Due By May 10 20211toxic Responses Of The Endocrine System Changes ✓ Solved

Due by MAY . 1. Toxic responses of the endocrine system: Changes in hormones induced by antipsychotic drugs Reference: Popovic, V., Doknic, M., Maric, N., Pekic, S. et al. (2007) Changes in neuroendocrine and metabolic hormones induced by atypical antipsychotics in normal-weight patients with schizophrenia. Neuroendocrinology 85:. a. Q1.

Rationale and design (10 points) - i. What evidence is cited in the paper of second-generation antipsychotic (SGA)-induced weight gain? ii. What questions did they try to answer with their study? iii. Was the study cross-sectional or prospective? iv. In the design, what type of patients did they recruit?

Why? What time points did they select for the study? b. Q2. Methods (10 points) – i. How did the authors select patients with schizophrenia and healthy controls?

What inclusion/exclusion criteria were used? ii. How did the authors measure hormone levels for insulin, growth hormone, ghrelin, leptin and prolactin? Was it mass spectrometry, fluorometric assays, RIAs (what are they?) or something else? c. Q3 – Patients compared to healthy controls (10 points) – i. What were three major differences between patients with schizophrenia (SCH) and healthy controls (Table 1 and text)? ii.

What is the significance of hormone differences for insulin (peak), cortisol, and prolactin? iii. What is HOMA-IR? d. Q4. Effects of switch form First generation antipsychotic (FGA to SGA) (20 points) i. What were the major effects observed at 1 and 3 months compared to baseline?

See Table 2 and Figure 1. What happened to BMI? ii. What happened to levels of leptin, cortisol, prolactin and growth hormone? iii. How did the authors interpret the changes in growth hormone, leptin and cortisol? iv. What is their main conclusion?

Paper for above instructions

Toxic Responses of the Endocrine System: Changes in Hormones Induced by Antipsychotic Drugs

Antipsychotic medications have established their significance in the treatment of various psychiatric disorders, particularly schizophrenia. However, healthcare practitioners and researchers alike are increasingly acknowledging the potential for these chemotherapeutic agents to induce adverse endocrine responses. This paper aims to summarise the findings from the study conducted by Popovic et al. (2007) concerning the neuroendocrine and metabolic changes associated with atypical antipsychotic medications in normal-weight patients diagnosed with schizophrenia.

Q1. Rationale and Design

The evidence cited in Popovic et al. (2007) regarding second-generation antipsychotic-induced weight gain accounts for the escalating clinical observations of metabolic syndrome in patients undergoing treatment. This raises concerns about the potential endocrine disruptions resulting from antipsychotic drug actions. The study aimed to understand the physiological mechanisms underlying the metabolic and neuroendocrine changes attributed to second-generation antipsychotics (SGAs) in individuals with schizophrenia. Specifically, the researchers sought to examine hormone changes associated with weight gain contributed by these medications.
The study was prospective in design, meaning that it followed the participants over a designated time frame to observe changes as they occurred. The authors recruited patients with schizophrenia who were undergoing treatment with SGAs, as well as matched healthy controls, to examine metabolic and hormonal differences between these groups. Participants were followed over three months, with assessments at baseline, one month, and three months, allowing the study to capture time-dependent changes (Popovic et al., 2007).

Q2. Methods

The authors employed stringent inclusion and exclusion criteria to ensure a robust study. Patients with schizophrenia were included based on ICD-10 diagnosis and had to be on an SGA for at least six weeks. Exclusion criteria encompassed prior exposure to antipsychotics, metabolic syndrome, significant medical conditions, and any documented history of endocrine disorders. Healthy controls were selected based on comparable demographic characteristics such as age, gender, and body mass index (BMI) to ensure that the groups were well-matched.
Hormone levels for insulin, growth hormone, ghrelin, leptin, and prolactin were accurately measured using a combination of immunoassays and enzyme-linked immunosorbent assay (ELISA) techniques (Popovic et al., 2007). The use of these assays provides a high degree of specificity and sensitivity in measuring hormone levels in biological samples.

Q3. Patients Compared to Healthy Controls

In comparing the results between patients with schizophrenia and healthy controls (as illustrated in Table 1 of Popovic et al. (2007)), several significant differences emerged. Firstly, patients with schizophrenia exhibited significantly higher levels of insulin. Secondly, they presented with elevated prolactin levels, a known consequence of dopamine antagonism commonly exhibited by antipsychotic medications. Thirdly, levels of ghrelin were observed to be lower in patients with schizophrenia compared to healthy controls, potentially impacting appetite regulation.
The significance of these hormone differences is profound. Elevated insulin levels indicate a risk for the development of insulin resistance and metabolic syndrome in this population. Actively monitored cortisol changes underscore stress-related dysregulations that could worsen mental health outcomes, while heightened prolactin levels could lead to reproductive and metabolic complications (Popovic et al., 2007). HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) serves as a practical index for estimating insulin resistance using fasting glucose and insulin levels, providing a valuable tool for monitoring metabolic changes in patients.

Q4. Effects of Switch from First Generation Antipsychotic (FGA) to SGA

The switch from first-generation antipsychotics to atypical antipsychotics highlighted several noteworthy effects within the study's timeframe (Popovic et al., 2007). By month one, patients demonstrated statistically significant increases in Body Mass Index (BMI) as compared to their baseline measures. Over the course of three months, the participants continued to experience additional weight gain, as anticipated given the known side effects of SGAs.
With respect to hormone levels, significant changes were documented for leptin, cortisol, prolactin, and growth hormone. Notably, levels of leptin—an adipocyte-derived hormone linked to appetite regulation and energy balance—exhibited a marked increase, aligning with the observed weight gain. Cortisol levels also displayed increases, further highlighting metabolic alterations. Prolactin levels remained persistently elevated due to the dopamine antagonism of SGAs, while growth hormone levels notably decreased over time.
These alterations in growth hormone and leptin levels demonstrate potential disruptions to normal metabolic pathways, linking to the development of obesity and insulin resistance (Popovic et al., 2007). The authors interpreted these changes to indicate that treatment with SGAs is closely associated with metabolic dysregulation, highlighting the need for careful monitoring in clinical settings. Their main conclusion emphasizes the potential public health implications of SGAs, advocating for ongoing longitudinal studies to evaluate the endocrinological side effects of antipsychotic medication.

Conclusion

The endocrine changes induced by antipsychotic drugs warrant significant clinical attention, as they can lead to serious metabolic complications and long-term health consequences. The body of evidence analyzed in this paper indicates the critical need for routine monitoring of hormonal levels and metabolic parameters in patients treated with SGAs. The findings from Popovic et al. (2007) serve as a vital reference point for clinicians and researchers seeking to navigate the complexities surrounding antipsychotic treatments while prioritizing patient safety and well-being.

References

1. Popovic, V., Doknic, M., Maric, N., Pekic, S., et al. (2007). Changes in neuroendocrine and metabolic hormones induced by atypical antipsychotics in normal-weight patients with schizophrenia. Neuroendocrinology, 85, 144-150.
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10. Correll, C. U., & Schooler, N. R. (2021). Management of schizophrenia: An update on the role of antipsychotics. American Journal of Psychiatry, 178(4), 338-346.
This comprehensive examination underscores the importance of understanding the neuroendocrine implications of antipsychotic treatments to enhance therapeutic outcomes while minimizing adverse effects.