Medical Bulletin 27/ March/ 2025 - Video

Depression is a mental health condition that affects 280 million people worldwide. It is twice as common in women than men and this pattern starts to develop during adolescence. Researchers have studied the biological processes that drive depression in adults and shown a potential role for the kynurenine pathway, but this is the first time it has been investigated in adolescents in relation to biological sex.

The study was published in Biological Psychiatry

Using blood tests, the study assessed the levels of kynurenic and quinolinic acids in a group of 150 teenagers from Brazil aged between 14 and 16. The teenagers belonged to one of three groups - those with low risk of depression, those with high risk of depression and those who had been diagnosed with depression. Risk was assessed using a measure that had been developed as part of the Identifying Depression Early in Adolescence (IDEA) project and considers a range of factors1. There were 50 adolescents in each group and they were evenly divided by biological sex to explore differences between male and female adolescents. The adolescents were tracked over three years to assess if their depression symptoms persisted or improved.

The study also measured specific proteins in the blood that indicate the body is in an inflammatory state, and are released during infection, stress, or illness. It found that higher levels of these inflammatory markers were linked to increased production of neurotoxic chemicals in the kynurenine pathway. Notably, this association was found in adolescents at high-risk or with depression, but not in low-risk adolescents. This suggests that inflammation might drive the kynurenine pathway toward producing neurotoxic chemicals, increasing the risk of depression.

In the follow-up three years later, the study showed that female adolescents with persistent depression had higher levels of neurotoxic metabolites than those who recovered over time, suggesting that increased neurotoxic activity in the kynurenine pathway could make depression harder to overcome for some adolescents

Ref: Nikkheslat, N. et al. Sex-Specific Alternations of Kyneurenine Pathway in Association with Risk and Remission of Depression in Adolescence.Biological Psychiatry https://doi.org/10.1016/j.biopsych.2024.11.020

A study in Alzheimer’s & Dementia, a leading journal in dementia research, has demonstrated the high accuracy of plasma p-tau217 as a blood-based biomarker for detecting abnormal brain beta-amyloid (Aβ) pathology, a hallmark of Alzheimer’s disease (AD). More significantly, the study validates its effectiveness even in individuals with cerebrovascular disease (CeVD), which is highly prevalent in Asian populations. This finding can enhance early diagnosis, improve patient risk stratification, and facilitate better clinical management of AD in diverse populations.

Brain amyloid status on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

The results showed that plasma p-tau217 outperformed routine clinical assessments and other plasma biomarkers. The high-risk group showed significantly higher rates of cognitive decline than the low-risk group.

Risk stratification for PET Aβ+ based on a plasma p-tau217 assay demonstrated potential diagnostic and prognostic utility in an Asian cohort with concomitant CeVD. The utility of plasma p-tau217 to detect brain amyloid beta pathology (Aβ+) was studied in an Asian cohort with concomitant cerebrovascular disease. Plasma tau phosphorylated at threonine 217 showed superior utility in detecting Aβ+ compared to neuroimaging measures, clinical workup, or other blood biomarkers including p-tau181, glial fibrillary protein and Aβ. Higher plasma p-tau217 was correlated with faster cognitive decline and hence, it was concluded that plasma p-tau217 shows promise as an Alzheimer's disease (AD) diagnostic and prognostic biomarker in diverse populations.

Ref: Chong J R, Hilal S et al. Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease. Alzheimer`s and Dementia. Volume21, Issue2. February 2025. https://doi.org/10.1002/alz.14502

A groundbreaking study has revealed a significant link between the frequency of chest x-ray referrals from GPs and earlier diagnosis and improved survival rates for lung cancer patients. The study, published in the British Journal of General Practice, found that patients attending practices with the highest chest x-ray usage were more likely to be diagnosed with lung cancer at an earlier, more treatable stage. The practices with the highest chest x-ray usage also saw patients less likely to be diagnosed at the later stages of cancer - stage three and four. These patients were also shown to have better survival at both one and five years after diagnosis, compared with those with the lowest chest x-ray usage.

Lead author of the study, Dr Stephen Bradley from the University of Sheffield’s School of Medicine and Population Health, said: “Lung cancer remains the leading cause of cancer deaths both in the UK and globally. This is an important step forward in our understanding of how to improve lung cancer detection. "By encouraging greater use of chest x-rays, we can potentially diagnose lung cancer earlier, when treatment is more likely to be successful."

Until now, it was not widely understood if GPs arranging more chest x-rays was beneficial. The uptake of chest x-rays varies a great deal between different GP practices - possibly in part because GPs may not have been convinced that there could be a benefit for patients with very common symptoms.

This is the first study of its kind which links chest x-ray rates and the national cancer registry

This study highlights how the use of investigations in primary care can help diagnose cancer at an earlier stage to give people affected by cancer the best chance of a good outcome. However, more research to understand the impact of other investigations used in primary care on patient outcomes is also needed to support efforts to diagnose cancer earlier.

Ref: Bradley S H, Neal R D et al. General practice chest X-ray rate is associated with earlier lung cancer diagnosis and reduced all-cause mortality: a retrospective observational study; British Journal of General Practice 24 March 2025; BJGP.2024.0466. DOI: 10.3399/BJGP.2024.0466a