Analysis of risk factors for tic disorders in children in Hubei region based on liquid chromatography-tandem mass spectrometry
Timing of exercise differentially modulates fear memory and hippocampal neurotransmitters in male rats
Current Landscape of Mental Health Conversational Agents From a Trauma-Informed Care Lens: Scoping Review
Background: Conversational agents (CAs) are increasingly used in mental health care to enhance access and engagement. However, their safe, ethical, and user-sensitive design remains a challenge. Despite growing attention to trauma-informed approaches in human-computer interaction, there is limited work on how the trauma-informed care (TIC) framework could be applied in the design of mental health CAs and no comprehensive synthesis to date. Objective: Guided by the Substance Abuse and Mental Health Services Administration’s TIC framework, this scoping review explored how TIC principles (safety; trustworthiness and transparency; collaboration and mutuality; empowerment, voice, and choice; peer support; and cultural, historical, and gender issues) are currently represented in the design and evaluation of mental health conversational agents (MHCAs) and identified gaps and opportunities to promote more trauma-informed design practices. Methods: Online databases, as well as a secondary survey of citation lists from an initial search, were used to identify English-language journal articles and conference proceedings from 2000 to 2024 that empirically evaluated an independent, web- or app-based, unassisted CA used for mental health and included concepts from TIC. Results: Our analysis included 38 publications (n=28, 73.7%, published in 2020 or later) covering 28 distinct MHCAs. Most studies used experimental methods (n=23, 60.6%) or user studies (n=11, 28.9%), with samples skewed toward female (men: mean 34.92%, SD 18.64%), young in age (mean 32.52, SD 14.6 y), and predominantly nonclinical (n=29, 76.3%). MHCAs were largely rule-based prototypes. No studies explicitly referenced the TIC framework as a guiding lens for MHCA design or evaluation. A total of 26 studies referenced terminology from TIC core principles but rarely defined them, while all 38 included language that could be linked to one or more principles. Overall, TIC-related concepts appeared most often within intervention design descriptions, qualitative assessments, or as items embedded in questionnaires evaluating broader constructs. Trustworthiness and transparency, safety, empowerment, voice and choice, and collaboration and mutuality were comparatively well addressed, while peer support and cultural, historical, and gender issues were largely absent. Design recommendations, where present, were relatively broad and emphasized secure, customizable, reliable, human-like, and context-sensitive MHCAs that offered multimodal interaction, goal setting and tracking, and transparency. Conclusions: Studies did not self-identify as using Substance Abuse and Mental Health Services Administration’s framework for TIC, making it more difficult to identify its elements. The fragmented terms, disciplines, and metrics used make it difficult to draw more systematic conclusions about the current research landscape related to TIC, but our analysis indicates TIC to be a descriptive and potentially unifying framework and provides a starting point for the explicit trauma-informed MHCA research and design.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/c41181a042ee9ad5f9b3c8394fcddce6" />
Combinatorial effects of multi-site stimulation on depression-related brain regions: clinical data analysis and predictive modeling
‘Type’ Casting: Flagship-Founded Serif Modifying DNA into New Therapy Class
What happens when the scalability and redosability of messenger RNA (mRNA) is combined with the durability and programmability of gene therapy?
According to Serif Biomedicines, a five-year-old startup that emerged from stealth mode this month, the result is “modified DNA,” a new class of therapeutics designed to be programmable, durable, scalable, and redosable—while minimizing the drawbacks of both mRNA and gene therapy.
Modified DNA builds upon generative protein and mRNA platforms created by Flagship Pioneering, the venture capital giant which founded Serif in 2021. On April 21, Flagship formally launched Serif with an initial commitment of $50 million in financing—capital that Serif intends to use toward developing its scalable platform for optimizing and manufacturing Modified DNA treatments, aided by artificial intelligence (AI), and advancing its first drug discovery programs.
“The reason we’re bringing the company out of stealth mode now is we think we have made progress. We’ve made real progress that we’re excited to share with the world, that we’re excited to get feedback from the broader scientific community on, and we want to tell that story more broadly,” Jacob (Jake) Rubens, PhD, Serif’s co-founder and CEO, and an Origination Partner at Flagship Pioneering, told GEN.
“It’s been on our minds for a long time: What might be possible when DNA becomes an engineerable biotechnology for the first time?”
It’s a question pursued by numerous researchers and companies over the years as they sought to capitalize on DNA’s qualities of being a durably expressing molecule capable of coding for any gene, producing proteins or RNAs in a cell-specific way, as well as being scalable to manufacture and capable of re-dosing for patients.
“Those are, I think, the key differentiating attributes of theoretical DNA medicines. So the question for us became not, would this be valuable if we could do it, but why hasn’t anyone done it yet?” Rubens explained. “We’ve known about the centrality of DNA in biology, the central information molecule in DNA. We’ve known this for 75 years since Watson and Crick’s seminal discoveries around how the structure of DNA enabled it to function as an information molecule.”
Two key problems

“And when we looked at this space,” he continued, “we saw that there were two key problems: The first is that DNA is a highly inflammatory molecule. The second is that DNA needs to be delivered not just into a cell, but into the nucleus, the center of the cell.”
To create Modified DNA, Serif alters the structural and chemical form of DNA in order to minimize innate immunogenicity as lipid nanoparticles drop off the DNA not in the nucleus, but in the cytoplasm of the cell.
Once inside the cell nucleus, Modified DNA reverts to unmodified DNA, enabling transcription into therapeutic RNA and proteins. The resulting treatments are designed to last longer, be given more than once, and be programmed for cell-specific expression. To enhance durability, Serif delivers with its Modified DNA proteins which help the DNA access the nucleus. The proteins, called mRNA co-factors, are designed to transiently express proteins that enhance entry into the nucleus and gene expression.
Pending an announcement it expects to make later this year, Serif isn’t revealing specifics of its initial drug discovery programs, except to say that they focus on rare diseases and immune programming.
“This is not meant to be a limited list of where we could go but the areas that we think we’re going to go first, which are likely in addressing protein deficiencies in genetic diseases,” Rubens said.
Modified DNA has shown itself to be disease agnostic, he added, reflecting DNA’s qualities as a general, programmable information molecule: “One of the reasons we’re so excited about, the future of modified DNA as a new biotechnology akin to RNA, akin to protein, is its centrality in biology. It is the fundamental information molecule inside of all of us, inside of every living thing on this planet. So that is really the existence proof that it is generalizable.”
Tolerability and sustained expression
Also later this year, Serif plans to present data at an as-yet-unspecified scientific conference that will show modified DNA’s tolerability in non-human primates, as well as sustained gene expression with therapeutic effects in preclinical models following intravenous (IV) administration.
Serif aims to transform Modified DNA into treatments as effectively and commercially successfully as Amgen, Genentech (now a member of the Roche Group), and later Regeneron did with engineered proteins, as Alnylam Pharmaceuticals did with small interfering RNA (siRNA), and as Moderna more recently accomplished with mRNA—most notably in developing its SpikeVax® COVID-19 vaccine, which the FDA authorized for emergency use in 2020 and fully approved in 2022.
Flagship launched Moderna in 2010; the company went public in 2018 by raising $604 million, the largest-ever U.S. biotech initial public offering (IPO) until Kailera Therapeutics raised $625 million earlier this month.
At Flagship, Rubens is a scientist entrepreneur who leads the firm’s Pioneering Business Unit, which establishes and grows companies based on new biotechnology. In addition to Serif, Rubens co-founded Quotient Therapeutics, which develops therapies based on its somatic genomics platform; Tessera Therapeutics, which writes therapeutic messages into the genome through a genome engineering approach called GeneWriting
; and Sana Biotechnology, a developer of treatments based on engineered cells. He also launched Kaleido Biosciences, a microbiome therapeutics company that ceased operations in 2022.
Before joining Flagship, Jake received his PhD in microbiology from MIT, working with Tim Lu, MD, PhD, a core member of the Synthetic Biology Center, through the support of a National Science Foundation Graduate Research Fellowship. At MIT, Jake helped enable “intelligent” cell therapies by inventing gene circuits that allow engineered cells to do novel analog, digital, and hybrid computations.
Based in Cambridge, MA, Serif employs about 50 people and as of Wednesday was disclosing five open positions on its website in its three areas of focus: Chemistry (associate scientist and senior scientist, both specializing in LNP formulations), Molecular Biology (research associate and senior scientist), and Research/Discovery (scientist specializing in bioanalytical assays).
“I’m not at this point going to provide any guidance on how much more we will or won’t grow,” Rubens said. “We’re quite agile and responsive to the company’s needs.”
The post ‘Type’ Casting: Flagship-Founded Serif Modifying DNA into New Therapy Class appeared first on GEN – Genetic Engineering and Biotechnology News.
Genoarchitecture and input–output organization of the mouse basal ganglia and thalamic parafascicular nucleus
Nature Neuroscience, Published online: 28 April 2026; doi:10.1038/s41593-026-02253-9
The authors investigate the transcriptomic and connectivity organization of the basal ganglia and parafascicular nucleus. The analyses suggest that combinatorial gene expression underlies the modular and cell-type-specific basal ganglia input–output networks.
Medication Treatment for Tics and Tourette’s
There are several kinds of medication than can help kids with Tourette’s or another tic disorder. But it’s important to note that not all kids who develop tics need treatment. Tics are very common. They often go away on their own, and they tend to bother parents more than they do the children experiencing them. Drawing attention to them can make them worse. So doing nothing can be the best strategy — at least initially.
Treatment comes into play if tics are upsetting your child, giving them pain, or making it hard for them to function in everyday life — say they’re disrupting class or getting bullied because of their tics.
The first recommended step in treatment is a specialized form of therapy called comprehensive behavioral intervention for tics (CBIT). CBIT is centered on habit reversal training, in which the child learns to recognize when they have an urge to tic and substitute a competing response — an easier, more comfortable, or less noticeable action or behavior that makes the tic impossible. For instance, if a child’s tic is jerking their head to the side, the strategy might be to put their chin down instead.
But if therapy isn’t effective in reducing a child’s tics, medication can help.
Guanfacine and clonidine for tics
First-line medications for Tourette’s and other tic disorders are a class of drugs called alpha-2 agonists, explains Paul Mitrani, MD, PhD, a child and adolescent psychiatrist at the Child Mind Institute. Alpha agonists decrease the release of a neurotransmitter called norepinephrine, which stimulates the nervous system. Alpha agonists serve as a kind of dimmer switch — by calming down the system, they make the urge to tic less frequent, less intense, and by extension, easier to control.
The two alpha-2 agonists usually prescribed for tics are guanfacine and clonidine. Dr. Mitrani reports that he usually starts by prescribing guanfacine because it comes in a longer-acting form (Intuniv), which reduces symptoms for a full 24 hours. Clonidine’s long-acting form (Kapvay) is effective for 12 hours.
Dr. Mitrani adds that there is a new liquid form of clonidine called Onyda XR that lasts 24 hours, but there isn’t yet a strong body of evidence regarding its effectiveness for tics. Onyda XR is FDA-approved for ADHD, as are Kapvay and Intuniv.
While no alpha agonist medications are FDA-approved specifically for tics, Kapvay and Intuniv are frequently used off-label for them. There is ample research on their effectiveness for tics, and they are recommended by clinical practice guidelines.
Some children respond better to several doses of short-acting guanfacine or clonidine, Dr. Mitrani notes, rather than a smoother dose of a long-acting medication. This may be because medication can be timed to peak at times when kids need tic suppression most, such as at school.
Alpha agonists are the preferred first line medications for tic disorders because their side-effects, including drowsiness and low blood pressure, are relatively mild.
Antipsychotics for tics
If alpha agonists aren’t helping, the next step would be to try an antipsychotic medication, which can be more effective for treating tics, Dr. Mitrani notes, but their side effects are potentially more difficult to tolerate.
Aripiprazole (Abilify), which is FDA-approved for tics, is often Dr. Mitrani’s first choice among the antipsychotic medications. Abilify is a second-generation, or atypical, antipsychotic, a group of medications that have fewer side effects than older antipsychotics. Side effects of Abilify can include restlessness, agitation and weight gain.
Haloperidol (Haldol) is also effective for tics, but it’s an older antipsychotic with more side effect concerns, Dr. Mitrani notes. “I’ve only had one patient ever on Haldol, and he tolerated it well and it really helped with his tics when other things did not.”
Risperidone (Risperdal) is another atypical antipsychotic that can help, but its side effects tend to be worse than Abilify. Risperidone can cause more concerning weight gain and metabolic, neurological, and hormonal changes that can be harmful. Sometimes other medications are used to manage the weight gain from antipsychotics.
When kids with tics also have ADHD
More than three-quarters of kids diagnosed with a tic disorder also have another disorder. When a child has multiple disorders, a clinician will want to evaluate which is causing the child the most difficulty and prioritize treating that.
The most common co-occurring disorder with tics is ADHD. “If tics are the bigger problem, we would start with treating them,” says Dr. Mitrani. “If the ADHD is the bigger problem, which it typically is, we usually treat that first.”
In the past, it was recommended that children with tics and ADHD avoid stimulant medication, based on research that showed it made tics worse. But newer studies counter that finding, Dr. Mitrani notes, concluding that the old research was based on very high doses of amphetamine-based medications. To lower the risk of exacerbating tics, he recommends starting kids with ADHD and tics on methylphenidate-based medication.
“If your child is starting a stimulant,” he adds, “and you see worsening of tics — and it’s clearly related to when the stimulant is in their system — the best approach might be a lower dose of stimulant combined with guanfacine or clonidine.”
One advantage to that combination, he notes, is that kids with ADHD who have behavior problems can benefit from the guanfacine or clonidine being active in the mornings before the stimulant starts working and in the evenings when it’s out of their system.
Kids with other co-occurring disorders
When children with tics have other co-occurring disorders, such as anxiety, OCD, or depression, treating them with medication needs to be done very carefully, Dr. Mitrani says. Since children are typically not bothered by the tics themselves, it’s almost always the other disorder that is more problematic for them. And, he adds, when the other problems cause distress, it can make the tics worse.
For anxiety, OCD, and depression, the first-line medication treatment is an antidepressant. Antidepressants can actually help alleviate tics indirectly, since they reduce anxiety. “Stress increases tics, so if there is significant anxiety and you treat the anxiety, the tics may get better,” Dr. Mitrani says. “And then maybe you don’t need the guanfacine or clonidine. But again, it depends on what the co-occurring disorders are and what’s the bigger problem for the child.”
Monitoring medication for tics
Due to the waxing and waning nature of tics, it can be challenging to see the full effect of medication and other interventions. It is important to give medication enough time to work, Dr. Mitrani notes, typically a few weeks, to see if the overall pattern, frequency, and severity of tics has improved. And children who are being treated should continue to be monitored regularly for any changes, as tics can recur or worsen, especially when a child is excited, tired, or experiencing more stress.
Most children with tics see a natural improvement or even resolution of tics as they progress through adolescence. If there seems to be a long-standing improvement, it is appropriate to consider reducing or stopping medication, especially if the child is experiencing side effects, Dr. Mitrani notes. If tics continue and are causing distress, it is important to keep treating them.
A child going off any of these medications — alpha agonists or antipsychotics — should do so gradually, by having their dose reduced over weeks or even longer, to avoid unpleasant or dangerous side effects of sudden withdrawal.
The post Medication Treatment for Tics and Tourette’s appeared first on Child Mind Institute.
GABA-Based Target for Alzheimer’s Therapy Identified
Researchers at the University of Galway have found evidence that targeting inhibitory signaling in the brain may help address cognitive dysfunction in Alzheimer’s disease (AD), a finding that runs counter to current therapeutic approaches that focus on influencing excitatory pathways. The research, published in Neuropharmacology, identifies how modulation of gamma-aminobutyric acid (GABA) signaling can restore disrupted neural balance and improve memory-related function in AD disease models.
“Given the ever-increasing burden of Alzheimer’s disease, the urgent need for the identification of novel targets for the development of disease-modifying therapy is clear,” said senior author Andrea Kwakowsky, PhD, associate professor of pharmacology and lead researcher at the School of Medicine, University of Galway.
Alzheimer’s disease is characterized by progressive cognitive impairment and is associated with hallmark pathological features including β-amyloid (Aβ) plaques and neurofibrillary tangles. In addition to these, disruption of the brain’s excitatory/inhibitory (E/I) balance has gained traction as a central mechanism contributing to memory loss. Today, most approved therapies for AD target excitatory neurotransmitter systems such as cholinergic and glutamatergic pathways, but “the symptomatic relief provided by these therapies is only marginal, and the progression or underlying causes of the disease are not addressed,” the researchers noted.
For their work, the University of Galway team instead focused on the inhibitory side of this balance, specifically the role of gamma-aminobutyric acid (GABA), the brain’s main inhibitory neurotransmitter. GABA regulates neuronal activity and is essential for maintaining stable network function and memory processes. In AD, however, E/I balance becomes dysregulated with increased extracellular GABA—triggered in part by Aβ—leading to overactivation of certain GABA receptors, particularly α5-containing GABA type A receptors (α5-GABA ARs), which are abundant in the hippocampus. The result is a dampening of neuronal signaling and which impairs learning and memory.
“Our research is significant in that it demonstrates that if we block this GABA receptor activity in nerve cells we can reverse Alzheimer-like effects caused by amyloid beta and improve cognitive performance,” Kwakowsky said.
To test whether blocking a5-GGABA A could help restore E/I balance, the team investigated α5IA, an α5-GABA AR-selective inverse agonist. α5IA works by reducing the activity of α5-GABA ARs, which decreases excess tonic inhibition. The data showed that in experimental models of AD, the compound improved long-term potentiation (LTP), a mechanism of synaptic plasticity and memory, reduced abnormal inhibitory conductance, and restored spatial memory performance.
Mechanistically, α5IA appears to act by restoring physiological levels of inhibition in the hippocampus which is critical for memory formation. By reducing excessive tonic inhibition, it rebalances E/I signaling, which allows neuronal circuits to function more effectively. “The data presented here suggest that in both ex vivo and in vivo AD models, α5IA improves cognitive function by restoring CA1 tonic inhibition, thereby re-establishing E/I balance and ameliorating the abnormal hippocampal network activity induced by Aβ1-42,” the researchers wrote.
This new study is the latest to indicate that targeting inhibitory neurotransmission could be an effective treatment approach for AD. Earlier research has shown that α5-GABA AR modulation enhances memory and reduces inhibitory signaling in both animal models and humans. But most of these studies have not directly examined the effect of α5IA in chronic neurodegenerative disease models.
The researchers noted there are some limitations to their work, pointing out that while α5IA improved cognitive outcomes, it did not reverse neuronal loss in vivo, suggesting that its effects may be primarily functional rather than neuroprotective at later stages of AD. Also, variability in drug exposure and timing may influence outcomes. Finally long-term use of α5IA has also been associated with safety concerns at high doses, including renal toxicity, so further research is needed to determine toxicity and dosing regimens and limits.
Nonetheless, the implications of this research indicate there is potential to develop new AD therapies that directly target network dysfunction rather than focusing solely on amyloid accumulation or excitatory signaling. By restoring E/I balance, this approach shows the potential to improve cognitive function even when AD pathology has taken root. The findings could also benefit diagnostic methods, as biomarkers of inhibitory dysfunction or altered GABA signaling could help identify patients who would benefit an approach that rebalances E/I signaling.
The post GABA-Based Target for Alzheimer’s Therapy Identified appeared first on Inside Precision Medicine.

