A researcher who completed numerous brain scans found that her cerebral cortex volume was 1% smaller while using hormonal contraceptives.
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A researcher who underwent dozens of brain scans discovered that the volume of her cerebral cortex was 1 per cent lower when she took hormonal contraceptives.
By Grace Wade
Higher polygenic risk scores for bipolar disorder were associated with favorable treatment outcomes after lithium augmentation in antidepressant non-responders with unipolar depression.
Question Are polygenic risk scores (PRS) for major psychiatric disorders associated with favorable treatment outcomes after lithium augmentation (LA) in major depression?
Findings In this cohort study with 193 patients with major depressive disorder (MDD) who did not respond to antidepressants, the PRS for bipolar disorder (BIP) was significantly associated with response and remission after at least 4 weeks of LA. Additionally, we found an association between the MDD-PRS and LA response.
Meaning Individuals with a higher polygenic burden for BIP and lower polygenic burden for MDD are more likely to experience favorable treatment outcomes following LA, offering new opportunities for personalized medicine approaches.
From the article:
Following a vegetarian diet can be a boon for your health, even possibly cutting your risk of certain chronic illnesses, according to the Mayo Clinic. Yet a recent study, conducted by nutrition experts and published in the Nature journal npj Aging, suggests that not everyone will experience the same benefits when they cut out meat entirely. Adults over the age of 60 may have different nutritional needs, meaning a more diverse diet could instead help them live longer… Utilizing data from the Chinese Longitudinal Healthy Longevity Survey, the study reviewed information from nearly 2,900 Chinese older adults who were considered to be healthy. Participants’ diets were categorized four ways:
- vegan (avoiding any animal products, including eggs, seafood, or dairy) — ovo-vegetarian (vegetarian plus the inclusion of eggs) — pesco-vegetarian (vegetarian plus the inclusion of fish and seafood) — omnivorous (eating both plant-and animal-based products)
After an average follow-up period of six years, “Individuals who maintained omnivorous diets from age 60 years had higher odds of achieving healthy aging” versus those who “consistently” followed vegetarian eating patterns. When the team further analyzed the health data of those who survived to age 80, omnivorous eaters were more likely than vegetarians to avoid major chronic disease, physical function impairment, and cognitive impairment.
“Given age-related physiological changes in digestive and metabolic systems” in aging adults, the study specifically flagged the potential for muscle loss and bone fracture for those adhering to vegetarian diets. Another interesting discovery: older adults following a vegan diet were “most strongly associated with adverse effects on healthy aging,” which the text attributes to an increased risk of protein deficiency.”
npj Aging — Vegetarian diet and healthy aging among Chinese older adults: a prospective study. npj Aging 11, 25 (2025). https://doi.org/10.1038/s41514-025-00213-4
Despite known links between inflammation and pathological aging outcomes, studies have found inconsistent associations between peripheral levels of inflammatory proteins, including CRP and GDF15, and markers of brain health and neurodegenerative disease (Dik et al. 2005 ; Ravaglia et al. 2007 ; Stevenson et al. 2020 ; Yang et al. 2015). A driver of these inconsistencies may be natural inter-and intra-day fluctuations and variability in plasma protein levels as well as potential measurement error (Conole et al. 2021 ; Moldoveanu et al. 2000 ; Stevenson et al. 2021). Moreover, many health conditions, as well as physical and psychological stressors, can cause transient changes in inflammatory proteins that may further contribute to variability in inflammatory protein abundance. A consequence of this variability is a difficulty in accurately estimating an individual’s long-term exposure to inflammatory stimuli, i.e., chronic inflammation. Alternatively, chronic inflammation can be measured by quantifying epigenetic signatures (DNA-methylation [DNAm]), which may act as determinants of inflammatory gene transcription (Gadd et al. 2022, 2024 ; Stevenson et al. 2021). Because DNAm, though modifiable, is more stable and less sensitive to inter-and intra-day fluctuations than circulating protein levels and is trained on the inputs of protein-DNAm associations from a large (13,399) number of individuals (Lu et al. 2022 ; Stevenson et al. 2020), blood-based DNAm scores can be derived to estimate one’s long-term exposure to a given protein.
Previously, DNAm measures of GDF15 and CRP have been used as a component of composite variables (e.g., GrimAge version 2) to capture the immunologic contributions to accelerated biological aging, morbidity, and mortality. DNAm CRP has been associated with adverse neurocognitive outcomes (Conole et al. 2021 ; Smith et al. 2024). Specifically, Conole and colleagues found that DNAm CRP was significantly associated with cross-sectional brain atrophy, white matter microstructure, and cognitive performance, and that epigenetic CRP measures were more strongly associated with measures of brain structure than were circulating CRP protein levels. Similarly, Smith et al. (2024) found that elevated DNAm CRP was cross-sectionally associated with lower MRI-defined brain volume, as well as greater dementia risk over a 16-year follow-up period (Smith et al. 2024). Although higher levels of GDF15 protein have also been linked to poor brain health and dementia risk (Isik et al. 2024 ; Walker et al. 2024 ; Walker, Chen, et al. 2023), less is known about the extent to which an epigenetic indicator of long-term GDF15 exposure (DNAm GDF15) relates to adverse neurocognitive outcomes (Gadd et al. 2024).
The current study examined DNAm measures of CRP and GDF15—two inflammatory proteins with distinct immunologic significance—and extended previous cross-sectional findings using longitudinal MRI imaging and cognitive data in a large cohort of Baltimore Longitudinal Study of Aging (BLSA) adults. We conducted a proteome-wide analysis to identify functional pathways associated with blood DNAm CRP and DNAm GDF15 scores and examined how each of these putative markers of chronic inflammation was associated with longitudinal measures of brain structure as well as cognitive function among older adults. Additionally, we compared the performance of the CRP and GDF15 DNAm scores to that of their plasma protein counterparts and determined whether the DNAm associations extended to near-and long-term dementia risk in two independent cohort studies.
