BackgroundSchizophrenia frequently co-occurs with alcohol use disorder (AUD), resulting in a complex clinical profile associated with poor functional outcomes and reduced quality of life (QoL). Although both conditions independently impair psychosocial functioning, few studies have examined the combined effects of clinical, social, and treatment-related factors on QoL in patients with this dual diagnosis.MethodsThis prospective observational study included 88 male inpatients diagnosed with schizophrenia and comorbid AUD and who were followed over a 6-month period. Quality of life was assessed using the World Health Organization Quality of Life–BREF (WHOQoL–BREF). The clinical variables included severity of psychotic symptoms (Positive and Negative Syndrome Scale), alcohol use severity (Michigan Alcohol Screening Test), and treatment characteristics. Social and personal factors, such as self-care capacity, social support, education, and legal problems, were also evaluated. Multivariable regression analyses were conducted to identify predictors of QoL at baseline and follow-up.ResultsAt baseline, higher QoL was significantly associated with greater self-care capacity, social support, and higher positive symptom scores, while the need for antipsychotic treatment was associated with lower QoL. At the 6-month follow-up, better QoL was predicted by greater self-care capacity, higher educational level, and receipt of anti-craving medication. By contrast, negative and general psychopathology, medico-legal problems, and the need for antidepressant treatment were associated with poorer QoL. Alcohol use severity, as measured by the MAST, was not independently associated with QoL at either timepoint.ConclusionsIn patients with schizophrenia and comorbid AUD, QoL is shaped by a complex interaction of clinical severity, functional capacity, and treatment-related factors. Beyond symptom control, interventions targeting self-care, social functioning, and integrated addiction treatment appear essential to improve long-term outcomes. These findings support the implementation of a multidimensional, recovery-oriented approach for the management of patients with the dual diagnosis.
Deep peptide recognition profiling decodes TCR specificity and enables disease-associated antigen discovery
Nature Biotechnology, Published online: 13 May 2026; doi:10.1038/s41587-026-03128-x
A deep-learning method predicts T cell receptor specificity and disease-associated antigens.
Extreme heat is worsening faster for Black Americans
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Good morning. After what sometimes felt like endless speculation, FDA Commissioner Marty Makary resigned from his role yesterday. Kyle Diamantas, the agency’s top food regulator, will step in as acting commissioner. STAT’s Lizzy Lawrence has the details. And Matt Herper has a hot take: Marty Makary was the worst FDA commissioner in 25 years.
Gene Therapy ETX101 Improves Seizures and Neurodevelopment in Dravet Syndrome in Phase I/II
Dravet syndrome has long represented one of the most challenging pediatric epilepsies encountered in neurology and genetic medicine. Caused primarily by loss‑of‑function variants in SCN1A, the disorder emerges in infancy with prolonged febrile seizures and evolves into a lifelong condition marked by treatment‑resistant epilepsy, developmental delay, and significant morbidity. As the gene and cell therapy community gathers for the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, the field’s attention is turning toward approaches capable not only of reducing seizures but also of altering the developmental trajectory that defines the disorder. This year’s Presidential Symposium features new data on ETX101, an investigational gene regulation therapy from Encoded Therapeutics, that appears to move the needle on both fronts.
Encoded Therapeutics, a clinical‑stage biotechnology company developing precision genetic medicines for severe neurological disorders, has engineered ETX101 as a one‑time AAV9‑based therapy designed to increase expression of SCN1A. Rather than replacing or editing the gene, ETX101 aims to restore physiologic sodium channel function in inhibitory interneurons. The company’s Phase I/II POLARIS program is evaluating the therapy across multiple international sites in children ranging from six months to seven years of age.
The dataset presented at the ASGCT Presidential Symposium expands the emerging clinical profile of ETX101, incorporating additional patients, early readouts from the highest dose level, and longer‑term follow‑up. Across the cohort, treatment with a single intracerebroventricular dose produced a robust and dose‑dependent antiseizure effect that persisted through 52 weeks of observation. At dose level three, children experienced a median seizure reduction of approximately 76%, a notable finding given that this developmental window is typically associated with escalating seizure burden despite standard therapies. Early data from the top dose level suggest even stronger responses in participants who did not receive sirolimus, consistent with preclinical evidence that the drug can dampen protein expression.
Beyond seizure control, the therapy appears to influence developmental domains that are rarely improved in Dravet syndrome. Children who reached one year of follow‑up demonstrated measurable gains across communication, motor function, and other adaptive behaviors, as assessed by caregiver‑reported Vineland Adaptive Behavior Scales. Particularly striking were the trajectories of children treated before age two. In this group, cognitive assessments showed early and sustained divergence from the stagnation observed in the ENVISION natural history study, with trajectories more consistent with neurotypical development over the first year after treatment.
Families and clinicians have taken note of the dual signal emerging from the POLARIS dataset. “Parents of children with Dravet syndrome live with the fear of every seizure and the heartbreak of watching development stall,” said Mary Anne Meskis, CEO of the Dravet Syndrome Foundation. “To see the early and robust seizure reductions paired with meaningful developmental gains is profoundly encouraging. Families have been waiting for therapies that don’t just manage symptoms but give their children a chance to keep learning and growing.”
Encoded’s chief medical officer, Sal Rico, MD, PhD, underscored the significance of the findings. “Watching these young children not only achieve durable seizure reduction but also show early evidence of neurodevelopmental rescue is truly remarkable,” he said. “These data reinforce our belief that ETX101 has the potential to change the course of the disease and future outlook for the Dravet community.”
ETX101 has been well tolerated across all four dose levels, with no treatment‑related serious adverse events. Transaminase elevations, a known AAV class effect, were the most common treatment‑related finding; they were asymptomatic and resolved with standard management.
As the ASGCT community continues to explore the boundaries of genetic medicine, ETX101’s early results highlight the promise of targeted gene regulation as a therapeutic modality. For a disorder like Dravet syndrome, the possibility of addressing both seizures and developmental delay marks an important moment for the field.
The post Gene Therapy ETX101 Improves Seizures and Neurodevelopment in Dravet Syndrome in Phase I/II appeared first on GEN – Genetic Engineering and Biotechnology News.
Opinion: RFK Jr.’s antidepressant deprescribing push gets one thing right — and others dangerously wrong
I recently helped a woman in her early 60s taper off fluoxetine (often known by the brand name Prozac), which she had taken for over 35 years, followed by bupropion (aka Wellbutrin), which she had taken for over a decade.
But Kennedy’s initiative conflates that genuine clinical need with claims unsupported by evidence — and some that are actively dangerous.
Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial
Nature Medicine, Published online: 13 May 2026; doi:10.1038/s41591-026-04386-7
As presented at the European Congress on Obesity, this randomized, placebo-controlled trial demonstrates that oral orforglipron, a nonpeptide GLP-1 receptor agonist, preserves weight loss and cardiometabolic benefits achieved with injectable GLP-1 receptor agonist therapies, making it a viable oral maintenance strategy.
Pasteurized Akkermansia muciniphila MucT for weight loss maintenance in people with overweight and obesity: a controlled randomized trial
Nature Medicine, Published online: 13 May 2026; doi:10.1038/s41591-026-04394-7
In a randomized trial, pasteurized Akkermansia muciniphila improved weight loss maintenance and metabolic health after a low-energy diet, especially in individuals with initially lower Akkermansia levels. The work suggests leveraging gut A. muciniphila as a potential target for weight management.
Framework for the pharmacological treatment of obesity and its complications from the European Association for the Study of Obesity (EASO): 2026 update
Nature Medicine, Published online: 13 May 2026; doi:10.1038/s41591-026-04397-4
This 2026 update integrates emerging trial evidence — particularly for weight loss and liver disease — to refine EASO’s treatment algorithm for obesity management.
<![CDATA[How antidepressant myths can raise suicide risk—and what evidence-based prescribing, tapering, and crisis supports really look like.]]>
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.