Genetics of Psychiatric Disorders — MCQs
Which of the following is a polygenic disorder?
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?
Which of the following is not considered a pharmacogenetic condition?
Which of the following translocations is not associated with Down syndrome?
What is the concordance rate for schizophrenia in monozygotic twins?
Patients with Down syndrome have a high risk of developing ________ in the future:
Which one of the following is an autosomal dominant disorder?
Increasing severity of intellectual disability of male members over generations is a result of ?
Which of the following is not associated with subcortical dementia?
Most common cause of first-trimester abortion is:
Genetics of Psychiatric Disorders Indian Medical PG Practice Questions and MCQs
Question 1: Which of the following is a polygenic disorder?
- A. Cystic fibrosis
- B. Phenylketonuria
- C. Multiple sclerosis
- D. Hypertension (Correct Answer)
Explanation: ***Hypertension*** - **Hypertension** is a classic example of a **polygenic disorder**, meaning it is influenced by multiple genes acting together, often in combination with environmental factors. - The inheritance pattern is **complex and multifactorial**, making it difficult to predict based on a single genetic marker. *Cystic fibrosis* - **Cystic fibrosis** is a **monogenic disorder** caused by mutations in a single gene, the **CFTR gene** [1]. - It follows an **autosomal recessive** inheritance pattern, meaning two copies of the mutated gene are required for the disease to manifest [1]. *Phenylketonuria* - **Phenylketonuria (PKU)** is also a **monogenic disorder** caused by a mutation in the **PAH gene**, leading to a deficiency of the enzyme **phenylalanine hydroxylase**. - It is an **autosomal recessive** disorder, requiring two copies of the mutated gene. *Multiple sclerosis* - **Multiple sclerosis** is considered a **complex, multifactorial disorder** with both genetic and environmental components [1]. - While there is a genetic predisposition, it does not strictly fit the definition of a simple polygenic disorder where multiple genes directly cause the disease; instead, it involves interactions between many genes and the environment [1].
Question 2: 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 3: Which of the following is not considered a pharmacogenetic condition?
- A. Adenosine deaminase deficiency (Correct Answer)
- B. Coumarin insensitivity
- C. G6PD deficiency
- D. Malignant hyperthermia
Explanation: ***Adenosine deaminase deficiency*** - **Adenosine deaminase deficiency** (ADA deficiency) is an **autosomal recessive** metabolic disorder causing severe immunodeficiency, primarily affecting gene function rather than drug response. - While it can be treated with enzyme replacement therapies or gene therapy, it is not primarily characterized by an altered response to standard therapeutic drugs. *Coumarin insensitivity* - **Coumarin insensitivity** refers to an individual's reduced response to **warfarin (a coumarin derivative)**, requiring higher doses to achieve effective anticoagulation. - This is a well-documented **pharmacogenetic condition**, often linked to variations in genes like *CYP2C9* and *VKORC1*. *G6PD deficiency* - **Glucose-6-phosphate dehydrogenase (G6PD) deficiency** is an X-linked genetic disorder that can lead to **hemolytic anemia** upon exposure to certain drugs (e.g., antimalarials, sulfonamides, aspirin) and fava beans [1]. - It is a classic example of a **pharmacogenetic condition** where genetic variations dictate drug-induced adverse reactions [1]. *Malignant hyperthermia* - **Malignant hyperthermia** is a life-threatening, inherited disorder triggered by certain **inhalation anesthetics** (e.g., halothane, isoflurane) and the **depolarizing muscle relaxant succinylcholine**. - This condition is caused by mutations in genes involved in calcium regulation in muscle cells (e.g., *RYR1*) and is a critical **pharmacogenetic response**.
Question 4: Which of the following translocations is not associated with Down syndrome?
- A. t(21;21)
- B. t(14;21)
- C. t(15;21)
- D. t(11;14) (Correct Answer)
Explanation: ***t (11: 14)*** - The **t(11;14) translocation** is commonly associated with **mantle cell lymphoma**, a B-cell non-Hodgkin lymphoma, and is not a cause of Down syndrome. - This translocation leads to the overexpression of the **cyclin D1 gene**, located on chromosome 11, which promotes cell growth and proliferation. *t (14; 21)* - This is a common **Robertsonian translocation** involving chromosomes 14 and 21, which results in an extra copy of chromosome 21 material [1]. - Individuals with this translocation can have **Down syndrome** because their cells end up with the equivalent of three copies of chromosome 21 [1]. *t (21; 21)* - This translocation is another type of **Robertsonian translocation** where two chromosome 21s fuse. - This specific translocation is rare and results in an extra copy of chromosome 21, leading to **Down syndrome** with a high recurrence risk in offspring. *t (15: 21)* - This is a **Robertsonian translocation** involving chromosomes 15 and 21, resulting in an extra copy of chromosome 21 material. - This translocation is a known cause of **Down syndrome** due to the dosage imbalance of genes on chromosome 21 [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 169-172.
Question 5: What is the concordance rate for schizophrenia in monozygotic twins?
- A. 1%
- B. 10%
- C. 50% (Correct Answer)
- D. 0.10%
Explanation: ***50%*** - The **concordance rate** for schizophrenia in **monozygotic (identical) twins** is approximately **50%**. - This high concordance rate indicates a strong **genetic predisposition** but also highlights the role of **environmental factors**, as it is not 100%. *1%* - A 1% risk is closer to the **general population prevalence** of schizophrenia, not the concordance rate in monozygotic twins. - This low percentage would significantly underestimate the genetic component observed in twin studies for schizophrenia. *10%* - A 10% concordance rate is a significant increase over the general population risk but is still substantially lower than what has been consistently found in studies of monozygotic twins. - This percentage might be more aligned with the risk for first-degree relatives or dizygotic twins, not identical twins. *0.10%* - A 0.10% concordance rate is an extremely low figure, far below the actual observed rate for monozygotic twins. - Such a low percentage would suggest virtually no genetic influence on schizophrenia, which contradicts extensive research findings.
Question 6: Patients with Down syndrome have a high risk of developing ________ in the future:
- A. Alzheimer's disease (Correct Answer)
- B. Lewy body dementia
- C. Parkinson syndrome
- D. Juvenile myoclonic epilepsy
Explanation: ***Alzheimer's disease*** [1] - Individuals with **Down syndrome** have an extra copy of chromosome 21, which includes the **amyloid precursor protein (APP) gene**. - Overexpression of the **APP gene** leads to increased production of **amyloid-beta**, accelerating the formation of **amyloid plaques** characteristic of **Alzheimer's disease**. *Lewy body dementia* - Characterized by the presence of **Lewy bodies** (abnormal protein deposits of alpha-synuclein) that develop in nerve cells in the brain. - While it can co-occur with **Alzheimer's pathology**, it is not specifically linked to the genetic predisposition in **Down syndrome** in the same direct manner as amyloid pathology. *Parkinson syndrome* - Primarily a **movement disorder** caused by the degeneration of dopaminergic neurons in the **substantia nigra**. - While people with **Down syndrome** may exhibit some **Parkinsonian features** at older ages, **Parkinson's disease** itself is not a direct consequence or high-risk development tied solely to the genetic anomaly of **trisomy 21**. *Juvenile myoclonic epilepsy* - This is an **epilepsy syndrome** typically beginning in adolescence, characterized by **myoclonic jerks**. - It is a distinct neurological condition that does not have a direct, strong associative link with **Down syndrome** as a high-risk long-term complication in the way **Alzheimer's disease** does.
Question 7: Which one of the following is an autosomal dominant disorder?
- A. Cystic fibrosis
- B. Hereditary spherocytosis (Correct Answer)
- C. Sickle cell anemia
- D. G-6PD deficiency
Explanation: ***Hereditary spherocytosis*** - It is characterized by **autosomal dominant inheritance** [1], leading to the destruction of red blood cells. - Mutations in proteins that maintain the **red blood cell membrane** integrity result in spherocyte formation [1]. *Cystic fibrosis* - This condition follows a **autosomal recessive inheritance pattern**, requiring two copies of the mutated gene for disease manifestation. - It is caused by mutations in the **CFTR gene**, affecting chloride transport and leading to thick secretions. *G-6PD deficiency* - This disorder is inherited in an **X-linked recessive manner** [2], primarily affecting males and transmitted through carrier females. - Characterized by **hemolytic anemia** triggered by certain medications or infections, it does not follow dominant inheritance [2]. *Sickle cell anemia* - Sickle cell anemia is also an **autosomal recessive disorder** [3], meaning affected individuals must inherit two copies of the sickle cell gene. - It results in a mutation in the **HBB gene**, leading to the production of abnormal hemoglobin (HbS) [3].
Question 8: Increasing severity of intellectual disability of male members over generations is a result of ?
- A. Y linked disorder
- B. Frameshift mutation
- C. Trinucleotide repeat mutation (Correct Answer)
- D. Mitochondrial DNA mutation
Explanation: ***Trinucleotide repeat mutation*** - This phenomenon, known as **anticipation**, is characteristic of disorders caused by trinucleotide repeat expansions like **Fragile X syndrome**, where the number of repeats increases in successive generations, leading to earlier onset and more severe symptoms. - The expansion of these repeats often occurs during **meiosis**, particularly **oogenesis** for Fragile X, contributing to the increasing severity observed in offspring. *Y linked disorder* - Y-linked disorders affect only males and are passed from father to son, but they do not typically show increasing severity over generations or the phenomenon of anticipation. - Their inheritance pattern is straightforward and generally consistent across generations, without progressive phenotypic changes. *Frameshift mutation* - A **frameshift mutation** involves the insertion or deletion of nucleotides that are not multiples of three, leading to a shift in the reading frame and an altered protein sequence. - While they can cause severe genetic disorders, **frameshift mutations** do not typically explain the observed increase in severity across generations (anticipation). *Mitochondrial DNA mutation* - Mitochondria are inherited exclusively from the mother, and mutations in **mitochondrial DNA** can cause a range of disorders affecting energy production. - While these disorders can vary in severity due to **heteroplasmy**, they do not typically show a pattern of increasing severity in successive generations due to an expanding repeat sequence.
Question 9: Which of the following is not associated with subcortical dementia?
- A. Wilson's disease
- B. Alzheimer's disease (Correct Answer)
- C. Huntington's chorea
- D. Parkinsonism
Explanation: ***Alzheimer's disease*** - Alzheimer's disease is primarily a **cortical dementia**, characterized by global cognitive decline, specifically affecting memory, language, and executive functions. - It involves the accumulation of **amyloid plaques** and **neurofibrillary tangles** predominantly in the cerebral cortex. *Parkinsonism* - Parkinsonism, particularly Parkinson's disease dementia, is a common cause of **subcortical dementia**. - It presents with prominent **motor symptoms** (bradykinesia, rigidity, tremor) along with cognitive impairment affecting executive function and attention. *Wilson's disease* - Wilson's disease is a genetic disorder leading to **copper accumulation**, which can cause significant damage to the basal ganglia and other subcortical structures. - This often results in a **subcortical dementia** characterized by motor symptoms, psychiatric disturbances, and cognitive decline. *Huntington's chorea* - Huntington's chorea is a neurodegenerative genetic disorder primarily affecting the **basal ganglia**, a key subcortical structure. - It is a classic example of **subcortical dementia**, presenting with characteristic choreiform movements, psychiatric disturbances, and cognitive impairment.
Question 10: Most common cause of first-trimester abortion is:
- A. Genetic factors (Correct Answer)
- B. Endocrine disorders
- C. Immunological disorders
- D. Infection
Explanation: ***Genetic factors*** - **Chromosomal abnormalities**, such as aneuploidies (e.g., **trisomy**), account for the majority of first-trimester spontaneous abortions. - These genetic errors often lead to **non-viable embryos**, resulting in early pregnancy loss as a natural selection mechanism. *Endocrine disorders* - While endocrine disorders like **luteal phase defect**, **uncontrolled diabetes**, or **thyroid dysfunction** can contribute to recurrent miscarriages, they are not the most common cause of *first-trimester abortions overall*. - Their impact is often more pronounced in **recurrent pregnancy loss** rather than sporadic first-trimester events. *Immunological disorders* - **Autoimmune disorders** such as **antiphospholipid syndrome** are important causes of **recurrent pregnancy loss** and can lead to first-trimester abortions. - However, they are **less common** than genetic factors as the primary cause of a single, sporadic first-trimester abortion. *Infection* - Certain **TORCH infections** (**T**oxoplasmosis, **O**ther [syphilis, varicella-zoster, parvovirus B19], **R**ubella, **C**ytomegalovirus, **H**erpes simplex virus) can cause miscarriage. - While significant, infections are a **less frequent cause** of first-trimester abortion compared to genetic anomalies.
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