Schizophrenia is a chronic, severe mental disorder affecting approximately 1% of the global population. This article reviews current understanding of its pathophysiology, diagnosis, and treatment.
PATHOPHYSIOLOGY
The Dopamine Hypothesis
The dopamine hypothesis remains central to our understanding of schizophrenia. Hyperactivity of the mesolimbic dopamine pathway is associated with positive symptoms, while hypoactivity of the mesocortical pathway contributes to negative and cognitive symptoms.
Glutamate Hypothesis
NMDA receptor hypofunction may contribute to the disorder, as evidenced by the psychotomimetic effects of NMDA antagonists like PCP and ketamine.
Neurodevelopmental Factors
Evidence suggests schizophrenia may be a neurodevelopmental disorder, with genetic and environmental factors during critical periods of brain development contributing to later symptom emergence.
CLINICAL PRESENTATION
Positive Symptoms
- Hallucinations (auditory most common)
- Delusions (persecutory, referential, grandiose)
- Disorganized speech
- Disorganized or catatonic behavior
Negative Symptoms
- Affective flattening
- Alogia (poverty of speech)
- Avolition
- Anhedonia
- Asociality
Cognitive Symptoms
- Working memory deficits
- Executive function impairment
- Attention difficulties
TREATMENT
FirstGeneration Antipsychotics (FGAs)
- High D2 receptor affinity
- Examples: haloperidol, chlorpromazine
- Risk of extrapyramidal symptoms and tardive dyskinesia
SecondGeneration Antipsychotics (SGAs)
- Broader receptor profile (5-HT2A, D2)
- Examples: risperidone, olanzapine, quetiapine, aripiprazole
- Lower EPS risk but metabolic side effects
Clozapine
Reserved for treatment-resistant schizophrenia (failed 2+ antipsychotics). Most effective but requires monitoring for agranulocytosis.
PROGNOSIS
The rule of thirds
- 1/3 significant improvement
- 1/3 moderate improvement with residual symptoms
- 1/3 chronic, severe course
Early intervention and consistent treatment improve outcomes.