• Clinical science

Schizophrenia

Summary

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.

Epidemiology

  • 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.

Etiology

Risk factors

  • Genetic factors: risk significantly increased if relatives are also affected [4]
    • 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 during early teens (associated with increased incidence and worse course of positive symptoms) [5][6]
    • Urban environment
    • Birth in late winter or early spring
    • Advanced paternal age at conception

Pathophysiology

Dysregulation of neurotransmitters [7]

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

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). [3]

Positive symptoms of psychosis

Hallucinations

  • Definition
    • Hallucinations: perceptual abnormalities in which sensory experiences occur in the absence of external stimuli
    • Illusions: a perceptual abnormality, in which real external stimuli are misinterpreted
  • Types
    • Auditory (most common)
    • Visual
    • Somatic (tactile)
    • Gustatory
    • Olfactory

Delusions

  • Definition: fixed, false beliefs that are maintained despite being contradicted by reality or rational arguments and are not related to one's religious beliefs or culture
  • 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
    • Grandiosity: The patient insists that they have special powers or importance.
    • Ideas of reference: The patient believes that normal events are of special importance to him or to her (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 delusion: The patient believes they are experiencing a bodily function or sensation when there is none present.
    • Mixed delusions: two or more delusions occurring simultaneously; No delusion is predominant over the other.
    • Unspecified delusions: a delusion that does not fit the criteria of other types or cannot be clearly defined

Disorganized thought and speech processes

  • Loose associations: incoherent thinking expressed as illogical, sudden, and frequent changes of topic
  • Word salad: incoherent thinking expressed as a sequence of words without a logical connection
  • Tangential speech: nonlinear thought expressed as a gradual deviation from a focused idea or question
  • 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
  • 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 regard to matters that are normally considered important
  • Emotional and social withdrawal

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.)

Other features

Subtypes and variants

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)
Characteristics
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

Catatonia

Diagnostics

  • Schizophrenia is a clinical diagnosis. Diagnostic criteria include (according to DSM-V): [11][3]
    • At least two of the following symptoms, at least one of which is from the top three:
    • The above symptoms persist for ≥ 1 month over a period of continuous disturbance for ≥ 6 months.
    • Symptoms must cause social, occupational, or personal functional impairment lasting ≥ 6 months.
    • Schizoaffective disorder and mood disorder with psychotic features have been ruled out.
    • Medical or substance use disorder has been ruled out.
  • 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:

Differential diagnoses

Psychotic disorders [3]
Duration of symptoms Clinical features Function
Schizophrenia
  • ≥ 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.

Treatment

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.

Prognosis

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

  • Predictive factors for an unfavorable course of illness [13]

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

  • 1. Saha S et al. A Systematic Review of the Prevalence of Schizophrenia. PLoS Med. 2005; 2(5): p. e141. doi: 10.1371/journal.pmed.0020141.
  • 2. McGrath et al. Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality. Epidemiol Rev. 2008; 30(1): pp. 67–76. doi: 10.1093/epirev/mxn001.
  • 3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM–5). . 2013. doi: 10.1176/appi.books.9780890425596.
  • 4. Kringlen E. Twin studies in schizophrenia with special emphasis on concordance figures. Am J Med Genet. 2002; 97(1): pp. 4–11. doi: 10.1002/(sici)1096-8628(200021)97:1<4::aid-ajmg2>3.0.co;2-j.
  • 5. Hamilton I. Cannabis, psychosis and schizophrenia: unravelling a complex interaction. Addiction. 2017; 112(9): pp. 1653–1657. doi: 10.1111/add.13826.
  • 6. Vaucher J, Keating BJ, Lasserre AM, et al. Cannabis use and risk of schizophrenia: a Mendelian randomization study. Mol Psychiatry. 2018; 23(5): pp. 1287–1292. doi: 10.1038/mp.2016.252.
  • 7. Cioffi CL. Modulation of NMDA receptor function as a treatment for schizophrenia. Bioorg Med Chem Lett. 2013; 23(18): pp. 5034–5044. doi: 10.1016/j.bmcl.2013.07.019.
  • 8. McIntosh AM et al. Longitudinal Volume Reductions in People at High Genetic Risk of Schizophrenia as They Develop Psychosis. Biol Psychiatry. 2011; 69(10): pp. 953–958. doi: 10.1016/j.biopsych.2010.11.003.
  • 9. Sigmundsson T et al. Structural Abnormalities in Frontal, Temporal, and Limbic Regions and Interconnecting White Matter Tracts in Schizophrenic Patients With Prominent Negative Symptoms. Am J Psychiatry. 2001; 158(2): pp. 234–243. doi: 10.1176/appi.ajp.158.2.234.
  • 10. Walther S, Stegmayer K, Wilson JE, Heckers S. Structure and neural mechanisms of catatonia. The Lancet Psychiatry. 2019; 6(7): pp. 610–619. doi: 10.1016/s2215-0366(18)30474-7.
  • 11. Tandon R, Gaebel W, Barch DM et al. Definition and description of schizophrenia in the DSM-5. Schizophr Res. 2013; 150(1): pp. 3–10. doi: 10.1016/j.schres.2013.05.028.
  • 12. Buchanan RW et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull. 2010; 36(1): pp. 71–93. doi: 10.1093/schbul/sbp116.
  • 13. Hor K, Taylor M. Review: Suicide and schizophrenia: a systematic review of rates and risk factors. Journal of Psychopharmacology. 2010; 24(4_suppl): pp. 81–90. doi: 10.1177/1359786810385490.
last updated 11/17/2020
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