Background: Ambulatory assessment and active and passive monitoring all offer a real-time, flexible approach to assessing mood and behavior in mood disorders. Despite their potential, concerns remain regarding the performance, usability, adherence, and potential safety of these tools. Objective: This study synthesizes the findings from 7 systematic reviews, integrating quantitative and qualitative data from randomized trials, observational studies, and user experience research to evaluate the performance, feasibility, acceptability, and clinical impact of ambulatory assessment and mood monitoring in people with depression and bipolar disorder. We assessed studies over the medium or long term (3 months or more). Methods: A summary of a series of systematic reviews was carried out by the authors—including meta-analyses (for quantitative data) and meta-syntheses (for qualitative data). Eight electronic databases were searched, and mixed methods studies were included. Studies were assessed for risk of bias. The results were checked for coherence, and recommendations were made by individuals with lived experience, methodologists, and psychiatrists. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality and strength of the evidence. Results: The 111 included studies included 19,945 participants and used 69 different ambulatory assessment protocols or mood-monitoring interventions. Key barriers to implementation were identified, including performance inconsistency, adverse effects, and user disengagement. Evidence-based recommendations are provided to guide future clinical and research applications. Conclusions: Ambulatory assessment and mood monitoring hold promise in research and clinical practice, yet their implementation requires more rigorous evaluation, greater personalization, and responsible, user-centered design. Crucially, these measures can add granularity and confirmation, but additional context is often required, and none of these measures are robust enough yet to replace current outcomes.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/a83582c454b5b6028210d2cb063318df" />
Mental Health Fitness Through a Youth Perspective
Insights on building and advancing mental health care solutions through collaboration — from the Global Youth Advisory Council at the SNF Global Center for Child and Adolescent Mental Health at the Child Mind Institute
Mai El Shoush, Partnerships Campaign Manager, Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute
Tatiana P. Claridad, MBA, Director of Board Affairs and Institutional Strategy, Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute
Mental health fitness is shaped by lived experience, context, and the systems of care that surround us. During Mental Health Awareness Month, we invited young leaders from the Global Youth Advisory Council (GYAC) at the Stavros Niarchos Foundation (SNF) Global Center at the Child Mind Institute — from Brazil, South Africa, and Greece — to share their unique perspectives.
Their reflections offer insight into how young people define, build, and experience mental fitness globally, highlighting the influence of their environments, communities and everyday realities. Their views are essential to shaping more relevant and effective support for young people everywhere.
From daily habits to systemic change, here’s how young people are reimagining mental health care as mental health fitness:
These reflections raise a broader question — how can global collaboration strengthen mental health support for children and adolescents?
While these insights from the GYAC members highlight the importance of collaboration, they also reflect a new paradigm of youth leadership.
What continues to inspire you as a young leader about the ideas and perspectives shared through the Global Youth Advisory Council, and what does it say about the future of mental health care?
“What continues to inspire me most is the diversity of perspectives across different countries, yet the shared commitment to improving youth mental health. There is something powerful about young people coming together across contexts, bridging gaps through a global lens while staying rooted in their lived experiences. It reminds me that the future of mental health care will be more inclusive, shaped by real voices, and focused on breaking stigma in ways that feel authentic and meaningful.”
Delice Lumbu, 20, Director of Youth Engagement, SNF Global Center
Contributors: Delice Lumbu, Director of Youth Engagement, Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute
The post Mental Health Fitness Through a Youth Perspective appeared first on Child Mind Institute.
Negative Online Experiences Are Common but Often Go Unreported Among Youth With Mental Health and Neurodevelopmental Concerns
New Child Mind Institute study finds more than one in four youth experienced a negative online experience in the past year, yet only one in five reported the incident through platform tools.
New York, NY — A new study from researchers at the Child Mind Institute finds that negative online experiences are common among children and adolescents with mental health and neurodevelopmental conditions, and that most incidents are not reported through platform reporting tools.
Published in JAACAP Open, the study examined negative online experiences among 1,009 youth ages 9 to 15 with a history of mental health or neurodevelopmental concerns, all of whom were current or previous participants in the Child Mind Institute’s Healthy Brain Network. More than one in four reported at least one negative online experience in the past year. Among those who had such an experience, nearly 69% reported multiple incidents, yet only 20% reported the incident through platform reporting tools.
The study defined “negative online experience” as any unwanted or uncomfortable experience while online, including cyberbullying, cyberstalking, doxxing, impersonation, sexual harassment, and related forms of digital harm. The research used a mixed-methods design, combining a quantitative survey with an in-depth qualitative follow-up involving a three-day moderated online bulletin board with a subset of participants.
“These findings point to a large and often hidden problem,” said Michael P. Milham, MD, PhD, Chief Science Officer at the Child Mind Institute and senior author of the study. “Many young people are encountering harmful or uncomfortable experiences online, but the systems designed to help them often do not receive a report. That creates a major gap for parents, educators, clinicians, and platforms trying to keep children safer online.”
The research team identified three major categories of barriers that prevent youth from reporting negative online experiences: reporting process barriers, such as not knowing how to make a report; reporting policy barriers, including uncertainty about what qualifies for reporting or how platform rules apply; and emotional barriers, such as embarrassment, fear, and worry about consequences.
The study also found that reporting decisions were often shaped by how young people interpreted the incident itself. In the qualitative follow-up, youth considered whether the harmful behavior seemed intentional, how malicious it appeared, and how severe or repeated the harassment was. When those cues were ambiguous, youth were less certain about whether reporting was appropriate.
“Reporting is not simply a matter of telling young people to speak up,” said Mirelle Kass, lead author of the study. “Youth are making complicated judgments about intent, severity, platform rules, and the possible consequences of disclosure. If we want young people to report harmful experiences, the tools and systems around them need to be clearer, safer, and easier to use.”
The findings suggest that online safety efforts should be tailored to the needs of youth who may already be managing mental health, developmental, or social challenges. Social aptitude, mental health symptoms, and parenting style were associated with youths’ likelihood of encountering negative online experiences and with the barriers they faced when deciding whether to report them.
Participants also expressed a clear desire for better tools and guidance. Most youth wanted platforms to provide more information about how to protect themselves online, how to use safety features such as blocking and reporting, and how to access support during and after the reporting process.
“Families, educators, clinicians, policymakers, and technology developers all have a role to play,” said Dr. Milham. “We need reporting systems that children can understand, policies that are transparent, and trusted adults who can respond without blame or overreaction. Safer digital spaces will require more than awareness. They will require systems designed around how young people actually experience online harm.”
The study underscores the importance of developmentally appropriate safety tools, clearer platform policies, and stronger support systems for youth navigating digital spaces. For children and adolescents with mental health and neurodevelopmental conditions, improving reporting pathways may be an important step toward reducing hidden online harms and building safer online environments.
This research was supported by funding from Google LLC’s User Safety team to the Child Mind Institute for work led by Michael P. Milham, MD, PhD.
About the Healthy Brain Network
The Healthy Brain Network is a community-centered research initiative from the Child Mind Institute that collects clinical, cognitive, behavioral, and neurobiological data from children and adolescents in the New York City area. Families who participate receive feedback and diagnostic consultation while contributing to open science research aimed at improving understanding of child and adolescent mental health.
About the Child Mind Institute
The Child Mind Institute is an independent nonprofit organization dedicated to transforming the lives of children and families struggling with mental health and learning disorders. Through cutting-edge research, evidence-based clinical care, and public education, the Child Mind Institute builds open science platforms and digital tools to accelerate discovery and improve youth mental health worldwide.
For press questions, contact cmiscience@ssmandl.com or mediaoffice@childmind.org.
The post Negative Online Experiences Are Common but Often Go Unreported Among Youth With Mental Health and Neurodevelopmental Concerns appeared first on Child Mind Institute.
JAACAP Open: Negative Online Experiences and Reporting Rates in Youth With Mental Health Conditions
Centering People, Centering Stories: Folklore as an Unlikely Ally in the OCD Misdiagnosis Crisis
By: Rebecca Bernstein, MA Folklore
The International OCD Foundation’s (IOCDF) recent landmark white paper reveals more than 80% of OCD cases in America remain undiagnosed (International OCD Foundation, 2025). Considering the size of this clinical challenge, it might seem odd to suggest that a small, humanities-based field like folklore— yes, folklore — has any role to play in the solution. As someone who studies OCD personal narratives (stories people tell about their lived experiences), my research suggests otherwise. In a situation that invokes the feeling of all-hands-on-deck, the tools and perspectives of this field may offer more benefit than we might initially give it credit for.
Folklore is the study of informal, creative communication. Dr. Lynn McNeill describes it as anything people “say, do, make, or believe” (McNeill, 2013). Folklore includes everything you’d think of (quilts, traditional music, fairy tales) and a lot of things you wouldn’t (occupational culture, gossip, internet memes.) We find examples of folklore everywhere. It’s in our holidays and our hobbies, our food and our fads, our jokes and our grieving. Folklorists study the infinite ways people express themselves in daily life. This, in turn, helps us better understand the cultural realities in which they live. And because what we “say, do, make, or believe” describes most of human behavior, the folkloric lens can be an indispensable one with which to investigate the world.
The benefit of studying how people express themselves is obvious when we recognize that in mental health, conversation and narrative are the primary tools we use to give and receive care. OCD isn’t just a diagnosis. It’s also a fundamentally creative experience. (Creative things don’t necessarily have to be beautiful, pleasing, or even wanted. They just have to be new and meaningful.) (Dictionary.com, 2023). Although ego-dystonic, extraordinary beliefs and elaborate rituals are hallmark features of OCD. When sufferers discuss their experiences, they are naturally inclined to do so through their own personal and cultural lenses. Therefore, descriptions of OCD vary infinitely. If the issue is our failure to recognize OCD when it presents itself, an approach designed to make sense of something as messy as human expression may offer insights that quantitative research methods still struggle to obtain.
How Folklorists Research
Just like in biomedical research, the research methods folklorists use matter. Our goal is to better understand people and their communities. That means we strategically build relationships, listen deeply, and intentionally embrace the complexity of those we talk to.
When I started researching OCD narratives, I wanted to know: What were the internal realities like for people who lived with this illness? What made their stories distinct? And how might those stories be connected? One of the biggest challenges I faced in my fieldwork was the potential for my participants to self-censor. As someone who also lives with OCD, I knew all too well the role shame and fear could play in the choice to fully share one’s reality with others. Using both field-tested approaches and my own lived knowledge, I conducted interviews with people with OCD, approaching them in a way I hoped would ease interviewees into difficult conversations:
- I provided anonymity. I held all interviews on Zoom, where participants were free to keep their cameras off. I also assigned each one an alphanumeric signifier (A1, B2, etc.) in my writing.
- I emphasized the importance of story. Although I asked specific questions, I also allowed participants to go off topic and engage in two-way conversation. The story was the point.
- I used the “kitchen table” interview method. Based on the work of Carl Lindahl, this method tries to recreate the intimacy of two individuals talking around a kitchen table. It discourages framing the interviewer as an objective party, recognizes storytellers as experts in their own experiences, and suggests that interviewers only ask questions they themselves would be willing to answer (Lindahl, 2012).
- I disclosed. My choice to openly discuss my own OCD diagnosis with interviewees allowed conversations to proceed with a certain warmth and vulnerability.
- I emphasized participants’ humanity. I treated each participant as a full individual rather than just a source of information. This meant I worked on a model of enthusiastic consent. It also meant I asked them for feedback on my writing to ensure I portrayed their experiences accurately.
- I compensated participants well. Each received a $100 gift card.
The Results
The universal theme I discovered during these interviews was a profound concern with social isolation. Every single participant mentioned this issue. Interviewees shared how OCD made it difficult for them to maintain relationships and how challenging it was to hide their illness from others. They also recalled their joy and gratitude when discussing moments in which they felt understood.
Their narratives also contained four other common themes:
1.) Logic and patterns of personal concern. Participants often discussed their particular obsessions and compulsions, and the influence those specific thoughts and behaviors had on their daily lives.
2.) Issues of negotiation. People talked about navigating certain types of conflicts as a result of their illness. These conflicts generally fell into two categories: self-negotiation and existential negotiation. In the first, people struggled with the desire to take their thoughts and urges seriously despite knowing they didn’t make sense. In the second, they wrestled with their relationships to the divine.
3.) Positive approaches to the illness. Many interviewees made a point to mention the silver linings they saw in being sick. They noted how OCD made them safer, more empathetic, or provided them with particular skills. Others discussed productive choices they’d made despite living with such a debilitating condition.
4.) Interactions with medical systems. Participants talked about their experiences as patients. For some, dealing with doctors, therapists, and other health professionals helped them understand their experience or relieved their suffering. For others, these encounters were confusing, unhelpful, or even traumatizing.
It’s important to note these themes represent a truly broad range of content. Not every story included every theme, and within those themes, the specific details I heard varied as much as the individuals themselves.
Implications
Say you were to hear four stories: one about someone’s preferred cleaning routine, one about someone’s waning belief in God, one about a good decision made in a difficult circumstance, and one about a doctor’s visit. It’s unlikely you’d consider these stories connected. And yet the data shows they are. The fact that stories with dramatically different content can reflect the same illness highlights the way OCD can remain elusive and camouflaged.
The problem with recognizing these stories as OCD stories isn’t just the variation in content. It’s also in how others hear them. In folklore, we don’t just study cultural expressions. We also study how they move from person to person. “Tellable narratives” travel easily. Both speakers and listeners understand what a certain type of story should sound like and the meaning it’s supposed to convey. If I tell you a tale about a persecuted young woman who escapes a bad home life and marries a prince, you can probably guess you’ve heard Cinderella. If we’re both excited that she went from rags to riches, we share an understanding that her journey is a positive one. In contrast, an “untellable narrative” hits some kind of barrier. If you’ve never heard Cinderella before or think the stepmother is actually the hero, my meaning in telling you the story gets lost. Untellable narratives can be misinterpreted.
This misalignment between the stories people tell and the ones listeners expect to hear happens all the time. We’ve all said things misunderstood by others. Sometimes this process is harmless; other times it results in difficult consequences. Dr. Kristiana Willsey writes about veterans who censor themselves in front of civilian audiences. Because civilians usually only expect to hear tales of “war heroes” or “PTSD survivors,” veterans often choose not to tell the full and complicated stories of their service experiences (Willsey, 2015). Dr. Amy Shuman and Carol Bohmer discuss the case of rejected asylum seekers. If asylum applicants don’t tell their stories of oppression and escape in a way that fits immigration officials’ expectations of what a traumatic asylum story should look like, their applications get denied (Shuman & Bohmer, 2016). If we consider just how different any two OCD stories can be and add the public assumption that OCD is an illness of specific doings (hand washing, checking locks) rather than tellings, it highlights just how difficult it is for most of these narratives to get heard, and heard correctly.
Patient/practitioner interactions can be particularly vulnerable to this type of miscommunication. The problem with considering OCD as just a medical issue is that most people don’t think of their lives as medical events. Practitioners enter the room ready to make sense of problems in clinical terms. Patients enter with stories. They share their concerns in a way that cannot be easily separated from their personal frames of reference or cultural understandings of life. Practitioners are often taught to mistrust the details that emerge from these narratives, to kindly but efficiently work around them in order to do their jobs. But for patients, these details are how they make meaning. If misdiagnoses also occur during these interactions, it’s worth taking a closer look at what’s being lost in translation.
Folklore ultimately offers the promise of new solutions to old problems. It allows us to reconsider how we listen to patients, collect data, and address communication issues— all clear benefits in the fight for better diagnostic care. It is also equipped to help us make sense out of the lived reality of OCD— perhaps uniquely so. I see folklore as an exciting potential ally to traditional research and clinical spaces. My hope is that this partnership can help us work more effectively toward our common goals: a better understanding of OCD, and quicker ease for its sufferers.
Works Cited
Dictionary.com. (2023). Creativity. In Random House Unabridged Dictionary. Random House, Inc. https://www.dictionary.com/browse/creativity.
International OCD Foundation. (2025). America’s OCD care crisis: National findings on the failure of effective OCD treatment to research patients. International OCD Foundation. https://iocdf.org/wp-content/uploads/2025/12/Full-Report-Americas-OCD-Care-Crisis-12-9-2025.pdf.
Lindahl, C. (2012). Legends of Hurricane Katrina: The right to be wrong, survivor-to- survivor storytelling, and healing. The Journal of American Folklore, 125 (496), 139–176. https://doi.org/10.5406/jamerfolk.125.496.0139.
McNeill, L. (2013). Folklore rules: A fun, quick, and useful introduction to the field of academic folklore studies. Utah State University Press. https://muse.jhu.edu/book/27822.
Shuman, A. & Bohmer, C. (2016). The stigmatized vernacular: Political asylum and the politics of visibility/recognition. In D. Goldstein & A. Shuman (Eds.), The stigmatized vernacular: Where reflexivity meets untellability. Indiana University Press.
Willsey, K. (2015). Falling out of performance: Pragmatic breakdown in veterans’ storytelling. In T.J. Blank & A. Kitta (Eds.), Diagnosing folklore: Perspectives on disability, health and trauma. University Press of Mississippi.
The post Centering People, Centering Stories: Folklore as an Unlikely Ally in the OCD Misdiagnosis Crisis appeared first on International OCD Foundation.
BrainBaseline Assessment of Cognition and Everyday Functioning (“BRACE”-ing for the Future): Establishing iPad-Based Norms for Cognitive Function in the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study Combined Cohort Study
Background: Digital cognitive assessments are increasingly used in large-scale studies to assess brain health, offering scalable, standardized, and self-directed testing solutions. Cognitive function remains a concern for people with HIV despite antiretroviral therapy. The BRACE (BrainBaseline Assessment of Cognition and Everyday Functioning) is a validated tablet-based screener for cognition in people with HIV. Preliminary pilot norms were established in a small sample (n=144), but full regression-based normative data have not yet been developed. Consequently, HIV serostatus differences based on standardized BRACE scores and cognitive correlates have not been systematically examined. Objective: This study aims to develop regression-based normative data for BRACE performance in people without HIV who were demographically and behaviorally comparable to people with HIV within biological sex; to examine differences in cognitive performance by HIV status and biological sex; and to evaluate sociodemographic, behavioral, and clinical correlates of BRACE performance. Methods: A total of 2937 participants (1063 people without HIV [499 women] and 1874 people with HIV [1053 women]) in the Multicenter AIDS Cohort Study/Women’s Interagency HIV Study Combined Cohort Study completed BRACE once between November 2020 and March 2025. BRACE includes the Trail Making Test (A and B), Stroop-Color, and visual spatial learning. Regression-based norms were derived from people without HIV using multiple demographic models (eg, age-only, age + education, and age + education + sex). The age + education model was selected for primary analyses because it provided the best balance of interpretability, parsimony, and generalizability while avoiding race-based corrections. HIV serostatus and sex differences were examined using ANOVA and tests, with effect sizes calculated using Cohen’s . Results: Cognitive performance was largely comparable between people with HIV and people without HIV across all BRACE outcome measures. Statistically significant differences were very small in magnitude (all effect sizes<0.11) and primarily observed among men on Stroop-Color. Across groups, older age and fewer years of education were associated with poorer raw BRACE performance, although these associations attenuated after demographic adjustment using T-scores. Most clinical and behavioral factors (eg, hypertension, smoking, and noncannabis substance use) were related to poorer raw scores but not standardized performance. However, diabetes and cannabis use remained independently associated with T-scores across multiple measures—diabetes with poorer scores and cannabis use with higher scores, an association that should be interpreted cautiously. HIV-specific clinical factors, such as nadir CD4 count and antiretroviral therapy duration, were linked primarily to raw scores. Conclusions: This study establishes the first regression-based normative data for BRACE, derived from a large, demographically diverse people without HIV, and demonstrates its applicability for evaluating cognitive function in people with HIV. Findings indicate minimal cognitive differences between people with HIV and people without HIV and highlight the influence of common sociodemographic and metabolic factors. These results support BRACE as a scalable, reliable, and self-administered digital tool for assessing cognitive health in diverse populations and underscore its potential for longitudinal monitoring and precision phenotyping in both research and clinical contexts.
New Study Identifies Different Biological Subtypes of Autism
Research findings help explain why symptoms present so differently from one child to the next, and why individualized supports and interventions are essential.
Autism can look very different from person to person. One child might differ from another in how they learn, process sensory information, and experience social and communication challenges. Scientists have long suspected these differences stem from distinct biology, but proving it has been challenging — until now.
A recent study published in Nature Neuroscience has identified two biological subtypes of autism linked to different pathways in the brain.
Researchers from the Child Mind Institute, the Istituto Italiano di Tecnologia, and other international partners analyzed brain connection patterns in nearly 2,000 individuals, including 940 autistic people from the Autism Brain Imaging Data Exchange (ABIDE). By combining human brain-imaging datasets with complementary biological data, they identified two consistent patterns in how different brain regions communicate.
One subtype showed reduced communication, or hypoconnectivity, among brain regions linked to pathways that help brain cells send signals to one another. The other showed increased communication, or hyperconnectivity, among brain regions linked to pathways associated with the immune system. The two subtypes exhibited differences in functional brain structure and modest differences on standardized autism assessments, with the hyperconnectivity subtype scoring moderately higher on autism severity measures.
These findings give scientists the first empirically biology-based framework for understanding autism’s complexities over time. This type of work could move the field closer to more precise, personalized approaches to medicine and care. However, this does not mean autism can now be divided into just two categories, nor does it create a new diagnostic framework. Autism is complex, and these two subtypes are likely part of a much larger picture.
The study also highlights the importance of open science. Through shared datasets like ABIDE, researchers can tackle questions too large for a single lab to answer alone.
The post New Study Identifies Different Biological Subtypes of Autism appeared first on Child Mind Institute.
When AI Colludes: Clinical Reliability of Training and Preference Data as a Trustworthy-AI Criterion
Research on artificial intelligence (AI) and mental health has focused largely on harms at deployment, including chatbot safety, sycophancy, and AI-associated delusions. Less attention has been paid to a prior question: whether the human-generated text and preference judgments that shape large language models are themselves clinically reliable, particularly when self-report may be distorted. This Viewpoint aims to develop the clinical psychiatric construct of collusion—the uncritical acceptance of an unreliable account—as an analytic lens for AI training and deployment, and to argue that the clinical reliability of training and preference data should be treated as an explicit trustworthy-AI criterion in mental-health–relevant systems. A conceptual synthesis of psychiatry, clinical psychology, and AI safety literature was undertaken. The analysis distinguishes three pipeline layers: pretraining corpora, preference data and posttraining methods, and deployment-time interaction. It maps the clinical construct of collusion against adjacent technical concepts, including sycophancy, reward overoptimization, grounding, refusal training, red-teaming, and live monitoring. The synthesis suggests that collusion-like dynamics are least applicable at the pretraining layer and most applicable at the preference-data and deployment layers, where unassessed user or labeler input can be reinforced without corroboration. Existing mitigations, including data curation, Constitutional AI, reward-model evaluation, grounded generation, refusal training, red-teaming, and postdeployment monitoring, address parts of this problem. However, these approaches are not yet organized around a clinically informed account of when self-report is unreliable. The central novelty is therefore not a generic claim about bias, but the proposal that clinical self-report reliability should be assessed as a distinct data-quality and governance dimension. Trustworthy-AI frameworks for mental-health–relevant applications should incorporate clinical expertise in self-report reliability into preference-data design, red-teaming, and postmarket surveillance. Adding the clinical reliability of training and preference data as an explicit criterion could complement existing technical safeguards while leaving empirical evaluation of clinician involvement as an open research agenda.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/5de93d37e885a1e423959daac50674dc" />
Efficacy of a World Health Organization–Guided Self-Help Intervention for Reducing Psychological Distress in Afghan Refugees: Randomized Controlled Trial
Background: Common mental health disorders are highly prevalent among refugees. There is an urgent need to address the mental health burden in this population. Objective: This study tested the efficacy of an individually supported self-help stress-management intervention developed by the World Health Organization—Doing What Matters in Times of Stress (DWM)—in reducing psychological distress and improving functioning among refugees in Indonesia, a major transit country in the Asia-Pacific region. Methods: A single-blind randomized controlled trial with 303 Farsi-speaking refugees was conducted between June 2024 and June 2025. Participants with moderate to high psychological distress (Kessler Psychological Distress Scale [K10] score≥20) were randomly allocated to the facilitator-guided individual DWM condition (n=202) or a repeated assessment control condition (n=101). The primary outcome was psychological distress (K10 score) at the posttreatment assessment. Secondary outcomes were posttraumatic stress disorder symptoms, functional impairment, social functioning, and personally identified problems. Results: Intent-to-treat analysis indicated that participants in the DWM condition showed greater reductions in K10 scores than those in the repeated assessment control condition (posttreatment: =−.563, SE=0.124; <.001; Cohen =0.56; 1-month follow-up: =−.447, SE=0.140; =.002; Cohen =0.45). Similarly, those participants in the DWM condition reported greater improvements in posttraumatic stress disorder symptoms, well-being, social functioning, functional impairment, and personally identified psychological problems. No serious adverse events were reported. Conclusions: The findings provide the first evidence for the effectiveness of DWM in reducing psychological distress and improving overall functioning among urban refugees living in a transit setting. Individually supported self-help interventions such as DWM mayoffer an effective, feasible, and scalable approach to improving mental health for refugees. Trial Registration: ANZCTR ACTRN12624000609550; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=387637&isReview=true
Drug Target for Fragile X Syndrome Identified Through Preclinical Study
UCLA Health researchers have identified a potential drug target for treating fragile X syndrome (FXS), the most common genetic cause of intellectual disability and autism that affects roughly one in 2,000 boys.
Fragile X syndrome is caused by a mutation in a single gene, FMR1, that results in the loss of a protein critical for normal brain development and function. Headed by Carlos Portera-Cailliau, MD, PhD, professor of neurology at UCLA and member of the UCLA Brain Research Institute, the researchers, the team’s work in genetically engineered mice lacking the Fmr1 gene identified the synaptic protein EPAC2 as a potential therapeutic target for fragile X syndrome. Their study showed that blocking EPAC2 in the fragile X mouse model restored abnormal patterns of brain activity and improved several FXS-associated behavioral symptoms.
Pertera-Cailliau is senior and corresponding author of the researchers published paper in Neuron, titled “Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of fragile X mice and identifies EPAC2 as a therapeutic target.”
Fragile X syndrome is a prototypical neurodevelopmental disorder (NDD) characterized by intellectual disability, social anxiety, atypical sensory processing characterized heightened sensitivity to sensory input such as sound and touch, and a higher risk of seizures. Many also meet the criteria for an autism spectrum disorder diagnosis. “Symptoms of fragile X syndrome (FXS), the leading monogenic cause of intellectual disability and autism, are thought to arise from an excitation/inhibition (E/I) imbalance,” the authors stated.
FXS is caused by mutations in the FMR1 gene, resulting in near complete loss of the fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein in neurons that plays different roles in cell compartments including the nucleus, axons and dendrites, including regulating mRNA translation at synapses, they explained. As it is caused by a change in a single gene, fragile X syndrome has long been considered a promising candidate for targeted therapies yet clinical trials to date have not produced an effective treatment. “Since the discovery of the genetic basis of FXS in 1991, several clinical trials have been undertaken—without success—and no specific treatments for FXS are currently available,” the investigators continued. “Thus, there is an urgent need to rethink therapeutic strategies for FXS.”
For their newly reported study the researchers used genetically engineered knockout (KO) mice that lack Fmr1 to simulate fragile X syndrome. Using genetic sequencing, they found that levels of the gene EPAC2 were increased in the brain of fragile X mice. This was of potential interest as a target for therapy because the gene’s protein, EPAC2, is localized to synapses and is known to be important for learning and memory.
The researchers then demonstrated that blocking EPAC2 in the fragile X mouse model, either genetically, or using an EPAC2 inhibitor compound, restored cortical circuit function and improved multiple behavioral symptoms associated with fragile X syndrome, including heightened sensitivity to touch, difficulties with social interaction and their susceptibility for seizures. “Perhaps the most exciting result is that treatment with an EPAC2 antagonist can rescue several behavioral phenotypes in Fmr1 KO mice,” the authors stated.
“EPAC2 emerged as an attractive target because it was consistently altered across multiple types of brain cells in our analysis,” said the study’s first author Anand Suresh, PhD, a post-doctoral fellow in the laboratory of Portera-Cailliau. “When we blocked it, either genetically or with a drug compound, we saw meaningful improvements in both brain circuit function and behavior.”
EPAC2 is expressed almost exclusively in the brain, which means drugs targeting it are less likely to cause unwanted effects elsewhere in the body. Suresh said this is an important consideration as researchers continue preclinical studies. “This bodes well for future preclinical trials and safety studies in humans, as compounds that target EPAC2 should not have off-target effects,” the authors stated in their report.
For their study the UCLA investigators used an RNA sequencing technique to examine gene activity separately in two major classes of brain cells: those that excite and those that inhibit neural activity. Fragile X syndrome is thought to arise from an imbalance between these two systems. The analysis revealed striking differences in how the genetic mutation underlying Fragile X syndrome affects each cell type but also identified a small set of genes, including the one that encodes EPAC2, that were dysregulated in both.
The researchers also found that EPAC2 levels appear to rise gradually as the brain matures, suggesting it may be a particularly relevant target for older children and adults with Fragile X syndrome, rather than only in early development. They concluded, “Our results should encourage the development of novel EPAC2 inhibitors for the treatment of FXS. More generally, our study exemplifies how transcriptomic approaches in animal models of neuropsychiatric conditions can be used to prioritize potential novel therapeutic targets.”
The post Drug Target for Fragile X Syndrome Identified Through Preclinical Study appeared first on GEN – Genetic Engineering and Biotechnology News.