Schizophrenia

Epidemiology

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Etiology

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Pathophysiology

• Dopamine hypothesis: ↑ dopamine activity in mesolimbic pathway (positive Sx), ↓ dopamine in mesocortical pathway (negative/cognitive Sx).
• Other neurotransmitters implicated: ↓ activity at NMDA glutamate receptors, role of serotonin (basis for SGA efficacy).

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Clinical features

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Subtypes and variants

Catatonia

• Etiology & Triggers:
  • Most common in severe bipolar disorder (mania or depression) and MDD with psychotic features > schizophrenia.
  • Medical triggers: CNS infections, anti-NMDA receptor encephalitis (young females with teratoma), BZD withdrawal.
• High-Yield Clinical Features:
  • Catalepsy: Maintenance of postures passively held against gravity.
  • Waxy Flexibility: Initial resistance to movement followed by smooth release (bending like a candle).
  • Mutism & Stupor: Alert pt unable/unwilling to speak or interact.
  • Negativism: Involuntary resistance to external instructions or movement.
  • Echolalia (mimicking speech) and echopraxia (mimicking movements).
  • Malignant variant: Acute rigidity, fever, and autonomic instability (mimics NMS).
• Diagnosis:
  • Lorazepam Challenge Test: Rapid, temporary symptom relief within 5–10 min after IV Lorazepam 1–2 mg confirms diagnosis.
  • Continuous EEG: Mandatory to rule out non-convulsive status epilepticus (NCSE).
• Differential Diagnosis:
  • NMS: Features severe “lead-pipe” rigidity, triggered by D2 antagonists; minimal response to lorazepam.
  • Serotonin Syndrome: Features hyperreflexia and ocular/inducible clonus + tremor + diarrhea.
• Management Algorithm:
  • Immediate Action: Stop all antipsychotics immediately (worsens catatonia and triggers malignant form).
  • 1st-Line: Lorazepam IV/PO (often requires high doses: 6–16 mg/day). c
  • Definitive / 2nd-Line: Electroconvulsive Therapy (ECT) (indicated if no response to BZDs in 48–72h, or first-line if malignant catatonia).
  • Supportive: Aggressive VTE prophylaxis (heparin/LMWH due to immobility) + IVF hydration.
• Key Complications:
  • DVT / Fatal PE (most common cause of death).
  • Rhabdomyolysis / AKI (elevated serum CK from sustained muscle contraction/immobility).
  • Dehydration, malnutrition, and aspiration pneumonia.

Diagnostics

• At least two of the following symptoms must be present, with at least one of these from the first three symptoms listed:
  • Delusions
  • Hallucinations
  • Disorganized speech
  • Grossly disorganized or catatonic behavior
  • Negative symptoms
    • Apathy: lack of motivation
    • Social withdrawal
    • Flat affect: emotional flattening/monotone speech
    • Poverty (lack) of speech
    • Anhedonia: inability to experience pleasure
• The above symptoms persist for ≥ 1 month.
• There are continuous cognitive or affective disturbances for ≥ 6 months.
• Symptoms must cause social, occupational, or personal functional impairment lasting ≥ 6 months.

Mnemonic

Patients can hear high definition voices. But they are not real. Like there are radiowaves spreading fake bullshit (BS) via a network

Differential diagnosis

• Schizophrenia: ≥ 6 months
• Schizophreniform disorder: 1–6 months
• Brief psychotic disorder: > 1 day but ≤ 1 month
  • Brief psychotic disorder usually develops after stressful life events.
  • With eventual full return to premorbid functioning. c
• Schizoaffective disorder
  • Meets criteria for Schizophrenia AND a Major Mood Disorder (MDD or Bipolar).
  • Differentiation Rule: Psychosis must occur for > 2 weeks in the absence of a major mood episode (depressive or manic) to rule out Mood Disorder w/ Psychotic Features.
    • MDD with psychotic features doesn’t have psychotic symptoms alone without mood symptoms
  • A single illness episode where both of the following occur concurrently:
    • Psychotic symptoms that meet the criteria for schizophrenia
    • Features of a major mood episode (major depressive episode OR manic episode OR mixed episode)
  • Psychotic symptoms occur at least once in the absence of mood disorder symptoms.
• Delusional disorder
  • ≥ 1 month
  • At least one delusion
  • No other prominent psychotic symptoms (e.g., hallucinations, disorganized speech, negative symptoms)
  • E.g., delusional parasitosis: the fixed belief that the body is infested with a parasite despite the lack of supporting evidence
  • Social and occupational functioning are not markedly impaired (vs psychosis) c

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Treatment

• Acute Phase / First-Line:
  • Second-Generation Antipsychotics (SGAs): Preferred first-line due to lower risk of EPS/TD.
    • Options: Risperidone, Olanzapine, Quetiapine, Aripiprazole, Ziprasidone.
  • First-Generation Antipsychotics (FGAs): High potency (e.g., Haloperidol, Fluphenazine); equally efficacious for positive symptoms, but higher EPS risk.
  • Acute Agitation: IM Haloperidol, IM Ziprasidone, or IM Olanzapine; combine with IM Lorazepam if severe.
• Maintenance & Non-Adherence:
  • Long-Acting Injectable (LAI) Antipsychotics: Indicated for recurrent relapses due to non-adherence (e.g., Paliperidone palmitate, Haloperidol decanoate, Aripiprazole depot).
    • Must establish oral tolerability first.
  • Antipsychotic medication be continued indefinitely to all pts to reduce the risk of relapse c
• Treatment-Resistant Schizophrenia (Refractory):
  • Clozapine: Indicated after failure of ≥2 adequate antipsychotic trials (including at least 1 SGA) or for persistent suicidality/aggression. c
  • Absolute Neutrophil Count (ANC) monitoring: Required due to risk of agranulocytosis (baseline and routine monitoring; stop if ANC <1000/µL).
• Psychosocial Interventions:
  • Family Therapy/Psychoeducation: Crucial to reduce high expressed emotion in the household (significantly lowers relapse rates). c
  • Cognitive Behavioral Therapy for psychosis (CBT-p), social skills training, Assertive Community Treatment (ACT) for high-utilization patients.

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Prognosis

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Good	Poor
Later onset	Onset in childhood or adolescence
Female sex	Male sex
Acute onset with precipitant	Gradual onset (prodrome), no precipitant
Predominantly positive symptoms	Predominantly negative symptoms
No family history	Family history of psychotic illness
Short duration of active symptoms	Long duration of untreated psychosis