastornos esquizofrénicos, Esquizofrenia no especificada, Esquizofrenia NEOM, Demencia Precoz, Schizophrenia NOS, [X]esquizofrenia, no especificada (trastorno), esquizofrenia no especificada (trastorno), esquizofrenia, SAI, [X]esquizofrenia, no especificada, esquizofrenia, SAI (trastorno), esquizofrenia no especificada, esquizofrenia (trastorno), esquizofrenia, trastornos esquizofrénicos (trastorno), trastornos esquizofrénicos, Esquizofrenia, Trastornos Esquizofrénicos |
Japanese | 早発性認知症, 統合失調症NOS, 詳細不明の統合失調症、状態像詳細不明, 詳細不明の統合失調症, ショウサイフメイノトウゴウシッチョウショウ, トウゴウシッチョウショウ, ショウサイフメイノトウゴウシッチョウショウジョウタイゾウショウサイフメイ, トウゴウシッチョウショウNOS, ソウハツセイニンチショウ, 精神分裂病, 分裂病, 精神乖離症, 精神分裂症, 精神分裂性障害, 分裂症, 統合失調症, 精神かい離症 |
Swedish | Schizofreni |
Czech | schizofrenie, Schizofrenní poruchy, Schizofrenie NOS, Dementia praecox, Blíže neurčená schizofrenie, Blíže neurčená schizofrenie, blíže neurčený stav, Schizofrenie |
Finnish | Skitsofrenia |
Russian | SHIZOFRENIIA, SLABOUMIE RANNEE, СЛАБОУМИЕ РАННЕЕ, ШИЗОФРЕНИЯ |
Korean | 정신분열병, 상세불명의 정신분열병 |
Croatian | SHIZOFRENIJA |
Polish | Otępienie wczesne, Schizofrenia |
Hungarian | Schizophrenia, Dementia praecox, Nem meghatározott schizophrenia, nem meghatározott állapot, Schizophreniás zavarok, Schizophrenia k.m.n., Nem meghatározott schizophrenia |
Norwegian | Schizofreni |