Epigenetics in Psychiatry — MCQs
Sumoylation of histone proteins is associated with
Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
DNA Methylation is not related to?
Mutations are due to changes in:
Chronic disorder characterized by compulsive use of drugs, resulting in physical, psychological, and social harm, and continued use despite evidence that it is harmful is called.
Choose the correctly matched pairs regarding the drugs used in schizophrenia: 1. D2 antagonism: Reduces positive symptoms 2. 5HT2A antagonism: Reduces negative symptoms 3. 5HT1A agonism: Weight loss 4. Muscarinic antagonism: Reduces extrapyramidal symptoms
Which of the following is false about bipolar disorder?
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?
Which of the following features is NOT commonly associated with 22q11.2 deletion syndrome?
Epigenetics in Psychiatry Indian Medical PG Practice Questions and MCQs
Question 1: Sumoylation of histone proteins is associated with
- A. Activation of gene transcription
- B. Condensation of chromosome
- C. Transcription repression (Correct Answer)
- D. DNA replication
Explanation: ***Transcription repression*** - **Sumoylation** is a post-translational modification involving the covalent attachment of **Small Ubiquitin-like Modifier (SUMO) proteins** to target proteins, which leads to transcriptional repression. - When histones are sumoylated, it alters chromatin structure and recruits **transcriptional corepressors**, making the DNA less accessible for transcription factors. - This is the **primary and well-established function** of histone sumoylation in gene regulation. *Activation of gene transcription* - **Histone acetylation** and specific methylation patterns (e.g., H3K4me3, H3K36me3) are associated with **transcriptional activation**, not sumoylation. - Sumoylation typically creates a repressive chromatin environment, hindering gene expression. *Condensation of chromosome* - While sumoylation can influence chromatin structure, **chromosome condensation** during cell division is primarily regulated by **condensins** and **cohesins**. - Sumoylation's role in condensation is indirect and not its primary function. *DNA replication* - DNA replication is a separate process from transcriptional regulation and involves DNA polymerases and replication machinery. - Histone sumoylation specifically affects **gene transcription**, not DNA replication.
Question 2: Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
- A. Gene Knockout
- B. Impaired DNA repair
- C. Genomic Imprinting (Correct Answer)
- D. RNA interference
Explanation: ***Genomic Imprinting*** - **Genomic imprinting** is an epigenetic phenomenon where certain genes are expressed in a **parent-of-origin-specific manner**. - In Prader-Willi syndrome, the disease results from the loss of function of specific genes on chromosome 15 (15q11-q13) inherited from the father, while Angelman syndrome results from the loss of function of a different gene (UBE3A) in the same region, but inherited from the mother. *RNA interference* - **RNA interference** is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules. - This process is not directly responsible for the parent-of-origin-specific expression patterns observed in these syndromes. *Gene Knockout* - A **gene knockout** is a genetic technique in which an organism's genes are made inoperative. - While it involves modifying gene function, it does not explain the differential expression based on parental origin. *Impaired DNA repair* - **Impaired DNA repair** refers to defects in the mechanisms that correct DNA damage. - This can lead to increased mutations and conditions like cancer, but it is not the underlying mechanism for Prader-Willi or Angelman syndromes.
Question 3: DNA Methylation is not related to?
- A. DNA Replication
- B. Gene silencing
- C. Capping (Correct Answer)
- D. Mismatch repair
Explanation: ***Capping*** - **Capping** is a modification of messenger RNA (mRNA) that occurs during **mRNA processing** in eukaryotes, involving the addition of a 7-methylguanosine cap to the 5' end of the mRNA molecule. - This process is crucial for mRNA stability, translation initiation, and nuclear export, and is entirely **independent of DNA modifications** like DNA methylation. *DNA Replication* - DNA methylation plays a role in **DNA replication** to distinguish newly synthesized strands from parental strands during **DNA repair**. - In bacteria, methylation at specific sites (**Dam methylase**) helps in **mismatch repair** by identifying the parental strand. *Gene silencing* - **DNA methylation** of CpG islands in promoter regions is a well-established mechanism for **gene silencing** by altering chromatin structure and preventing transcription factor binding. - This epigenetic modification leads to stable transcriptional repression and is critical for processes like X-chromosome inactivation and genomic imprinting. *Mismatch repair* - In prokaryotes, **DNA methylation** marks the parental strand, which is used by the **mismatch repair system** to correct errors on the newly synthesized, unmethylated strand. - In eukaryotes, while not directly marking strands, DNA methylation can influence the efficiency of mismatch repair pathways by altering chromatin accessibility.
Question 4: Mutations are due to changes in:
- A. DNA nucleotide sequence (Correct Answer)
- B. RNA nucleotide sequence
- C. Amino acid sequence of ribonuclease
- D. Cell membrane
Explanation: ***DNA nucleotide sequence*** - **Mutations** are defined as changes in the **genetic material**, which is primarily composed of **DNA**. - These changes in the **nucleotide sequence** of DNA can alter the genetic code, leading to changes in **protein structure and function**. *RNA nucleotide sequence* - While RNA can have its nucleotide sequence altered, these changes are generally not considered true **mutations** in the heritable sense for most organisms. - RNA is typically a temporary molecule, and changes to its sequence are usually not passed down to subsequent generations. *Amino acid sequence of ribonuclease* - An altered **amino acid sequence** in a protein like ribonuclease is a consequence of a **mutation in the DNA**, not the mutation itself. - **Ribonucleases** are enzymes that catalyze the degradation of RNA, and their structure is determined by the **DNA sequence**. *Cell membrane* - The cell membrane is a **lipid bilayer** with embedded proteins that regulates cellular transport and communication. - While its components can be affected by genetic mutations, alterations in the cell membrane itself do not constitute the primary definition of a **mutation**.
Question 5: Chronic disorder characterized by compulsive use of drugs, resulting in physical, psychological, and social harm, and continued use despite evidence that it is harmful is called.
- A. Substance intoxication
- B. Drug addiction (Correct Answer)
- C. Drug abuse
- D. Drug dependence
Explanation: ***Drug addiction*** - This definition accurately describes **drug addiction** as a chronic disorder involving compulsive drug use despite harmful consequences across physical, psychological, and social domains. - Key components include the **compulsive nature** of use, the **harmful outcomes**, and the persistence of use even with awareness of these harms. *Substance intoxication* - **Substance intoxication** refers to the acute, reversible effects of a substance on the central nervous system, leading to clinical changes in perception, mood, and behavior. - It does not encompass the chronic, compulsive use or the long-term physical, psychological, and social harms characteristic of addiction. *Drug abuse* - **Drug abuse** is a pattern of harmful use of a psychoactive substance, but it doesn't necessarily include the compulsive, chronic nature and the concept of continued use despite acknowledging harm that defines addiction. - The term "abuse" is often considered outdated in favor of "substance use disorder" in clinical contexts to better reflect the chronic disease model. *Drug dependence* - **Drug dependence** refers to a physiological state where the body adapts to a substance, leading to **withdrawal symptoms** if the substance is stopped and **tolerance** to its effects. - While it is a component of addiction, it does not fully capture the compulsive drug-seeking behavior or the broader psychological and social harms that define addiction itself.
Question 6: Choose the correctly matched pairs regarding the drugs used in schizophrenia: 1. D2 antagonism: Reduces positive symptoms 2. 5HT2A antagonism: Reduces negative symptoms 3. 5HT1A agonism: Weight loss 4. Muscarinic antagonism: Reduces extrapyramidal symptoms
- A. 1,4
- B. 1,2,4
- C. 1,2,3,4
- D. 1,2 (Correct Answer)
Explanation: ***1,2*** - **D2 antagonism** is the primary mechanism by which antipsychotics reduce **positive symptoms** of schizophrenia, such as hallucinations and delusions. - **5HT2A antagonism** is a key mechanism of atypical antipsychotics contributing to the reduction of **negative symptoms** (e.g., apathy, anhedonia, flat affect) and cognitive deficits, while also reducing the risk of extrapyramidal symptoms. *1,2,3,4* - This option is incorrect because **5HT1A agonism** is not associated with **weight loss**. While 5HT1A partial agonism (as seen with aripiprazole and brexpiprazole) may improve negative symptoms, anxiety, and cognitive function, it does not directly cause weight loss. - Additionally, **muscarinic antagonism** does not reduce extrapyramidal symptoms as a primary mechanism. Rather, anticholinergic (muscarinic antagonist) drugs like benztropine are used to **treat** EPS after it occurs. The reduction of EPS in atypical antipsychotics primarily comes from 5HT2A antagonism and lower D2 binding affinity. *1,2,4* - This option is incorrect because **muscarinic antagonism** is not a mechanism that reduces EPS. Anticholinergic agents are used therapeutically to counteract EPS caused by dopamine blockade, but anticholinergic effects themselves do not prevent or reduce EPS. - The reduction of EPS with atypical antipsychotics is mainly due to **5HT2A antagonism** balancing dopaminergic blockade, selective limbic over striatal binding, and fast D2 dissociation kinetics. *1,4* - This option is incorrect because it omits **5HT2A antagonism**, which is crucial for reducing **negative symptoms** in schizophrenia. - It also incorrectly includes muscarinic antagonism as a mechanism that reduces EPS, when in reality anticholinergics are used to treat EPS rather than prevent it.
Question 7: Which of the following is false about bipolar disorder?
- A. Unipolar mania is more common than bipolar disorder (Correct Answer)
- B. Genetic factors play important role
- C. Rapid cycling is more common in females
- D. Age of onset is earlier than unipolar depression
Explanation: ***Unipolar mania is more common than bipolar disorder*** - This statement is **false** because **unipolar mania is extremely rare**, while **bipolar disorder (which includes both manic and depressive episodes)** is significantly more common. - **Unipolar mania** refers to recurrent manic episodes without any depressive episodes, a presentation that is seldom observed clinically. *Genetic factors play important role* - This statement is **true**, as **bipolar disorder has a strong genetic component**, with **heritability estimated between 60-80%**. - **First-degree relatives** of individuals with bipolar disorder are at a significantly higher risk of developing the condition. *Rapid cycling is more common in females* - This statement is **true**; **rapid cycling (4 or more mood episodes per year)** occurs more frequently in females with bipolar disorder. - **Women with bipolar disorder** are also more likely to experience **mixed features** and **more depressive episodes** compared to males. *Age of onset is earlier than unipolar depression* - This statement is **true** because the **typical age of onset for bipolar disorder is in early adulthood (late teens to early 20s)**, whereas **unipolar depression often has a later average onset**, though both can occur at any age. - An earlier age of onset in bipolar disorder is linked to poorer prognosis and more severe illness course.
Question 8: 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 9: 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").
Question 10: Which of the following features is NOT commonly associated with 22q11.2 deletion syndrome?
- A. Mental retardation (Correct Answer)
- B. Schizophrenia
- C. ADHD
- D. Congenital heart defects
Explanation: **Explanation:** **22q11.2 Deletion Syndrome** (also known as DiGeorge or Velocardiofacial Syndrome) is the most common microdeletion syndrome in humans. The correct answer is **Mental retardation (Option A)** because, while patients frequently exhibit borderline intellectual functioning or learning disabilities, global "mental retardation" (moderate to severe intellectual disability) is **not** a defining or universal feature of the syndrome. Most patients have an IQ in the 70–85 range. **Analysis of Incorrect Options:** * **Schizophrenia (Option B):** This is a hallmark psychiatric association. Approximately 25–30% of individuals with this deletion develop schizophrenia, making it one of the strongest known genetic risk factors for the disorder. * **ADHD (Option C):** Neurodevelopmental disorders are highly prevalent; ADHD is the most common psychiatric diagnosis in children with 22q11.2 deletion, affecting roughly 30–40% of patients. * **Congenital heart defects (Option D):** These are classic physical manifestations, particularly conotruncal defects (e.g., Tetralogy of Fallot, interrupted aortic arch), occurring in about 75% of cases. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic (CATCH-22):** **C**ardiac defects, **A**bnormal facies, **T**hymic hypoplasia (T-cell deficiency), **C**left palate, **H**ypocalcemia (hypoparathyroidism), due to **22**q11 deletion. * **Psychiatry Link:** It is often tested as the "genetic link to schizophrenia." * **Diagnosis:** Confirmed via **FISH** (Fluorescence In Situ Hybridization) or chromosomal microarray. * **Key Gene:** The **TBX1** gene is primarily responsible for the physical phenotypes.
Want unlimited practice?
Get full access to all questions, explanations, and performance tracking.
Start For Free