Pharmacogenomics in Psychiatry — MCQs
An SSRI antidepressant, such as fluoxetine, will be prescribed for an adult patient. You should advise him or her that two of the most likely side effects or adverse responses that may eventually occur at therapeutic blood levels are which of the following?
The risk of carbamazepine-induced Stevens-Johnson syndrome is increased in the presence of which of the following genes?
Which of the following produces neuropsychiatric symptoms?
Which antipsychotic is most likely to cause metabolic syndrome?
Which of the following cytochromes is involved in monooxygenase mediated detoxification of drugs?
Which amino acid-derived neurotransmitter is primarily targeted in the pharmacological treatment of depression?
What deficiency may contribute to relapse in a patient who has experienced remission with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs)?
Which of the following drugs is metabolized by CYP2D6?
A 6-year-old child has poor school performance. On scolding by teacher abnormal behavior is noted. EEG is performed. Which of the following drugs will cause worsening of the patient?
Which of the following drugs is not used in Juvenile Myoclonic Epilepsy (JME):
Pharmacogenomics in Psychiatry Indian Medical PG Practice Questions and MCQs
Question 1: An SSRI antidepressant, such as fluoxetine, will be prescribed for an adult patient. You should advise him or her that two of the most likely side effects or adverse responses that may eventually occur at therapeutic blood levels are which of the following?
- A. Sexual dysfunction and sleep disturbances (Correct Answer)
- B. Sexual dysfunction and nausea
- C. Headache and diarrhea
- D. Tremor and weight gain
Explanation: ***Sexual dysfunction and sleep disturbances*** - **Sexual dysfunction** is one of the most common and persistent adverse effects of SSRIs, affecting 40-65% of patients and continuing throughout treatment at therapeutic levels [2], [3]. - **Sleep disturbances** (insomnia or altered sleep architecture) can persist during long-term SSRI therapy and are among the eventual side effects patients experience [1], [2], [3]. - Both effects are characteristic of chronic SSRI use and significantly impact patient compliance and quality of life. *Sexual dysfunction and nausea* - While **sexual dysfunction** is indeed very common and persistent, **nausea** is typically a transient side effect that occurs during the first 1-2 weeks of treatment and usually resolves with continued use [2]. - The question specifically asks about *eventual* occurrence at therapeutic levels over time, making nausea less appropriate as it is not a chronic issue. *Tremor and weight gain* - **Tremor** is not among the most common side effects of SSRIs and occurs less frequently than sexual dysfunction or sleep disturbances. - **Weight gain** can occur with some SSRIs (particularly paroxetine), but fluoxetine is actually considered weight-neutral or may even cause weight loss in some patients, making this combination less likely for fluoxetine specifically [1]. *Headache and diarrhea* - Both **headache** and **diarrhea** are common initial side effects when starting SSRIs but typically improve or resolve within the first few weeks of treatment [1]. - These are transient effects rather than eventual persistent side effects that characterize long-term therapeutic use.
Question 2: The risk of carbamazepine-induced Stevens-Johnson syndrome is increased in the presence of which of the following genes?
- A. HLA-B* 5801
- B. HLA-B* 1502 (Correct Answer)
- C. HLA-B* 5701
- D. HLA-B*27
Explanation: ***HLA-B\* 1502*** - The **HLA-B\*1502** allele is strongly associated with an increased risk of **carbamazepine-induced Stevens-Johnson syndrome (SJS)** and **toxic epidermal necrolysis (TEN)**, particularly in individuals of Asian ancestry. - Screening for this allele is often recommended before initiating **carbamazepine** in at-risk populations. *HLA-B\* 5801* - The **HLA-B\*5801** allele is associated with an increased risk of **allopurinol-induced severe cutaneous adverse reactions (SCARs)**, including SJS and TEN. - It is not directly linked to carbamazepine-induced SJS. *HLA-B\* 5701* - The **HLA-B\*5701** allele is strongly associated with a higher risk of **abacavir hypersensitivity reaction** [1]. - It is recommended to screen for this allele before starting abacavir therapy. *HLA-B 27* - **HLA-B27** is primarily associated with **seronegative spondyloarthropathies**, such as **ankylosing spondylitis** and **reactive arthritis**. - It does not have a known association with carbamazepine-induced SJS.
Question 3: Which of the following produces neuropsychiatric symptoms?
- A. Cephalosporin
- B. Ethambutol
- C. Cyclosporine
- D. Cycloserine (Correct Answer)
Explanation: ***Cycloserine*** - **Cycloserine** is an antimicrobial agent that can cause a wide array of neuropsychiatric symptoms, including **headache**, **anxiety**, **depression**, **psychosis**, **seizures**, and **peripheral neuropathy**. - Its mechanism of action involves interfering with cell wall synthesis, but it also crosses the **blood-brain barrier**, leading to central nervous system effects. *Cephalosporin* - While some **cephalosporins** (especially at high doses or in patients with renal impairment) can cause CNS effects like **seizures**, they are not typically associated with a broad range of neuropsychiatric symptoms to the same extent as cycloserine. - The primary side effects of cephalosporins are usually **gastrointestinal disturbances** and **allergic reactions**. *Ethambutol* - **Ethambutol** is known for its ocular toxicity, specifically **optic neuritis**, which can lead to reduced visual acuity and **color blindness**. - It does not typically cause the generalized neuropsychiatric symptoms seen with cycloserine. *Cyclosporine* - **Cyclosporine**, an immunosuppressant, can cause neurological side effects such as **tremor**, **headache**, and **seizures**, and rarely **posterior reversible encephalopathy syndrome (PRES)**. - However, it is not primarily associated with the broad spectrum of psychiatric symptoms like depression or psychosis, unlike cycloserine.
Question 4: Which antipsychotic is most likely to cause metabolic syndrome?
- A. Olanzapine
- B. Haloperidol
- C. Clozapine (Correct Answer)
- D. Risperidone
Explanation: ***Clozapine*** - **Clozapine** has the **highest risk** of causing **metabolic syndrome** among all antipsychotics, characterized by significant **weight gain**, **dyslipidemia**, **insulin resistance**, and **new-onset diabetes mellitus**. - Multiple meta-analyses consistently show clozapine causes the **most severe metabolic disturbances**, with weight gain often exceeding 5-10 kg in the first year of treatment. - The mechanism involves potent antagonism of **5-HT2C receptors**, **histamine H1 receptors**, and effects on **leptin signaling** and **glucose metabolism**. - Its use requires careful **metabolic monitoring** including baseline and periodic measurement of weight, BMI, waist circumference, fasting glucose, and lipid profile. - Despite these risks, clozapine remains the gold standard for **treatment-resistant schizophrenia**, but its metabolic effects necessitate risk-benefit consideration. *Olanzapine* - **Olanzapine** has the **second-highest risk** for metabolic syndrome after clozapine, also causing significant weight gain and metabolic disturbances. - Like clozapine, it has potent **5-HT2C** and **H1 antagonism**, leading to increased appetite and altered glucose-lipid metabolism. - The metabolic risk is substantial but generally slightly less severe than clozapine in head-to-head comparisons. *Haloperidol* - **Haloperidol** is a first-generation (typical) antipsychotic with a **significantly lower risk** of metabolic syndrome compared to clozapine or olanzapine. - Its primary adverse effects are **extrapyramidal symptoms** (akathisia, dystonia, parkinsonism) and **hyperprolactinemia** rather than metabolic disturbances. - It causes minimal weight gain and has low risk for diabetes or dyslipidemia. *Risperidone* - **Risperidone** has an **intermediate metabolic risk** among atypical antipsychotics, lower than clozapine or olanzapine but higher than some others like aripiprazole or ziprasidone. - While it can cause weight gain and metabolic changes, the magnitude is generally more modest. - Its more prominent side effect is **hyperprolactinemia** due to potent D2 antagonism.
Question 5: Which of the following cytochromes is involved in monooxygenase mediated detoxification of drugs?
- A. Cytochrome b5
- B. Cytochrome P450 (Correct Answer)
- C. Cytochrome c
- D. NADPH-cytochrome P450 reductase
Explanation: ***Cyt P 450*** - **Cytochrome P450** enzymes are a superfamily of **monooxygenases** that play a critical role in the metabolism and detoxification of a wide variety of endogenous and exogenous substances, including drugs. - They facilitate phase I reactions (e.g., **oxidation**, reduction, hydrolysis), which typically introduce or expose functional groups to make compounds more polar and easier to excrete. *Cytochrome b5* - **Cytochrome b5** is involved in various metabolic reactions, including **fatty acid desaturation** and cholesterol biosynthesis, and can sometimes interact with P450 systems but is not the primary monooxygenase for drug detoxification. - It also participates in the reduction of methemoglobin and can act as an electron donor, but its role in drug detoxification is secondary and accessory to P450. *Cytochrome c* - **Cytochrome c** is a key component of the **electron transport chain** in mitochondria, primarily involved in cellular respiration and ATP production. - It has a crucial role in **apoptosis** when released into the cytosol, but it is not directly involved in drug monooxygenase detoxification. *NADPH-cytochrome P450 reductase* - **NADPH-cytochrome P450 reductase** is an enzyme that transfers electrons from NADPH to **cytochrome P450 enzymes**, enabling their monooxygenase activity. - While essential for P450 function, it is the **reductase** (electron donor) and not the monooxygenase enzyme itself, which is Cytochrome P450.
Question 6: Which amino acid-derived neurotransmitter is primarily targeted in the pharmacological treatment of depression?
- A. Histamine
- B. None of the options
- C. Serotonin (Correct Answer)
- D. Acetylcholine
Explanation: ***Serotonin*** - **Serotonin** is an amino acid-derived neurotransmitter (from **tryptophan**) known to play a crucial role in mood regulation, sleep, appetite, and other functions, making it a primary target for **antidepressant medications**. - Medications like **Selective Serotonin Reuptake Inhibitors (SSRIs)** increase serotonin levels in the brain to alleviate symptoms of depression. *Histamine* - **Histamine** is an amino acid-derived neurotransmitter (from **histidine**) primarily involved in allergic reactions, inflammation, and regulating wakefulness. - While it has some central nervous system effects, its primary role is not directly in the treatment of **depression**. *Acetylcholine* - **Acetylcholine** is a neurotransmitter involved in muscle contraction, learning, memory, and attention, and is not derived from amino acids; it is synthesized from **choline** and acetyl-CoA. - It is not directly used for treating **depression**, although imbalances can play a role in cognitive aspects of some psychiatric disorders. *None of the options* - This option is incorrect because **Serotonin** is indeed an amino acid-derived neurotransmitter (from tryptophan) targeted for treating **depression**. - Many antidepressant drugs work by modulating **serotonergic pathways**.
Question 7: What deficiency may contribute to relapse in a patient who has experienced remission with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs)?
- A. Pyridoxine
- B. Cobalamin
- C. Ascorbate
- D. Folate (Correct Answer)
Explanation: ***Folate*** - **Folate (vitamin B9) deficiency** is strongly linked to depression and is a well-established cause of relapse in patients treated with antidepressants. - Folate plays a crucial role in the **one-carbon metabolism pathway**, which is essential for the synthesis of monoamine neurotransmitters including **serotonin, norepinephrine, and dopamine**. - Studies show that **low folate levels** are associated with poor response to SSRIs and TCAs, and folate supplementation can improve antidepressant efficacy. - Approximately **30% of depressed patients** have folate deficiency, making it a clinically significant factor in treatment resistance and relapse. *Cobalamin* - **Cobalamin (vitamin B12)** deficiency can cause neuropsychiatric symptoms including depression and cognitive impairment. - While B12 is important for myelin formation and neurotransmitter synthesis, it is less specifically implicated in antidepressant relapse compared to folate. - B12 deficiency more commonly presents with **cognitive and neurological symptoms** rather than pure mood symptoms. *Pyridoxine* - **Pyridoxine (vitamin B6)** is a cofactor in neurotransmitter synthesis, including serotonin and dopamine. - While B6 deficiency can contribute to mood disturbances, it is not commonly implicated as a primary cause of relapse in antidepressant-treated depression. *Ascorbate* - **Ascorbate (vitamin C)** is an antioxidant with some role in neurotransmitter metabolism. - Severe vitamin C deficiency (scurvy) can have psychiatric manifestations, but it is not typically associated with relapse in patients treated with SSRIs or TCAs.
Question 8: Which of the following drugs is metabolized by CYP2D6?
- A. Propranolol (Correct Answer)
- B. Warfarin
- C. Statins
- D. Amiodarone
Explanation: ***Correct Answer: Propranolol*** - **Propranolol** is a non-selective beta-blocker that undergoes extensive **first-pass metabolism**, primarily via the **CYP2D6** and CYP1A2 enzymes. - Genetic variations in **CYP2D6** can significantly affect propranolol's metabolism, leading to altered drug levels and therapeutic responses. *Incorrect: Warfarin* - **Warfarin** is predominantly metabolized by **CYP2C9**, with minor contributions from other CYP enzymes. - Genetic polymorphisms in **CYP2C9** are a major factor in determining individual warfarin dose requirements. *Incorrect: Statins* - Most **statins** (e.g., simvastatin, lovastatin, atorvastatin) are primarily metabolized by **CYP3A4**. - **Fluvastatin** is an exception, being mainly metabolized by CYP2C9, while **rosuvastatin** is largely unmetabolized. *Incorrect: Amiodarone* - **Amiodarone** is primarily metabolized by **CYP3A4** and to a lesser extent by CYP2C8. - Due to its **long half-life** and extensive metabolism, amiodarone has numerous drug interactions, often involving CYP3A4 inhibition.
Question 9: A 6-year-old child has poor school performance. On scolding by teacher abnormal behavior is noted. EEG is performed. Which of the following drugs will cause worsening of the patient?
- A. Ethosuximide
- B. Valproate
- C. Carbamazepine (Correct Answer)
- D. Clonazepam
Explanation: ***Carbamazepine*** - The EEG image shows **generalized spike-wave complexes at 3 Hz**, which are characteristic of **absence seizures** (also known as petit mal seizures). - **Carbamazepine** is known to **exacerbate absence seizures** and should be avoided in patients with this diagnosis. *Ethosuximide* - This is a **first-line drug** specifically for treating **absence seizures**. - It works by blocking **T-type calcium channels** in the thalamus, effectively reducing spike-wave discharges. *Valproate* - **Valproate** is a broad-spectrum anticonvulsant effective against various seizure types, including **absence seizures**, generalized tonic-clonic seizures, and myoclonic seizures. - It is an appropriate choice if ethosuximide is ineffective or if other seizure types coexist. *Clonazepam* - **Clonazepam** is a **benzodiazepine** that can be used as an add-on therapy for **absence seizures**, especially in refractory cases. - While it has sedative side effects, it does not typically worsen absence seizures; rather, it helps control them.
Question 10: Which of the following drugs is not used in Juvenile Myoclonic Epilepsy (JME):
- A. Carbamazepine (Correct Answer)
- B. Zonisamide
- C. Valproate
- D. Topiramate
Explanation: ***Carbamazepine*** - **Carbamazepine** is known to **exacerbate myoclonus** in patients with JME and can worsen seizures due to its mechanism of action, which can increase cortical excitability or asynchronous firing in this specific epilepsy syndrome. - Its use can **worsen seizure control** in JME, leading to more frequent or severe myoclonic jerks and generalized tonic-clonic seizures. *Zonisamide* - **Zonisamide** is a broad-spectrum antiepileptic drug that is effective in treating JME by affecting multiple pathways, including **sodium and calcium channels**, and enhancing GABAergic transmission. - It effectively **reduces myoclonic, absence, and generalized tonic-clonic seizures** typically seen in JME. *Valproate* - **Valproate** is considered a **first-line treatment** for JME due to its broad-spectrum efficacy against all seizure types associated with the syndrome (myoclonic, absence, and generalized tonic-clonic). - It works by increasing **GABA levels**, reducing neuronal excitability, and modulating sodium and T-type calcium channels. *Topiramate* - **Topiramate** is also a broad-spectrum antiepileptic drug used in JME, effective for various seizure types, including generalized tonic-clonic, myoclonic, and absence seizures. - Its mechanism involves **blocking voltage-gated sodium channels**, enhancing GABA activity, and modulating AMPA/kainate glutamate receptors.
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