Schizophrenia

1. See Also
   1. Schizophrenia Diagnosis
   2. Psychosis
   3. Psychosis Symptoms
   4. Psychosis Exam
   5. Psychosis Types
   6. Psychosis Differential Diagnosis
   7. Drug Induced Psychosis
   8. Psychosis Diagnostic Testing
   9. Delirium
2. Epidemiology
   1. Prevalence: 0.3 to 0.7% worldwide across all ethnicities, nationalities (up to 1% in U.S.)
      1. Most common Psychotic Disorder
      2. However, in U.S., black patients are disproportionately diagnosed over non-hispanic whites
      3. Gara (2012) Arch Gen Psychiatry 69(6): 593-600 [PubMed]
   2. Gender: Equal among men and women
      1. Men present ages 18 to 25 years old
      2. Women present age 25 to mid-30s and also after age 40 years old
      3. Children rarely present age <15 years (but case reports in children as young as 5 years old)
   3. Age
      1. Age onset in transition from Adolescence to Adulthood
      2. Men present earlier than women (see above)
      3. First attack usually occurs before 40 years old (although some women may present later)
3. Pathophysiology
   1. Polygenic Threshold Model
      1. Combination of genetic predisposition and environmental factors
   2. Heredity Concordance
      1. Monozygotic twins: 69%
      2. Dizygotic: 13%
   3. Schizoid Personality Disorder
      1. Associated with Schizophrenia (RR=50)
   4. Protective factors in the family environment
      1. Uncommon criticism
      2. Straightforward communication
   5. Altered Neurotransmission
      1. Glutamate, Serotonin and Dopamine have altered activity in the Hippocampus, Midbrain, corpus striatum and prefrontal cortex
      2. Increased and dysregulated Dopamine exacerbates positive symptoms (Antipsychotics primarily reduce Dopamine)
   6. Other factors
      1. Inflammatory Cytokines
      2. Endocrine, Physical associations are only coincidental
      3. Neurohumoral: Super sensitive receptors
      4. Neurophysiologic: Spiking or slow waves at Hippocampus
4. Risk Factors
   1. Family History or Genetic Risk Factors (most significant risk)
      1. However, most patients with Schizophrenia have no Family History
      2. Schizophrenia confers an increased risk of mental illness to family members
         1. Increased risk includes Schizophrenia, schizoaffective disorder, Bipolar Disorder, Major Depression
      3. Monozygotic twin: 50% lifetime Incidence
      4. Dizygotic twin: 17% lifetime Incidence
      5. First degree relative: 6-17% lifetime Incidence
      6. Lewis (2000) Neuron 28:325-34 [PubMed]
   2. Environmental Risk Factors
      1. Obstetric complications (e.g. neonatal hypoxic events)
      2. Maternal or early childhood infections (e.g. Toxoplasmosis, Rubella, HSV 2, Influenza)
      3. Maternal or early childhood nutritional deficiency (e.g. Folic Acid Deficiency, Iron Deficiency, Vitamin D Deficiency)
      4. Early childhood CNS Infection
      5. Advanced paternal age (over 55 years old)
      6. Childhood Trauma
      7. Marijuana (or Cannabis) use
         1. Excess Stimulation of Cannabinoid Receptor 1 may trigger increased Dopamine release
         2. Risk increases with degree of consumption
         3. Arseneault (2002) BMJ 325(7374): 1212-3 [PubMed]
         4. Marconi (2016) Schizophr Bull 42(5): 1262-9 [PubMed]
5. Types
   1. See Psychosis Types
6. History
   1. See Psychosis
   2. Abrupt onset
      1. Psychosis for > 1 month
      2. Signs of disorder for > 6 months
   3. Deterioration
      1. Social
      2. Occupational function
      3. Self care
7. Symptoms: Phases
   1. Premorbid Phase
      1. Typically asymptomatic
   2. Prodromal phase
      1. Social withdrawal
      2. Loss of interest in school or work
      3. Hygiene and grooming deteriorate
      4. Angry outbursts
      5. Unusual behavior
   3. Syndromic Phase
      1. See Psychosis Symptoms
      2. See Schizophrenia Diagnosis
   4. Chronic or Residual Phase
      1. Variable depending on Medication Compliance and social support
8. Signs
   1. See Psychosis Exam
9. Labs
   1. See Psychosis Labs
   2. Indicated to exclude other causes in the Psychosis Differential Diagnosis
10. Differential Diagnosis
    1. See Psychosis Differential Diagnosis
11. Diagnosis
    1. See Schizophrenia Diagnosis
    2. Schizophrenia is a clinical diagnosis
       1. Lab and imaging are solely indicated to exclude other possible causes in the differential diagnosis
       2. Schizophrenia has no specific lab or imaging findings
12. Associated Conditions
    1. Anxiety Disorder
    2. Panic Disorder
    3. Postraumatic Stress Disorder
    4. Obsessive Compulsive Disorder
13. Management: General
    1. See Psychosis for acute management
    2. See Neuroleptic Medications
    3. Urgent psychiatry referral
       1. Admission to a controlled setting is preferred for acute Psychosis
    4. Medication initiation
       1. Patients should be offered medication management at the time of initial diagnosis
       2. In the primary care setting, consult with a psychiatrist if considering the start of an Antipsychotic
       3. Medication adverse effects and monitoring requirements should be discussed prior to starting Antipsychotics
       4. Do not use a loading dose of Antipsychotics
       5. Response to first 2-4 weeks of therapy is predictive of longterm response
          1. Maximal effect may not be evident for months after initiating therapy
       6. Medications help patients return to baseline functioning (esp. social), quality of life and prevent longterm Disability
          1. Schizophrenia medication management is intended for lifelong, continuous use
          2. Relapse and decompensation occurs when medications are stopped
    5. Adjunctive therapy (improves quality of life, relapse rates, Medication Compliance)
       1. Cognitive Behavioral Therapy for Psychosis should be offered to patients with Schizophrenia
       2. Family interventions
       3. Social skill training
       4. Electroconvulsive Therapy
14. Management: Pitfalls
    1. Atypical Antipsychotics offer no significant effectiveness benefit over first generation agents
       1. Select agents based on which adverse effects are expected to be least tolerated
       2. First generation agents cause Extrapyramidal Side Effects most significantly
       3. Second generation agents (atypicals) cause weight gain and metabolic changes most significantly
    2. Patients stop their medications frequently
       1. Patients who stopped meds within 18 months: 74%
       2. Relapse is very high risk after stopping medications (within 1-2 years)
       3. Lieberman (2005) New Engl J Med 353:1209-23 [PubMed]
    3. Delay in treatment significantly worsens prognosis
       1. Best outcomes are with early diagnosis
       2. Wyatt (1997) Psychol Med 27:261-8 [PubMed]
    4. Monotherapy with a single Antipsychotic may be preferred
       1. However more than 50% of Schizophrenia patients may be on more than one Antipsychotic
       2. Consider adjunctive use of Antidepressants or mood stabilizers where appropriate
       3. Consider switching to a different Antipsychotic after an adequate duration and dose
       4. Consider Clozapine in treatment resistant Schizophrenia (review Clozapine adverse effects)
       5. Consider long-acting injectables when Medication Compliance is low
       6. If a second Antipsychotic is required, consider an agent that balances the adverse effects of the first
       7. Barbui (2009) Schizophr Bull 35(2):458-68 [PubMed]
15. Prognosis
    1. High risk of Suicide
       1. Lifetime risk: 5-10% (13 fold higher than the general population)
       2. Increased risk with Auditory Hallucinations, Delusions, Substance Abuse or prior Suicide attempt
    2. Higher rate of overall mortality
       1. Death rates are 2-4 fold higher than the general population
       2. Increased risks of cardiovascular disease, respiratory disease, stroke, cancer and Venous Thromboembolism
       3. Encourage Tobacco Cessation
16. References
    1. (2000) DSM IV, American Psychiatric Association, p. 297-343
    2. (2013) DSM V, American Psychiatric Association, p. 99
    3. Crawford (2022) Am Fam Physician 106(4): 388-96 [PubMed]
    4. Freedman (2003) N Engl J Med 349:1738-49 [PubMed]
    5. Holder (2014) Am Fam Physician 90(11): 775-82 [PubMed]
    6. Lewis (2000) Neuron 28:325-34 [PubMed]
    7. Schultz (2007) Am Fam Physician 75:1821-9 [PubMed]