ObjectiveThis study investigated whether combining exercise with transcranial direct current stimulation (tDCS) improves overall cognition, memory, and executive function in older adults.MethodsFollowing PRISMA guidelines, we systematically searched databases including PubMed, Web of Science, CNKI, and Wan Fang for randomized controlled trials (RCTs) examining the combined effect of exercise and tDCS on cognitive function in older adults. Used RStudio (version 4.2.0) to merge effect sizes and represent them as SMD with a 95% confidence interval (CI). The main effects are synthesized using a random effects model, and heterogeneity sources are explored through subgroup regression and sensitivity analysis.ResultsThe combined exercise and tDCS intervention significantly improved global cognitive function in older adults (SMD = 0.62, 95% CI: 0.36 to 0.89, p < 0.0001). Significant enhancements were observed in executive function (SMD = 0.54, 95% CI: 0.16 to 0.92, p = 0.005) and general cognitive ability (SMD = 0.75, 95% CI: 0.21 to 1.30, p = 0.006), while memory showed a non-significant improvement (SMD = 0.58, 95% CI: −0.03 to 1.19, p = 0.063). Both interventions lasting less than 6 weeks (SMD = 0.94, 95% CI: 0.60 to 1.27, p < 0.0001) and those lasting 6 weeks or longer (SMD = 0.24, 95% CI: 0.10 to 0.37, p = 0.0006) positively impacted cognitive function. However, the effect size was larger for cognitively healthy older adults (SMD = 0.69, 95% CI: 0.20 to 1.18, p = 0.006) compared to those with cognitive impairment (SMD = 0.60, 95% CI: 0.29 to 0.92, p = 0.0002). The combination of tDCS and integrated exercise produced the largest effect size (SMD = 1.74), despite high heterogeneity, while the combination of tDCS and Tai Chi produced the smallest but most robust effect (SMD = 0.25, I 2 = 0%), indicating that exercise type significantly regulates the intervention effect of tDCS (p = 0.0015). Regression analysis shows that tDCS stimulation time has a significant positive regulatory effect on cognitive function in elderly people (p = 0.0002), while the combined intervention period (p = 0.030) and single exercise time (p = 0.034) both have a significant negative regulatory effect.ConclusionBased on limited evidence, we found that a combined intervention of exercise and tDCS is a potentially effective means of improving cognitive function in older adults. However, the extent of improvement varies with the cognitive domain, baseline performance level, and intervention plan.
Computer-based tree drawing test in adolescents and adults with depression
ObjectiveTo evaluate the value of the computer-based Tree Drawing Test in the auxiliary diagnosis of depressive disorders and to analyze the differences in the performance of adolescent and adult depression patients in the Tree Drawing Projection Test.MethodsThis study was conducted at Guo Yang County People’s Hospital in Anhui, China, and involved a total of 184 participants: 43 adults with depression, 82 adolescents with depression, and 59 healthy controls. The Tree Drawing Test and scale assessments were administered to patients with depressive disorders (adult group and adolescent group) and a control group. Computer image recognition and calculation techniques were used to analyze the results statistically.ResultsSignificant differences were observed between the adult depression group and the control group in terms of crown area, trunk area, total area, and HDRS scores (p < 0.001). Statistically significant differences were also found between the adult depression group and the adolescent depression group in terms of trunk area (p < 0.01), total area (p < 0.001), HDRS scores (p < 0.001), and HAMA scores (p < 0.01). The crown area (r = -0.261, p < 0.001), trunk area (r = -0.154, p = 0.037), total area (r = -0.285, p < 0.001), and HDRS scores in the Tree Drawing Test were significantly correlated.ConclusionThe computer-based Tree Drawing Test has certain value in the auxiliary diagnosis of depression. Future research should include larger sample sizes and participants from different regions and cultural backgrounds to further validate the generalizability and cultural adaptability of the Tree Drawing Test for depression assessment.
Extended Group Written Exposure Therapy for Comorbid PTSD and BPD (Traits)
Conditions: Posttraumatic Stress Disorder (PTSD); Borderline Personality Disorder (BPD)
Interventions: Behavioral: Group Written Exposure Therapy
Sponsors: St. Joseph’s Healthcare Hamilton
Not yet recruiting
Interventions: Behavioral: Group Written Exposure Therapy
Sponsors: St. Joseph’s Healthcare Hamilton
Not yet recruiting
Reestablishing Normal Gut-brain Interaction in Anorexia Nervose With Normal Gut Microbiota
Conditions: Anorexia Nervosa
Interventions: Biological: Psychotherapy as usual combined with single dose normal gut microbiota; Other: Psychotherapy treatment as usual (TAU)
Sponsors: Haukeland University Hospital; The Dam Foundation
Not yet recruiting
Interventions: Biological: Psychotherapy as usual combined with single dose normal gut microbiota; Other: Psychotherapy treatment as usual (TAU)
Sponsors: Haukeland University Hospital; The Dam Foundation
Not yet recruiting
Barriers and Facilitators in the Implementation of the Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health Digital Intervention in Rural India: Mixed Methods Process Evaluation Study
<strong>Background:</strong> An estimated 150 million people have mental health care needs in India, but only 15% are able to access care. Depression and anxiety contribute to a large proportion of mental morbidity. The Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health trial used a mobile-based clinical decision support system for primary care doctors and community health workers (CHWs) to identify and treat people at risk of depression, anxiety disorders, and self-harm. A community-based antistigma campaign was also delivered. The intervention led to improved remission rates for depression and anxiety and lower stigma scores. <strong>Objective:</strong> A process evaluation assessed (1) implementation fidelity, barriers, and facilitators; (2) perceptions of doctors and CHWs on the use of SMART Mental Health; and (3) the causal pathways that led to trial outcomes. <strong>Methods:</strong> A mixed methods evaluation combining backend program data and qualitative data was conducted. A total of 38 focus group discussions and 37 key informant interviews were conducted with primary doctors, CHWs, government officials, local community leaders, and research project staff. The data were coded and analyzed using a framework analysis approach based on the UK Medical Research Council guidance on process evaluations and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. <strong>Results:</strong> The intervention had high implementation fidelity. Across clusters, the median proportion of participants with at least 1 CHW follow-up was 98% (IQR 96.6%-100%). The referral rate for a psychiatrist was low (224/1697, 13.2%), and only 23.6% (53/224) of those referred visited the psychiatrist. The median exposure to antistigma audiovisual content was 84% (IQR 65.7%-95.9%). At the community level, key implementation barriers included cultural inhibitions in seeking mental health care and the unavailability of patients due to competing demands. Proximity and tight social connections between CHWs and their communities were important facilitators in seeking medical help. Doctor and CHW training, mentoring, and feedback provided by program staff were important facilitators to support the use of the digital health components by the health workforce. <strong>Conclusions:</strong> A complex intervention that included both community-based antistigma and clinical digital health interventions achieved high implementation fidelity. Key areas to consider for maintenance of such interventions include (1) the need for sustained community-based strategies to address stigma and other cultural barriers; (2) health workforce strengthening policies, including supportive supervision for CHWs and doctors to increase capability in the use of mental health digital health tools; and (3) strategies to improve access to specialist care for those with more complex care needs. <strong>Trial Registration:</strong> Clinical Trial Registry India CTRI/2018/08/015355; https://tinyurl.com/5r63suxp
Digital Therapeutic Content for Substance Use Disorder Treatment: Development and Evaluation Study
Background: Substance use disorders (SUDs) are a major public health concern, contributing to significant individual and societal costs. Despite this, the uptake of evidence-based pharmacologic and behavioral interventions remains limited. The digital delivery of SUD treatment has emerged as a potentially scalable way to reduce access barriers and increase treatment use. Existing digital therapeutic interventions are often created without clinician involvement, evidence-based materials, interdisciplinary input, or content review. The implementation of a structured and methodologically rigorous development process is needed across digital health interventions to help ensure patient-facing materials are validated, understandable, and actionable for the end user. Objective: This early report seeks to describe and evaluate an iterative, interdisciplinary, platform-agnostic process for adapting and refining existing print materials for digital therapeutic modules in SUD treatment. The a priori goal was to evaluate if a structured, human-centered approach would generate digital modules that were rated as understandable and actionable based on a validated assessment for written materials. Methods: Fourteen therapeutic modules were adapted from existing Mayo Clinic–written, patient-facing education materials originally developed by a board-certified addiction psychiatrist and a doctoral-level education specialist for clinical use. A team of 4 purposively recruited licensed alcohol and drug counselors with lived experience with a SUD, all in recovery, and a doctoral-level therapeutic specialist met weekly for one hour over a 6-month period to iteratively adapt this existing content for smartphone delivery (2‐3 hours per module). The process flow included selecting source material, restructuring content for viewing on a phone screen, simplifying language, improving organization and flow to promote understanding, and including specific actions users could take based on the content. The counselors then independently evaluated the modules using the Patient Education Materials Assessment Tool for printable materials (PEMAT-P). PEMAT-P scores for understandability and actionability were calculated as percentages, and descriptive statistics were used to summarize scores in aggregate and across modules. A target of >70% was set for each PEMAT-P domain, consistent with accepted benchmarking standards. Results: Mean understandability and actionability for all modules were 87.2% (SD 4.8%; range 81.4%‐96.9%) and 75.1% (SD 12.3%; range 57.1%‐95.0%), respectively, exceeding the recommended threshold. While all modules were adequately understandable, 35.7% (5/14) scored below the actionability threshold. Conclusions: This early report highlights the value of a human-centered, iterative process for adapting therapeutic materials for digital delivery in SUD treatment. Although the modules performed well overall on PEMAT-P benchmarks, actionability was less consistent than understandability, and aggregate scores masked weaknesses in several individual modules. This indicates that a standardized process does not guarantee actionable material across all content types. Involving current patients in this process may improve the end product by incorporating a perspective that was previously missed.
Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice
Interest in glucagon-like peptide 1 receptor agonists (GLP-1s) continues to surge due to their effectiveness in reducing body weight and improving metabolic outcomes. This includes interest in small molecule oral GLP-1s which are more bioavailable and more easily manufactured than their injectable counterparts.
Now data from a new study in mice performed by scientists at the University of Virginia shows that this emerging class of weight-loss drugs suppress hedonic eating by modulating a reward circuit deep in the brain that is separate from previously described mechanisms that broadly affect appetite. The scientists believe that this pathway could be an avenue by which GLP-1s treat other dysfunctions in reward processing such as substance use disorders.
Details of the National Institutes of Health-funded study were published this week in a Nature paper titled “A brain reward circuit inhibited by next-generation weight-loss drugs in mice.” In it, the team reported that they investigated the small-molecule GLP-1s including Eli Lilly’s recently approved drug orforglipron, also known by the brand name Foundayo, as well as danuglipron, an oral GLP-1 that was being developed by Pfizer until the company decided to discontinue its development in 2025.
Previous studies that explored the effects of larger peptide GLP-1s such as semaglutide in the brain have found that they suppress hunger-driven eating by engaging networks in the hypothalamus and hindbrain. What has been less clear is the mechanism by which small-molecule GLP-1s work. “As the accessibility of these medications continues to rise and patient uptake increases, it’s crucial that we understand the neural mechanisms underlying the effects we’re seeing,” said Lorenzo Leggio, MD, PhD, clinical director of NIH’s National Institute on Drug Abuse.
The current study gets scientists one step closer to that goal. According to the paper, the scientists first used gene editing to modify the GLP-1 receptors of mice to make them more humanlike. They then administered orforglipron or danuglipron to the mice, and identified brain regions where the drugs induced activity. The results showed that in addition to inducing activity in familiar pathways, the drugs also triggered the central amygdala, a region associated with desire that is deeper in the brain than scientists previously thought GLP-1s could directly reach. Further testing showed that once activated, the central amygdala reduced the release of dopamine into key hubs of the brain’s reward circuitry during hedonic feeding.
“We’ve known that GLP-1 drugs suppress feeding behavior driven by energy demand,” said co-corresponding author Ali Guler, PhD, a professor of biology at the University of Virginia. “Now it seems oral small-molecule GLP-1s also dial back eating for pleasure by engaging a brain reward circuit.”
Given the effect of these drugs on eating for pleasure, future studies could explore whether small-molecule GLP-1s can also suppress cravings for other addictive substances. It is a question that the team hopes to explore in follow up studies focused specifically on substance use disorder.
The post Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.
Autism Screening Proposed for Children with Epilepsy
Children with epilepsy are up to 10 times more likely than others to also have autism, according to research that exposes the scale of the association between the two conditions.
The findings, in more than 30,000 children, stress the importance of screening for developmental concerns among those with epilepsy, so support can be delivered as early as possible.
The study, Developmental Medicine & Child Neurology, revealed that girls with autism spectrum disorder (ASD) were more likely than boys to also have epilepsy.
Higher rates of intellectual disability were also seen in children with autism who additionally had epilepsy, and they were also diagnosed with the neurodiversity at an earlier age.
“Our findings emphasize the importance of screening for autism in this population to support earlier diagnosis and timely intervention, both of which are key to improving long-term outcomes,” said senior investigator Elaine Wirrell, MD, from the Mayo Clinic.
ASD and epilepsy are complex disorders of neuronal connectivity that frequently co-occur because of shared molecular and biological mechanisms.
While the increased risk of ASD in children with epilepsy is well documented, there are gaps in knowledge around its incidence and prevalence, and risk factors for their co-occurrence.
To investigate further, Wirrell and team studied the medical records of 30,490 children in Olmsted County, Minnesota, of whom 257 (0.84%) were diagnosed with epilepsy before the age of 19 years.
They found that children with epilepsy were more likely have ASD across all three research and clinical definitions compared with other children, with this likelihood increased between six and 10-fold.
The prevalence was a corresponding 21.4% versus 3.2% using broad research criteria, 14.0% versus 1.6% across stricter research criteria, and 7.9% versus 0.7% for a clinical diagnosis.
Among children with autism, those also with epilepsy were more likely to have a lower IQ on standardized testing than those in whom epilepsy was absent (56.5% versus 15.4%). Specifically, an IQ of less than 70 was observed in 57.4% of children with co-occurring epilepsy and autism compared with only 15.4% autism alone.
Those with autism and epilepsy were also more often female than those with autism alone (38.2% versus 25.8%), and were identified with autism at a younger age, at a mean of seven years and five months versus eight years and eight months).
“These insights underscore the critical need for comprehensive and early screening protocols to better address and manage the intersection of autism and epilepsy, ensuring timely interventions and tailored support for affected individuals,” the researchers concluded.
The post Autism Screening Proposed for Children with Epilepsy appeared first on Inside Precision Medicine.
<![CDATA[Online tool personalizes antidepressant choice in primary care, cutting dropouts and improving 24-week depression and anxiety scores.]]>
PMAT enhances sexual dimorphism of fear behaviors and facilitates female mice’s generalized contextual fear extinction
Enhanced signaling of dopamine and/or serotonin during highly arousing situations can be reduced in part by monoamine transporters, such as plasma membrane monoamine transporter (PMAT, Slc29a4). An absence of selective pharmacological inhibitors means genetically modified mice constitutively deficient in PMAT remain the best tool for studying PMAT’s organism-level functional effects. Fear conditioning is a high arousal process. Generalization of fear is evolutionarily advantageous, whereby information learned from one experience is applied to other new but similar encounters. Pathological fear generalization, in contrast, is a core feature of most anxiety disorders. Given our previous findings indicating PMAT function reduces male mice’s context fear and enhances extinction of female mice’s cued fear, we hypothesized PMAT would similarly reduce generalization (i.e., enhance discrimination) of context and cued fear in male and female mice, respectively. Our context and cued fear conditioning experiments in adult PMAT wildtype (+/+) and heterozygous (+/−) male and female mice partially supported our hypotheses. We discovered PMAT facilitates extinction of contextually generalized fear, plus subsequent extinction of context-specific fear, selectively in females. Moreover, when specific fear cues or contexts were temporally presented before cues or contexts that were similar enough to make generalization possible, PMAT enhanced biological sex differences. Growing evidence reports common PMAT polymorphisms elicit measurable effects when PMAT function is reduced. Thus, we suspect future experiments may reveal positive associations between PMAT polymorphisms and risk for anxiety disorder symptoms, particularly in people assigned female at birth. Inclusion of these genetic variations in pharmacogenomic analyses may prove therapeutically beneficial.