Persistent Depressive Disorder Persistent Depressive Disorder Neurobiology & Etiology 1 — Questions and Answers
Question 1: Which neurotransmitter system is most commonly implicated in the pathophysiology of persistent depressive disorder?
- Dopamine
- Serotonin (Correct answer)
- GABA
- Acetylcholine
Correct answer: Serotonin
Serotonergic system dysfunction is the most consistently identified neurotransmitter abnormality in PDD, which is why SSRIs are a primary pharmacological treatment.
Question 2: Which neuroendocrine axis shows chronic dysregulation in persistent depressive disorder, resulting in elevated basal cortisol?
- Hypothalamic-pituitary-thyroid (HPT) axis
- Hypothalamic-pituitary-adrenal (HPA) axis (Correct answer)
- Hypothalamic-pituitary-gonadal (HPG) axis
- Renin-angiotensin-aldosterone system
Correct answer: Hypothalamic-pituitary-adrenal (HPA) axis
Chronic HPA axis hyperactivity leads to elevated cortisol, which damages hippocampal neurons and perpetuates mood dysregulation in PDD.
Question 3: Which brain structure consistently shows reduced volume on neuroimaging in patients with persistent depressive disorder?
- Cerebellum
- Hippocampus (Correct answer)
- Basal ganglia
- Occipital lobe
Correct answer: Hippocampus
The hippocampus shows volume reduction in PDD due to chronic glucocorticoid exposure suppressing neurogenesis and causing dendritic atrophy.
Question 4: What is the estimated heritability of persistent depressive disorder (dysthymia)?
- 10–15%
- 20–25%
- 35–45% (Correct answer)
- 60–70%
Correct answer: 35–45%
Twin and family studies estimate the heritability of persistent depressive disorder at approximately 35–45%, indicating a moderate but significant genetic contribution.
Question 5: Which inflammatory markers have been consistently found elevated in individuals with persistent depressive disorder?
- White blood cells and platelets
- Pro-inflammatory cytokines such as IL-6 and TNF-α (Correct answer)
- Anti-inflammatory cytokines such as IL-10 and IL-4
- Complement proteins C3 and C4
Correct answer: Pro-inflammatory cytokines such as IL-6 and TNF-α
Elevated pro-inflammatory cytokines like IL-6 and TNF-α are found in PDD and can cross the blood-brain barrier to affect neurotransmitter metabolism and neuroplasticity.
Question 6: What is the primary mechanism by which reduced brain-derived neurotrophic factor (BDNF) contributes to persistent depressive disorder?
- It directly lowers serotonin synthesis
- It impairs synaptic plasticity and hippocampal neurogenesis (Correct answer)
- It elevates cortisol production from the adrenal glands
- It increases dopamine reuptake in the striatum
Correct answer: It impairs synaptic plasticity and hippocampal neurogenesis
BDNF deficiency disrupts synaptic plasticity and reduces hippocampal neurogenesis, impairing the brain's ability to adapt to stress and maintain mood stability.
Question 7: Early childhood adversity increases risk for persistent depressive disorder primarily through which mechanism?
- Direct permanent structural brain damage
- Epigenetic modifications affecting stress response gene expression (Correct answer)
- Permanent reduction in immune function
- Direct mutation of serotonin transporter genes
Correct answer: Epigenetic modifications affecting stress response gene expression
Early adversity induces epigenetic modifications (such as methylation of glucocorticoid receptor genes) that alter HPA axis reactivity and increase vulnerability to PDD across the lifespan.
Persistent Depressive Disorder Persistent Depressive Disorder Neurobiology & Etiology 1
Which neurotransmitter system is most commonly implicated in the pathophysiology of persistent depressive disorder?