Tag: 16/1/23

Categories : Mental Health NeurologyTags : Leave a comment

Neuroimaging can’t Identify Psychiatric Disorders – Yet

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MRI images of the brain
Photo by Anna Shvets on Pexels

Neuroimaging technologies hold great promise in helping clinicians link specific symptoms of mental health disorders to abnormal patterns of brain activity. But a new study published in the American Journal of Psychiatry shows there are still kinks to be ironed out before doctors can translate images of the brain to psychiatric disorders such as post-traumatic stress disorder (PTSD).

Several years ago, The National Institutes of Mental Health launched a multi-billion-dollar research effort to locate biomarkers of brain activity that point to the biological roots of a host of mental health diseases, which today are typically identified by clinical evaluation of a constellation of often overlapping symptoms reported by patients.

“The idea is to forget classification of disease by symptoms and find underlying biological causes,” said Yale’s Ilan Harpaz-Rotem, professor of psychiatry and psychology and senior author of the study.

For the new study, the Yale-led team attempted to replicate the findings of an earlier nationwide neuroimaging study, in which scientists linked clusters of brain activity to a variety of outcomes among patients who had arrived at US emergency departments following traumatic events. Specifically, when researchers measured patients’ brain activity during the performance of simple tasks such as mapping responses to threats and rewards, they detected a cluster of brain activity that showed high reactivity to both threat and reward signals and seemed to predict more severe symptoms of PTSD later on.

However, when Yale researchers analysed similar neuroimaging data collected from recent trauma survivors in Israel, they were not able to replicate these findings. While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms.

“That is not to say one set of data is right and the other is wrong, just that there is a lot of fundamental work that needs to be done to develop reliable models that could generalise across different studies,” said Yale’s Ziv Ben-Zion, a postdoctoral associate at Yale School of Medicine and the corresponding author of the study.

In fact, Yale researchers are currently working with the investigators of the original study to merge datasets “to search for common underlying patterns of brain activity associated with different responses to trauma,” Ben-Zion said.

“It took about 100 years to come up with current classifications of mental illness, but we’ve only been exploring refining psychiatric diagnoses using biomarkers for the last 10 years,” said Harpaz-Rotem. “We still have a long way to go.”

Source: Yale University

Categories : GastrointestinalTags : Leave a comment

Unusual Sympathetic Nervous Activity in IBS Patients

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Photo by Andrea Piacquadio on Pexels

Using a wearable device to record nerve activity, researchers in Japan have discovered that the sympathetic nervous system of patients with irritable bowel syndrome (IBS) activated a few minutes before defecation, and persisted for a few minutes afterwards. Their results are published in the journal PLoS ONE.

Irritable bowel syndrome (IBS) is a difficult disease to treat, characterised by chronic abdominal pain related to bowel movements, of which there are four types: diarrhoeal, constipation, mixed, and unclassifiable. Patients with IBS report a reduction in quality of life and experiences of social discomfort, as they are forced to restrict their activity, such as work or travel, because of the sudden and unpredictable need to use the toilet. While there have been studies of IBS-related abnormalities in the autonomic nervous system based on 24-hour electrocardiogram measurement, until now none of them examined changes in the autonomic nervous system during bowel movements.

Associate Professor Fumio Tanaka and his research group at the Osaka Metropolitan University Graduate School of Medicine recorded the autonomic nervous system activity of IBS patients and healthy subjects using a wearable device and tracked activities such as defecation and sleep. As a result, they found that unlike healthy subjects, the sympathetic nervous system of IBS patients was activated two minutes before defecation and persisted until 9 minutes after defecation. Furthermore, the activation of the sympathetic nervous system was found to be associated with greater abdominal pain and lower quality of life.

“This research is characterised by the fact that autonomic nervous system functions are measured using a clothing-type wearable device, and that lifestyle events such as defecation and abdominal symptoms are input simultaneously in real time, using a smartphone application originally developed by our group. As a result, autonomic nervous system activity during defecation was accurately evaluated. We hope that further research will improve the quality of life of IBS patients and help elucidate the pathophysiology,” Professor Tanaka concluded.

Source: Osaka Metropolitan University

Categories : Mental HealthTags : Leave a comment

Walking the Tightrope of Prescribing Benzodiazepines

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Photo by Towfiqu Barbhuiya on Unsplash

Antidepressants and psychotherapy typically are the preferred treatment options for anxiety and depression, although benzodiazepines can be helpful in treating acute or persistent anxiety that does not respond to first-line therapy. In “Walking the Benzodiazepine High Wire,” published in Psychiatric Services, two experts advocate advocate a multipronged strategy for the cautious prescribing of this class of anxiety medications rather than a stringent and exclusively regulatory approach to their use.

Kurt Kroenke, MD, of the Regenstrief Institute and Indiana University School of Medicine, and Matthew E. Hirschtritt, MD, MPH, of Kaiser Permanente Northern California and University of California, San Francisco,

Noting that the number of benzodiazepine prescriptions in the US has substantially increased over the past decade, leading to a parallel rise in rates of misuse and overdose, Dr Kroenke and Dr Hirschtritt counsel that to stem this disquieting tide, provider and patient education, coupled with prescribing surveillance, may be preferable to overly strict governmental regulation of benzodiazepines.

“Benzodiazepines should not be tried first or probably even second, but as with opiates which can be appropriate for acute pain at end of life or following a severe injury or major surgery, there are appropriate reasons for prescribing benzodiazepines for severe anxiety,” said Dr Kroenke.

He is a pioneer in the field of medical symptomology and international leader in the interpretation and treatment of psychological and physical symptoms. He has co-developed brief survey measures in worldwide clinical use to track symptoms of anxiety (GAD-7); depression (PHQ-9); suicide risk (P-4); and other conditions. These tools have been translated into more than 100 languages and assist clinicians around the world in selecting treatments and evaluating their effectiveness.

The authors conclude: “The tightrope between the benefits and risks of prescribing a medication that may be useful for some patients and harmful for others exists not only for controlled drugs but also for treatments such as antibiotics, which continue to be overprescribed, leading to antibiotic resistance. A multipronged strategy for BZD [benzodiazepine] use that includes ongoing education of providers, patients, and the general population; surveillance to optimise selective and appropriate use; and closer oversight of outlier prescribing patterns is preferable to a stringent and exclusively regulatory approach.”

Source: Regenstrief Institute

Categories : Gender LungTags : Leave a comment

Why Many Lung Diseases are Sex-biased

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Anatomical model of lungs
Photo by Robina Weermeijer on Unsplash

By studying sex differences in expression across more than 2500 genes in mouse lung cells, researchers may have found an explanation for sex biases in the prevalence and severity of lung diseases, such as the greater severity of COVID for males. In particular, very high numbers of X-linked genes escape transcriptional silencing in lung alveolar type 2 (AT2s) cells, according to their study published in Stem Cell Reports.

“Our study is the first to compare male and female AT2 cells for gene expression, and our findings suggest that there are likely sex differences in lung repair following viral-induced injury,” says co-senior author Montserrat Anguera, an associate professor at the University of Pennsylvania.

Sex differences exist for many lung diseases, but the mechanistic basis for this remains unclear. “We started this project during the beginning of the pandemic, because we were curious about the sex bias with COVID disease, where more older men have increased morbidity, and wondered whether X-chromosome inactivation (XCI) might contribute to this sex bias,” Anguera says. “We realised that the SARS-CoV2 virus first encounters AT2 cells in the lung, and that the virus enters cells through the angiotensin-converting enzyme 2 (Ace2) receptor, which is located on the X chromosome.”

XCI is a process by which one of the copies of the X chromosome is inactivated in female mammals. The inactive X chromosome is silenced by being packaged into a transcriptionally inactive structure called heterochromatin. XCI prevents female mammals from having twice as many X-chromosome gene products as males, who only possess a single copy of the X chromosome.

In the new study, Anguera and co-senior author Andrew Vaughan, an assistant professor at the University of Pennsylvania, investigated XCI maintenance and sex-specific gene expression profiles using male and female AT2s. The results showed that approximately 68% of expressed X-linked genes in mouse AT2s escape XCI. These genes include Ace2, which serves as the entry point into cells for SARS-CoV-2, but is also involved in lung repair.

There were genome-wide expression differences between male and female AT2s, possibly contributing to sex differences in lung injury and repair in multiple settings. Taken together, the findings demonstrate that AT2 cells have the highest levels of XCI escape for mouse cells reported to date and support a renewed focus on AT2s as a potential contributor to sex-biased differences in lung disease.

In addition, the results showed that AT2 cells, similar to immune cells, do not strictly follow the classic rules of XCI. “We were surprised to find that female AT2 cells lack canonical epigenetic modifications that are typically enriched on the inactive X as a result of XCI. These include the long noncoding RNA Xist and heterochromatic histone modifications H3K27me3 and H2AK119-ubiquitin,” Anguera says. “Because the inactive X in female AT2 cells has fewer epigenetic marks, this enables more gene expression chromosome wide, including the Ace2 gene.”

For now, it remains an open question whether ACE2 escapes XCI in human AT2 cells. to The authors say this is a likely scenario because there are significantly higher numbers of XCI escape genes in human cells compared to mouse cells.

Moving forward, the authors plan to investigate how expression from the inactive X in AT2 cells is affected by SARS-CoV2 infections. They also will continue to study how expression from the X chromosome is regulated in other cell types that do not exhibit conventional XCI maintenance. “Our findings open the door to future work investigating the genetic and epigenetic basis, residing within the X chromosome, of sex differences in immune responses to inhaled viruses,” Anguera says.

Source: Science Daily

Categories : Cancer Metabolic DisordersTags : Leave a comment

A Metabolic Switch for Childhood Obesity and Cancer

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Researchers have unlocked a means to modify the function of an enzyme crucial to fat production, a finding could lead to more effective treatments for childhood obesity and cancer.

While the research, published in the Proceedings of the National Academy of Sciences, was in fruit fly larvae, the ability to alter the rates of lipid metabolism could have significant implications for human health, said Hua Bai, an associate professor of genetics, development and cell biology at Iowa State University.

“We’ve identified what’s basically a metabolic switch. It’s like the accelerator on a car,” he said.

The initial aim was investigating how ageing was affected by fatty acid synthase, an enzyme that plays a role in de novo lipogenesis, which is the process of turning excess dietary carbohydrates into fat. Typically, levels of fatty acid synthase rise and fall based on an animal’s cellular needs and diet.

Surprisingly, the researchers noticed that early in a fruit fly’s development, de novo lipogenesis increases without an accompanying boost in the expression of fatty acid synthase. That suggested there must be some other factor at play, Bai said.

After proteins such as fatty acid synthase are created based on genetic code, their function can be altered by one of several different types of post-translational modification. Bai’s team found one of those processes, acetylation, affected one of the 2540 amino acids that combine to make fatty acid synthase, changing how effective it was at producing fat.

In addition to its role in obesity, elevated levels of de novo lipogenesis are linked to cancer, so controlling it through a single amino acid could lead to highly targeted treatments, Bai said.

“Fine tuning the acetylation levels of fatty acid synthase would be a much more precise treatment than blocking the entire protein,” he said.

Though the findings may be applicable to humans, any medical application in humans is years away, he said.

“The potential is high, but further testing is needed in other animals,” he said.

Source: Iowa State University