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.
- 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
- ↓ 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). 
Positive symptoms of schizophrenia
- and/or (auditory hallucinations are most common)
- , , e.g., , ,
- or : e.g., , ,
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
- Impaired memory
- Poor executive functioning
- Mood symptoms and anxiety
- Neurological abnormalities: sensory disturbances and impaired coordination
- Metabolic abnormalities: hypertension, diabetes, hyperlipidemia
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)|
|Disorganized schizophrenia|| |
|Catatonic schizophrenia|| |
|Undifferentiated schizophrenia|| |
|Residual schizophrenia|| |
- Definition: 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 )
- Benzodiazepines (Intravenous or sublingual lorazepam): first-line for all forms of catatonia
- Electroconvulsive therapy
- Discontinue dopamine blocking drugs (e.g., antipsychotics); only reinitiate after catatonia resolves
- Treat the underlying psychiatric condition with appropriate pharmacotherapy
- Supportive measures
- Schizophrenia is a clinical diagnosis. Diagnostic criteria include (according to DSM-V): 
- 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:
- 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:
- Treatment nonadherence: Use long-acting injectable formulations.
- Treatment-resistant schizophrenia: 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 “ .”
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.
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