MCQ Quiz: Pathophysiology of Psychotic Spectrum Disorders

The pathophysiology of psychotic disorders like schizophrenia is a complex and evolving field of neuroscience. While the exact mechanisms are not fully understood, current models point to a multifaceted interplay between neurotransmitter systems, brain circuits, and neurodevelopmental processes. Understanding this pathophysiology is essential for pharmacists to grasp the rationale behind pharmacotherapy and the mechanisms of drug action. This quiz will test your knowledge on the core pathophysiological theories and brain changes associated with psychotic spectrum disorders.

1. The “dopamine hypothesis” of schizophrenia suggests that positive symptoms (e.g., hallucinations) are related to hyperactivity of dopamine in which pathway?

• a. Nigrostriatal pathway
• b. Mesolimbic pathway
• c. Mesocortical pathway
• d. Tuberoinfundibular pathway

Answer: b. Mesolimbic pathway

2. A hypoactive mesocortical dopamine pathway is hypothesized to be responsible for which symptoms of schizophrenia?

• a. Positive symptoms
• b. Negative and cognitive symptoms
• c. Motor side effects
• d. Hormonal side effects

Answer: b. Negative and cognitive symptoms

3. The “glutamate hypothesis” of schizophrenia suggests a key role for the hypofunction of which receptor?

• a. AMPA receptor
• b. Kainate receptor
• c. NMDA receptor
• d. G-protein coupled glutamate receptor

Answer: c. NMDA receptor

4. The fact that NMDA receptor antagonists like PCP and ketamine can induce psychosis-like symptoms provides support for which hypothesis?

• a. The dopamine hypothesis
• b. The serotonin hypothesis
• c. The glutamate hypothesis
• d. The cholinergic hypothesis

Answer: c. The glutamate hypothesis

5. Which neurotransmitter system is thought to modulate the dopamine system, with 5-HT2A receptor antagonism being a key feature of second-generation antipsychotics?

• a. GABA
• b. Acetylcholine
• c. Serotonin
• d. Glycine

Answer: c. Serotonin

6. A common structural brain abnormality observed in some individuals with schizophrenia is:

• a. An enlarged hippocampus.
• b. Increased gray matter volume.
• c. Enlarged lateral ventricles.
• d. A smaller overall skull size.

Answer: c. Enlarged lateral ventricles.

7. The neurodevelopmental model of schizophrenia proposes that the disease arises from:

• a. A single gene mutation that manifests in adulthood.
• b. A combination of genetic predisposition and early environmental insults that disrupt brain development.
• c. A purely psychological trauma in late adolescence.
• d. Poor diet and lack of exercise.

Answer: b. A combination of genetic predisposition and early environmental insults that disrupt brain development.

8. The “synaptic pruning” theory suggests that schizophrenia may involve what process during adolescence?

• a. An insufficient amount of synaptic pruning.
• b. An excessive or aberrant amount of synaptic pruning.
• c. A complete lack of synaptic pruning.
• d. Pruning of the wrong types of neurons.

Answer: b. An excessive or aberrant amount of synaptic pruning.

9. Blockade of dopamine D2 receptors in the nigrostriatal pathway is responsible for which common side effect of antipsychotics?

• a. Weight gain
• b. Sedation
• c. Extrapyramidal Symptoms (EPS)
• d. Dry mouth

Answer: c. Extrapyramidal Symptoms (EPS)

10. Blockade of dopamine D2 receptors in the tuberoinfundibular pathway leads to an increase in which hormone?

• a. Cortisol
• b. Prolactin
• c. Testosterone
• d. Thyroid-stimulating hormone (TSH)

Answer: b. Prolactin

11. The term “hypofrontality,” often seen in schizophrenia, refers to:

• a. Increased activity in the frontal lobes.
• b. Decreased metabolic activity in the prefrontal cortex.
• c. A smaller-than-average forehead.
• d. A type of delusion.

Answer: b. Decreased metabolic activity in the prefrontal cortex.

12. The pathophysiology of positive symptoms like delusions and hallucinations is thought to be most closely linked to:

• a. The mesocortical pathway
• b. The nigrostriatal pathway
• c. The tuberoinfundibular pathway
• d. The mesolimbic pathway

Answer: d. The mesolimbic pathway

13. GABA is the primary inhibitory neurotransmitter. Some theories suggest that a deficit in GABAergic interneurons may contribute to:

• a. Disinhibition of pyramidal neurons and cortical hyperactivity in schizophrenia.
• b. A decrease in dopamine release.
• c. An increase in serotonin levels.
• d. The motor symptoms of Parkinson’s disease.

Answer: a. Disinhibition of pyramidal neurons and cortical hyperactivity in schizophrenia.

14. All currently effective antipsychotic medications have some degree of affinity for which receptor?

• a. Serotonin 5-HT2A
• b. Histamine H1
• c. Dopamine D2
• d. Muscarinic M1

Answer: c. Dopamine D2

15. A key difference in the pathophysiology of positive versus negative symptoms is that negative symptoms are thought to arise from dopamine ____ in the ____ pathway.

• a. excess, mesolimbic
• b. deficit, mesolimbic
• c. excess, mesocortical
• d. deficit, mesocortical

Answer: d. deficit, mesocortical

16. The serotonin 5-HT2A receptor antagonism of atypical antipsychotics is thought to increase dopamine release in which pathway, potentially improving negative symptoms?

• a. Mesolimbic
• b. Nigrostriatal
• c. Mesocortical
• d. Tuberoinfundibular

Answer: c. Mesocortical

17. The pathophysiology of psychotic disorders is best understood as:

• a. A simple imbalance of a single neurotransmitter.
• a. A complex dysregulation across multiple neurotransmitter systems and brain circuits.
• c. A purely genetic disorder.
• d. A purely environmental disorder.

Answer: b. A complex dysregulation across multiple neurotransmitter systems and brain circuits.

18. A “psychosis” is a symptom, not a disease, characterized by:

• a. A loss of contact with reality.
• b. A feeling of sadness.
• c. A high level of anxiety.
• d. A compulsive behavior.

Answer: a. A loss of contact with reality.

19. Which of the following is NOT a primary component of the pathophysiology of schizophrenia?

• a. Genetic predisposition
• b. Environmental risk factors
• c. Neurotransmitter dysregulation
• d. Autoimmune destruction of the myelin sheath

Answer: d. Autoimmune destruction of the myelin sheath

20. The fact that symptoms of schizophrenia often emerge in late adolescence aligns with the timing of what major brain development process?

• a. Neurogenesis
• b. Myelination
• c. Synaptic pruning
• d. Apoptosis

Answer: c. Synaptic pruning

21. The glutamate system’s role in psychosis is complex, but one theory suggests NMDA receptor hypofunction leads to downstream:

• a. Decreases in dopamine release.
• b. Dysregulated, excessive firing of pyramidal neurons.
• c. Increased GABAergic tone.
• d. A decrease in all neurotransmitter activity.

Answer: b. Dysregulated, excessive firing of pyramidal neurons.

22. An understanding of pathophysiology helps the pharmacist to:

• a. Explain the rationale for a chosen medication.
• b. Anticipate and explain potential side effects.
• c. Both a and b.
• d. Neither a nor b.

Answer: c. Both a and b.

23. “Avolition,” a negative symptom, is a deficit in:

• a. Emotional expression
• b. Fluent speech
• c. Goal-directed behavior (motivation)
• d. Experiencing pleasure

Answer: c. Goal-directed behavior (motivation)

24. The pathophysiology of a delusion involves a disorder of:

• a. Perception
• b. Mood
• c. Thought content
• d. Cognition

Answer: c. Thought content

25. A pharmacist counseling a patient that their antipsychotic works by “rebalancing chemicals in the brain” is providing a simplified explanation based on:

• a. The drug’s pharmacokinetics.
• b. The neurochemical pathophysiology of the disorder.
• c. The drug’s formulation.
• d. The cost of the medication.

Answer: b. The neurochemical pathophysiology of the disorder.

26. The term “mesocorticolimbic” refers collectively to which dopamine pathways?

• a. The mesolimbic and mesocortical pathways.
• b. The nigrostriatal and mesolimbic pathways.
• c. The tuberoinfundibular and mesocortical pathways.
• d. All four dopamine pathways.

Answer: a. The mesolimbic and mesocortical pathways.

27. An increase in dopamine in the mesolimbic pathway is associated with what type of experience?

• a. Motor control
• b. Negative symptoms
• c. The “salience” or importance of stimuli, which can become aberrant in psychosis.
• d. Lactation

Answer: c. The “salience” or importance of stimuli, which can become aberrant in psychosis.

28. Current research into the pathophysiology of schizophrenia is exploring the role of:

• a. Immune system dysfunction and neuroinflammation.
• b. Genetics and epigenetics.
• c. Abnormal brain connectivity.
• d. All of the above.

Answer: d. All of the above.

29. The pathophysiology of tardive dyskinesia is thought to be related to:

• a. A down-regulation of D2 receptors in the nigrostriatal pathway.
• b. A supersensitivity of D2 receptors in the nigrostriatal pathway after chronic blockade.
• c. A blockade of serotonin receptors.
• d. An increase in acetylcholine.

Answer: b. A supersensitivity of D2 receptors in the nigrostriatal pathway after chronic blockade.

30. Understanding that extrapyramidal side effects are caused by D2 blockade in the nigrostriatal pathway allows a pharmacist to understand why they are treated with:

• a. More D2 blockers.
• b. Anticholinergic medications to restore the dopamine/acetylcholine balance.
• c. SSRIs.
• d. Beta-blockers.

Answer: b. Anticholinergic medications to restore the dopamine/acetylcholine balance.

31. Which of the following is considered a “negative” symptom of schizophrenia?

• a. Disorganized behavior
• b. Grandiose delusions
• c. Affective flattening (blunted affect)
• d. Auditory hallucinations

Answer: c. Affective flattening (blunted affect)

32. The cognitive deficits seen in schizophrenia (e.g., impaired working memory, executive function) are thought to be linked to dysfunction in which brain region?

• a. The brainstem
• b. The cerebellum
• c. The dorsolateral prefrontal cortex
• d. The amygdala

Answer: c. The dorsolateral prefrontal cortex

33. The pathophysiology of psychotic disorders is a purely biological process, with no social or environmental influence.

• a. True
• b. False

Answer: b. False

34. The fact that there is a delay in the therapeutic effect of antipsychotics suggests that the pathophysiology involves more than just acute receptor blockade, likely including:

• a. Slow absorption from the gut.
• b. The need for a very high dose.
• c. Downstream neuroadaptive changes in gene expression and receptor density.
• d. The placebo effect only.

Answer: c. Downstream neuroadaptive changes in gene expression and receptor density.

35. A “disorder of thought process,” such as loose associations, reflects a breakdown in the logical connection between ideas.

• a. True
• b. False

Answer: a. True

36. From a pathophysiological perspective, the ideal antipsychotic would:

• a. Block all dopamine receptors equally throughout the brain.
• b. Selectively decrease dopamine in the mesolimbic pathway while increasing it in the mesocortical pathway.
• c. Only block serotonin receptors.
• d. Only increase GABA activity.

Answer: b. Selectively decrease dopamine in the mesolimbic pathway while increasing it in the mesocortical pathway.

37. Which of the following is NOT a primary hypothesis for the pathophysiology of schizophrenia?

• a. Dopamine hypothesis
• b. Glutamate hypothesis
• c. Neurodevelopmental hypothesis
• d. Opioid excess hypothesis

Answer: d. Opioid excess hypothesis

38. The term “psychosis” is a broad term for a state of mind, while “schizophrenia” is a specific diagnosis with a characteristic pathophysiology and course.

• a. True
• b. False

Answer: a. True

39. Understanding the pathophysiology helps to explain why:

• a. Second-generation antipsychotics have a lower risk of EPS.
• b. There is a risk of metabolic side effects with many SGAs.
• c. There is a risk of hyperprolactinemia.
• d. All of the above.

Answer: d. All of the above.

40. A pharmacist’s knowledge of pathophysiology is essential for effective:

• a. Patient counseling
• b. Interprofessional communication
• c. Medication therapy management
• d. All of the above

Answer: d. All of the above

41. The pathophysiology of drug-induced psychosis (e.g., from stimulants) involves a massive increase in which neurotransmitter?

• a. Acetylcholine
• b. GABA
• c. Serotonin
• d. Dopamine

Answer: d. Dopamine

42. Which of the following is a structural feature, not a neurotransmitter imbalance?

• a. Dopamine hyperactivity
• b. NMDA receptor hypofunction
• c. Reduced gray matter volume
• d. Serotonin receptor blockade

Answer: c. Reduced gray matter volume

43. The heritability of schizophrenia provides strong evidence for a ____ component in its pathophysiology.

• a. genetic
• b. purely environmental
• c. dietary
• d. viral

Answer: a. genetic

44. A patient’s experience of their psychotic symptoms is subjective, but the underlying pathophysiology is a biological process.

• a. True
• b. False

Answer: a. True

45. Which of the following is NOT a core domain of symptoms in schizophrenia?

• a. Positive symptoms
• b. Negative symptoms
• c. Cognitive symptoms
• d. Motor symptoms (as a primary domain)

Answer: d. Motor symptoms (as a primary domain)

46. A “hallucination” is a disorder of ______, while a “delusion” is a disorder of ______.

• a. thought, perception
• b. perception, thought
• c. mood, affect
• d. affect, mood

Answer: b. perception, thought

47. The pathophysiology of psychosis in bipolar mania is thought to involve similar dopaminergic dysregulation as in schizophrenia.

• a. True
• b. False

Answer: a. True

48. An understanding of pathophysiology allows the pharmacist to:

• a. Appreciate the rationale for specific treatments.
• b. Educate patients and families about the biological nature of the illness, helping to reduce stigma.
• c. Both a and b.
• d. Neither a nor b.

Answer: c. Both a and b.

49. The overall pathophysiology of psychotic disorders is best characterized by:

• a. A simple, single cause.
• b. A complex disruption of brain development and neurocircuitry.
• c. A condition that is easy to treat and cure.
• d. A problem that is not biological in nature.

Answer: b. A complex disruption of brain development and neurocircuitry.

50. The ultimate goal of understanding the pathophysiology of psychotic disorders is to:

• a. Be able to more effectively and compassionately manage the pharmacotherapy for patients suffering from these illnesses.
• b. Pass the psychiatry exam.
• c. Be able to diagnose schizophrenia.
• d. Memorize all the brain pathways.

Answer: a. Be able to more effectively and compassionately manage the pharmacotherapy for patients suffering from these illnesses.