ChatGPT-3.5 Shows Moderate Accuracy in Medical Genetics Exam, reveals research

Researchers have found in a new study that ChatGPT-3.5 performed with moderate accuracy and stable results on a specialist medical genetics exam, indicating potential for educational support. However, its limitations in handling complex, domain-specific reasoning highlight the need for continued advancement before wider application. The study was published in Laboratory Medicine journal by Klaudia P. and colleagues.

To test the performance of ChatGPT-3.5, scientists chose 456 available questions from the Polish national specialist exam in medical laboratory genetics that are available online. The questions were classified by topic, genetic changes, diagnostic techniques, clinical case, and calculations, and by complexity (simple, complex). Each question was asked three times on ChatGPT to test not just the correctness but also the reliability of responses across multiple rounds of interaction. Statistical tests were then used to compare differences in performance by category, level of complexity, and repeatability.

Key Findings

  • Overall Accuracy: ChatGPT correctly answered 59% of the questions, statistically significant (P < 0.001).

By Category:

  • Calculation-based questions: 71% accurate

  • Genetic methods and genetic changes: ~60% accuracy

  • Clinical case–based questions: 37% accuracy

By Complexity:

  • Simple questions: 63% accurate

  • Complex questions: 43% accuracy (P = .001)

  • Consistency: The AI model had consistent performance throughout three repeated sessions (P = 0.43), which reflects reliability in output even when being asked repeatedly.

This research concluded that although ChatGPT-3.5 performs moderate accuracy and stable performance in responding to medical laboratory genetics exam questions, it lags behind in dealing with complex and clinical case–based reasoning. Consequently, its version at present may assist in education but is not yet adequate for advanced or high-stakes implementation in genetic medicine. Further advancement in AI reasoning and domain adaptation will be required before these tools can be introduced to professional medical education or practice with confidence.

Reference:

Klaudia Paruzel, Michał Ordak, Assessment of ChatGPT-3.5 performance on the medical genetics specialist exam, Laboratory Medicine, 2025;, lmaf038, https://doi.org/10.1093/labmed/lmaf038

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PRP Found Effective in Enhancing Wound Healing in Burn Patients: Study

Researchers have found in a review that Platelet-Rich Plasma (PRP) significantly improves wound healing and reduces complications such as infections in burn patients. However further research is recommended to validate these benefits and support wider clinical application.

Burn injuries cause significant mortality, morbidity, and financial and psychological burdens for patients and families. Platelet-rich plasma (PRP) has shown some benefits in burn wound healing, but its efficacy is unproven. This meta-analysis aimed to evaluate PRP’s effects on burn wounds. A comprehensive search of Scopus, PubMed, Web of Science, and Cochrane Library was conducted until January 22, 2025, for randomized controlled trials (RCTs) on PRP’s effect on burn wounds. The mean difference (MD), standardized MD (SMD), or odds ratio (OR) of the studies was calculated. Results: Nine RCTs with 413 participants were included. PRP significantly reduced wound healing time (MD: −6.68 days, 95% CI (−10.96, −2.39)), wound infection incidence (OR: 0.18, 95% CI (0.04, 0.88)), and dressing change frequency (MD: −14.50 times, 95% CI (−16.45, −12.55)). There was a significant increase in the healed area percentage in the intervention group (MD: 6.82%, 95% CI (2.58, 11.06)). However, there was no significant difference between the intervention and control groups in pain score or graft take percentage. This review shows that PRP enhances wound healing and reduces adverse events like wound infection in burn patients. Future studies should further explore PRP’s effects to support its broader clinical use.

Reference:

Yi H, Li R, Li C. Platelet-rich Plasma for the Management of Burn Wound: A Meta-Analysis. The International Journal of Lower Extremity Wounds. 2025;0(0). doi:10.1177/15347346251359067

Keywords:

PRP, Found, Effective, Enhancing, Wound, Healing, Burn Patients, Study , Yi H, Li R, Li C. Platelet-rich Plasma

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Medical Device Imports Still at 70%, India Spent Over USD 25 Billion in 5 Years: Parliament Informed

Delhi: India spent over USD 25 billion in foreign exchange on imports of electromedical equipment, including ventilators and diagnostic imaging devices, and surgical instruments between FY2020-21 and FY2024-25, the Parliament was informed.

According to data submitted by the government in the Rajya Sabha, the cumulative import value for electromedical equipment stood at USD 24,586 million and for surgical instruments at USD 951 million.

This comes in response to a query raised by Shri Narain Dass Gupta seeking details of foreign exchange outflow on imports, the vulnerabilities arising from import dependence, and policy interventions to reduce it. As per the official reply provided by Minister of State for Chemicals and Fertilizers Anupriya Patel on July 29, 2025, “as per import data maintained by the Directorate General of Commercial Intelligence and Statistics, the value of imports of electromedical equipment, including ventilators and diagnostic imaging equipment, and surgical instruments during the last five years is as under: (In million US$)

FY2020-21

FY2021-22

FY2022-23

FY2023-24

FY2024-25

Electromedical equipment (including ventilators and diagnostic imaging equipment)

3,569

5,441

4,884

5,408

5,284

Surgical instruments

104

169

210

205

263

In response to questions on India’s high import dependence, the government noted that it had assessed the situation and initiated several schemes to boost local manufacturing. “In 2020, assessing that the domestic medical devices market was heavily dependent on imports, which contributed to more than 85% of the market, Government launched the following schemes,” the reply stated.

The “PLI Scheme for Promoting Domestic Manufacturing of Medical Devices” was launched with a total budgetary outlay of Rs 3,420 crore and a five-year performance-linked incentive period from FY2022-23 to FY2026-27. Under this scheme, “selected companies are eligible for financial incentive for incremental sales of domestically manufactured medical devices… So far, 21 greenfield projects have been commissioned, and production has started for 54 products, which include high-end medical devices on which the country has been import-dependent, such as linear accelerators, MRI, Ultrasound, CT scans, Mammograms, C-Arm and X-ray machines.” Till March 2025, “cumulative eligible sales Rs 10,413.40 crore have been achieved under the scheme, including exports worth Rs 5,002 crore.”

Additionally, the “Scheme for Promotion of Medical Devices Parks” was launched to create common infrastructure and testing facilities. “Three parks have been approved and are at an advanced stage of development in Greater Noida (Uttar Pradesh), Ujjain (Madhya Pradesh) and Kanchipuram (Tamil Nadu). The total project cost of these parks is over Rs 871.11 crore, with Central assistance to the tune of Rs 100 crore each.”

Further policy actions include the announcement of the “National Medical Devices Policy, 2023” aimed at accelerating growth of the sector. Under this, several initiatives were undertaken:

“The Promotion of Research and Innovation in Pharma MedTech Sector (PRIP) scheme has been launched with an outlay of Rs 5,000 crore… Under this, a Centre for Excellence in medical devices has been established at the National Institute of Pharmaceutical Education and Research, Ahmedabad with an outlay of Rs 100 crore.”

“The Uniform Code for Market Practices in Medical Devices, 2024 has been issued.”

“The Scheme for Strengthening Medical Device Industry has been launched with a financial outlay of Rs 500 crore to provide support in manufacturing of key components and accessories, skill development, support for clinical studies, development of common infrastructure and industry promotion.”

Despite these measures, the Minister informed the House that India’s import dependence in the sector remains high. “In November 2024, assessing that the dependence on imports continues to be about 70%, Government has launched the Scheme for Strengthening Medical Device Industry…”

In response to whether any target had been set to reduce import dependence to below 40%, the government replied: “No, Sir.”

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Indian Review Stresses Prevention Strategies, Early Referral, and Timely Liver Transplantation in Pediatric Acute Liver Failure

India: The rising incidence of Pediatric Acute Liver Failure (PALF) is a growing concern in India, with experts stressing the need for early detection, prevention, and timely referral to specialized centers. A recent review article, authored by Dr. Smita Malhotra from the Department of Pediatric Gastroenterology and Hepatology, Indraprastha Apollo Hospital, New Delhi, provides an in-depth overview of the condition, its causes, and approaches to management.

Acute liver failure in children is a medical emergency with rapid progression, often transforming a healthy child into a critically ill patient within hours or days. “Acute liver failure is a catastrophic condition. A child who is perfectly fine can deteriorate dramatically in a very short time, making timely intervention vital,” stated Dr. Smita in her conversation with Medical Dialogues. 

The review, published online in Apollo Medicine, highlights that in India, infections remain the predominant cause of PALF, with Hepatitis A virus (HAV) being the most common etiology. Unlike Western countries, where paracetamol toxicity is a leading cause, infections account for the majority of pediatric cases in developing nations. Dr. Smita emphasized that Hepatitis A is a vaccine-preventable disease, yet the vaccine is not part of the government’s universal immunization program. “We often see children progressing to liver failure simply because they were not vaccinated against Hepatitis A. Promoting this vaccination and creating awareness are critical to preventing such cases,” she noted.

The article also addresses other important etiologies, including metabolic disorders, drug or toxin-induced injuries, and, in some instances, indeterminate causes. A significant concern raised by Dr. Smita is the increasing number of cases linked to the use of alternative or herbal medications. “Certain Ayurvedic and herbal preparations can be toxic to the liver. These, along with inadvertent paracetamol overdosing, are preventable causes of acute liver failure and require public awareness,” she said.

Early diagnosis plays a pivotal role in improving outcomes. According to Dr. Smita, most peripheral centers detect PALF only when neurological symptoms such as irritability or altered consciousness appear. However, simple monitoring of coagulation parameters like INR can help diagnose the condition earlier, allowing timely referral before irreversible complications set in.

Management of PALF is complex and requires a multidisciplinary team, including pediatric hepatologists, intensivists, nephrologists, transplant surgeons, and specialized nursing support. Cerebral edema remains one of the most feared complications due to its potential to cause irreversible brain damage. Preventive strategies include early ventilation, maintaining low ammonia levels through timely dialysis, and minimizing stress or transfer with appropriate medical protocols, with a medical expert in attendance once encephalopathy sets in.

Liver transplantation continues to be the definitive treatment for severe PALF. Dr. Smita highlighted that pediatric liver transplantation in India has advanced significantly over the past two decades, with survival rates exceeding 95% in many centers. She also emphasized the importance of promoting both cadaveric and living-related donation. “There are still misconceptions about donor safety, but with proper evaluation, living donors remain safe, and the liver regenerates after partial donation, especially in pediatric cases where only a small segment is required,” she explained.

The review highlights the urgent need for awareness campaigns focusing on Hepatitis A vaccination, regulation of alternative medicines, strengthening early diagnostic capabilities in smaller centers, and expanding infrastructure for pediatric liver transplantation. As Dr. Smita summarized, “Early recognition, timely referral, and a multidisciplinary approach are the key factors that can turn the tide in saving young lives affected by acute liver failure.”

Reference:

Kaur, J., Malhotra, S., Kumar, K., & Sibal, A. Management of Acute Liver Failure in Children. Apollo Medicine. https://doi.org/10.1177/09760016241299530

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Beta-HPV can directly cause skin cancer in immunocompromised people

Researchers at the National Institutes of Health (NIH) have shown for the first time that a type of human papillomavirus (HPV) commonly found on the skin can directly cause a form of skin cancer called cutaneous squamous cell carcinoma (cSCC) when certain immune cells malfunction. cSCC is one of the most common cancers in the United States and worldwide. Previously, scientists believed HPV merely facilitated the accumulation of DNA mutations caused by ultraviolet (UV) radiation, usually the primary driver of cSCC. The findings were published today in The New England Journal of Medicine.

“This discovery could completely change how we think about the development, and consequently the treatment, of cSCC in people who have a health condition that compromises immune function,” said Andrea Lisco, M.D., Ph.D., of NIH’s National Institute of Allergy and Infectious Diseases (NIAID). “It suggests that there may be more people out there with aggressive forms of cSCC who have an underlying immune defect and could benefit from treatments targeting the immune system.”

There are many different types of HPV, each tending to infect cells in a particular tissue and part of the body. The types of HPV found mostly on the skin-beta-HPV-are considered benign members of the skin microbiome that typically do not integrate into the DNA of skin cells. This contrasts with the alpha types of HPV, known to integrate into the DNA of mucous membrane cells and directly cause cancer of the genitals, anus, head and neck.

The NIH researchers made their discovery in a 34-year-old woman who came to the NIH Clinical Center for evaluation and treatment of recurrent cSCC on her forehead. She had undergone multiple surgeries and a round of immunotherapy to try to remove or kill the tumor, but it repeatedly grew back. Her local doctors thought this was due to an inherited inability to repair DNA damaged by UV radiation plus an impairment in immune cells called T cells. The tumor was one of many progressively worsening HPV-related diseases the woman was experiencing.

Through a sophisticated genetic analysis, the NIH researchers discovered that a beta-HPV had integrated into the cellular DNA of the woman’s well-established tumor and was extensively producing viral proteins there. This contradicted the prevailing theory that beta-HPV only facilitates the establishment of cSCC without integrating into cellular DNA and plays no role in maintaining the cancer. Further genetic analysis of the woman’s cells showed they were fully capable of repairing DNA damage from UV radiation, suggesting the virus alone had caused cSCC.

To understand how beta-HPV could take the unusual steps of integrating into the woman’s skin-cell DNA and multiplying there unchecked, the investigators studied the woman’s inherited immune disorder. They found that her genetic mutations greatly hampered T cells from activating in response to skin-cell infection by beta-HPV. This suggested that the immune disorder itself was responsible for the woman’s worsening HPV-related diseases, including the beta-HPV cSCC on her forehead, and that treating this disorder might cure all of them.

Accordingly, NIH investigators developed a personalized plan to give the woman a stem cell transplant to replace her defective T cells with healthy ones. The process required extreme care because she was immunocompromised even before treatment began. The transplant proceeded without complications. Afterward, all her HPV-related diseases including the recurrent, aggressive cSCC resolved and have not recurred during the more than three years since the transplant. This confirms that the woman’s inherited disorder had prevented her T cells from keeping beta-HPV in check, allowing the virus to directly cause and sustain cSCC.

“This discovery and successful outcome would not have been possible without the combined expertise of virologists, immunologists, oncologists and transplant specialists, all working under the same roof of the NIH Clinical Center,” said Dr. Lisco.

According to the study authors, their finding suggests that other people with defective T-cell responses may also be susceptible to cancer caused directly by beta-HPV.

Reference:

Peiying Ye, Resolution of Squamous-Cell Carcinoma by Restoring T-Cell Receptor Signaling, New England Journal of Medicine, DOI: 10.1056/NEJMoa2502114.

 

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Low FODMAP diet improves leaky gut in study

In a study, patients with irritable bowel syndrome with diarrhea, or IBS-D, who went on a low FODMAP diet saw an improvement of colonic barrier dysfunction, commonly known as “leaky gut.”

The results, published in Gastroenterology, represent the first evidence of low FODMAP’s potential ability to improve intestinal permeability and mast cell activation in patients with IBS.

“Diet and microbiome have been believed to be related to leaky gut, but the reasons why were not well understood,” said Prashant Singh, MBBS, Michigan Medicine gastroenterologist and senior author on the paper.

“This research illuminates the mechanism of how food can interact with gut microbiome and gut immune system to influence colonic barrier dysfunction—and validates the low FODMAP diet as a treatment option that not only improves symptoms but underlying dysfunction in IBS.”

The low FODMAP diet is a proven intervention for patients with IBS.

Most IBS sufferers report food-triggered symptoms and prefer dietary inventions to pharmacotherapy.

Leaky gut refers to symptoms caused by increased permeability of the intestinal lining.

This permeability is thought to have a variety of negative consequences, including the dissemination of bacterial toxins and products as well as sensitization of local nerves which can cause pain in IBS.

Researchers studied human patients to test the potential of low FODMAP to address leaky gut, while mice treated with stool from these patients were used to investigate the mechanisms of how diet potentially improves the colonic barrier.

Forty-eight patients with IBS-D (irritable bowel syndrome with diarrhea) were put on a four-week low FODMAP diet (restriction phase) and provided with the low FODMAP meals for the study duration.

Of the 42 participants to complete the study, 34 responded to the low FODMAP diet, all of whom experienced lessened diarrhea and abdominal pain.

Prior studies have shown that patients with IBS-D have increased number of mast cell (type of inflammatory cell in colon lining), and leaky gut.

Studies have shown that mast cells are also more likely to be activated in IBS-D.

In this study, barrier function, and mast cell activation was assessed in a variety of ways before and after the four-week period.

Researchers found that in addition to improvement in leaky gut, low FODMAP also reduced the number and activation of mast cells in the colon lining in these patients.

Researchers also worked toward an explanation of how low FODMAP improves leaky gut (and how a diet high in FODMAP foods can contribute to barrier dysfunction.)

Lipopolysaccharides are molecules derived from gut microbiome that can cause immune-system responses when they escape the gut.

In this latest study, an analysis using mice, researchers showed that high FODMAP diet in IBS-D patients increases fecal LPS levels to activate mast cells which in turn make the barrier leakier.

Given these results, researchers recommend that providers consider mast cell stabilizers in addition to a low FODMAP diet-or as an alternative to the low FODMAP diet when it is contraindicated.

“Our study shows diet is not a quick fix-it’s a real solution for some patients with IBS,” Singh said.

The authors hope future studies will include a larger sample size, specifically of patients who do not respond to low FODMAP diet, and a variety of IBS types besides IBS-D.

Reference:

Gao, Jun, Low FODMAP diet improves colonic barrier function and mast cell activation in patients with IBS-D: A mechanistic trial, Gastroenterology. 

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Ajanta Pharma Gets Relief in Erectile Dysfunction Drug Export Case, Penalty Set Aside

Mumbai: In relief to Ajanta Pharma Ltd, the Customs, Excise & Service Tax Appellate Tribunal (CESTAT), Mumbai has set aside a Rs 2 lakh penalty imposed on the company in connection with the alleged misdeclaration of exported erectile dysfunction drugs including Kamagra Oral Jelly, Super Kamagra Tablets, and Kamagra Gold Tablets.

The matter relates to 43 consignments exported between September 11, 2018, and March 10, 2021, which included Kamagra Oral Jelly, Super Kamagra Tablets, and Kamagra Gold Tablets. Although the shipping bills, invoices, and packing lists carried correct descriptions of the goods, the corresponding airway bills were marked as “medical apparatus.” The customs department treated this as misdeclaration under Para 2.06(a) of Chapter 2 of the Foreign Trade Policy 2015-20 and DGFT notification dated 12.03.2015, imposing a penalty under Section 117 of the Customs Act.

Ajanta Pharma challenged this decision before the Tribunal. During the hearing, Dr Suvendu Kumar Pati, Member (Judicial), observed:

“Section 117 is restricted to imposition of penalties for contravention of provisions of Customs Act only or for its abetment… No such violation is noticeable here.”

The Tribunal noted that the Customs authorities themselves admitted that the shipping documents bore accurate product descriptions, and only the airway bills – a document handled by freight forwarding agents – carried the alternate terminology. The show cause notice and the Order-in-Original were based on provisions from the Foreign Trade Policy, but no direct violation of the Customs Act was alleged or proven.

The CESTAT also referred to the Supreme Court’s ruling in M/s. Amrit Foods Vs. Commissioner of Central Excise (2005 (190) ELT 433 SC), which underscores that penalty cannot be sustained without the assessee being informed of the exact nature of the contravention.

Based on these findings, the Tribunal ruled;

“I am of the considered view that no provision of the Customs Act has been violated nor even alleged to have been violated by the Appellant-Exporter, for which it can be made liable to penalty under Section 117 of the Customs Act, 1962.”

Subsequently, the appeal was allowed, and the penalty order issued by the Commissioner of Customs (Appeals), Mumbai-III vide Order-in-Appeal No. MUM-CUSTM-AXP-APP-886/2022-23 dated 24.08.2022 was set aside, granting consequential relief to Ajanta Pharma.

To view the original judgment, click on the link below:

https://indiankanoon.org/doc/36778581/

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NPPA Panel Defers Biological E’s Pneumonia Vaccine Price Exemption, Seeks Clarification

New Delhi: The National Pharmaceutical Pricing Authority (NPPA)’s Multidisciplinary Committee of Experts has asked Biological E Limited to submit inputs and clarifications regarding the composition of its Pneumococcal Polysaccharide Conjugate Vaccine ((PNEUBEVAX 14), before it decides on the company’s application for exemption under Para 32 (i, ii & iii) of the DPCO, 2013.

The matter was taken up during the 69th meeting of the Multidisciplinary Committee held on July 3, 2025, chaired by Shri Sanjay Kumar, Advisor (Cost). It had previously been listed in the 64th, 66th, and 67th meetings, but was deferred each time pending comments from the Department for Promotion of Industry and Internal Trade (DPIIT).

As recorded in the minutes, “the matter was earlier placed in 64th meeting of MDC held on 6.12.2024, wherein the agenda was deferred and the committee directed that the matter may be pursued with DPIIT for nomination of suitable officer.” A DPIIT representative eventually attended the 66th meeting and informed the Committee that “the subject application as forwarded by NPPA is at an advanced stage of examination.”

However, in the 67th meeting held on 02.04.2025, “neither any comments have been received nor the meeting was attended by representative of DPIIT. Accordingly, the Committee deferred the agenda and directed to pursue the matter with DPIIT for early inputs in the matter.”

At the 69th meeting, an officer from DPIIT provided written inputs. As per the minutes:

“It has been also informed that in claim 1 submitted to the patent office, strength of each serotype is not mentioned. However, the strengths are mentioned in claim 6 submitted to the patent office.”

Additionally, “O/o CGPDTM has highlighted that strength of each serotype is different in granted claim 6 and composition mentioned in application filed to NPPA. The applicant mentioned the strength in application filed to NPPA as per DCGI approval.”

It was further noted that:

“O/o CGPDTM has also informed that ‘it is observed that the composition as specified in Row 4 of Form-1 dated 21/04/2023 and the claims granted by Indian Patent Office in this matter are almost equivalent when the granted claim 1 is read with claim 6.’”

In light of these submissions, the Committee stated:

“Accordingly, the Committee after deliberations directed to get the inputs/clarification of the applicant company in view of inputs of the DPIIT before final taking the final decision in the matter.”

Biological E’s application pertains to its patented vaccine product PNEUBEVAX 14 and requests exemption from price control under Para 32 of the Drugs (Prices Control) Order, 2013, which allows such exemptions for new patented drugs.

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Twin Challenges: Study Investigating the Co-Development of Perinatal Insomnia and Depression

Recent study examined the heterogeneous progression, interrelationships, and predictive factors of perinatal insomnia and depression across the perinatal period. The researchers used group-based trajectory modeling to identify distinct trajectories of insomnia and depressive symptoms from early pregnancy to 6 months postpartum.

Distinct Trajectories of Insomnia and Depression

The results showed three distinct insomnia trajectories: a “no insomnia” group (27.7%), a “subclinical insomnia” group (54.5%), and a “clinical insomnia” group (17.8%). For depressive symptoms, three trajectories were also identified: a “low-stable” group (38.7%), a “moderate-stable” group (43.9%), and a “high-improving” group.

Interrelationships Between Insomnia and Depression

The dual trajectory analysis revealed significant interrelationships between insomnia and depression, with the severity of symptoms co-occurring. Women in the low-stable depression group predominantly had no insomnia, while those in the moderate-stable depression group mostly had subclinical insomnia, and the high-improving depression group had the highest rates of clinical insomnia.

Predictive Factors for Insomnia and Depression Trajectories

Baseline factors including anxiety scores ≥24, insomnia scores ≥8, and depression scores ≥10 were common predictors of both adverse insomnia and depression trajectories. However, social capital was not a significant predictor.

Implications and Recommendations for Integrated Interventions

These findings highlight the importance of integrated screening and treatment approaches that simultaneously address comorbid insomnia and depression during the perinatal period. Tailored interventions based on symptom trajectory profiles could help improve maternal mental health outcomes. Future research should further explore the temporal dynamics and underlying mechanisms linking these conditions.

Key Points

1. The study examined the heterogeneous progression, interrelationships, and predictive factors of perinatal insomnia and depression across the perinatal period using group-based trajectory modeling.

2. The results showed three distinct trajectories for both insomnia and depressive symptoms – a “no insomnia”/”low-stable” group, a “subclinical insomnia”/”moderate-stable” group, and a “clinical insomnia”/”high-improving” group.

3. The dual trajectory analysis revealed significant interrelationships between insomnia and depression, with the severity of symptoms co-occurring across the three trajectory groups.

4. Baseline factors including anxiety scores ≥24, insomnia scores ≥8, and depression scores ≥10 were common predictors of both adverse insomnia and depression trajectories, but social capital was not a significant predictor.

5. The findings highlight the importance of integrated screening and treatment approaches that simultaneously address comorbid insomnia and depression during the perinatal period.

6. Tailored interventions based on symptom trajectory profiles could help improve maternal mental health outcomes, and future research should further explore the temporal dynamics and underlying mechanisms linking these conditions.

Reference –

Xinlong Pan et al. (2025). Dual Trajectory Of Insomnia And Depressive Symptoms In Women From Early Pregnancy To 6 Months Postpartum: A Prospective Cohort Study. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07649-2.

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Ketamine could treat depression by interacting with the brain’s ‘opioid system: Study

Ketamine is a highly effective, fast-acting antidepressant that works even for patients who have not responded to other medications. However, the brain mechanisms important for these rapid treatment effects are yet to be determined.

Researchers at King’s College London, who are investigating why ketamine could be a good treatment for some people with depression, have discovered that the drug’s antidepressant effects involve the brain’s opioid system.

The study, led by King’s College London and published in Nature Medicine, included 26 individuals with clinically diagnosed depression who were given a low dose ketamine infusion across two sessions during neuroimaging.

Before receiving the ketamine infusion, in one session they were given naltrexone, which blocks the opioid receptors in the brain, and in the other they were given a placebo.

Participants were monitored during the infusion in a brain scanner using a method called magnetic resonance spectroscopy (MRS). MRS measured dynamic changes in a brain chemical called glutamate. Depressive symptoms were then assessed using the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) 24-hours after infusion, when ketamine’s antidepressive symptoms peak.

They found that blocking the opioid system reduced both the brain’s glutamatergic response and the antidepressant effects observed the following day, suggesting that the opioid system plays a key role in mediating the antidepressant response.

The study also identified a sex-related effect: the effect of naltrexone on glutamatergic activity appeared more pronounced in males with depression than in the females with depression.

These insights into how ketamine works for different people is essential to personalising treatments.

Dr Luke Jelen, lead author of the study and a Clinical Lecturer in Psychiatry at King’s College London, said: “Ketamine often makes the news for negative reasons. However, at a low dose, ketamine shows enormous potential to offer relief from the symptoms of depression.”

“Understanding whether the opioid system is involved ketamine’s antidepressant effects is a really important question, given how much we still don’t know about how ketamine works. “Our study shows that the opioid system is involved and offers insight into how it contributes to ketamine’s effects.”

The authors are keen to highlight that ketamine is not classified as an opioid and does not bind to opioid receptors with high affinity like morphine or heroin. Instead, the findings point to a dynamic interplay between the glutamatergic and opioid systems, which may work together to support ketamine’s rapid antidepressant effects.

Opiates can offer relief from the systems of depression however they are highly addictive. Understanding if and how the opioid system is involved in the effects of ketamine is important to understand why ketamine works and develop new, alternative treatments.

Low-dose ketamine is currently being used to treat depression in private clinics and a small number of NHS clinics. At higher doses it is also used in medicinal anaesthesia. However, it is also used recreationally and if misused can cause serious health problems including irreversible damage to the bladder and kidneys.

Professor Mitul Mehta, a professor of neuroimaging & psychopharmacology at King’s College London, said: “The brain’s different neurochemical systems work together to produce our experiences and behaviour so it is no surprise that the opiate system may have a role in ketamine’s antidepressant effect.”

“We need these kinds of studies to understand exactly what the important brain mechanisms are for antidepressant effects. Understanding more about how ketamine works can lead to treatment being personalised for different people, which is vital for creating safe and effective treatments.”

Reference:

Jelen, L.A., Lythgoe, D.J., Stone, J.M. et al. Effect of naltrexone pretreatment on ketamine-induced glutamatergic activity and symptoms of depression: a randomized crossover study. Nat Med (2025). https://doi.org/10.1038/s41591-025-03800-w

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