Medical Bulletin 02/ November/ 2024

Professor Clifton’s team at the Mater Research Institute-University has identified 13 distinct glucocorticoid receptor isoforms in the placenta, with one particular variant showing a surprising response to maternal stress. In a revealing Genomic Press Interview published in Brain Medicine, Professor Vicki Clifton shares transformative discoveries about the placenta’s unexpected influence on maternal mental health, potentially revolutionizing our understanding of pregnancy-related anxiety and depression.

“We have discovered that the placenta has 13 different isoforms of the glucocorticoid receptor, with one isoform expressed in the presence of maternal stress, anxiety, and depression that activates an inflammatory response in the placenta in the presence of high cortisol concentrations,” Professor Clifton explains.

This groundbreaking finding challenges conventional understanding of stress responses during pregnancy. While most glucocorticoid receptors typically suppress inflammation, this newly identified variant appears to enhance it, potentially explaining the complex relationship between stress and inflammation in pregnant women.

Professor Clifton’s research has unveiled crucial differences between male and female fetuses, mediated through sex-specific placental functions. Her work suggests that maternal physiology varies depending on fetal sex, opening new possibilities for personalized interventions in pregnancy care.

Reference: https://url.genomicpress.com/mr3ey5p7

A genetic signature in newborns can predict neonatal sepsis before symptoms even start to show, according to a new study. The study, led by UBC and SFU researchers in collaboration with the Medical Research Council (MRC) Unit The Gambia, has the potential to help healthcare workers diagnose babies earlier, including in lower- and middle-income countries (LMICs) where neonatal sepsis is of particular concern. The research, published in eBiomedicine.

Diagnosing sepsis is challenging for doctors and families. The symptoms can look like many other illnesses, and tests to check if sepsis is present can take several days, aren’t always accurate, and are largely only available in hospitals. The uncertainty can delay urgent treatment with antibiotics.

The researchers participated in a large study in The Gambia where blood samples were taken from 720 infants at birth. Out of this cohort, 15 babies developed early-onset sepsis. The researchers used machine learning to map the expression of genes active at birth, in search of biological markers that could predict sepsis.

“We found four genes that, when combined in a ‘signature’, could accurately predict sepsis in newborns nine times out of 10,” said co-senior author Dr. Amy Lee, assistant professor in the SFU department of molecular biology and biochemistry. “This was a unique opportunity where samples were available from all babies in this cohort on the day of birth, meaning we could study the genes expressed in the sepsis babies before they got sick. Most other studies have only published markers that were present when the babies were already ill, and this would therefore not be a predictive signature.” The researchers hope the signature will one day be incorporated not only into PCR tests in hospitals, but also in portable, point-of-care devices.

Reference: Andy Y. An, Erica Acton, Olubukola T. Idoko, Casey P. Shannon, Travis M. Blimkie et al. Predictive gene expression signature diagnoses neonatal sepsis before clinical presentation, eBioMedicine, 2024, 105411, ISSN 2352-3964, https://doi.org/10.1016/j.ebiom.2024.105411.

Researchers at UCLA Health have found that a person’s risk of developing psychotic-like experiences may be influenced by both childhood attention problems and their genetic makeup. The findings, published in Nature Mental Health, build upon a long-studied association between childhood attention problems and the likelihood of later developing schizophrenia. Using data from about 10,000 children over six years, UCLA researchers led by Dr. Carrie Bearden sought to determine how attentional variability influenced the risk of broader psychotic-like symptoms as children grow into adolescence.

Specifically, the team looked at how the youths’ risk for psychotic-like experiences varied based on their attention span and genetic variants that may predispose them to different neuropsychiatric conditions.

The researchers found:

A higher genetic risk for a broad set of neuropsychiatric and cognitive disorders was associated with greater severity of psychotic like experiences and greater attention issues.

Additionally, attention span variability partially acted as an intermediate between the relationships between genetic risk for neuropsychiatric disorders and the expression of psychotic-like symptoms. Attention span issues explained 4-16% of these associations.

While the majority of youth who experience psychotic-like symptoms will not go on to develop schizophrenia, these events do increase the likelihood for future psychotic disorders and mental illness. The study used cognitive, brain and genetic data from more than 10,000 participants in the ongoing Adolescent Brain and Cognitive Development (ABCD) study. The study, led by a national consortium of research institutes including UCLA Health, is examining brain development in nearly 12,000 youth starting at age 9 and followed over the next decade into their early adulthood.

Reference: https://www.uclahealth.org/news/release/childhood-attention-issues-and-genetic-factors-may-predict