Blood-based test used to predict who is likely to develop psychotic disorders

Researchers from the Royal College of Surgeons in Ireland (RCSI) have discovered that testing the levels of certain proteins in blood samples can predict whether a person at risk of psychosis is likely to develop a psychotic disorder years later. The scientists identified these proteins by analyzing blood samples taken from people at clinical high risk of psychosis and following up on the patients to see who did or did not develop a psychotic disorder. Many of the associated proteins are involved in inflammation, suggesting that there are early changes in the immune system in people who go on to develop a psychotic disorder. The findings also suggest that it is possible to predict their outcomes using blood samples taken several years in advance. The most accurate test was based on the 10 most predictive proteins. It correctly identified those who would go on to develop a psychotic disorder in 93% of high-risk cases, and it correctly identified those who would not in 80% of cases. The scientists published their work Aug. 26, 2020, in JAMA Psychiatry. “Our research has shown that, with help from machine learning, analysis of protein levels in blood samples can predict who is at truly at risk and could possibly benefit from preventive treatments,” said David Cotter, the study's senior author and professor of molecular psychiatry at RCSI. “We now need to study these markers in other people at high risk of psychosis to confirm these findings.”

Study could lead to more personalized choices for OCD treatment

A study performed at the University of Michigan suggests the possibility of predicting which of two types of therapy will help teens and adults with obsessive-compulsive disorder (OCD): One that exposes them to the specific subject of their obsessive thoughts and compulsive behaviors, or one that focuses on general stress reduction and a problem-solving approach. Published Aug. 28, 2020, in the American Journal of Psychiatry, the study examined advanced brain scans of 87 teens and adults with moderate to severe OCD who were randomly assigned 12 weeks of one of the two types of therapy. The researchers found that in general, both types of therapy reduced the symptoms that participants experienced. The approach known as exposure therapy, a form of cognitive behavioral therapy (CBT), was more effective and reduced symptoms more as time went on, compared with stress-management therapy (SMT). But when the researchers looked back at the brain scans taken before the patients began therapy, and linked them to individual treatment response, they found striking patterns. The brain scans were taken while patients performed a simple cognitive task and responded to a small monetary reward if they did the task correctly. Those who started out with more activation in brain circuits for processing cognitive demands and reward during the tests were more likely to respond to CBT – but those who started out with less activation in those same areas during the same tests were more likely to respond well to SMT. Among those who responded best to CBT, the researchers saw stronger pre-treatment activation in areas of the brain associated with learning how to extinguish fear-based responses to something that has caused fear in the past. Because exposure therapy for OCD involves facing the thing or situation that provokes obsessive and fearful responses, having a stronger ability to be motivated by rewards might help someone stick with therapy despite having to face their triggers. The findings suggest a path to personalizing the choice of therapy by using everyday tests that measure the kinds of characteristics that might predict better success with one therapy or the other.

Nerve cells differ before birth in people with ASD

A new study published June 22, 2020, in Biological Psychiatry has shown in human brain cells that the atypical development starts at the very earliest stages of brain organization, at the level of individual brain cells. Deepak Srivastava, from King's College London, said: "In this study we used induced pluripotent stem cells, or iPSCs, to model early brain development. Our findings indicate that brain cells from autistic people develop differently to those from typical individuals." The researchers isolated hair samples from nine people with autism spectrum disorder (ASD) and six typical people. By treating the cells with an array of growth factors, the scientists were able to drive the hair cells to become nerve cells. At various stages, the authors examined the developing cells' appearance and sequenced their RNA, to see which genes the cells were expressing. At day nine, developing neurons from the typical participants formed neural rosettes, an intricate, dandelion-like shape indicative of typically developing neurons. Cells from the ASD participants formed smaller rosettes or did not form rosettes at all. Additionally, key developmental genes were expressed at lower levels in cells from those with ASD. At days 21 and 35, the cells from the typical and ASD participants differed significantly in several ways, suggesting that the makeup of neurons in the cortex differs in the autistic and typically developing brain. In contrast to the differences seen in cortical neurons, cells directed to develop as midbrain neurons – a brain region not implicated in autism dysfunction – showed only negligible differences between the typical and ASD participants. "The use of iPSCs allows us to examine more precisely the differences in cell fates and gene pathways that occur in neural cells from autistic and typical individuals. These findings will hopefully contribute to our understanding of why there is such diversity in brain development," said Srivastava.

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