MCQ Quiz: Background and Etiology of Mood Disorders

This quiz is dedicated to the foundational principles underlying mood disorders, a critical area of study for PharmD students. Understanding the “why” and “how” behind conditions like depression and bipolar disorder is the first step toward mastering their pharmacotherapy. This quiz will test your knowledge of the core etiological theories, from the classic monoamine hypothesis to the roles of neuroplasticity, genetics, and neuroendocrine systems. Delve into the intricate pathophysiology of these conditions to build a stronger framework for the clinical decisions you will make as a future pharmacist.

1. The monoamine hypothesis of depression primarily suggests a deficiency in which group of neurotransmitters?

• A. Acetylcholine, histamine, and GABA
• B. Serotonin, norepinephrine, and dopamine
• C. Glutamate, aspartate, and glycine
• D. Endorphins, enkephalins, and substance P

Answer: B. Serotonin, norepinephrine, and dopamine

2. Chronic stress is a major risk factor for depression and is believed to cause hyperactivity of which neuroendocrine system?

• A. Hypothalamic-Pituitary-Thyroid (HPT) axis
• B. Renin-Angiotensin-Aldosterone System (RAAS)
• C. Hypothalamic-Pituitary-Adrenal (HPA) axis
• D. Sympathetic-Adrenal-Medullary (SAM) axis

Answer: C. Hypothalamic-Pituitary-Adrenal (HPA) axis

3. According to the neurotrophic hypothesis of depression, a reduction in which protein is associated with decreased neurogenesis and neuronal atrophy, particularly in the hippocampus?

• A. Nerve Growth Factor (NGF)
• B. Glial-Derived Neurotrophic Factor (GDNF)
• C. Ciliary Neurotrophic Factor (CNTF)
• D. Brain-Derived Neurotrophic Factor (BDNF)

Answer: D. Brain-Derived Neurotrophic Factor (BDNF)

4. The mechanism of action of Selective Serotonin Reuptake Inhibitors (SSRIs) provides evidence for which etiological theory of depression?

• A. The neuroinflammatory hypothesis
• B. The monoamine hypothesis
• C. The glutamate hypothesis
• D. The circadian rhythm hypothesis

Answer: B. The monoamine hypothesis

5. In the pathophysiology of mood disorders, prolonged elevation of cortisol due to HPA axis dysfunction can lead to what change in the hippocampus?

• A. Increased volume and neuronal growth
• B. Atrophy and decreased neurogenesis
• C. Enhanced long-term potentiation
• D. A reduction in glucocorticoid receptors

Answer: B. Atrophy and decreased neurogenesis

6. The “kindling” hypothesis has been proposed to explain the progressive nature of bipolar disorder. What does this hypothesis suggest?

• A. Each mood episode is less severe than the last.
• B. Each mood episode increases the patient’s sensitivity to medication.
• C. Each mood episode makes the brain more susceptible to future episodes with less stress required to trigger them.
• D. The brain becomes resistant to stress over time, preventing future episodes.

Answer: C. Each mood episode makes the brain more susceptible to future episodes with less stress required to trigger them.

7. From a pathophysiological perspective, what is the role of the amygdala in mood disorders?

• A. It is primarily responsible for executive function and decision-making.
• B. It is involved in processing memory and learning.
• C. It is often hyperactive, leading to exaggerated responses to negative or fearful stimuli.
• D. It controls motor function and coordination.

Answer: C. It is often hyperactive, leading to exaggerated responses to negative or fearful stimuli.

8. The glutamate hypothesis of depression suggests that there is dysregulation of the primary excitatory neurotransmitter. This provides a rationale for the mechanism of which rapid-acting antidepressant?

• A. Fluoxetine
• B. Venlafaxine
• C. Esketamine
• D. Mirtazapine

Answer: C. Esketamine

9. Genetic factors play a significant role in the etiology of mood disorders. Which disorder has the highest estimated heritability?

• A. Major Depressive Disorder
• B. Bipolar I Disorder
• C. Dysthymia (Persistent Depressive Disorder)
• D. Cyclothymic Disorder

Answer: B. Bipolar I Disorder

10. An imbalance between excitatory and inhibitory neurotransmission is implicated in mood disorders. Which neurotransmitter is the primary inhibitory force in the central nervous system?

• A. Glutamate
• B. Serotonin
• C. Dopamine
• D. Gamma-aminobutyric acid (GABA)

Answer: D. Gamma-aminobutyric acid (GABA)

11. The observation that it takes several weeks for antidepressants to exert their full therapeutic effect, despite an immediate increase in synaptic neurotransmitters, supports which etiological concept?

• A. The rapid action of neurotransmitter reuptake blockade.
• B. The need for downstream changes in gene expression and receptor sensitivity.
• C. The primary role of anticholinergic effects in treatment.
• D. The saturation of metabolic enzymes as the main therapeutic factor.

Answer: B. The need for downstream changes in gene expression and receptor sensitivity.

12. Neuroinflammation is an emerging etiological theory for depression. This theory is supported by the finding of elevated levels of what substances in some depressed patients?

• A. Anti-inflammatory cytokines like IL-10
• B. Pro-inflammatory cytokines like IL-6, TNF-alpha, and IL-1beta
• C. Brain-Derived Neurotrophic Factor (BDNF)
• D. Monoamine neurotransmitters

Answer: B. Pro-inflammatory cytokines like IL-6, TNF-alpha, and IL-1beta

13. In the context of the monoamine hypothesis, the mechanism of action of reserpine (an older antihypertensive) provided early evidence for the theory because it caused depression by:

• A. Selectively blocking serotonin reuptake.
• B. Inhibiting monoamine oxidase.
• C. Depleting presynaptic vesicles of monoamines.
• D. Blocking postsynaptic dopamine receptors.

Answer: C. Depleting presynaptic vesicles of monoamines.

14. What is the role of the prefrontal cortex (PFC) in the pathophysiology of depression?

• A. It shows increased activity, leading to obsessive thoughts.
• B. It controls basic functions like breathing and heart rate.
• C. It often exhibits reduced activity and volume, impairing executive functions like planning and mood regulation.
• D. It is primarily involved in the formation of new memories.

Answer: C. It often exhibits reduced activity and volume, impairing executive functions like planning and mood regulation.

15. The “diathesis-stress” model is a widely accepted etiological framework for depression. What does this model propose?

• A. Depression is caused exclusively by genetic factors.
• B. Depression is caused exclusively by stressful life events.
• C. Depression results from an interaction between a pre-existing vulnerability (genetic or biological) and a precipitating stressful event.
• D. All individuals have the same risk of developing depression regardless of genetics or stress.

Answer: C. Depression results from an interaction between a pre-existing vulnerability (genetic or biological) and a precipitating stressful event.

16. How does the blood-brain barrier (BBB) present a challenge in the pharmacology of mood disorders?

• A. It allows all substances to freely enter the brain.
• B. It restricts the passage of many potential therapeutic molecules into the central nervous system.
• C. It actively transports all antidepressants out of the brain.
• D. It is completely absent in patients with mood disorders.

Answer: B. It restricts the passage of many potential therapeutic molecules into the central nervous system.

17. The pathophysiology of bipolar disorder is thought to involve dysregulation in intracellular signaling pathways. Lithium’s mechanism is believed to involve the inhibition of which second messenger system?

• A. The cyclic AMP (cAMP) pathway
• B. The inositol phosphate pathway
• C. The nitric oxide pathway
• D. The MAP kinase pathway

Answer: B. The inositol phosphate pathway

18. A key difference in the neurobiology of bipolar disorder compared to major depression is the cyclical nature of the illness, suggesting dysregulation in what?

• A. Monoamine synthesis only
• B. Neurotransmitter degradation only
• C. Homeostatic mechanisms that regulate mood stability and circadian rhythms
• D. The blood-brain barrier permeability

Answer: C. Homeostatic mechanisms that regulate mood stability and circadian rhythms

**19. From an etiological standpoint, early-life trauma is a significant environmental risk factor for developing mood disorders later in life by causing long-lasting changes in: **

• A. Hair and eye color.
• B. Bone density.
• C. HPA axis function and gene expression.
• D. Adult height.

Answer: C. HPA axis function and gene expression.

20. In the pathophysiology of depression, downregulation of postsynaptic serotonin receptors (e.g., 5-HT2A) is considered a potential long-term effect of what process?

• A. Acute monoamine depletion
• B. Chronic treatment with SSRIs
• C. Single dose of a placebo
• D. Blockade of dopamine transporters

Answer: B. Chronic treatment with SSRIs

21. Mitochondrial dysfunction has been implicated in the etiology of bipolar disorder. This could lead to a deficit in what crucial cellular process?

• A. Cell division
• B. Energy production (ATP synthesis)
• C. Protein synthesis
• D. DNA replication

Answer: B. Energy production (ATP synthesis)

22. Which brain neurotransmitter system is most closely associated with the anhedonia (inability to feel pleasure) seen in major depression?

• A. The cholinergic system
• B. The histaminergic system
• C. The mesolimbic dopamine system
• D. The GABAergic system

Answer: C. The mesolimbic dopamine system

**23. The observation that deep brain stimulation (DBS) of certain brain circuits can alleviate treatment-resistant depression supports the idea that mood disorders are: **

• A. Purely a result of chemical imbalances.
• B. Caused by viral infections.
• C. Disorders of specific neuroanatomical circuits.
• D. Solely a psychological condition with no biological basis.

Answer: C. Disorders of specific neuroanatomical circuits.

24. The mechanism of action of mirtazapine, which blocks presynaptic α2-adrenergic receptors, directly supports which aspect of the monoamine hypothesis?

• A. That a lack of dopamine is the sole cause of depression.
• B. That blocking these autoreceptors increases the release of both serotonin and norepinephrine.
• C. That postsynaptic receptor blockade is the only effective treatment.
• D. That MAO enzyme activity is the primary problem.

Answer: B. That blocking these autoreceptors increases the release of both serotonin and norepinephrine.

25. Alterations in sleep architecture, such as decreased REM latency and reduced slow-wave sleep, are common biological markers in depression, suggesting a dysregulation of:

• A. Renal function
• B. Cardiac output
• C. Circadian rhythms
• D. Gastric motility

Answer: C. Circadian rhythms

26. Which of the following best describes the background for using an atypical antipsychotic as an adjunct in treating MDD?

• A. They primarily act by increasing BDNF levels directly.
• B. They modulate dopamine and serotonin pathways that are not fully addressed by SSRIs or SNRIs alone.
• C. They are potent anti-inflammatory agents.
• D. They enhance the metabolism of the primary antidepressant.

Answer: B. They modulate dopamine and serotonin pathways that are not fully addressed by SSRIs or SNRIs alone.

**27. The phenomenon of “serotonin transporter gene polymorphism” (e.g., 5-HTTLPR) is a key concept in the etiology of depression because it may: **

• A. Guarantee that an individual will develop depression.
• B. Influence an individual’s susceptibility to depression, particularly in the context of stressful life events.
• C. Determine the color of an individual’s eyes.
• D. Only affect the risk of developing bipolar disorder, not depression.

Answer: B. Influence an individual’s susceptibility to depression, particularly in the context of stressful life events.

28. An excess of which excitatory neurotransmitter is thought to contribute to excitotoxicity and neuronal damage in severe, chronic mood disorders?

• A. GABA
• B. Serotonin
• C. Dopamine
• D. Glutamate

Answer: D. Glutamate

29. The “gut-brain axis” is an emerging area in the etiology of depression, suggesting a link between mood and what?

• A. The composition of the intestinal microbiota
• B. The length of the small intestine
• C. The rate of gastric emptying
• D. The production of bile acids

Answer: A. The composition of the intestinal microbiota

**30. In the background of mood disorders, a “first-pass” effect refers to: **

• A. The first mood episode a patient experiences.
• B. The hepatic metabolism that a drug undergoes after oral administration before reaching systemic circulation.
• C. The first antidepressant a patient tries.
• D. A type of cognitive bias in depression.

Answer: B. The hepatic metabolism that a drug undergoes after oral administration before reaching systemic circulation.

**31. The delayed onset of action of most antidepressants suggests that the direct inhibition of neurotransmitter reuptake is not the sole therapeutic mechanism, but rather initiates a cascade of: **

• A. Immediate receptor saturation.
• B. Acute neuronal apoptosis.
• C. Adaptive changes in receptor density and intracellular signaling.
• D. Rapid clearance of the drug from the system.

Answer: C. Adaptive changes in receptor density and intracellular signaling.

32. The etiology of mood disorders is multifactorial. Which of the following is considered an environmental factor?

• A. A polymorphism in the SERT gene
• B. A family history of bipolar disorder
• C. A history of childhood adversity or neglect
• D. The presence of the APOE4 allele

Answer: C. A history of childhood adversity or neglect

**33. In mania, neuroimaging studies have often shown increased activity in brain regions associated with reward and emotion, along with decreased activity in regions responsible for: **

• A. Auditory processing
• B. Visual perception
• C. Impulse control and executive function
• D. Balance and coordination

Answer: C. Impulse control and executive function

**34. The “membrane hypothesis” of mood stabilizer action, particularly for lithium and valproate, suggests they work by: **

• A. Directly blocking neurotransmitter transporters.
• B. Altering the physical properties of neuronal membranes.
• C. Modulating G-proteins and downstream signaling cascades to restore cellular homeostasis.
• D. Increasing the production of all monoamines.

Answer: C. Modulating G-proteins and downstream signaling cascades to restore cellular homeostasis.

**35. A key difference in the proposed etiology of psychosis in schizophrenia versus psychosis in severe mood disorders is that in mood disorders, psychosis is typically: **

• A. Always present throughout the illness.
• B. Mood-congruent and occurs only during severe mood episodes.
• C. Unrelated to the patient’s emotional state.
• D. The primary and defining feature of the illness.

Answer: B. Mood-congruent and occurs only during severe mood episodes.

36. A reduction in the levels of the serotonin metabolite 5-HIAA in the cerebrospinal fluid (CSF) has been linked to which of the following?

• A. Increased pleasure-seeking behavior
• B. Impulsive and suicidal behavior
• C. Enhanced cognitive function
• D. Manic episodes

Answer: B. Impulsive and suicidal behavior

**37. The rationale for using thyroid hormone as an augmentation strategy in depression is based on the etiological link between mood regulation and the: **

• A. Hypothalamic-pituitary-adrenal (HPA) axis
• B. Hypothalamic-pituitary-thyroid (HPT) axis
• C. Renin-angiotensin system
• D. Dopaminergic reward pathway

Answer: B. Hypothalamic-pituitary-thyroid (HPT) axis

**38. The fact that antagonists of the NMDA receptor can produce rapid antidepressant effects supports the hypothesis that mood disorders involve a dysregulation of: **

• A. Cholinergic neurotransmission
• B. Glutamatergic neurotransmission
• C. Histaminergic neurotransmission
• D. Opioidergic neurotransmission

Answer: B. Glutamatergic neurotransmission

**39. Epigenetic modifications, such as DNA methylation and histone acetylation, are considered a key mechanism through which: **

• A. The genetic code is permanently changed.
• B. Environmental factors can influence gene expression without altering the DNA sequence itself.
• C. Drugs are metabolized in the liver.
• D. Neurotransmitters are synthesized.

Answer: B. Environmental factors can influence gene expression without altering the DNA sequence itself.

40. In the etiology of mood disorders, a decrease in the density of glial cells, such as astrocytes, has been observed in key brain regions. What is a primary function of these cells?

• A. Transmitting nerve impulses
• B. Supporting neuronal function and regulating the synaptic environment
• C. Producing cerebrospinal fluid
• D. Forming the myelin sheath

Answer: B. Supporting neuronal function and regulating the synaptic environment

41. The action of tricyclic antidepressants on histamine H1 receptors is not related to their therapeutic effect but is a key background reason for which common side effect?

• A. Nausea
• B. Insomnia
• C. Sedation and weight gain
• D. Hypertension

Answer: C. Sedation and weight gain

42. Deficits in “emotional regulation” are a core component of mood disorders. This function is primarily attributed to the interaction between which two brain regions?

• A. The cerebellum and the brainstem
• B. The prefrontal cortex and the amygdala
• C. The occipital lobe and the parietal lobe
• D. The basal ganglia and the thalamus

Answer: B. The prefrontal cortex and the amygdala

**43. The “biopsychosocial model” is a comprehensive framework for understanding the etiology of mood disorders. It posits that the condition arises from: **

• A. Only biological factors.
• B. Only psychological factors.
• C. Only social and environmental factors.
• D. A complex interplay of biological, psychological, and social factors.

Answer: D. A complex interplay of biological, psychological, and social factors.

44. Mania in bipolar disorder has been linked to an overactivity of which neurotransmitter pathway, which is a target for antipsychotic medications?

• A. Serotonin pathways in the raphe nuclei
• B. Dopamine pathways, particularly the mesolimbic pathway
• C. Acetylcholine pathways in the basal forebrain
• D. Histamine pathways in the hypothalamus

Answer: B. Dopamine pathways, particularly the mesolimbic pathway

45. What is the fundamental difference in the etiology of unipolar depression versus bipolar depression?

• A. Unipolar depression involves only episodes of depression, while bipolar depression is part of an illness that also includes mania or hypomania.
• B. The monoamine hypothesis only applies to unipolar depression.
• C. Genetic factors are only involved in bipolar disorder.
• D. HPA axis dysfunction is only seen in unipolar depression.

Answer: A. Unipolar depression involves only episodes of depression, while bipolar depression is part of an illness that also includes mania or hypomania.

**46. The background theory for the use of valproic acid and other anticonvulsants as mood stabilizers is that they may reduce neuronal hyperexcitability, a state sometimes referred to as: **

• A. Neurotrophic enhancement
• B. Synaptic pruning
• C. “Brain-storm” or kindling
• D. Long-term depression (LTD)

Answer: C. “Brain-storm” or kindling

**47. Oxidative stress is another biological factor implicated in the pathophysiology of mood disorders. This refers to an imbalance between reactive oxygen species and: **

• A. The body’s antioxidant defenses.
• B. The levels of monoamine neurotransmitters.
• C. The activity of the HPA axis.
• D. The concentration of sodium ions.

Answer: A. The body’s antioxidant defenses.

48. Why is it important for a pharmacist to understand the various etiological theories of mood disorders?

• A. It allows them to definitively tell a patient the single cause of their illness.
• B. It helps explain the rationale behind different treatment approaches and the reasons for delayed therapeutic onset.
• C. It is only useful for academic research and has no clinical relevance.
• D. It proves that all mood disorders can be cured with a single medication.

Answer: B. It helps explain the rationale behind different treatment approaches and the reasons for delayed therapeutic onset.

**49. The observation that some medical conditions (e.g., hypothyroidism, stroke) can cause depressive symptoms provides evidence for the: **

• A. Purely psychological nature of depression.
• B. Idea that depression is always a side effect of medication.
• C. Biological underpinnings of mood regulation.
• D. Lack of any connection between the brain and the body.

Answer: C. Biological underpinnings of mood regulation.

50. What is a key feature of the “background” of bipolar disorder that complicates its diagnosis and distinguishes it from major depression?

• A. Symptoms are always constant and do not fluctuate.
• B. The first presentation of the illness is often a depressive episode.
• C. It is always diagnosed in early childhood.
• D. There are no effective treatments available.

Answer: B. The first presentation of the illness is often a depressive episode.