Stress and HPA Axis — MCQs
Which of the following neuroanatomical areas is/are considered to be involved in the etiology of depression?
Stress hyperglycemia occurs due to all except -
Which of the following hormones are under inhibitory control of the hypothalamus?
Adrenal medulla secretes all EXCEPT:
What would be the most probable diagnosis for a 50-year-old chronic smoker who presents with hemoptysis, truncal obesity, and hypertension, and has an elevated ACTH level that is not suppressible with high-dose dexamethasone?
All the following mediate their action using cAMP as second messenger except:
Nitric Oxide (NO) is a novel neurotransmitter which is considered to have an effect in the pathophysiology of which of the following psychiatric conditions?
Under which one of the following conditions, the HPA axis suppression is likely to result in crisis due to adrenal insufficiency following withdrawal of glucocorticoids?
A 45-year-old male's blood test shows an increase in Homovanillic acid (HVA). Which of the following conditions is this finding most likely associated with?
Increased suicidal tendency is associated with which neurochemical imbalance?
Stress and HPA Axis Indian Medical PG Practice Questions and MCQs
Question 1: Which of the following neuroanatomical areas is/are considered to be involved in the etiology of depression?
- A. Striatum
- B. Amygdala
- C. Hippocampus
- D. All of the options (Correct Answer)
Explanation: ***All of the options*** - The **amygdala**, **hippocampus**, and **striatum** are all part of complex neural circuits that have been implicated in the pathophysiology of depression. - Dysregulation in these areas can lead to emotional processing deficits, memory impairments, and anhedonia, which are core symptoms of depression. *Amygdala* - The **amygdala** is primarily involved in processing emotions, particularly fear and anxiety, and shows increased activity in depressed individuals, contributing to negative mood. - While significant, it is just one component of a broader network involved in depression. *Hippocampus* - The **hippocampus** plays a crucial role in memory and mood regulation, and studies often show reduced volume and function in depressed patients, affecting learning and emotional context. - Although it is significantly affected, depression involves multiple brain regions, not solely the hippocampus. *Striatum* - The **striatum**, particularly the **ventral striatum**, is vital for reward processing, motivation, and motor control, and its dysfunction can contribute to anhedonia and lack of motivation in depression. - While critical for reward pathways, the striatum is part of a larger interconnected system implicated in this condition.
Question 2: Stress hyperglycemia occurs due to all except -
- A. Increased level of ACTH
- B. Decreased level of norepinephrine (Correct Answer)
- C. Insulin resistance
- D. Increased level of cortisol
Explanation: ***Decreased level of norepinephrine*** - **Norepinephrine** is a **catecholamine** that generally **increases blood glucose** by stimulating **glycogenolysis** and **gluconeogenesis**. - Therefore, a *decrease* in norepinephrine would *reduce* stress-induced hyperglycemia, making this the exception. *Increased level of ACTH* - **ACTH (Adrenocorticotropic Hormone)** stimulates the adrenal glands to release **cortisol**, which contributes significantly to stress hyperglycemia. - Increased ACTH levels therefore *promote* hyperglycemia in stress. *Insulin resistance* - **Insulin resistance** is a common feature during stress, where target cells become less responsive to insulin's effects. - This reduced insulin sensitivity leads to higher circulating glucose levels, contributing to hyperglycemia. *Increased level of cortisol* - **Cortisol** is a key **stress hormone** that promotes **gluconeogenesis** (production of glucose from non-carbohydrate sources) and **glycogenolysis** (breakdown of glycogen to glucose). - Elevated cortisol levels directly lead to an increase in blood glucose, causing hyperglycemia.
Question 3: Which of the following hormones are under inhibitory control of the hypothalamus?
- A. Both GH and prolactin (Correct Answer)
- B. GH
- C. Prolactin
- D. Neither GH nor prolactin
Explanation: ***Both GH and prolactin*** - **Growth hormone (GH)** secretion is inhibited by **somatostatin** (growth hormone-inhibiting hormone) from the hypothalamus. - **Prolactin** secretion is tonically inhibited by **dopamine** (prolactin-inhibiting hormone) from the hypothalamus. *GH* - While GH is under inhibitory control, this option does not account for prolactin, which is also primarily regulated by **hypothalamic inhibition**. - The primary stimulator of GH is GHRH, but **somatostatin** provides significant *inhibitory* control. *Prolactin* - While prolactin is under inhibitory control, this option does not account for GH, which is also significantly regulated by **hypothalamic inhibition**. - **Dopamine** is the main hypothalamic factor providing tonic inhibition of prolactin secretion. *Neither GH nor prolactin* - This statement is incorrect as both GH and prolactin are significantly regulated by **inhibitory hormones** released from the hypothalamus. - Absence of inhibitory control would lead to uncontrolled secretion of these hormones.
Question 4: Adrenal medulla secretes all EXCEPT:
- A. Epinephrine
- B. Norepinephrine
- C. Dopamine
- D. Cortisol (Correct Answer)
Explanation: ***Cortisol*** - **Cortisol** is a **glucocorticoid** hormone primarily secreted by the **adrenal cortex**, not the adrenal medulla. - Its main functions include regulating metabolism, suppressing the immune system, and aiding in stress response. *Epinephrine* - **Epinephrine** (adrenaline) is the primary hormone secreted by the **adrenal medulla**, constituting about 80% of its output. - It plays a crucial role in the **"fight-or-flight" response**, increasing heart rate, blood pressure, and glucose levels. *Norepinephrine* - **Norepinephrine** (noradrenaline) is also secreted by the **adrenal medulla**, making up about 20% of its secretion. - It works alongside epinephrine in the **sympathetic nervous system** to constrict blood vessels and increase alertness. - Norepinephrine also serves as a precursor in the biosynthesis of epinephrine. *Dopamine* - **Dopamine** is an important **neurotransmitter** that also serves as a precursor in the synthesis of norepinephrine and epinephrine. - While dopamine itself is secreted in small amounts by the adrenal medulla, its primary role is generally considered in the central nervous system and as an intermediate in catecholamine synthesis.
Question 5: What would be the most probable diagnosis for a 50-year-old chronic smoker who presents with hemoptysis, truncal obesity, and hypertension, and has an elevated ACTH level that is not suppressible with high-dose dexamethasone?
- A. Ectopic ACTH producing lung cancer (Correct Answer)
- B. Adrenal adenoma
- C. Bilateral adrenal hyperplasia
- D. Pituitary tumor
Explanation: ***Ectopic ACTH producing lung cancer*** - The combination of **hemoptysis** in a **chronic smoker** points towards a pulmonary malignancy, which can produce **ectopic ACTH**, leading to Cushing's syndrome symptoms [2, 5]. - The **elevated ACTH** that is **not suppressible with high-dose dexamethasone** is characteristic of ectopic ACTH production, as the tumor cells do not respond to feedback inhibition [1]. *Adrenal adenoma* - An **adrenal adenoma** causes **ACTH-independent Cushing's syndrome**, meaning ACTH levels would be low [1]. - While it can cause symptoms like truncal obesity and hypertension, it does not explain the hemoptysis or elevated ACTH. *Bilateral adrenal hyperplasia* - **Bilateral adrenal hyperplasia** can cause Cushing's syndrome, but it is typically **ACTH-dependent** and often responsive to high-dose dexamethasone if it's pituitary-driven [1]. - It does not account for the hemoptysis or the **non-suppressible ACTH** level in this particular presentation. *Pituitary tumor* - A **pituitary tumor** (Cushing's disease) produces ACTH, causing Cushing's syndrome, and typically shows **suppression with high-dose dexamethasone** (though not always fully). - It would not explain the symptom of **hemoptysis** associated with a chronic smoker [2].
Question 6: All the following mediate their action using cAMP as second messenger except:
- A. Glucagon
- B. Dopamine
- C. Corticotropin
- D. Vasopressin (Correct Answer)
Explanation: ***Vasopressin (ADH)*** - Vasopressin has **dual signaling mechanisms** depending on receptor type: - **V2 receptors** (kidney collecting duct): Use **Gs-protein → cAMP pathway** for water reabsorption via aquaporin-2 insertion - **V1 receptors** (vascular smooth muscle): Use **Gq-protein → IP3/DAG pathway** for vasoconstriction - In the context of this question, vasopressin is considered the exception because it has **significant non-cAMP mediated actions** through V1 receptors, unlike the other hormones listed which **predominantly or exclusively** use cAMP - **Note**: This is a teaching point about receptor subtypes; vasopressin DOES use cAMP at V2 receptors *Glucagon* - **Exclusively uses cAMP pathway** in hepatocytes and adipocytes - Binds to **glucagon receptor** (GPCR) → **Gs-protein** → adenylyl cyclase activation → **increased cAMP** → PKA activation - Promotes glycogenolysis, gluconeogenesis, and lipolysis *Dopamine* - **D1 and D5 receptors** are **Gs-coupled** → **stimulate adenylyl cyclase** → **increase cAMP** - Important for neurotransmission (motor control, reward) and renal vasodilation - D2-family receptors (D2, D3, D4) inhibit cAMP but D1-family predominates in many physiological contexts *Corticotropin (ACTH)* - Binds to **melanocortin-2 receptor (MC2R)** on adrenal cortex - **Gs-protein coupled** → adenylyl cyclase activation → **increased cAMP** → PKA activation - Stimulates steroidogenesis and cortisol secretion - **Exclusively cAMP-dependent mechanism**
Question 7: Nitric Oxide (NO) is a novel neurotransmitter which is considered to have an effect in the pathophysiology of which of the following psychiatric conditions?
- A. Schizophrenia
- B. Substance Misuse
- C. OCD
- D. Mood Disorders (Correct Answer)
Explanation: ***Mood Disorders*** - **Nitric oxide (NO)** has been implicated in the pathophysiology of **mood disorders**, such as major depressive disorder and bipolar disorder, due to its role in **neurotransmission** and **neuronal plasticity**. - NO can modulate the activity of various neurotransmitter systems (e.g., serotonergic, dopaminergic) that are known to be dysregulated in mood disorders, influencing **affect** and **emotional regulation**. *Schizophrenia* - While **NO dysfunction** has been investigated in schizophrenia, its role is less clearly established as a primary effector compared to neurotransmitters like **dopamine** and **glutamate**. - Research in schizophrenia often focuses on the **dopamine hypothesis** or **glutamate hypofunction**, with NO having a more modulatory role. *Substance Misuse* - NO is known to be involved in pathways related to **reward** and **addiction**, but it is generally considered a **modulator** of neurotransmission rather than a primary neurotransmitter in the development of substance misuse. - The pathophysiology of substance misuse is highly complex, involving multiple neurotransmitter systems and circuits, including **dopamine** and the mesolimbic reward system. *OCD* - The primary neurotransmitter theories for **Obsessive-Compulsive Disorder (OCD)** largely focus on **serotonin dysregulation**, with treatments like SSRIs being highly effective. - While NO may have some modulatory effects on brain circuits involved in OCD, it is not considered a central player in its pathophysiology compared to other conditions.
Question 8: Under which one of the following conditions, the HPA axis suppression is likely to result in crisis due to adrenal insufficiency following withdrawal of glucocorticoids?
- A. If glucocorticoids have been prescribed repeatedly within the previous year (Correct Answer)
- B. If the dose is less than equivalent of 5 mg prednisolone per day
- C. If glucocorticoids have been given by intravenous route for five days
- D. If glucocorticoids have been administered orally for one week
Explanation: ***Correct: If glucocorticoids have been prescribed repeatedly within the previous year*** - While a **single short course** of glucocorticoids typically does not cause significant HPA axis suppression, **repeated exposure over time** (multiple courses within a year) can lead to **cumulative suppression** of the hypothalamic-pituitary-adrenal axis - This is particularly true if the courses are **frequent, prolonged, or at high doses** without adequate recovery periods between treatments - **Chronic or repeated suppression** impairs the body's ability to produce sufficient endogenous cortisol when exogenous glucocorticoids are withdrawn, increasing the risk of **adrenal insufficiency crisis** - Among the given options, this represents the **highest risk scenario** for HPA axis suppression requiring careful withdrawal management *Incorrect: If the dose is less than equivalent of 5 mg prednisolone per day* - Doses **< 5 mg prednisolone equivalent per day** are considered **physiologic replacement doses** - Such low doses do **NOT suppress** the HPA axis significantly - This represents a **low-risk scenario** for adrenal insufficiency - Standard teaching: HPA suppression risk increases with doses **> 20 mg/day prednisolone equivalent** *Incorrect: If glucocorticoids have been given by intravenous route for five days* - **Short-course therapy (< 7-10 days)**, even at high doses and by IV route, typically does **NOT cause prolonged HPA axis suppression** - The HPA axis usually **recovers rapidly** after brief exposure - Abrupt discontinuation after 5 days **does not typically require tapering** and is unlikely to cause adrenal crisis - The route of administration (IV vs oral) is less important than **duration and total dose** *Incorrect: If glucocorticoids have been administered orally for one week* - Similar to the IV scenario, **one week of oral therapy** is considered a **short course** - Such brief duration typically does not cause significant HPA axis suppression requiring taper - The adrenal glands usually maintain responsiveness after only **7 days** of treatment - **Duration > 3 weeks** at supraphysiologic doses is the traditional threshold for concern about HPA suppression
Question 9: A 45-year-old male's blood test shows an increase in Homovanillic acid (HVA). Which of the following conditions is this finding most likely associated with?
- A. Phenylketonuria (PKU)
- B. Schizophrenia (Correct Answer)
- C. Depression
- D. Parkinson's disease
Explanation: **Explanation:** The correct answer is **Schizophrenia**. This question tests your knowledge of neurotransmitter metabolites and their clinical significance in psychiatric disorders. **1. Why Schizophrenia is correct:** **Homovanillic acid (HVA)** is the primary metabolic byproduct of **Dopamine**. According to the **Dopamine Hypothesis of Schizophrenia**, the disorder is characterized by dopaminergic hyperactivity, particularly in the mesolimbic pathway. Increased turnover of dopamine leads to elevated levels of HVA in the blood, cerebrospinal fluid (CSF), and urine. Monitoring HVA levels is often used in research to gauge central dopamine activity. **2. Why the other options are incorrect:** * **Phenylketonuria (PKU):** This is a metabolic disorder caused by a deficiency of phenylalanine hydroxylase. It leads to an accumulation of Phenylalanine, not HVA. * **Depression:** Depression is primarily associated with decreased levels of **5-HIAA** (5-Hydroxyindoleacetic acid), which is the metabolite of Serotonin. While dopamine can be involved, HVA is not a diagnostic marker for depression. * **Parkinson’s Disease:** This condition involves the degeneration of dopaminergic neurons in the substantia nigra. Therefore, one would expect a **decrease** in HVA levels due to dopamine deficiency, rather than an increase. **High-Yield Clinical Pearls for NEET-PG:** * **Dopamine → HVA** (Homovanillic Acid) * **Serotonin → 5-HIAA** (Decreased in suicide attempts and impulsive aggression) * **Norepinephrine → VMA** (Vanillylmandelic Acid) and **MHPG** (3-methoxy-4-hydroxyphenylglycol). * **VMA** is a crucial marker for diagnosing **Pheochromocytoma** and **Neuroblastoma**. * In Schizophrenia, HVA levels often correlate with the severity of positive symptoms (hallucinations/delusions).
Question 10: Increased suicidal tendency is associated with which neurochemical imbalance?
- A. Increased Noradrenaline
- B. Decreased Serotonin (Correct Answer)
- C. Decreased Dopamine
- D. Increased GABA
Explanation: **Explanation:** The neurobiology of suicidal behavior is most strongly linked to the **Serotonergic system**. Research consistently shows that low levels of **Serotonin (5-HT)** and its primary metabolite, **5-HIAA (5-hydroxyindoleacetic acid)**, in the cerebrospinal fluid (CSF) are associated with increased impulsivity, aggression, and completed suicide. This finding holds true across various psychiatric diagnoses, including depression and schizophrenia. **Analysis of Options:** * **Decreased Serotonin (Correct):** Low 5-HT levels in the ventromedial prefrontal cortex are linked to a failure in "top-down" inhibition, leading to impulsive-aggressive behaviors and suicidal acts. * **Increased Noradrenaline (Incorrect):** While noradrenergic dysregulation is seen in stress responses and anxiety disorders, it is not the primary neurochemical marker for suicidal tendency. * **Decreased Dopamine (Incorrect):** Low dopamine is primarily associated with anhedonia and motor symptoms (as seen in Parkinson’s or depression), but it is not as specific a predictor for suicide as serotonin. * **Increased GABA (Incorrect):** GABA is the brain's primary inhibitory neurotransmitter. Increased GABA activity is generally associated with sedation and reduced anxiety, not increased suicidality. **NEET-PG High-Yield Pearls:** * **CSF Marker:** The most high-yield fact is that **low CSF 5-HIAA** is the strongest biochemical predictor of violent suicide attempts. * **Post-mortem findings:** Studies of suicide victims often show decreased serotonin receptor binding in the prefrontal cortex. * **Genetics:** The Tryptophan Hydroxylase (TPH) gene mutation, which affects serotonin synthesis, is often studied in relation to suicidal behavior. * **Clinical Correlation:** Antidepressants (SSRIs) may initially increase the risk of suicide in young adults by increasing energy before improving mood (the "activation syndrome").
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