• Clinical science



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: = [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
    • One schizophrenic parent: ∼ 10%
    • Two schizophrenic parents: ∼ 40%
    • Concordance rate in monozygotic twins: 30–40%
    • Concordance rate in dizygotic twins: 10–15%
  • Environmental factors
    • Stress and psychosocial factors
    • Frequent use of cannabis
    • Urban environment
    • Birth in late winter or early spring
    • Advanced paternal age at conception



Dysregulation of neurotransmitters [8]

Structural and functional changes to the brain [9][10]

Clinical features

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).

Features of schizophrenia
Positive symptoms of psychosis
  • Hallucinations: perceptual abnormalities in which sensory experiences occur in the absence of external stimuli.
  • Types include:
    • Auditory (most common)
    • Visual
    • Somatic
    • Gustatory
    • Olfactory
  • Illusions: a perceptual abnormality, in which real external stimuli are misinterpreted
  • Delusions: fixed, false beliefs that are maintained despite being contradicted by reality or rational arguments.
  • Types
    • Bizarre delusions: delusions that cannot be true or are inconsistent with the patient's social and cultural norms (e.g., a patient insisting that they can fly)
    • Nonbizarre delusions: delusions that can be true or are consistent with the patient's social and cultural norms (e.g., a patient insisting that they have won the lottery when this is not the case)
  • Subtypes of delusions
    • Grandiosity: The patient insists that they have special powers or importance.
    • Ideas of reference: The patient believes that normal events are of special importance (e.g., an individual might feel that a television reporter is talking about them).
    • Paranoia: The patient has an exaggerated distrust of others and is suspicious of their motives.
    • Persecutory: The patient insists that they are being cheated on, conspired against, or harassed.
    • Erotomania: The patient believes that other individuals are in love with them.
    • Jealousy: The patient believes their partner is unfaithful without justification.
    • Somatic: The patient believes they are experiencing a bodily function or sensation when there is none present.
  • Disorganized thought and speech processes
  • Loose associations: incoherent thinking expressed as illogical, sudden, and frequent changes of topic
  • Word salad: incoherent thinking expressed as sequence of words without a logical connection
  • Neologisms: the creation of new words with idiosyncratic meanings
  • Echolalia: involuntary repetition of other's words or sentences
  • Flight of ideas: quick succession of thoughts usually demonstrated in a continuous flow of rapid speech and abrupt changes in topic
  • Clang association: use of words based on rhyme patterns rather than meaning
  • Circumstantial speech: non-linear thought expressed as a long-winded manner of explanation, with multiple deviations from the central topic, before finally expressing the central idea
  • Tangential speech: non-linear thought expressed as a gradual deviation from a focused idea or question
  • Thought-blocking: an objective observation of an abrupt ending in a thought process, expressed as a sudden interruption in speech
  • Pressured speech: accelerated thoughts that are expressed as rapid, loud, and voluminous speech; often in the absence of social stimulation
Negative symptoms of psychosis
  • 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 regards to matters that are normally considered important
  • Emotional and social withdrawal
Cognitive symptoms
  • Inattention
  • Impaired memory
  • Poor executive functioning
Mood symptoms and anxiety
  • A behavioral syndrome characterized by abnormal movements and reactivity to the environment
    • Retarded catatonia: immobility, posturing, negativism (resisting external commands), staring, mutism
    • Excited catatonia: excessive, purposeless movement in both the upper and lower limbs, restlessness, and impulsivity
    • Malignant catatonia: fever, autonomic instability (e.g., tachycardia, tachypnea, abnormal BP, and sweating), rigidity, and delirium (resembles neuroleptic malignant syndrome)
Neurological abnormalities
  • Sensory disturbances and impaired coordination
Metabolic abnormalities

Subtypes and variants

DSM-5 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


  • Schizophrenia is a clinical diagnosis. Diagnostic criteria include (according to DSM-5):
  • Brain imaging of patients with schizophrenia often shows cortical atrophy, decreased hippocampal and temporal mass) and enlargement of the cerebral ventricles.
  • Rule out medical or substance use disorder by performing the following tests:

Negative symptoms of schizophrenia include the 5A’s: Affect (flat), Avolition, Asociality, Anhedonia, and Apathy.


Differential diagnoses

Psychotic disorders [3]

Duration of symptoms Clinical features Function
  • ≥ 6 months
  • Impaired
Schizophreniform disorder
  • 1–6 months
Brief psychotic disorder
  • > 1 day but ≤ 1 month
Schizoaffective disorder
  • Impaired
Mood disorder with psychotic features
  • Impaired
Delusional disorder
  • ≥ 1 month
  • Not markedly impaired
Delusional symptoms in partner of individual with delusional disorder
  • Not determined
  • Normal

Personality disorders

Other causes of psychosis

Mood-congruent delusions are usually seen in severe depression/mania, whereas schizoaffective disorder manifests with delusions that are not congruent with the mood!


The differential diagnoses listed here are not exhaustive.


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). [14]

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last updated 09/14/2020
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