In a randomized Phase 1 study, the company’s new drug, called ALKS 7290, was well tolerated and showed a signal of efficacy, Alkermes said Monday.
Participants in the study started with a median score of 39 on a diagnostic known as the Adult ADHD Investigator Symptom Rating Scale, indicating that they had moderate to severe symptoms. After two weeks, those taking a high dose of 50 milligrams of ALKS 7290 experienced a 19-point reduction on the scale, indicating that their symptoms had become mild.
Conditions: Appetite Loss in Aging; Anorexia of Aging
Interventions: Other: Physical activity; Other: Appetite assessment; Other: Food intake assessment; Other: Assessment of the efficiency; Biological: Blood test at baseline; Biological: Blood test at the end of the study; Other: Functional capacities assessment; Other: weight measurment
BackgroundSleep disorders are a common clinical condition characterized primarily by difficulty falling asleep, trouble maintaining sleep, and impaired daytime functioning, with a high prevalence among adults. This condition can lead to a persistent decline in sleep quality, trigger mental health issues such as anxiety and depression, and ultimately reduce overall quality of life. Traditional Chinese mind-body exercise therapies are considered potentially effective non-pharmacological interventions due to their low risk, high accessibility, and dual mind-body regulation effects. However, the relative efficacy of different exercise therapies on sleep quality, mental health, and quality of life in patients with sleep disorders remains unclear. This study employed a web-based meta-analysis to systematically evaluate the effects of three interventions—Tai Chi, Baduanjin, and Tai Chi combined with transcranial magnetic stimulation—on three outcome measures and to rank their efficacy, aiming to provide evidence-based support for clinical decision-making.MethodsThis study conducted a systematic search of the PubMed, Embase, Web of Science, Cochrane, EBSCO, and CNKI databases and included 18 randomized controlled trials that met the inclusion criteria. Outcome measures included sleep quality, mental health, and quality of life. A network meta-analysis using a random-effects model was performed to calculate standardized mean differences and 95% confidence intervals, and the cumulative ranking probability curve area was used to rank the efficacy of the interventions.ResultThis study included a total of 18 randomized controlled trials. Regarding sleep quality, TCCWTMS yielded the best results (SMD = −1.15, 95% CI [−2.07, −0.22]). Regarding mental health, only the Tai Chi intervention achieved statistical significance (SMD = 0.64, 95% CI [0.07, 1.21], P = 0.03); although Baduanjin ranked first in the SUCRA ranking (92.6%), pairwise comparisons did not reach statistical significance (P = 0.07). Regarding quality of life, both Tai Chi (SMD = -0.47, 95% CI [-0.71, -0.24], P < 0.0001) and Baduanjin (SMD = -0.57, 95% CI [-0.91, -0.23], P = 0.001) were significantly effective. There were significant heterogeneous differences in the efficacy of the three interventions across different outcome measures.ConclusionThis study indicates that the TCCWTMS is the most effective intervention for improving sleep quality in patients with sleep disorders. Regarding quality of life, both Baduanjin and Tai Chi demonstrated significant effects, with Baduanjin showing superior efficacy. Regarding mental health, the current evidence is insufficient to determine the optimal intervention strategy. There are significant differences in the efficacy of the three interventions across various outcome measures; clinical decisions can be made by selecting the appropriate intervention based on the patient’s score needs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261415202, identifier CRD420261415202.
There is considerable room for innovation in neuropsychiatric drug development and Palomar Labs, a venture studio, is hoping to capitalize on that by building companies around drug candidates with prior human validation. As Shlomi Raz, a managing partner at Palomar Labs, explained it, the company’s “mission is to find promising drug candidates with some history of human use” that specifically target “conditions associated with late life.” The goal is to take candidates, which already have some documented evidence of safety and efficacy, through the clinic and through to proof-of-concept.
And now the venture studio, which was formerly called Negev Labs, has made its first move towards those goals by spinning out its first portfolio company, Ariadne Bio, with a lead program already in hand. Raz steps into the role of CEO for the company and Daniel Jeffries, PhD, a partner at Palomar Labs, will take on the role of chief development officer for the company. Ariadne Bio will focus on developing AB-300, a clinical-stage molecule that functions as a non-hallucinogenic serotonin 2A receptor agonist. The company is developing the molecule to treat apathy in people with Parkinson’s disease.
Shlomi Raz, Founder & CEO, Ariadne Bio
“A significant portion of people with Parkinson’s will lose the drive to do the things that make life worth living, and not a single approved medicine is designed to bring it back,” Raz said. “We built Ariadne Bio around a single question: whether motivation can be restored pharmacologically. AB-300 is how we intend to answer it.”
Ariadne Bio makes a compelling case for targeting apathy. As Jeffries notes, “apathy is among the most disabling non-motor features of Parkinson’s disease.” The condition is defined clinically as a persistent reduction in goal-directed behavior. It is estimated to affect approximately 40% of people with Parkinson’s disease over the course of the illness.
Higher rates of the condition are reported in people in the mid to late stages of the disease. In fact, studies of caregiver burden in Parkinson’s rank neuropsychiatric symptoms like apathy ahead of motor symptoms as drivers of distress. It is important to note here that while apathy and depression have some overlapping features, they are distinct conditions. Selective serotonin reuptake inhibitors (SSRIs) remain the appropriate treatment for Parkinson’s associated depression, but some evidence links their use to emotional blunting and worsening apathy.
In contrast, there are currently no approved therapies for apathy in any indication. If AB-300 successfully makes its way through clinical trials and clears regulatory approval, it could be one of the first. And Raz and his team are driven to accomplish that goal. In fact, this is the second neuropsychiatry-focused company that Raz is launching. Previously, he founded Eleusis, which claims to be the first company that was dedicated to developing medicines derived from psychedelic compounds. Eleusis was acquired by Beckley Psytech in 2022. That company combined Atai Life Sciences to form AtaiBeckley in 2025. As of July, 2026, Eli Lilly entered into a definitive agreement to acquire AtaiBeckley.
A non-hallucinogenic history
Raz moved to Palomar Labs after a stint at Beckley Psytech because of what he saw as a “significant opportunity” with similar themes to psychedelics—drugs with demonstrated therapeutic potential that never translated into U.S. Food and Drug Administration-approved therapies. There are several drugs that could fall into this category but Raz admits he is a bit biased towards serotonin therapies because of his background in psychedelics. “Coming out of the psychedelic space, the way I view it is that the first generation of that drug class were these very potent classical psychedelics like psilocybin and LSD,” he said during the conversation. The second generation featured drugs with formulation changes that altered their pharmacodynamics in different ways.
Raz and his team are most interested in what he categorized as the third-generation. These are potential therapies that activate the same receptors as psychedelic drugs without the corresponding hallucinogenic effects, making them ideal for use in older adults. AB-300 is one such compound. For some of its back story, the compound is based on one that was previously tested in the 1970s and documented to lack hallucinogenic effects, Jefferies told GEN. Since then, several groups have dug into why this particular molecule does not cause hallucinations like other serotonin agonists.
Earlier this year, scientists published a paper in January in Nature that pointed to signaling bias as the likely reason. “When you activate serotonin 2A, there’s multiple intracellular pathways that can be engaged,” Jeffries said. According to the paper’s findings in a preclinical model, the parent compound that AB-300 is based on “preferentially activated the non-hallucinogenic pathway” without removing any therapeutic benefit.
Daniel Jeffries, PhD, Chief Development Officer, Ariadne Bio
The fact that this compound does not act on dopamine receptors is crucial. “Classically, mental stimulation comes through a variety of drugs that either block the re-uptake of dopamine or activate dopamine receptors directly,” Raz notes. “The problem of course is that they aren’t necessarily well tolerated by older adults. And so we saw the promise of developing a therapy that indirectly modulates motivation through serotonin receptor activation” without the hallucinogenic effects. Apathy in Parkinson’s disease cases is the immediate target but Raz acknowledged that there are other diseases of aging that involve unaddressed apathy. And Ariadne Bio is actively exploring ways to address those conditions in future. “The more research we did, the more we realized how profound the unmet need there was.”
Building up to Phase Ib
In May 2026, at the American Society of Clinical Psychopharmacology, (ASCP) Ariadne Bio presented results from tests of its lead candidate in a preclinical model of tetrabenazine (TBZ)-induced motivational deficit, assessed by progressive-ratio lever pressing. In this model of effort-based motivated behavior, AB-300 plus TBZ increased motivational behavior by 89% relative to the TBZ only group, which is a statistically significant improvement.
The company claims that AB-300 is the first serotonin 2A receptor agonist drug candidate shown to restore motivated behavior in a dopamine-depleted model. They also claim that in off-target screening, AB-300 shows no measurable activity at dopamine receptors or the dopamine transporter, which indicates that it engages motivational circuitry through a mechanism independent of dopaminergic signaling.
Raz and Jeffries dug into the details of the study using the tetrabenazine-induced model in more detail during their conversation with GEN. “One of the interesting things about developing apathy, is that this indication has an in vivo model that’s arguably more translatable than some of the other more mainstream neuropsychiatric indications,” Jeffries explained. Tetrabenazine is an FDA-approved drug used in Huntington’s disease with detailed data on its ability to induce a low motivational apathetic phenotype in clinical and preclinical models. Part of what makes the drug so interesting is that it depletes the levels of circulating dopamine in the brain, similar to what is seen in Parkinson’s cases.
That is an important point, Jefferies emphasized. Because “essentially what that allows developers to do is to test their investigative agent in a motivational model with the background of dopamine depletion,” he said. In terms of the results, the team saw positive effects at doses that are predicted to be within a therapeutic range in the clinic. Furthermore, the team also observed some of the negative effects of using SSRIs to treat apathy in their model. These results mirrored clinical observations of patients, whose apathy was treated with SSRIs and saw their symptoms worsen. These results show the efficacy of AB-300 and “it’s giving us a lot of motivation … to move forward,” he added.
That next step is a Phase Ib clinical trial that will test AB-300 in healthy volunteers and Parkinson’s patients, most of whom will be receiving the current standard of care treatments and potentially on antidepressants for their apathy. In addition to assessing safety and efficacy of the treatment, Ariadne’s team and their partners will also assess potential interactions between their compound and those other drugs.
The trial will begin likely at the end of Q3 or the beginning of Q4 at centers in Austria and Israel. Ariadne Bio has already had a Type B pre-IND meeting with the FDA regarding the development of AB-300 for Parkinson’s disease-associated apathy.
The planned trial will be a three-part study, Jeffries told GEN. The first part will be a single ascending dose in healthy patients followed by a single ascending dose in Parkinson’s disease patients. In both parts, the scientist will explore “a variety of biomarkers [and a] range of doses” to identify the maximally efficacious dose. “We have the preclinical data [that] tells us generally where we should be looking, but we need to really see that in patients who are on Parkinson’s disease medications to confirm that in fact that is the right range for what we anticipate to be a clinically effective dose or at least to evaluate that potential,” Raz added. The third part of the trial will be a 28-day placebo-controlled double-blind of AB-300 against placebo in patients with clinically relevant apathy.
Ariadne Bio’s launch is backed by funding from Palomar Labs as well as from The Michael J. Fox Foundation through its Parkinson’s disease therapeutics pipeline program. That program supports preclinical and translation research aimed at evaluating promising therapeutic approaches and helping to support their clinical development. While Ariadne officials declined to disclose exactly how much it has received in funding, Raz told GEN that the company has enough in house to complete the proposed clinical trial at this time.
ObjectiveAdults with ADHD report challenges engaging in cognitive-behavioral therapy (CBT). This study investigates practices that might be applied to improve intervention fit and therapeutic engagement of CBT for adults with ADHD.MethodWe conducted an Innovation Tournament (IT) and member checking with participants (N=102) who were adults with ADHD and mental health practitioners who regularly treat adults with ADHD. Go-Zone plots were utilized to identify strategies with the highest feasibility and importance as well as strategies with low feasibility and/or importance that might be candidates for de-implementation. Barriers to CBT engagement and practitioner implementation of practices were also evaluated qualitatively.ResultsA range of engagement barriers were identified, chief among them practitioner low understanding of ADHD (44.4%) and lack of attention to relevant impairments (33.3%). The highest rated focal areas for CBT were task management, organization, planning, and prioritization, emotion regulation strategies, responding to negative/maladaptive thoughts, anti-procrastination and self-motivation strategies, and long-term goal setting. Top recommendations for engagement strategies include ensuring high therapist knowledge of ADHD and 17 elements consistent with Motivational Interviewing. Some practices commonly found in CBTs for ADHD were rated as unpopular with stakeholders, most notably providing weekly ratings of ADHD symptoms as progress monitoring. Some practices rated as important to adults with ADHD were rated as not feasible to practitioners—most notably reducing shame and nurturing confidence. Implementation barriers identified were primarily related to low practitioner knowledge and skills, but also sometimes systemic constraints on practice.ConclusionsImplementation of recommended practices noted in this study should be tested empirically to understand the extent to which they increase engagement and effectiveness over standard practice.
School refusal behavior (SRB) is increasingly recognized across educational, pediatric, and mental health settings, yet its conceptual boundaries remain unclear, and the term is frequently conflated with school refusal, truancy, school withdrawal, school exclusion, and broader school attendance problems. This study used Walker and Avant’s concept analysis method to clarify the meaning, defining attributes, antecedents, consequences, and empirical referents of SRB. PubMed, Web of Science, Scopus, and PsycINFO were searched for English-language literature published through January 2026, supplemented by Google Scholar and manual citation searching. A total of 100 sources were included and analyzed through iterative comparison of conceptual definitions, recurrent characteristics, contextual conditions, outcomes, and indicators used in research and practice. The analysis showed that SRB has evolved from earlier anxiety-centered descriptions toward a broader behavioral and functional construct. Four defining attributes were identified: difficulty initiating, sustaining, or completing school attendance or participation; young person–expressed attendance difficulty; aversive school-related experiences or emotional distress; and heterogeneous avoidance- or reinforcement-related maintaining functions. Antecedents were distributed across individual, family, peer and interpersonal, and school-contextual domains, while consequences extended across academic, psychological, social, family, and service-related domains and may accumulate over time. Empirical identification requires the integration of observable attendance patterns, emotional, behavioral, and somatic responses, functional assessment, and contextual information from young people, caregivers, and school personnel. Moving beyond the summary of existing definitions, this analysis proposes an integrative framework that distinguishes the observable form of attendance difficulty from its emotional presentation, maintaining functions, and ecological context. SRB is therefore best understood as a persistent or recurrent, young person–expressed pattern of disrupted school attendance or participation that is clinically meaningful but cannot be reduced to a single diagnosis, cause, or attendance threshold. By clarifying what constitutes SRB and how it differs from other forms of school attendance problems, this framework may support earlier recognition of emerging attendance difficulties, more comprehensive assessment of underlying needs, and better coordination among mental health professionals, families, and schools.
IntroductionAdolescent mental health problems, including depression, anxiety, and stress, are an increasing public health concern, yet the factors associated with different mental health outcomes may vary across domains. This study investigated shared and outcome-specific predictive features of depression, anxiety, perceived stress, and psychological well-being using explainable machine learning models.MethodsA cross-sectional study was conducted among 1,088 adolescents aged 13–18 years recruited from secondary schools in Wuhan, China, using multistage cluster sampling. Participants completed validated measures of emotional dysregulation, loneliness, social media addiction, self-esteem, sleep quality, academic stress, family support, physical activity, and mental health outcomes. Four algorithms—linear regression, support vector regression, Random Forest, and XGBoost—were trained using an 80/20 train-test split with five-fold cross-validation, and model performance was evaluated using test-set R², RMSE, and MAE. SHapley Additive exPlanations (SHAP) were used to examine feature contributions. To minimize target leakage, outcome-specific feature sets were used, with PSQI and RSES excluded from the depression model because of direct or substantial conceptual overlap with PHQ-9 content, and PSQI excluded from the well-being model because of overlap with WHO-5 content.ResultsXGBoost showed the strongest out-of-sample predictive performance across all four outcomes, explaining 49% of the variance in depression (R² = 0.49, 95% CI: 0.44–0.53; RMSE = 3.52; MAE = 2.81), 55% in anxiety (R² = 0.55, 95% CI: 0.50–0.59; RMSE = 3.04; MAE = 2.47), 60% in perceived stress (R² = 0.60, 95% CI: 0.56–0.64; RMSE = 3.71; MAE = 2.87), and 50% in psychological well-being (R² = 0.50, 95% CI: 0.45–0.54; RMSE = 3.38; MAE = 2.68).DiscussionEmotional dysregulation and loneliness were consistently among the most influential features, while academic stress, family support, social media addiction, self-esteem, and sleep quality showed outcome-specific contributions. SHAP rankings for the depression model were stable across five-fold cross-validation, with emotional dysregulation and loneliness consistently occupying the highest ranks.
BackgroundMental health problems are increasingly prevalent among college students and represent an important public health concern. Neurophysiological indicators derived from electroencephalography (EEG) may provide objective markers for identifying psychological vulnerability. The theta/beta ratio (TBR) has been widely associated with attentional regulation and cognitive control; however, its relationship with multidimensional psychological symptoms in non-clinical populations remains insufficiently understood.MethodsResting-state EEG was recorded from 222 undergraduate students aged 18–25 years during an eyes-closed condition. Psychological symptoms were assessed using the Symptom Checklist-90. Theta (4–7 Hz) and beta (14–30 Hz) power were extracted from frontal electrodes (F3 and F4), and the theta/beta ratio was calculated. Group comparisons and correlation analyses were conducted to examine associations between EEG measures and psychological symptom severity.ResultsStudents with higher levels of psychological symptoms showed significantly greater frontal theta and beta power compared with those reporting low-score levels. In addition, the theta/beta ratio was significantly higher in students with greater psychological symptom severity and was positively correlated with the total SCL-90 score as well as several symptom dimensions.ConclusionsThese findings suggest that resting-state frontal TBR is associated with psychological symptom severity in college students. The theta/beta ratio may serve as a potential neurophysiological candidate correlate of mental health vulnerability in non-clinical populations and provide a reference for objective auxiliary assessment of mental health in university populations.
A genome-wide association study involving over one million people reveals genetic contributions to personality traits, with potential causal effects on physical and mental health and behaviors.
