Neurobiological basis of delusions

Neurobiological basis of delusions

Neurobiological basis of delusions

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Dopamine Hypothesis - Dopamine's Delusional Dance

  • Core Theory: ↑ Dopamine (DA) in the mesolimbic pathway is central to delusion formation.
  • Key Pathway: Ventral Tegmental Area (VTA) → Nucleus Accumbens (NAc).
    • This pathway governs motivation, reward, and salience.
    • 📌 Mnemonic: Very Taxing Affairs get Noticed Always Constantly (VTA → NAc).
  • Mechanism: Hyperdopaminergia leads to aberrant salience. Neutral stimuli are assigned undue importance, creating a delusional narrative.

⭐ The effectiveness of D2 receptor antagonists (antipsychotics) in reducing delusions is the strongest evidence supporting this hypothesis.

Dopamine Pathways and Psychotic Symptoms

Aberrant Salience - Salience Gone Wild

  • Core Idea: A dysregulated dopamine (DA) system causes the brain to misattribute profound importance to neutral, everyday stimuli.
  • Mechanism:
    • Hyperactive mesolimbic DA pathway assigns "salience" to random events.
    • The cortex then attempts to explain these oddly significant experiences by creating a delusional narrative.

⭐ While the mesolimbic pathway's hyperactivity (↑DA) drives positive symptoms (delusions, hallucinations), the mesocortical pathway's hypoactivity (↓DA) is linked to negative symptoms.

Dopamine pathways and psychosis

Brain Structures - The Brain's Belief Engine

  • Belief Evaluation System: Primarily the right prefrontal cortex (PFC), responsible for "reality testing." Dysfunction impairs the ability to reject implausible ideas.
  • Salience Network:
    • Limbic System (Amygdala): Assigns excessive emotional importance to neutral stimuli.
    • Ventral Striatum/Basal Ganglia: Dopamine hyperactivity leads to aberrant salience, making mundane events seem profoundly significant.

⭐ The "two-factor" theory suggests delusions arise from an initial abnormal experience (factor 1) plus a failure of the right PFC-mediated belief evaluation system to reject it (factor 2).

Cognitive Biases - Faulty Thought Alarms

  • Jumping to Conclusions (JTC): Key reasoning bias in delusion formation.
    • Data-gathering impairment: Decisions made on scant evidence.
    • Beliefs formed rapidly and held with high conviction.
  • Attributional Biases:
    • Externalizing: Blaming others for negative outcomes.
    • Personalizing: Interpreting neutral events as self-referential.
  • Theory of Mind (ToM) Deficits:
    • Difficulty inferring others' mental states, leading to misinterpretation of social cues.

Cognitive and Neurobiological Model of Delusions

High-Yield: The "Jumping to Conclusions" (JTC) bias is strongly associated with delusion formation. Patients require substantially less information than healthy controls before reaching a firm conclusion.

Other Neurotransmitters - Glutamate & Serotonin Roles

  • Glutamate:
    • Hypofunction of NMDA receptors is implicated in delusional thought.
    • Reduced NMDA signaling is thought to cause downstream hyperactivity of mesolimbic dopamine pathways.
    • NMDA antagonists like PCP and ketamine can induce psychosis.
  • Serotonin (5-HT):
    • Blockade of 5-HT2A receptors is a core mechanism of atypical antipsychotics.
    • This action modulates dopamine systems, improving negative symptoms and reducing motor side effects.

High-Yield: Atypical antipsychotics' high 5-HT2A to D2 receptor blockade ratio is a key differentiator from typicals, contributing to a lower risk of extrapyramidal symptoms (EPS).

Neurobiological Basis of Delusions

High-Yield Points - ⚡ Biggest Takeaways

  • Dopamine hyperactivity in the mesolimbic pathway is a central theory for delusion formation.
  • The primary therapeutic action of antipsychotics is D2 receptor antagonism.
  • Prefrontal cortex dysfunction is linked to the formation and maintenance of delusional beliefs.
  • The limbic system, including the amygdala and hippocampus, is involved in the emotional component of delusions.
  • A “two-hit” model proposes aberrant salience (dopamine) and impaired cognitive evaluation (frontal lobe).

Practice Questions: Neurobiological basis of delusions

Test your understanding with these related questions

Two dizygotic twins present to the university clinic because they believe they are being poisoned through the school's cafeteria food. They have brought these concerns up in the past, but no other students or cafeteria staff support this belief. Both of them are average students with strong and weak subject areas as demonstrated by their course grade-books. They have no known medical conditions and are not known to abuse illicit substances. Which statement best describes the condition these patients have?

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Flashcards: Neurobiological basis of delusions

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Delusion disorder typically presents with _____ delusions

TAP TO REVEAL ANSWER

Delusion disorder typically presents with _____ delusions

non-bizarre ((bizarre or non-bizarre))

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