- 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% 
- Sex: ♂ = ♀ 
Age of onset: late teens to mid-30s 
- Men: typically early 20s
- Women: typically late 20s
Epidemiological data refers to the US, unless otherwise specified.
- Genetic factors: risk significantly increased if relatives are also affected
- Environmental factors
Dysregulation of neurotransmitters 
- ↓ Dopamine in prefrontal cortical pathway may cause .
- ↑ Dopamine in mesolimbic pathway may lead to .
- ↑ Serotonergic activity and ↓ dendritic branching
- ↓ Glutamatergic neurotransmission may lead to psychosis.
- ↓ GABA leads to ↑ dopamine activity.
Structural and functional changes to the brain 
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|| || |
| || |
| || |
|Negative symptoms of psychosis|| |
|Cognitive symptoms|| |
|Mood symptoms and anxiety|
|Neurological abnormalities|| |
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|| |
|Catatonic schizophrenia|| |
|Undifferentiated schizophrenia|| |
|Residual schizophrenia|| |
- Schizophrenia is a clinical diagnosis. Diagnostic criteria include (according to DSM-5):
- 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 ≥ 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:
Negative symptoms of schizophrenia include the 5A’s: Affect (flat), Avolition, Asociality, Anhedonia, and Apathy.
Psychotic disorders 
|Duration of symptoms||Clinical features||Function|
|Schizophrenia|| || || |
|Schizophreniform disorder|| |
|Brief psychotic disorder|| |
|Schizoaffective disorder|| || |
|Mood disorder with psychotic features|| |
|Delusional disorder|| || |
|Delusional symptoms in partner of individual with delusional disorder|| || |
Schizotypal personality disorder
- Odd and eccentric behavior
- Magical thinking (inventing causal relationships between behaviors and events with no evidence) that is inconsistent with the patient's cultural norms
- Discomfort in close relationships
Schizoid personality disorder
- Having no interest in social relationships
- Restricted emotional expression and anhedonia
Paranoid personality disorder
- Distrustful of others
- Suspicious of friends and family
- Superficial relationships
Other causes of psychosis
- Organic causes of psychosis
The differential diagnoses listed here are not exhaustive.
- Establish a therapeutic alliance when taking care of patients with delusions.
- Acknowledge the patient's emotional state.
- Avoid validation of delusions or confronting patients about the delusional nature of their symptoms.
- Initial response to treatment during the first 2–4 weeks is associated with a better long-term response.
- Hospitalization if acutely psychotic
- Acute psychotic episode: short-acting antipsychotics
- Acute manic episode: mood stabilizers (e.g., lithium, valproate, carbamazepine)
- First-line treatment: (e.g., risperidone, quetiapine), which are especially effective at treating positive psychotic symptoms
- Alternative treatment: fluphenazine, haloperidol, chlorpromazine) in depot form for those at risk of poor adherence (e.g.,
- Treatment-resistant schizophrenia: clozapine for persistent positive symptoms (i.e., delusions, hallucinations, and/or disorganized speech) despite trials of ≥ 6 weeks of 2 different antipsychotics at their maximum doses
- Treatment during pregnancy: (e.g., haloperidol) as a first-line treatment
- Treatment of depression: tricyclic antidepressants (e.g., sertraline, imipramine) or
- Treatment of anxiety: SSRIs
- See for more details.
Psychoeducation (used as an adjunct to avoid relapse)
- Patient, family, and group psychosocial therapy and education
- Cognitive-behavioral therapy
- Supportive social measures
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.
- Predictive factors for an unfavorable course of illness