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Brain Histamine Map Links Genetic Factors to Mental Health and Psychiatric Disorders

A study headed by researchers at King’s College London and the University of Porto has mapped the histamine system in the brain. Histamine, a molecule more commonly associated with allergies, plays a separate but poorly understood role in brain function. The new study addresses this gap, building the first multiscale map of the histamine system which spans from genetics to behavior and related mental health conditions.

The findings provide a new framework for understanding how this often-overlooked chemical system contributes to brain function and could point towards new treatment strategies for histamine-related conditions such as depression, ADHD, and schizophrenia. The study was funded by the National institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre.

Daniel Martins, MD, PhD, visiting senior research fellow at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London, said, “This work provides a crucial foundation for future research. By integrating molecular biology, brain imaging, and computational analysis, it offers a new perspective on how neurotransmitter systems are organized across the human brain. As neuroscience moves toward more integrated and personalized models of mental health, understanding systems like histamine may prove essential for unlocking new approaches to diagnosis and treatment.”

Martins is first and corresponding author of the team’s published paper in Nature Mental Health, which is titled “Mapping histamine pathway networks in the human brain across cognition and psychiatric disorders.” In their paper the team concluded, “This study provides an integrated characterization of the histaminergic system in the human brain, leveraging transcriptomic, neuroimaging, and functional datasets to delineate its molecular organization and relevance to brain function underlying cognition and psychiatric disorders.”

Histamine is a neurotransmitter, a molecule crucial for neurons to communicate with one another, the authors explained. “Neuronal histamine plays a crucial role in the regulation of brain function, serving as a neuromodulator with widespread influence across multiple neurotransmitter systems.” However, neuroscience research has classically focused on understanding other neurotransmitter systems such as dopamine and serotonin.

As the investigators noted, the organization of histamine in the human brain remains incompletely characterized. However, they explained, dysregulation of the histaminergic system has been implicated in a number of neuropsychiatric conditions, including anxiety, depression, schizophrenia, and autism spectrum disorder (ASD), as well as neurodegenerative diseases including Alzheimer’s, Parkinson’s, and Huntington’s diseases. “Therefore, targeting the brain histamine system has garnered significant attention as a potential new therapeutic strategy for treating these disorders, with pharmacological interventions aimed at modulating histamine receptor activity showing promise in preclinical models.”

Histamine acts through four known histamine receptors, which are responsible for how the signal will influence receiver neurons. Each of these histamine receptors, (histamine receptor H1 (encoded by HRH1), H2 (HRH2), H3  (HRH3) and H4 (HRH4)), mediates distinct functions. For their newly reported study, Martins and colleagues carried out what they described as multimodal analysis, integrating transcriptomic, neuroimaging, developmental and functional datasets to map the architecture of the histaminergic system.

To build a comprehensive map of how histamine acts in the brain, researchers first combined genetic and molecular data with physical maps of the brain.

This revealed which brain regions receive more input from the brain’s histamine system, and which parts show greater capacity to respond to histamine. These molecular data were then linked with positron emission tomography imaging of histamine receptors in living individuals, as well as functional neuroimaging databases that map brain regions to specific cognitive processes and mental health conditions. This type of scan shows how different parts of the brain are working by tracking a tiny amount of radioactive tracer in real time.

Their results found that different histamine receptors were found on brain cells that either turn activity up (excitation) or turn it down (inhibition). “The findings reveal that histaminergic genes exhibit distinct cellular and regional expression profiles, closely aligning with known histaminergic neuroanatomy and function,” they wrote. “At the single-cell level, histamine receptor H1 and histamine receptor H2 were enriched in excitatory neurons, whereas histamine receptor H3 showed preferential expression in inhibitory populations.” This suggests histamine may be important in maintaining the balance between excitation and inhibition, a fundamental property of healthy brain function.

Brain regions with higher histamine-related gene expression were consistently associated with processes such as emotional regulation, stress and fear responses, decision-making, impulsivity, reward, sleep, and memory.

The parts of the brain where histamine-related genes were most active also overlapped significantly with brain regions known to be affected in several psychiatric conditions, including attention-deficit/hyperactivity disorder, major depressive disorder, schizophrenia, and anorexia nervosa. This is in keeping with previous hypotheses linking histamine to these disorders. “By linking histaminergic gene expression to brain-cell types, neurotransmitter systems, cognitive domains and psychiatric disorders, these correlational findings generate several hypotheses concerning histamine’s critical role in brain organization, neurodevelopment and mental health, which further experimental mechanistic work should prioritize and build onto investigate causal relationships,” the investigators concluded.

Martins said, “Current psychiatric treatments largely target neurotransmitters such as serotonin and dopamine, yet histamine interacts closely with these systems and influences their activity. By providing a detailed map of histamine-related pathways, this work suggests new opportunities for developing treatments that target this system more directly, particularly for symptoms such as cognitive dysfunction, fatigue, and impaired motivation.

While these findings do not establish a direct causal role, they suggest that histamine signalling may contribute to regional vulnerability in these disorders. This aligns with a growing view in psychiatry that mental health conditions arise from disruptions across interacting brain systems rather than a single chemical imbalance.”

This new map paints a neural picture of a previously lesser-studied molecule. It opens up future avenues of research into exactly what histamine is doing in various cell types and parts of the brain.

“We want to emphasise that these findings are hypothesis-generating and based on large-scale datasets that capture patterns rather than direct mechanisms,” commented senior author Steve Williams, PhD, professor of neuroimaging at IoPPN King’s College London. Future studies will focus on testing how histamine signaling changes in living individuals, for example through pharmacological interventions or longitudinal imaging approaches.

Co-author Daniel Van Wamelen, PhD, clinical senior lecturer in neuroscience at IoPPN, King’s College London and one of the authors on the paper said: “This kind of work is already taking place at King’s College London, for example in the iMarkHD project. In this project we use Positron Emission Tomography scans to study a specific histamine receptor (called H3) in people with Huntington’s disease, an inherited condition that affects the brain. The goal is to see how histamine activity changes in different parts of the brain over time, and how these changes relate to symptoms such as apathy, depression, and anxiety.”

The post Brain Histamine Map Links Genetic Factors to Mental Health and Psychiatric Disorders appeared first on GEN – Genetic Engineering and Biotechnology News.

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Surf Therapy: A Powerful Low-Intensity Approach in Global Youth Mental Health Care

By Mai El Shoush, Partnerships Campaign Manager, Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute

In Conversation with Waves for Change

The world’s oceans have long been profound forces that shape coastlines, cultures, and scientific discovery. And today, through targeted programs, they also serve as therapeutic environments transforming youth mental health worldwide.

As global health systems continue to explore solutions that minimize resource constraints while addressing child and adolescent mental health demands, innovative approaches like surf therapy are demonstrating remarkable effectiveness as low-intensity initiatives. From the beaches of California to the coastal communities of South Africa, Australia, Hawai’i, the United Kingdom, and Senegal, these programs are creating accessible entry points for young people.

Wave for Change (W4C) — a South Africa-based organization and valued implementation partner of the Stavros Niarchos Foundation (SNF) Global Center at the Child Mind Institute — has developed an evidence-based Surf Therapy program for youth in underserved communities. We spoke with their chief development officer Paula Yarrow and senior grant manager Jill Sloan about the award-winning program. As a highly regarded Cape Town‑based NGO that uses surfing as a therapeutic tool to support youth mental health, W4C offers safe spaces, evidence‑based emotional regulation tools, community mentorship, and a pathway to resilience for young people growing up in challenging environments.

The partnership includes the identification of workforce gaps and training needs for frontline workers such as NGOs, to further expand evidence-based support and brief interventions through culturally appropriate, low-intensity psychological therapy approaches. The context-specific training materials are expected to be piloted later in the year in South Africa and are intended to improve access to quality mental health care for young people.

W4C launched Surf Therapy in 2009, which has since helped more than 10,000 adolescents experiencing high-stress environments gain valuable coping skills across its hubs in the Western and Eastern Cape as well as Cape Town. Participants learn how to build positive social networks and develop self-regulation skills to support healthy emotional and behavioral responses to stress, with coaches themselves aged between 18-25. The program creates a fun, culturally relevant environment through the Take 5 model — a framework W4C has designed to be adapted for a range of sports, arts, and cultural initiatives. The model has been utilized by several leading global organizations, including UNICEF.

Waves for Change also played a key role in the founding of the International Surf Therapy Organization (ISTO), connecting practitioners, clinicians, and researchers to advance science research, raise awareness, and support surf therapy.

Catching a wave at Surf Therapy – Image Nelson Rosier Coulhan

How does Waves for Change use evidence-based Surf Therapy and capacity building as a solution to fill the gap in youth mental health care?

Approximately 90 percent of the world’s adolescents live in low- and middle-income countries (LMICs). In the most underserved communities, adolescents may experience repeated exposure to violence, unmet basic needs, and limited access to safe spaces or trusted caregivers. Typically, there are very few mental health services that are accessible to such youth.

The more Adverse Childhood Experiences (ACEs) a child or adolescent has whilst growing up, the more likely they are to develop toxic stress — an ongoing stress state without respite. This can often lead to mental health conditions such as anxiety, depression, substance misuse, and cognitive impairment. This can also result in the development of physical health conditions such as heart disease as they grow into adulthood.

The main problem we’ve identified is that there aren’t enough trained workforces (e.g., sports coaches, youth facilitators) that are able to deliver simple, fun, structured play-based sessions with consistency at scale. Our work provides a response to this issue within the adolescent mental health promotion and illness prevention arena. Additionally, our initiatives significantly increase the number of individuals — coaches, teachers, mentors or others — who are already in contact with young adolescents and can provide them with mental health support to foster their immediate and longer-term mental health.

How has Waves for Change adapted the organization’s Surf Therapy program to develop the Take 5 model?

Waves for Change’s Take 5 training model has been incubated, tested, and rigorously evaluated within W4C’s award-winning Surf Therapy program. Take 5 distils the key components of our Surf Therapy program, providing coaches with the essential skills they need to build and sustain caring relationships with children. And it uses a simple teaching routine that creates consistently engaging, fun, structured programs for children and adolescents that suit their language, culture, and context.

Take 5 is low intensity and cost-effective — tailored for high-stress environments and the unique mental wellness needs of adolescents living in multidimensional poverty, conflict, or crisis.

How has partnering with young people to research and co-develop programs made the work more impactful?

In research studies we’ve conducted, adolescent participants (ages 10-16) reported experiencing between 6-8 adverse events every year, including violence and abuse. When asked what sorts of spaces they wanted to see at Waves for Change, the adolescents identified core components such as access to a safe space where they could have fun, be heard, and learn skills to cope. These components now form the bedrock of our Surf Therapy program. We initially worked with 9-12-year-olds and have since developed the follow-on programme for adolescents up to age 16 who have graduated the Surf Therapy programme. This is called Surf Club and is available to all Surf Therapy graduates.

Waves for Change also conducts pre- and post-intervention surveys with participants to monitor the impact of our work. Our coaches (ages 18-25) are at the frontline of delivering our services. A key role they play is to listen with care and respect to the adolescents’ concerns, and to share them with our Child Protection team for review and follow-up when needed.

Surf Therapy at Hout Bay – Photo credit Waves for Change

What makes your partnership with the SNF Global Center at the Child Mind Institute unique?

Working with the Child Mind Institute allows Waves for Change to collaborate with and learn from colleagues doing similar work in the adolescent mental health space across South Africa, the United Kingdom, and Brazil. The partnership offers an opportunity to learn about approaches that have been successful in other health systems. It has also allowed Waves for Change to share detailed information about the training and supervision protocol used to develop key competencies in the coach workforce that leads Surf Therapy in South Africa. This has helped the Child Mind Institute to develop a comprehensive guide for other similar workforces.

Can you expand on the importance of partnerships in strengthening youth mental health care and community empowerment?

Partnerships allow for the consolidation of skills and resources so that a greater impact can be achieved. For example, at Waves for Change, we work with over 70 referral partners every year to identify young adolescents who can benefit from our Surf Therapy program. We are also partnering with the Department of Cultural Affairs and Sport to use our Take 5 model to train MOD and YearBeyond coaches and mentors, who are already reaching large numbers of children and young adolescents through their work. And we’re contributing to building the broader ecosystem of mental health support for adolescents and children by training large national NGOs, government agencies, and humanitarian organizations with our Take 5 model.

How can non-profits further help foster strong peer networks and inclusive safe spaces?

Some of the key lessons we have learnt are the following:

  • In the field of youth mental health, make youth the leaders on program implementation
  • Provide youth with skills, opportunities, supervision, and support so that they can grow and develop further
  • Maintain a strong culture of protection, respect, and communication so that all participants feel safe, welcome, accepted, and heard

Read more about W4C’s Surf Therapy from Youth Liaison Officer, Azola Sibanda and Training Manager Jamie-Lee Davids

The post Surf Therapy: A Powerful Low-Intensity Approach in Global Youth Mental Health Care appeared first on Child Mind Institute.

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What Is Traumatic Separation?

You may have a memory of being separated from a parent when you were a child, even just for a few minutes. Maybe you lost them in a crowd or wandered a little too far at the store and felt panicked and afraid.

A moment like this might be among your earliest memories because the feeling was so intense, says Caitlyn Downie, LCSW, the Director of Trauma and Resilience at the Child Mind Institute. That offers some insight into the fear of a child of any age who is separated from a parent or caregiver in a more serious way. The effects of this stress are so powerful they can actually change the way a child develops.

A toddler whose mother goes to prison. A kindergartener whose father is detained and deported. A teen who is placed in foster care. These are a few examples of what experts call traumatic separation, a clinical concept based on the importance of the parent-child bond and the profound effects that can result from breaking it.

What is traumatic separation?

Traumatic separation isn’t a clinical diagnosis, but research shows that it can be profoundly harmful to kids. What makes it traumatic (as opposed to routine partings, like when an adult regularly leaves their child to go to work) is the character of the separation: ones that are sudden, unexpected, or confusing, or those that come about through larger distressing events, like a natural disaster or war. It’s not defined by the time spent apart — both short and long-term separations can be harmful.

Some common examples of separation that can become traumatic include:

  • Parental deportation
  • Immigration (e.g., forced separation at the border)
  • Parental military deployment
  • Parental incarceration
  • Termination of parental rights

Separating from a parent or primary caregiver can be distressing to a child even when it’s deemed necessary for their safety, as in cases where the parent they have been separated from has abused them, says Kimberly Alexander, PsyD, a psychologist at the Child Mind Institute. “There’s still a natural attachment that occurs. And the separation disrupts that relationship, even if it’s for the support and care of the child.”

Why is traumatic separation harmful?

More than eight decades of research has shown the profound developmental importance of the parent-child bond. This is the guiding principle of attachment theory, which was pioneered by a British psychologist who studied children who were evacuated during the Blitz, the aerial bombardment of London in World War II.

Here’s what the research tells us about the harms of traumatic separation:

It can disrupt secure attachment

Think of secure attachment as a “fundamental sense of security and safety” that a child feels with a parent or caregiver, says Dylan Gee, PhD, a psychologist at Yale University who studies how early-life stress affects children’s development.

“Attachment is the lens through which children come to know what they can expect from the world around them,” she explains. “Is this going to be a safe place or a dangerous place? This is foundational to a child’s sense of their ability to navigate the world. Traumatic separation can shatter that sense of safety.”

It can affect neurobiological development

Children’s brains are especially plastic, says Dr. Gee, constantly learning to understand their environment and how to deal with stress. “Trauma that occurs in childhood can be even more consequential than trauma that occurs later in life,” she says, and experiencing these disruptions in childhood can affect the way your brain and body are primed to react to stress later on.

But heightened plasticity is a paradox, she adds. “It confers more vulnerability, but it also confers more potential for resilience — children have heightened potential for supportive intervention and for healing and recovery.”

What do the effects of traumatic separation look like?

There are acute and short-term effects that are common across kids of all ages:

Sleep problems: “It’s often one of the first things that we see: nightmares, trouble falling asleep, or a lot of crying as kids are trying to fall asleep,” Dr. Gee says.

Separation anxiety: This might look like distraction, withdrawal, or clinginess because of fear of being separated from their new caregivers, Dr. Alexander says.

But signs may take weeks or months to show up. Dr. Alexander advises caregivers to consider the child’s baseline — their typical patterns of eating, sleeping, or engaging with others. “If they’re having more trouble with sleep, they’re eating more, eating less, they’re withdrawing or expressing a lot of worried thoughts three or four months later — that’s something worth getting looked at by a clinician,” she says.

Signs of traumatic separation at different ages

“Sometimes people ask, ‘Well, when is separation the most harmful?’ It can be extremely harmful at any age,” Dr. Gee emphasizes. But there are specific signs at different developmental stages:

Infants

Babies may not be as consciously aware of being separated from a parent as older children, “but they’re fundamentally aware that their primary source of regulation and safety is missing,” Dr. Gee says. Because infants are so reliant on caregivers for nurturing and sustenance, the separation “can be experienced as a threat to their survival.” That might look like “crying a lot or becoming withdrawn,” she says. “And at any age we can see intense fear.”

Toddlers and young children (3–6)

Toddlers and young children might become extra clingy with new caregivers or show regressive behaviors like bedwetting or baby talk. Regressive behaviors happen when kids are overwhelmed by stress and can’t express themselves another way, Downie says. “It’s like your nervous system goes kind of haywire,” she explains, “so it uses the body to signal that something is wrong.”

Similarly, kids at this age might act out more, throwing more tantrums, or withdraw. They might develop selective mutism, a condition where kids are too anxious or distressed to speak, even when they want to, in certain situations or with certain people.

School-age children

School-age children might act out or experience separation anxiety. They may also struggle to understand the meaning of the separation, why it happened, or who is at fault for it. Thus, kids at this age are more prone to magical or distorted thinking and feelings of guilt, thinking or saying things like, “I’m the one that caused this” or “This is my fault.”

The weight of these distorted thoughts or other worries, Dr. Alexander says, might make it appear as though a child is struggling to concentrate or that they’re disengaged or distracted. They might withdraw in a group or be averse to stepping outside of their comfort zone.

Children who are school age or older can also experience emotional desensitization — a kind of emptiness of feeling — Downie says, which can look like spikes in irritability, a lack of empathy, not smiling or expressing positive emotions, or an inability to relate to others.

Preteens and teenagers

“I’ve seen teenagers have a lot of mistrust with systems and be very oppositional,” says Downie. “Like, ‘I don’t trust you. I don’t trust my teacher. I don’t trust this child services worker.’” It might make sense that, say, a teen in foster care would be wary of the foster care system. But Downie says it’s often a larger instinct for anger and mistrust, one that extends beyond any specific entity or person.

The teenage years are also when kids are forming their identity, and traumatic separation can fundamentally alter that process. For example, a teen with younger siblings may step into a parent role, taking on new worries and responsibilities. Conversely, teens may become more reckless in a caregiver’s absence, putting them at risk for substance abuse or incarceration.

How to help kids separated from a parent

Adults caring for a child who has been separated from a parent — family members, foster parents, teachers — “can play a profound role in supporting their mental health and resilience,” says Dr. Gee.

Validate feelings

One of the most important things caregivers can do is be present as a child reacts to their experiences, especially if and when scary feelings come up. But be careful not to lead kids or assume they feel a certain way. “You don’t want to make something more distressing to a child if it’s not presenting itself,” says Downie.

If a child expresses guilt, or says something like, “This is my fault,” there are still ways to validate the feeling without endorsing the statement, says Dr. Alexander. You might say something like: “I can understand why that thought comes to mind and how difficult it is to feel that way. When you’re ready, let’s think about other possibilities to this situation.”

Create consistency and stability

One of the hardest things about traumatic separation is the uncertainty — Where did they go? When will they come back? What is happening? Giving kids some sense of consistency and stability can help them feel safe despite the unknowns. So as much as possible, help them stick to any routines: going to school, seeing friends, doing activities they enjoy.

Dr. Alexander advises focusing on things you can control — for example, shielding kids from potentially worrying discussions in a family where a parent has been deported.

“There would likely be a lot of conversations in the home about the situation, maybe a lot of watching the news, maybe making a lot of phone calls to attorneys,” she explains. “So where are you having those conversations, and can you have them in an area or at a time of day where your kid isn’t overhearing the discussions out of context?”

For young kids, it might be as simple as asking them to play in their room. For teens, it might be better to have certain conversations when they are out of the house and invite them to participate directly in others.

Be honest but reassuring

Caregivers might not have all the answers — like knowing when a child’s parent is coming back — but they can create a sense of consistency and stability in how they respond to kids’ questions, too.

Avoid undue reassurance (“Everything is going to be fine”) or over-promising (“They’ll be back in two weeks”) by focusing on what kids can expect, says Dr. Gee. For example: “What I can tell you is that I’m here for you, and I’m going to be with you until he’s back,” or “You’re safe with me, and I’m going to stay with you through this really hard time.”

Model handling stress

Children are sensitive to tone, Dr. Alexander says. “So, if you’re having really big emotions that are out of context for a child, the child is looking at these emotions and trying to understand what’s happening. ‘Am I in danger in this specific moment?’”

She says it helps to have conversations about these moments, especially with younger kids. “Like, ‘I know you noticed mommy crying. We’re feeling really big feelings, and this is how we’re going to deal with those big feelings. I’m going to take a break. I’m going to get a sip of water. Whenever you’re having big feelings, I want you to let me know so that I can help you try doing the same things,’” Dr. Alexander says, explaining the importance of naming the emotion and then teaching kids that there are ways of dealing with it.

Long-term risks of traumatic separation

The effects of traumatic separation can persist even after a child and their caregiver are reunited. Traumatic separation, like other adverse childhood experiences, puts kids at risk for a host of long-term medical and mental health conditions, including depression, anxiety, attention issues, and post-traumatic stress disorder (PTSD).

But Downie notes that not everyone who experiences traumatic separation develops PTSD. “Just because someone’s experiencing trauma now doesn’t mean that it’s going to become a PTSD diagnosis,” she says. “A lot of the behaviors that we’re talking about are normal and expected. There’s an adjustment period when a separation happens.” But if symptoms persist or escalate over several months, a child may need more serious support.

Treatment for a trauma diagnosis

While not every child who experiences a separation may receive a trauma diagnosis or require treatment, cognitive behavioral therapy (CBT) — and the more specific trauma-focused cognitive behavioral therapy (TF-CBT) — is the “gold standard,” says Downie. TF-CBT is specifically for children experiencing trauma-related symptoms. An important component of TF-CBT is creating a trauma narrative, where kids create a story about what happened to help them process it. “But if you have a child who is not ready to process and integrate that trauma, you can’t force the pacing of the treatment,” she says.

In short, a good clinician will follow a child’s lead — even if that means just sitting in the same room with them to build trust. “People really need to feel like they’re being heard and that they can trust someone,” Downie says. Which is why a supportive caregiver or trusted adult can make a big difference.

“If people can take anything away from this, it’s that you want to make kids understand that that they’re not responsible for what’s happened and that people do care about them,” Downie says. “Kids are really resilient, and they can adapt in a good-enough environment. They don’t have to have everything to be successful.”

The post What Is Traumatic Separation? appeared first on Child Mind Institute.

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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
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Noise, air pollution exposure and attention-deficit/hyperactivity disorder: a meta-analysis

ObjectiveThis meta-analysis evaluated the associations between noise exposure, air pollutants, and attention-deficit/hyperactivity disorder (ADHD) in children, aiming to inform future prevention strategies.MethodsStudies were systematically retrieved from CNKI, Wanfang, PubMed, Web of Science, Embase, and the Cochrane Library, covering publications from inception to November 2025. Heterogeneity was assessed using Cochran’s Q test and the I² statistic. Subgroup analyses, meta-regression, and sensitivity analyses were performed to evaluate the robustness of the findings.ResultsNoise exposure was associated with a small increase in ADHD risk (odds ratio [OR] = 1.03, 95% confidence interval [CI]: 1.01–1.05), with stronger associations for childhood exposure, whereas prenatal exposure showed no significant effect. Given the modest effect size, this finding should be interpreted cautiously. Particulate matter (PM2.5 and PM10) was significantly associated with ADHD in continuous-exposure models—PM2.5 (OR = 1.32, 95% CI: 1.16–1.50) and PM10 (OR = 1.47, 95% CI: 1.15–1.87). In dichotomous models, PM2.5 was not significant, while PM10 remained positively associated (OR = 1.58, 95% CI: 1.11–2.26). Elevated nitrogen dioxide (NO2) exposure was also associated with a modest increase in ADHD risk (OR = 1.11, 95% CI: 1.02–1.20), whereas nitrogen oxides (NOx), ozone (O3), and sulfur dioxide (SO2) did not show significant associations.ConclusionsNoise and several air pollutants (PM2.5, PM10, and NO2) were significantly associated with increased ADHD risk, particularly during childhood exposure. Other pollutants, including O3 and SO2, did not demonstrate significant effects. These findings suggest that environmental noise and several air pollutants may be associated with ADHD; however, some observed associations, particularly for noise and NO2, were modest in magnitude and should be interpreted cautiously. These results reflect observational associations rather than evidence of a strong or causal effect, while the evidence for some pollutants remains limited or inconclusive. Further research is needed to clarify pollutant-specific associations and the role of exposure timing.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42024593274, identifier CRD42024593274; https://www.crd.york.ac.uk/PROSPERO/view/CRD42025632899, identifier CRD42025632899.
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Psilocybin-Induced Brain Changes May Explain Therapeutic Effects

Researchers at University of California, San Francisco and Imperial College London have shown that a single dose of psilocybin, the psychedelic compound found in magic mushrooms, causes likely anatomical brain changes that last for up to a month after the experience.

The study, involving healthy volunteers who had never taken a psychedelic, links temporary shifts in brain “entropy”—which is the diversity of neural activity occurring in the brain—to insight. This suggests the psychedelic trip itself is important to the drug’s longer term therapeutic effects.

The researchers found that a high dose of psilocybin led to increased entropy in the minutes and hours after taking the drug. The degree of entropy predicted how much insight, or emotional self-awareness, the participants felt the next day; and this, in turn, forecasted improvements in their sense of wellbeing a month later.

The findings may help to explain psilocybin’s therapeutic effects on conditions such as depression, anxiety, and addiction. “Psychedelic means ‘psyche-revealing,’ or making the psyche visible,” said senior author Robin Carhart-Harris, PhD, the Ralph Metzner distinguished professor of neurology at UCSF. “Our data shows that such experiences of psychological insight relate to an entropic quality of brain activity and how both are involved in causing subsequent improvements in mental health. It suggests that the trip—and its correlates in the brain—is a key component of how psychedelic therapy works.”  Carhart-Harris is senior and corresponding author of the team’s published paper in Nature Communications, titled “Human brain changes after first psilocybin use.”

“Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown,” the authors wrote. Psilocybin is the precursor of the compound psilocin, a serotonin receptor agonist. “Converging evidence supports a role for serotonin 2A receptor  (5-HT2AR) agonism in eliciting the characteristic brain and subjective effects of this and related psychedelics in humans,” the team continued.

For their newly reported study, Carhart-Harris and colleagues carried out an exploratory, placebo-controlled, within-patient study in 28 psychedelic-naïve participants who each received a single, high-dose (25 mg) of psilocybin. The researchers used an assortment of brain imaging and brain measurement techniques, some of which were carried out during the peak of the psychedelic experience, as well as before and one-month after drug administration. “This was an exploratory, hypothesis-generating mechanistic study in healthy volunteers,” the authors noted. None of the 28 people in the study had a diagnosed mental health condition, which gave the scientists greater freedom to do more testing.

In the first part of the experiment the subjects were given a 1 mg dose of psilocybin, which the researchers regarded as a placebo, and were then monitored with EEG, which records brain activity from electrodes on the scalp.  Over the next few weeks, the researchers measured their subjects’ psychological insight, wellbeing, and cognitive ability. They examined brain activity with functional MRI (fMRI) and brain connectivity with diffusion tensor imaging (DTI).

One month after the placebo, the subjects were given 25 mg of psilocybin, a dose capable of eliciting a strong psychedelic trip. During the experience, researchers again measured the subjects’ brain activity with EEG, and in the following weeks they repeated the same tests they had given after the 1 mg dose.

This enabled the scientists to compare the effects of the psychedelic trip on the brain and mind to the effects of the placebo. “The multimodal neuroimaging design allowed us to observe changes in brain function and (potential) anatomy from 1-h (EEG) to 1-month (DTI) after high-dose psilocybin,” they explained.

The investigators found that within 60 minutes of taking the 25 mg dose of psilocybin, EEG revealed higher entropy, suggesting that the brain was processing a richer body of information under the psychedelic. A month later, the researchers looked at their subjects’ brains using DTI, which measures the diffusion of water along neural tracts in the brain, and found that they were denser and had more integrity. This is the opposite of what happens in aging, which makes these tracts more diffuse.

The researchers cautioned that more work needs to be done to better understand the meaning of this finding, but the result is a never-before-seen sign of how psychedelics can change the brain. ”The inclusion of DTI enabled us to test for long-term changes in the integrity of white matter tracts post psilocybin,” the authors stated. “Results revealed decreased axial diffusivity in prefrontal-subcortical tracts 1-month post 25mg psilocybin.”

The day after the 25 mg dose, all but one of the 28 subjects rated the trip as the “single most” unusual state of consciousness they had ever experienced. The remaining person rated it as among their top five. The study participants said they had experienced more psychological insight after taking the 25 mg of psilocybin than they had after the 1 mg placebo.  The subjects also reported increased wellbeing two and four weeks after the study. This was measured from responses to statements such as, “I’ve been feeling optimistic about the future,” and “I’ve been dealing with problems well.”

As the scientists noted in their paper, “A predictive relationship was also found between brain entropy and longer-term mental-health changes—namely, improved wellbeing. Improved wellbeing could be predicted directly from acute increases in brain entropy as early as 1-h post dosing.”

A month after the study the study individuals also scored better on a test of cognitive flexibility.  “Psilocybin seems to loosen up stereotyped patterns of brain activity and give people the ability to revise entrenched patterns of thought,” said first author Taylor Lyons, PhD, a research associate at Imperial College London. “The fact that these changes track with insight and improved well‑being is especially exciting.”

The scientists found that the subjects who had experienced the largest increases in brain entropy in the minutes to hours after taking psilocybin were the most likely to have increased insight the next day and increased wellbeing a month later. The researchers concluded that improved wellbeing was driven by the experience of insight.

The authors suggest that the study findings could improve treatment for people with mental illness using psilocybin, for example, by ensuring that the right dosage is used to produce the right amount of brain entropy to promote insight. “We already knew psilocybin could be helpful for treating mental illness,” Carhart-Harris said. “But now we have a much better understanding of how.”

In their paper the team concluded, “The present multi-modal neuroimaging study in healthy participants sheds light on the brain effects of first-time high-dose psychedelic use and the therapeutic action of psilocybin-therapy, suggesting that therapeutically relevant changes—i.e., improved wellbeing—can be forecast via an acute human brain action, i.e., an entropic brain effect, that is well-known to relate to the psychedelic experience … Results support a role for psychological insight in mediating the causal association between the entropic brain effect and potentially enduring improvements in wellbeing.”

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Meta-analysis of the effects of exercise intervention on physical health in individuals undergoing compulsory isolation

BackgroundPhysical health is the basic indicator to evaluate the health of drug addicts after the process of drug rehabilitation. In order to better improve the deficiency degree of physical health of drug addicts, it is necessary to carry out a systematic review.ObjectiveTo explore the effects of exercise intervention on the physical health of individuals undergoing compulsory drug rehabilitation using Meta-Analysis, aiming to provide evidence-based support for improving their physical health.MethodsRandomized controlled trials (RCTs) published between 2019 and December 2024, examining the impact of exercise intervention on the physical health of compulsory detoxification individuals, were retrieved from databases including Web of Science, PubMed, Cochrane Library, Medline, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Chinese Journal Database. The quality of included studies was assessed using the Cochrane risk-of-bias assessment tool. RevMan 5.4 software was employed for heterogeneity testing, effect size synthesis (using mean difference [MD] and 95% confidence interval [CI]), and generation of forest plots, funnel plots, and quality assessment diagrams. Subgroup analyses were performed to evaluate sensitivity and heterogeneity of the included studies.ResultsExercise intervention effectively improved the physical health of compulsory drug rehabilitation individuals, particularly in physical fitness indicators: sit-and-reach test [MD = 3.92, 95%CI = (3.23, 4.62), P<0.001], single-leg standing with eyes closed [MD = 7.03, 95%CI = (6.05, 8.02), P<0.001], grip strength [MD = 1.23, 95%CI=(0.06, 2.39), P = 0.04], and choice reaction time [MD=-0.03, 95%CI=(-0.05, -0.01), P = 0.002]. Improvements in physical function were also observed; however, the increase in vital capacity [MD = 86.81, 95%CI=(-1.56, 175.17), P = 0.05] did not reach statistical significance.ConclusionThis meta-analysis provides evidence that exercise intervention significantly improves specific physical health deficits—namely flexibility (sit-and-reach), balance (single-leg stance), muscular strength (grip strength), cardiopulmonary function (vital capacity), and sensorimotor coordination (choice reaction time)—in individuals undergoing compulsory rehabilitation. It is recommended to adopt a combination of aerobic and traditional fitness exercises, with at least 3 sessions per week, each lasting no less than 40 minutes, and a duration of over 12 weeks, providing scientific evidence for drug rehabilitation practices. These indicators were selected because they directly reflect the multisystem damage (muscular, neural, and cardiorespiratory) caused by chronic substance use. However, this study acknowledges the limitation that psychological and neurocognitive outcomes (e.g., cravings, mood, executive function), which are crucial in addiction treatment, were not included in the eligibility criteria and systematic analysis. The follow-up research will combine physical and psychological indicators to conduct a comprehensive evaluation of the intervention effect of exercise on drug rehabilitation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251029820.
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How adolescent cannabis use reshapes the developing brain — a systematic review

Background and hypothesisCannabis use initiation during adolescence has increased globally, raising concerns about neurodevelopmental consequences during this critical period when the brain undergoes extensive remodeling in cannabinoid receptor-rich regions.Study designThis systematic review examines neurodevelopmental consequences of adolescent cannabis use, focusing on structural brain changes, cognitive impacts, addiction vulnerability, and long-term outcomes. We searched PubMed, EMBASE, PsycINFO, and Web of Science (2000-2025) for studies examining cannabis effects in adolescent populations. Following PRISMA guidelines, two reviewers screened 3,421 records and assessed 156 full-text articles, including studies with neuroimaging, cognitive assessments, or longitudinal follow-up.Study resultsThirty-six studies involving 8,432 participants met criteria: 23 longitudinal cohorts (62.2%), 8 cross-sectional (22.2%), 4 RCTs (11.1%), and 1 case-control study (2.8%). Neuroimaging revealed dose-dependent alterations including reduced prefrontal cortical and hippocampal/amygdala volumes, accelerated cortical thinning in longitudinal studies, and impaired white matter connectivity correlating with initiation age. Cognitive findings were mixed — some showed persistent deficits after prolonged abstinence in adolescent-onset users, others found no effects after controlling for confounders. Epidemiological studies consistently showed elevated addiction risk (ORs 3.9–7.2) in adolescents versus adults. Long-term associations included educational difficulties, mental health problems, and functional impairment, though causal relationships remained unclear.ConclusionsAdolescent cannabis use associates with structural brain changes, elevated addiction risk, and variable cognitive effects, suggesting greater vulnerability versus adult-onset use. However, methodological limitations including confounders, heterogeneous definitions, and observational designs limit causal inference. Findings support age-specific prevention and specialized interventions while highlighting needs for rigorous longitudinal research establishing causality.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifierCRD420251165329.
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Prediction of Relapse Using Digital Technology in People in Recovery From Substance Use Disorders: Early Economic Evaluation With a Case Study of the Subreal App

Background: Many people relapse after achieving abstinence in substance use disorders. Health care providers may scan the horizon for new technologies to predict response that allow interventions to be targeted rather than routine. Currently, no such predictive technologies are available in the United Kingdom. The Subreal app is available for use in research contexts, but no clinical data specific to the app are yet available. Early health economic modeling can use data from the literature to explore characteristics essential for the new technology to be cost-effective. This information can guide developers in setting performance targets and pricing and estimating potential cost savings and/or cost-effectiveness for health care providers. Objective: This study was supported by a UK industry funding body to explore the potential of digital technologies such as the Subreal app to offer cost savings or cost-effectiveness for health care providers. We explored the threshold price and clinical effectiveness required to deliver cost savings and cost-effectiveness in 2 subpopulations with substance use disorders in a UK setting. Methods: Deterministic models were used to estimate costs per relapse and quality-adjusted life years over 1-, 5-, and 20-year time horizons for people who have achieved abstinence after treatment for alcohol or opioid misuse. The intervention was a digital technology predicting relapse, provided—in addition to standard care—for 1 year post achievement of abstinence. In Subreal, biomarker data are collected daily through the app, and artificial intelligence–enhanced risk assessment flags patients who require additional support. The comparator was event-driven, reactive response to relapse. Costs and quality-of-life estimates were calculated using Markov models with data from existing published sources. The base-case estimate of 15% reduction in first-year relapse rates was based on a previous study on a similar but simpler digital technology. Results: Digital technologies such as the Subreal app have the potential to be cost-saving from a UK health and social care perspective, especially when used over a longer time horizon. Assuming a reduction of 15% in first-year relapse rates, digital technologies have the potential to be cost-saving, provided that they do not cost more than £300 (US $400.09) and £460 (US $613.47) per patient per annum for alcohol and opioid use disorders, respectively. No cost was included for postalert care, as it was assumed that this could be met within existing resources. Cost savings would be achieved predominantly through a reduction in treatment requirements as fewer people relapse. Price thresholds would reduce correspondingly if a <15% reduction in relapse rates were achieved. Conclusions: Developers of digital technologies that aim to reduce relapse need to focus on the generation of evidence of clinical effectiveness and develop a commercially sustainable pricing model that allows health care providers to benefit from cost savings.
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A longitudinal analysis of the prevalence of restrictive interventions involving women with mental health conditions, learning disabilities or autism in mental health services in England

IntroductionRestrictive interventions, including physical restraint, seclusion, chemical restraint, and segregation, continue to be used within mental health services, despite sustained policy efforts to promote least-restrictive and trauma-informed care. However, little is known about national trends affecting women, for whom restrictive interventions often carry heightened risks of re-traumatisation and stigma.MethodsWe conducted a longitudinal secondary analysis of publicly available administrative data from the Mental Health Bulletin covering NHS-funded mental health services in England between 2017 and 2025. Annual counts of restrictive interventions involving women were examined relative to the number of women detained under the Mental Health Act to estimate annual rates per 1,000 detained. Regression modelling was used to assess temporal trends overall, by age group and type of restrictive intervention, and interrupted time-series analyses to examine changes following implementation of the Mental Health Units (Use of Force) Act 2018 (“Seni’s Law”). Trends were also examined alongside available national data on restrictive interventions involving men.ResultsRates of restrictive interventions involving women increased by approximately 12 percent per year over the study period, with no evidence of a reduction following the introduction of Seni’s Law. Increases were most pronounced for chemical restraint, seclusion, and segregation, while physical and mechanical restraint remained stable. Restrictive interventions declined among women under 18 but increased consistently across all adult age groups, indicating a widening age-related divergence. Although overall trends broadly mirrored those observed among men, the types of restrictive interventions used and their potential impact may differ, highlighting gendered dimensions in how restrictive practices are experienced and applied.DiscussionDespite extensive national initiatives, restrictive interventions involving women have continued to rise in England, highlighting a persistent gap between policy intent and practice. The findings suggest that legislative frameworks alone are insufficient to achieve meaningful reductions without operational changes in clinical practice, organisational culture, and monitoring systems. Internationally, the study contributes rare gender-disaggregated longitudinal evidence and highlights the need for comparable monitoring systems and coordinated research to inform rights-based, trauma-informed strategies to reduce restrictive interventions in mental health services.