Schizophrenia Overview Quiz

Schizophrenia Overview

• Schizophrenia is classified as a psychotic disorder
• Psychosis involves a loss of contact with reality.
• Approximately 1/100 people in North America are affected.
• The estimated annual cost of schizophrenia in the U.S. is around $60 billion, largely due to treatment and lost wages.
• It's a common disorder with severe consequences for patients and their loved ones.

Myths about Schizophrenia

• Myth: People with schizophrenia are violent and dangerous.

• Fact: Individuals receiving treatment are not more violent than others. Untreated individuals, however, are most at risk of harming themselves.

• Myth: People with schizophrenia have multiple personalities.

• Fact: Schizophrenia is not the same as multiple personality disorder.

• Myth: People with schizophrenia see things that aren't there.

• Fact: Auditory hallucinations are a major symptom, while visual hallucinations are less common.

Characteristics of Schizophrenia

• Positive symptoms: experiences beyond normal: hallucinations (auditory most common), and delusions (irrational beliefs or paranoia misrepresenting reality, i.e., erotomanic delusions).
• Negative symptoms: deficits or absence of normal behavior: apathy, limited thought/speech, emotional or social withdrawal.
• Cognitive symptoms (disorganized): erratic changes in speech, motor behavior, and emotions (e.g., disorganized speech, inappropriate emotional reactions).

DSM-5 Diagnostic Criteria

• Individuals must have at least one of the following: delusions, hallucinations, or disorganized speech.
• Symptoms must be present for a significant portion of a one-month period, or less if treated effectively.

Development of Schizophrenia

• Usually diagnosed during late adolescence or early adulthood.

• A period of 1-2 years often exists between the first onset of symptoms and diagnosis.

• 85% of cases have a prodromal stage: a 1-2-year period with subdued symptoms.

• Common prodromal symptoms: magical thinking, minor illusions (feeling of presence when alone), and ideas of reference.

Development and Prognosis

• Complete remission is rare, with most people experiencing relapse and recovery.
• Prognosis is poorer compared to other disorders, but more favorable with:
  • Good social adjustment before onset.
  • Low proportion of negative symptoms.
  • A strong social support system.
• Symptoms may decrease with age or "level out".

Etiology - Genetics

• Schizophrenia has a genetic component (approximately 40% heritability).
• The risk is higher for identical twins than fraternal twins.
• Involved genes affect dopamine function, among others.

Etiology - Perinatal Factors

• Prenatal problems, shortly after birth, can increase schizophrenia risk.
• Environmental stressors impacting development can activate a predisposition.
• Viral/infectious exposure (e.g., influenza, Toxoplasmosis gondii) in the womb might impact fetal brain development, leading to schizophrenia symptoms later.
• Pregnancy/delivery complications might also increase risk.
• Prenatal nutrition or stress might play a role, like the Dutch Hunger Winter.

Anatomical Basis of Schizophrenia

• Enlarged lateral ventricles. Ventricle size, reflecting brain tissue, is a factor.
• Reduced dendritic spine density in the prefrontal cortex. Dendritic spines are small knobs on dendrites representing post-synaptic terminals.
• Reduced hippocampal volume, correlated with illness severity.
• Disorganized neurons in the hippocampus.

Antipsychotic Drugs

• Chlorpromazine, discovered in the 1950s, was a revolutionary antipsychotic drug, diminishing agitation and allowing for a return to normal life.
• Antipsychotics work mainly by blocking dopamine receptors, specifically D2 receptors (D2 antagonists).

Methods Minute: Positron Emission Tomography (PET)

• PET is an imaging technique that detects changes in blood flow and compound uptake.
• Radioactively labeled molecules track glucose or oxygen uptake, revealing metabolic activity in the brain regions.

Anatomy Minute: The Striatum

• The striatum is part of the basal ganglia involved in habit learning, motor and action planning.
• The dorsal striatum participates in habit learning, as well as planning.
• The ventral striatum, aka nucleus accumbens, participates in reward learning, motivation.

Symptoms of Schizophrenia Relate to Overstimulation of D2 Receptors

• Dopamine D2 receptors in the striatum are critical for schizophrenia, especially positive symptoms linked to excessive stimulation.
• Radioactive dopamine ligand (11C-NMSP) binding in the striatum can be diminished by antipsychotics, such as haloperidol.

Further Evidence for Dopamine's Role

• Cocaine and amphetamine can induce psychosis due to increased dopamine, supporting the role in psychosis.
• Drugs to decrease dopamine signaling might reduce psychosis.

More About Dopamine

• Hypofrontality: Under-stimulation of dopamine D1 receptors in the prefrontal cortex in some schizophrenia cases can impact planning, problem-solving and sophisticated reasoning.
• Researchers are searching for a drug that blocks D2 but activates D1 receptors in this context.

But Wait - There's More! (Glutamate Hypofunction)

• Glutamate and GABA imbalances affect the neuronal network; the balance impacts cognition and negative symptoms and impacts synaptic pruning.
• Synaptic pruning is the removal of extra synapses, critical in brain development and is impacted differently in adolescence in schizophrenia cases compared to neurotypical brains.
• Immune factors, alongside glutamates, impact brain development and potentially underlay schizophrenia’s neurodevelopmental aspects.

Summary (Neuroscience of Schizophrenia)

• Schizophrenia has a genetic component (40% heritability), impacting neurodevelopment.
• Excess dopamine activity in subcortical regions links to positive symptoms (delusions, hallucinations).
• Reduced dopamine in the frontal cortex can cause cognitive problems.
• Glutamate/GABA imbalance impacts motivation and cognitive functions.
• Abnormal brain development, especially excessive synaptic pruning in adolescence, aligns with the "two-hit" hypothesis.