This week, we are sharing another USMLE® Step 1-style practice question to test your knowledge of medical topics. Today’s case focuses on a 73-year-old woman with shortness of breath. Past medical history is notable for hypertension, chronic obstructive pulmonary disease, and type II diabetes mellitus. Can you figure it out?
A 25-year-old man is brought to the physician by his parents due to abnormal behavior. The family tells the physician that their son has been acting strangely over the past eight months. He sometimes appears to be talking to people who are not there and responds to voices that no one in the room can hear. The patient tells the physician that he hears voices telling him about his family and his life. He adds that these voices have told him to do “bad things” to his family, but he refuses because he loves his family. Additionally, the family states that he has been accusing them of working with the government to insert a chip in his brain. The patient currently refuses to eat food cooked by his parents because he thinks they may have inserted the chip in his food. One year ago, he dropped out of college due to declining grades and poor performance. Past medical history is noncontributory. Which of the following is the most likely pathophysiology of this patient’s auditory hallucinations?
A. Increased dopaminergic activity in the mesolimbic pathway
B. Decreased dopaminergic activity in the mesocortical pathway
C. Decreased dopamine levels in the tuberoinfundibular pathway
D. Decreased dopamine levels in the nigrostriatal pathway
E. Decreased dopaminergic activity in the mesolimbic pathway
Scroll down to find the answer!
The correct answer to today’s USMLE® Step 1 Question is…
A. Increased dopaminergic activity in the mesolimbic pathway
Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
The incorrect answers to today’s USMLE® Step 1 Question are…
B. Decreased dopaminergic activity in the mesocortical pathway
Incorrect: Decreased activity of the mesocortical pathway leads to the negative symptoms seen in schizophrenia. Positive symptoms, as seen in this patient (e.g., hallucinations, delusions), are due to increased dopamine levels in the mesolimbic pathway.
C. Decreased dopamine levels in the tuberoinfundibular pathway
Incorrect: Decreased dopamine activity in the tuberoinfundibular pathway leads to increased prolactin levels, which results in galactorrhea, decreased libido, and gynecomastia. While antipsychotic medications used to treat schizophrenia may cause elevated prolactin levels via this pathway, this patient’s positive schizophrenia symptoms (e.g., hallucinations, delusions) are instead related to increased dopamine levels in the mesolimbic pathway.
D. Decreased dopamine levels in the nigrostriatal pathway
Incorrect: Decreased dopamine levels in the nigrostriatal pathway lead to extrapyramidal symptoms like Parkinsonian symptoms. This patient’s positive schizophrenia symptoms (e.g., hallucinations, delusions) are instead related to increased dopamine levels in the mesolimbic pathway.
E. Decreased dopaminergic activity in the mesolimbic pathway
Incorrect: It is increased dopaminergic activity in the mesolimbic pathway which leads to the positive symptoms of schizophrenia (e.g., hallucinations, delusions), not decreased.
Main Explanation
This patient has been experiencing auditory hallucinations and delusions for more than 6 months, suggesting a diagnosis of schizophrenia.
The pathophysiology of schizophrenia is thought to be partly due to abnormalities in the neurotransmitters in the brain. In particular, schizophrenia is thought to be caused by abnormalities in dopamine neurotransmission, specifically abnormalities in the D2 receptor’s activity. Understanding the four dopamine pathways in the brain is critical to understanding the pathophysiology of schizophrenia and its treatment: the mesolimbic pathway, the mesocortical pathway, the tuberoinfundibular pathway, and the nigrostriatal pathway (as illustrated in the graphic below).
- The mesolimbic pathway extends from the ventral tegmental nucleus (VTA) to the limbic system. Increased dopaminergic activity of this pathway is associated with the positive symptoms of schizophrenia (e.g., hallucinations, delusions).
- The mesocortical pathway: This pathway extends from the VTA to the cortex. Decreased dopaminergic activity of this pathway is associated with the negative symptoms of schizophrenia (e.g., anhedonia, poverty of speech, lack of motivation).
- The tuberoinfundibular pathway: This pathway projects from the hypothalamus to the pituitary gland. Decreased dopaminergic activity in this pathway is associated with increased prolactin levels – leading to galactorrhea, gynecomastia, and infertility. This pathway is responsible for these classic symptoms seen in patients with schizophrenia who are taking antipsychotics (i.e. dopaminergic antagonists).
- The nigrostriatal pathway: This pathway projects from the substantia nigra to the caudate nucleus. This pathway is connected to the extrapyramidal system, and thus decreased dopaminergic activity in this pathway leads to characteristic motor symptoms (extrapyramidal “Parkinsonian” symptoms) which can be seen in patients with schizophrenia who are taking antipsychotics (i.e. dopaminergic antagonists).
Additionally, abnormalities in serotonin, glutamate, and GABA neurotransmitters have also been implicated in the neurochemical abnormalities in schizophrenia.
Major Takeaway
Neurotransmitter abnormalities (particularly dopamine) have been implicated in the pathogenesis of schizophrenia. Increased dopaminergic activity in the mesolimbic pathway is associated with the positive symptoms of schizophrenia (e.g. hallucinations), while decreased dopaminergic activity in the mesocortical pathway is associated with the negative symptoms of schizophrenia (e.g., anhedonia, poverty of speech, lack of motivation).
→ Reinforce your understanding with more self-assessment items on Osmosis.
References
Patel, K. R., Cherian, J., Gohil, K., & Atkinson, D. (2014). Schizophrenia: overview and treatment options. P & T: a peer-reviewed journal for formulary management, 39(9), 638–645.
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