Schizophrenia and Related Concepts

Key Concepts about Lithium

  • Lithium Properties:
    • A type of ion
    • Inhibitor of GSK3
    • Modulator of the Wnt pathway
    • Modulator of the IP3 pathway
    • Conclusion: Lithium is involved in all the above functions.

Understanding Benzodiazepines

  • Key Characteristics:
    • Inhibits GABA effect
    • Competes for GABA binding site
    • Antagonistic to 5-HT2a receptor
    • Binds to GABAa receptor at a separate site from GABA
    • Stabilizes inactivated state of voltage-gated sodium channels.

Overview of Schizophrenia

  • Definition:
    • Derived from Greek words "schizo" (split) and "phrene" (mind).
    • Not synonymous with multiple personalities or directly related to modern stressors.
    • A chronic, severe, and disabling brain disorder affecting 1% of the population (approx. 2 million Americans).
    • Notable individual: John Nash, Nobel Laureate in Economics 1994.

Diagnosis of Schizophrenia

  • Current Methods:
    • No definitive physical or lab tests for diagnosing schizophrenia.
    • Diagnosis primarily based on clinical symptoms assessed by a psychiatrist.

Symptoms of Schizophrenia

  • Cognition and Emotion:
    • Profound disruptions in language, thought, perception, affect, and sense of self.

Positive Symptoms

  • Definition:
    • Symptoms indicating an excess or distortion of normal functions.
  • Examples:
    • Delusions: False beliefs, e.g., feeling followed or receiving special messages through media.
    • Hallucinations: Misperceptions across senses, commonly auditory (hearing voices).
    • Disorganized Thinking/Speech: Incoherent speech or tangential conversations.
    • Grossly Disorganized Behavior: Ineffective goal-directed behaviors; unpredictable agitation.
    • Catatonic Behavior: Marked unresponsiveness, rigid postures, or aimless movements.
  • Other Positive Symptoms:
    • Inappropriate emotional responses, unusual movements (pacing/rocking), and feelings of derealization.

Summary of Positive Symptoms

  • Main types:
    • Delusions, hallucinations, disorganized thinking, disorganized behavior, catatonic behavior, inappropriate responses.
  • Treatment Efficacy: Positives usually respond well to treatment.

Negative Symptoms

  • Definition:
    • Symptoms indicating a reduction or loss of normal function.
  • Examples:
    • Affective Flattening: Diminished emotional expression.
    • Alogia: Reduced speech fluency, characterized by short responses.
    • Avolition: Difficulty initiating or sustaining goal-directed activities, often perceived as lack of interest (e.g., social withdrawal).

Summary of Negative Symptoms

  • Characterized by:
    • Lack of emotion, low energy, reduced interest in life, affective flattening, alogia, poor social skills, social isolation.

Disorganized Symptoms

  • Considered controversial; involving thought disorder, confusion, disorientation, memory issues.

Cognitive Symptoms

  • Cognitive difficulties include:
    • Disorganized thinking, slow processing, poor memory, challenges in integrating thoughts and behaviors.

Diagnosis Summary

  • Diagnosis requires at least one of the following positive symptoms:
    • Hallucinations, delusions, disorganized speech.

Types of Schizophrenia (DSM-IV)

  • Classifications (not in DSM-5):
    • Paranoid: Delusions and auditory hallucinations.
    • Disorganized: Disorganized behavior and emotional responses.
    • Catatonic: Involves specific motor behaviors and postures (e.g., rigidity).

Heritable Risk Factors for Schizophrenia

  • General Population Risk: 1%
  • Relatives:
    • First cousins: 2%
    • Aunts/Uncles: 2%
    • Parents: 6%
    • Siblings: 9%
    • Identical Twins: 48%.
    • Conclusion: Genetic and environmental factors (e.g., toxins, psychological stressors) contribute to risk.

Clinical Features

  • Prevalence: 1% worldwide; gradual onset, typically late adolescence to early adulthood but can manifest at any age.
  • Characteristics include a progressive decline in function, with family history of schizophrenia frequently noted.

Neuropathology of Schizophrenia

  • Structural changes observed in the brain:
    • Slight reduction in brain volume, enlargement of ventricles and associated abnormalities.

Structural Symptoms

  • Abnormalities in specific brain regions (frontal, temporal lobes, temporal lobe damage leading to schizophrenia, decreased activity in prefrontal cortex).

Genetic Contributions

  • Research hints at common and rare variants:
    • Linkage studies and GWAS (Genome-Wide Association Studies) identify potential genes associated with schizophrenia risk.

Risk Genes Identified

  • Significant genes: ZNF804A (risk for schizophrenia and bipolar disorder), DISC1, and others across various studies.

Rare Variants and Their Role

  • CNV (copy number variations): Deletions or duplications of DNA significantly impacting gene function.

Important Points to Remember

  • Symptoms of schizophrenia and their types.
  • Structural changes in the brain; approaches to identify risk genes using linkage studies and GWAS.
  • Understanding CNV and its implications for schizophrenia risk assessment.