Neurobiology and Genetics of Mental Disorders

Neurobiology and Genetics of Mental Disorders Indian Medical PG 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

Neurobiology and Genetics of Mental Disorders 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.

Neurobiology and Genetics of Mental Disorders Indian Medical PG 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

Neurobiology and Genetics of Mental Disorders 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.

Neurobiology and Genetics of Mental Disorders Indian Medical PG Question 3: 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

Neurobiology and Genetics of Mental Disorders 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.

Neurobiology and Genetics of Mental Disorders Indian Medical PG Question 4: Which of the following produces neuropsychiatric symptoms?

• A. Cephalosporin
• B. Ethambutol
• C. Cyclosporine
• D. Cycloserine (Correct Answer)

Neurobiology and Genetics of Mental Disorders 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.

Neurobiology and Genetics of Mental Disorders Indian Medical PG Question 5: A patient with bipolar disorder shows poor response to lithium. Which feature best explains this?

• A. Early age of onset
• B. Classical mania
• C. Family history of bipolar
• D. Mixed episodes (Correct Answer)

Neurobiology and Genetics of Mental Disorders Explanation: ***Mixed episodes*** - The presence of **mixed episodes** (simultaneous manic and depressive symptoms) in bipolar disorder predicts a poorer response to **lithium** monotherapy. - Patients experiencing mixed features often require **antipsychotics** or **mood stabilizers** like valproate or carbamazepine in addition to or instead of lithium. *Early age of onset* - While an early age of onset can indicate a more severe course of bipolar disorder, it doesn't specifically predict **poor response to lithium**. - In fact, lithium can be effective in reducing the frequency of episodes for many patients with early-onset bipolar disorder. *Classical mania* - **Classical mania** (euphoric, agitated, pressured speech) is generally associated with a **good response to lithium**. - Lithium is considered a first-line treatment for classic euphoric mania. *Family history of bipolar* - A **family history of bipolar disorder** suggests a genetic predisposition but does not inherently predict a poor response to lithium. - Genetic factors can influence treatment response, but a positive family history alone is not a contraindication or predictor of lithium failure.

Neurobiology and Genetics of Mental Disorders Flashcard 1 of 5

Question: _____ syndrome is associated with impulsive, aggressive behavior and mild mental retardation, due to a mutation in MAO-A gene

Answer: Brunner

Neurobiology and Genetics of Mental Disorders Flashcard 2 of 5

Question: Functional imaging of individuals with major depression has pinpointed excessive metabolic activity in Brodmann area _____, the subgenual prefrontal cortex

Answer: 25

Neurobiology and Genetics of Mental Disorders Flashcard 3 of 5

Question: What neurotransmitter increase has been linked to the both positive and negative symptoms in schizophrenia?_____

Answer: Serotonin

Neurobiology and Genetics of Mental Disorders Flashcard 4 of 5

Question: P50 _____ evoked potential is a marker for schizophrenia

Answer: auditory

Neurobiology and Genetics of Mental Disorders Flashcard 5 of 5

Question: What neurotransmitter decrease has been linked to increased dopamine activity seen in schizophrenia?_____

Answer: GABA