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.