Last updated: May 2, 2022

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Schizophrenia is a severe psychiatric disorder characterized by chronic or recurrent psychosis. The majority of individuals with schizophrenia initially experience symptoms in their 20s. The exact mechanism is unknown but is thought to relate to increased dopaminergic activity in the mesolimbic neuronal pathway and decreased dopaminergic activity in the prefrontal cortical pathway. Clinical features include positive psychotic symptoms, negative psychotic symptoms, cognitive impairment, abnormal motor behavior (e.g., catatonia), and mood symptoms. The mainstay of treatment is psychoeducation and antipsychotic therapy with dopamine antagonists.

  • Prevalence: < 1% [1]
  • Sex: > (∼1.4:1) [2]
  • Age of onset: late teens to mid-30s [3]
    • Men: typically early 20s
    • Women: typically late 20s

Epidemiological data refers to the US, unless otherwise specified.

Risk factors

  • Genetic factors: risk significantly increased if relatives are also affected [4]
  • Environmental factors
    • Stress and psychosocial factors
    • Frequent use of cannabis during early teens (associated with increased incidence and worse course of positive symptoms) [5][6]
    • Urban environment
    • Advanced paternal age at conception

Dysregulation of neurotransmitters [7]

Structural and functional changes to the brain [8][9]

Schizophrenia typically manifests with a prodrome of negative symptoms and psychosis (e.g., social withdrawal) that precedes the positive psychotic symptoms (e.g., hallucinations and bizarre delusions). [3]

Positive symptoms of schizophrenia


Abnormal motor behavior

  • Grossly disorganized behavior: an abnormal behavior characterized by inadequate goal-directed activity (e.g., purposeless movements) and bizarre emotional responses (e.g., smiling or laughing when inappropriate)
  • Catatonia (See “Subtypes and variants” below.)

Negative symptoms of schizophrenia

  • Flat affect: reduced or absent emotional expression
  • Avolition: reduced or absent ability to initiate purposeful activities
  • Alogia: impaired thinking that manifests with reduced speech output or poverty of speech (e.g., always replying to questions with one-word answers)
  • Anhedonia: inability to feel pleasure from activities that were formerly pleasurable or from any new positive stimuli
  • Apathy: lack of emotion or concern, especially with regard to matters that are normally considered important
  • Emotional and social withdrawal

Other features

DSM-V omits subtypes of schizophrenia previously included in DSM-IV (disorganized, paranoid, catatonic, undifferentiated, residual) because they are no longer thought to reflect the heterogeneity of schizophrenia.

Subtypes of schizophrenia according to DSM-IV (no longer in use)
Disorganized schizophrenia
  • Predominantly disorganized
  • Onset is usually before 25 years of age.
Paranoid schizophrenia
Catatonic schizophrenia
Undifferentiated schizophrenia
  • Usually has features of more than one subtype
Residual schizophrenia
  • At least one psychotic episode
  • Followed by flat affect, odd behavior, social withdrawal


Long-acting injectable antipsychotics should be considered for patients struggling with compliance and frequent relapses.

Negative symptoms are more difficult to treat and often persist even after the resolution of positive symptoms.

Because both generations of antipsychotics have similar efficacy, the choice of the agent is based on its side-effect profile.

Clozapine and olanzapine should not be used as first-line agents for first-episode patients because of their adverse effects, such as agranulocytosis (clozapine only), weight gain, hyperglycemia, and hyperlipidemia.

Schizophrenia is a progressive disorder that causes significant impairment, with many patients presenting with psychosocial dysfunction.

Patients with schizophrenia are at an increased risk for alcohol use disorder, depression, violence, and suicide (∼ 5% complete suicide).

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  11. Walther S, Stegmayer K, Wilson JE, Heckers S. Structure and neural mechanisms of catatonia. The Lancet Psychiatry. 2019; 6 (7): p.610-619. doi: 10.1016/s2215-0366(18)30474-7 . | Open in Read by QxMD
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