Stage-specific ERP correlates of audiovisual facial emotion processing across depressive tendencies

Emotional dysregulation can emerge as early as the initial stages of depression. This study aimed to examine event-related potential characteristics during the perception of negative, positive, and neutral facial expressions in healthy individuals across depressive tendencies. Twenty-six healthy participants underwent ERP measurements during emotion recognition using a facial emotion recognition task in visual and audiovisual modalities. The Emotion Regulation Questionnaire (ERQ), the Difficulties in Emotion Regulation Scale (DERS-16), and the Beck Depression Inventory II (BDI-II) assessed cognitive strategy, emotion regulation difficulties, and depression severity, respectively. Facial affect elicited larger amplitudes compared to neutral faces, from the N170 and early posterior negativity (EPN) in the temporo-occipital region to the late positive potential (LPP) in the centroparietal region. Under audiovisual conditions, P1 peak latency to negative stimuli in the temporal region exhibited significant negative correlations with DERS-16 and BDI-II scores. N170 peak latency to positive stimuli also demonstrated a significant negative correlation with BDI-II scores. Under visual conditions, EPN amplitude to negative stimuli in the occipital region exhibited a significant positive correlation with BDI-II scores. P1 and N170 latencies, or neural response speeds, and EPN amplitude, which represents emotional reaction strength, correlate with depressive tendencies in healthy individuals. These early components function as initial neural signals that may serve as electrophysiological markers of abnormal emotional processing within neuropsychological functions prior to clinical depression.

Esketamine ameliorates depression-like behavior in mice via modulation of the NRG1–ErbB4 pathway

BackgroundEsketamine has a significant and rapid antidepressant effect. Although studies have shown that Neuregulin 1 (NRG1) and it’s signaling pathway are associated with depression, the possible regulatory relationship of esketamine on the NRG1-ErbB4 pathway is not yet clear.MethodsTo induce depressive-like behavior in mice, a Chronic Social Defeat Stress (CSDS) model was established. Behavioral indicators were then employed to assess depression in these mice, categorized into control, susceptible, and resilient groups. Following intraperitoneal injection of a subanesthetic dose of esketamine, behavioral tests were conducted at 30 minutes and 24 hours post-injection to observe any improvements in depressive-like behavior. Additionally, changes in immunofluorescence and protein expression levels of NRG1-ErbB4 and GAD67 in the prefrontal cortex were evaluated.ResultsCompared with the control group, the CSDS susceptible group mice showed decreases in social interaction ratio in the contact area, sucrose preference ratio, NRG1 immunofluorescence protein expression in the prefrontal cortex and NRG1 expression in tissue homogenate; showed significant increases in immobility time; the expression of NRG1 decreased;no significant change in GAD67 and ErbB4 expression level. in After 30 minutes of intraperitoneal injection of esketamine, the expression of NRG1 in the prefrontal cortex of susceptible mice increased significantly. no significant change in GAD67 and ErbB4 expression level. After 30 minutes and 24 hours of intraperitoneal injection of esketamine, the social interaction ratio of susceptible group improved compared to the control group, and the duration of forced swimming immobility was significantly shortened.ConclusionThe subanesthetic dose of esketamine may regulate the NRG1-ErbB4 signaling pathway and improve depressive like behavior in mice.

Top 5 Firms Engineering Healthcare in the CNS Space

Central nervous system (CNS) treatments are having a major comeback. These five precision medicine players plan to ride the resurgence.

After a decade of stagnation, the CNS space is seeing a revival in sales and R&D spending as the market was last year projected to surpass $80 billion for the first time since 2013 and hit around $127 billion.

Recent landmark approvals have brought attention back to the CNS, including the U.S. Food and Drug Administration (FDA)’s greenlight of Eisai/Biogen’s lecanemab (Leqembi) for the treatment of Alzheimer’s disease in 2023, and the FDA approval of Bristol-Myers Squibb’s schizophrenia treatment xanomeline/trospium chloride (Cobenfy) in 2024.

At the same time, Johnson & Johnson’s depression treatment, esketamine (Spravato), is on its way to blockbuster status, showcasing the growth potential of the CNS market.

These successes accompany an emerging shift in psychiatry clinical trials from subjective rating scales to more objective endpoints, including digital and physiological measures, with the potential to better tailor treatments to a patient’s biological makeup.

Startups and scaleups are attracting increasing investor attention for their potential to change the way we treat CNS conditions. Check out our list of the most exciting companies that have netted the biggest investor dollars.

 

1. Aerska

Founded: 2025 | Headquarters: Dublin, Ireland

Aerska logo

Aerska’s name is derived from an Irish proverb stating that people survive in each other’s shelter, emphasising the strength of its team.

This team includes co-founder Jack O’Meara, previously co-founder of the liver-focused RNA interference (RNAi) biotech Ochre Bio, who is driven by the experience of loved ones suffering from Alzheimer’s disease.

Aerska is developing RNAi therapies for neurodegenerative conditions, including Parkinson’s and Alzheimer’s disease.

While there are already FDA-approved RNAi therapies on the market, such as Alnylam’s patisiran (Onpattro), these are typically focused on liver and cardiometabolic conditions rather than the CNS.

Aerska’s technology consists of antibody “brain shuttles” that bind to proteins on the blood-brain barrier (BBB). They then carry a payload RNA into the brain.

The payload, which is designed based on data-driven patient stratification and disease biomarkers, then silences specific genes driving the disease.

Aerska has already raised $60 million since its launch, including a $21 million seed round in October 2025 and a $39 million Series A round in February 2026, co-led by EQT Life Sciences and age1.

The company, which has research operations in the U.K., is using the latest funding to drive its pipeline programs toward clinical testing.

 

2. Beacon Biosignals

Founded: 2019 | Headquarters: Boston, Massachusetts, U.S.

Beacon Biosignals logo

Beacon Biosignals was co-founded by a team including its CEO—MIT neuroscientist Jacob Donoghue, MD, PhD—and its CTO, the machine learning researcher Jarrett Revels.

Boasting more than 100 employees, the company’s goal is to provide objective biomarkers in drug development that neurology and psychiatry have traditionally lacked compared with other areas of precision medicine.

Its FDA-cleared Waveband device measures the brain’s activity, known as electroencephalography (EEG), while patients sleep at home. The EEG data is then stored, quality-controlled, and fed into AI models that can guide the design of clinical trials.

For example, Beacon’s EEG data can identify patients with Alzheimer’s disease who have worse outcomes and might need a more targeted treatment or a different clinical trial than other patients.

Beacon raised $27 million in a Series A round in 2021 and an oversubscribed Series B round worth $86 million in November 2025.

The B round, which included investors such as Innoviva, Google Ventures, and Nexus NeuroTech, will help the startup to accelerate the discovery of neurobiomarkers and broaden clinical adoption of the technology.

Beacon acquired the French sleep monitoring company Dreem in 2023 to access its monitoring data and headband technology. Beacon then acquired the Ohio-based CleveMed in April 2025 to harness technology measuring breathing, oxygen, and other signals.

 

3. Brainomix

Founded: 2010 | Headquarters: Oxford, U.K.

Brainomix logo

Brainomix was founded by a team including CEO Michalis Papadakis, PhD, who was scientific director of the preclinical stroke lab at the University of Oxford.

Brainomix is dedicated to speeding up patient care in cases of stroke, where speedy treatment is key.

Brainomix’s flagship product, Brainomix 360 Stroke, is designed to harness AI to interpret brain scans and detect blood clots in patients with stroke, speeding up clinical decision-making.

The product involves a group of tools that automatically analyze images, including results from computed tomography (CT), CT angiography, magnetic resonance imaging (MRI), and CT perfusion.

Brainomix’s technology doubled the rate of thrombectomy treatment in patients with stroke and reduced hospital triage and transfer delays, according to a 2025 study.

The University of Oxford spinout is at a commercial stage, with operations in more than 20 countries, and is expanding into the U.S.

Brainomix raised a $21.2 million Series B round in 2021 and extended its Series C round from $6.5 million in March 2025 to $25.4 million in February 2026, with leading investors including Parkwalk Advisors and Hostplus. The proceeds will fuel the company’s expansion into the U.S. market.

Brainomix has also partnered with heavyweights, including Nvidia, Boehringer Ingelheim, Medtronic, and GE Healthcare.

Brainomix also has a product dedicated to disease monitoring in pulmonary fibrosis.

 

4. Circular Genomics

Founded: 2021 | Headquarters: San Diego, California, U.S.

Circular Genomics Logo

Circular Genomics was spun out of the University of New Mexico, with its founders including CSO Nikolaos Mellios, PhD, and Alexander Hafez, PhD.

The company later moved its headquarters from Albuquerque to San Diego in March 2025 to access scientific and operational know-how from Eli Lilly at Lilly Gateway Labs.

Circular Genomics aims to equip medical professionals with a blood test to detect CNS conditions early, in addition to stratifying and guiding the treatment of patients.

Its technology involves using a polymerase chain reaction (PCR) test of a patient’s blood sample to screen for specific circular RNA molecules produced in the brain that can cross into the blood and be measured as a biomarker of disease in the CNS.

Commercially launched in 2024, Circular Genomics’ MindLight SSRI Antidepressant Response Test predicts whether a patient will benefit from common antidepressants called SSRIs with around 77% accuracy. This is designed to predict a patient’s most suitable antidepressants without needing months of trial-and-error approaches.

The company is applying its technology in Alzheimer’s disease, where the approvals of disease-modifying therapies such as Leqembi have led to demand for tests that can detect the disease at earlier stages than traditional tests.

Circular Genomics raised $15 million in a Mountain Group Partners-led Series A round in December 2025 to finance the development of its technology and expansion of its technology in Alzheimer’s disease.

The company also has its sights on other CNS conditions, including multiple sclerosis and Parkinson’s disease.

 

5. Omniscient Neurotechnology

Founded: 2019 | Headquarters: Sydney, Australia

o8t logo

Omniscient (o8t)’s founders include CMO Michael Sughrue, MD, a neurosurgeon aiming to improve anatomy maps for other surgeons, and machine learning expert Stephane Doyen, PhD.

o8t’s FDA-approved product Quicktome involves using a patient’s MRI brain scans and AI models to map out a patient’s brain circuitry. These maps, accessible from an electronic tablet, can guide surgery to minimize the risk of brain damage compared to using a generalized anatomical diagram.

Quicktome is already in use at major hospitals around the world, including major centers in the U.S. Its partners include U.S. surgical support firm META Dynamic and the U.S. medical device innovation center, The Jacobs Institute.

o8t has raised more than $60 million, and bagged $14 million (AUD 20 million) in January 2026 as part of a Series D round targeted to reach $25 million (AUD 36 million). The round was led by Australia’s National Reconstruction Fund (NRFC) and OIF Ventures, with the aim of keeping the company based in Australia.

The funding is earmarked to fuel the development and commercialization of Quicktome, and grow o8t’s Australian workforce by more than 40. The company also has operations in Atlanta, Georgia, U.S.

o8t also plans to expand the technology into high-growth markets, including brain computer interface targeting, stroke and traumatic brain injury.

 

Jonathan Smith, PhD, is a freelance science journalist based in the U.K. and Spain. He previously worked in Berlin as a reporter and news editor at Labiotech, a website covering the biotech industry. Prior to this, he completed a PhD in behavioral neurobiology at the University of Leicester and freelanced for the U.K. organizations Research Media and Society of Experimental Biology. He has also written for medwireNews, Biopharma Reporter, and Outsourcing Pharma.

The post Top 5 Firms Engineering Healthcare in the CNS Space appeared first on Inside Precision Medicine.

<![CDATA[A relationship between inflammatory skin disease and depression revealed in new research.]]>

The Unspoken Toll: Why Exam Pressure Must Be Part of the Youth Mental Health Discussion

A Conversation with Tatum Redmond and Amanda van der Vyver-Anderson from Community Keepers, South Africa


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


Community Keepers is an award-winning organization based in Stellenbosch, South Africa, which works to improve the social and emotional well-being of learners and their caregivers. The SNF Global Center at the Child Mind Institute works with the organization to further advance the comprehensive mission of transforming schools into safe spaces where student well-being is prioritized alongside academic achievement. This includes strengthening the workforce to expand evidence-based support and brief interventions through low-intensity psychological therapy approaches.

While addressing the workforce gaps, the partnership has yielded valuable insight into the essential competencies front line workers require to effectively support young people experiencing mental health challenges. Together with other NGOs, Community Keepers has also been instrumental in strengthening the process of developing context-sensitive and culturally appropriate training materials scheduled for pilot implementation in South Africa later this year – representing an important step towards strengthening mental health care systems for underserved communities. The partnership also extends beyond training development, as the SNF Global Center at the Child Mind Institute continues to collaborate closely with Community Keepers on an upcoming randomized control trial (RCT). The scientific evaluation will assess both the feasibility of establishing a virtual clinic for young people and the effectiveness of remotely delivered cognitive behavioral therapy (CBT) interventions via video consultations. The research is intended to expand access to equitable and quality mental health care for young people across South Africa. Tatum Redmond has been a care facilitator in one of the Community Keepers’ high school-based offices, while Amanda van der Vyver-Anderson is an educational psychologist and heads the training and development of Mental Health First Aiders for internal and external staff.

Amanda van der Vyver-Anderson

How important is it to approach issues such as academic pressure within the wider conversation around youth mental health in South Africa, and beyond?

It is critical to integrate discussions of exam stress into the broader dialogue surrounding youth mental health, both here in South Africa and internationally. We see countless students under immense pressure to not only pass, but also secure their future prospects and meet family expectations. This is unfortunately often dismissed as “just school” or a “normal” experience. However, it impacts a substantial number of young people, often more severely than we acknowledge. And the level of support available is not equitable across the board. Addressing this is crucial because of the detrimental effects on core cognitive functions — and ultimately, academic performance — as well as the significant toll on mental health. This can manifest as anxiety, burnout, and even depression.

In what ways can exam-related stress connect to broader mental health challenges?

While a certain level of stress can serve as a beneficial motivator, severe distress can lead to cognitive shutdown. This specifically impacts the executive functions — planning, organizing, prioritizing, working memory, focus, and concentration — that are fundamental to preparing for exams. This shutdown can then create a detrimental, ongoing cycle of heightened stress about exams or the future, coupled with a decline in the ability to take effective action.

It’s vital to recognize that exam stress does not merely stay in the exam room — it can be a gateway to larger mental health challenges. Constant stress regarding school performance, marks, or the fear of failure can escalate into conditions like anxiety, chronic overwhelm, or depression. Students may experience sleep disruption, poor nutrition, and feelings of inadequacy. And these symptoms often persist long after the test is over. Compounding this is the reluctance of most students to seek help because they believe their feelings are normal or fear appearing weak. Yet, if left unaddressed, sustained pressure along with these symptoms can profoundly affect their psychological well-being.

Tatum Redmond

What role do community-focused organizations such as Community Keepers play in linking academic stress to systematic youth mental health support and improvement?

Organizations like Community Keepers play a truly pivotal role — not merely as emergency responders but as an integrated support system within educational institutions as well. Crucially, they move beyond immediate crisis response by collaborating with schools to develop long-term support and to provide safe spaces to engage in dialogue. They offer genuine attention and care when learners are struggling with school demands, exams, and family pressures.

The approach is not just “addressing stress today” but asking, “How can we create an enduring environment where young people feel safe, supported, and connected?” Doing this requires collaboration with the learners themselves, educators and school staff, as well as parents, caregivers, and community leaders.

What factors make schools uniquely positioned to be safe and supportive spaces?
Schools are exceptionally well-positioned to serve as safe and supportive spaces for students for several key reasons:

  • Learners spend a substantial portion of their day at school, making it a primary setting where adults can observe signs of distress, anxiety, or coping difficulties.
  • Schools have the opportunity to house critical personnel — teachers, counselors, and external partners like Community Keepers — who are on hand to offer support or a listening ear.
  • The curriculum can extend beyond academic skills and learning. It can include mental health and emotional literacy, stress management, and peer support.
  • When a school actively fosters an environment of safety, respect, and validation, it fundamentally alters how learners navigate pressure, stress, or complex personal problems. Having a guaranteed safe space at school is deeply stabilizing for the mind.

How can the goal of securing mental health support as a pillar of education be reached?
Achieving the goal of establishing mental health support as a solid, non-negotiable pillar of education requires several strategic commitments:

  • Schools must actively allocate resources for it, ensuring adequate numbers of support staff, rather than relying on minimal provision. Teachers need training to recognize signs of distress and respond helpfully and appropriately.
  • Mental health literacy must be integrated into the curriculum. Instead of only focusing on academic subjects, topics like stress management, emotional intelligence, and maintaining healthy relationships should be covered.
  • The government must demonstrate a serious commitment, including mental health support in education budgets, developing clear policies, and ensuring rigorous follow-through.

How have your practices and initiatives in promoting and supporting schools as safe spaces made meaningful change?
We’ve observed tangible change in the learners’ attitudes; those who feel comfortable expressing their emotions are generally happier and more resilient because they have established a safe, non-judgmental space where trust is built.

What role can teachers and school leadership play as partners in creating an evidence-based supportive learning environment? Where are the gaps in building capacity and how can they be better supported?
Educators and school leadership are essential partners in establishing an environment that successfully supports learner mental health and cultivates a culture of well-being. They can do so by:

  • Prioritizing both the physical space and curriculum time necessary for learners to engage with support services.
  • Serving as role models who embody and encourage emotional regulation and actively normalize help-seeking behaviour.
  • Remaining deeply cognisant of factors that contribute to learner distress so as to not inadvertently exacerbate it.

Investing in staff wellness and support, capacity building, and policy reform is not merely beneficial, but a foundational requirement to capacitate educators effectively. This allows them to sustainably support the mental health of their entire school community.

The SNF Global Center’s work in South Africa is carried out through the Child and Adolescent Mental Health Initiative (CAMHI South Africa). We are proud to expand the partnership with Community Keepers and value their collaboration towards co-creating scalable, school-centered mental health approaches that authentically respond to the diverse lived-experiences of young people.

The post The Unspoken Toll: Why Exam Pressure Must Be Part of the Youth Mental Health Discussion appeared first on Child Mind Institute.

Additive and Multiplicative Effects of Socially Stigmatized Identities Using Linear Regression to Model Effects on Self-Reported Overall Health as Reported in the All of Us Research Program: Quantitative Analysis

Background: Individuals with one or more socially stigmatized identities experience extensive health disparities, resulting in poorer health outcomes. However, most studies consider the effects of only individual stigmatized identities. Objective: We aimed to quantitatively estimate the additive and multiplicative effects of stigmatized identities on self-reported overall health. Methods: We used survey data from 387,411 participants in the All of Us Research Program, which has assembled a disease-agnostic cohort intended to reflect the US population, to statistically estimate the first- and second-order effects of 47 stigmatized identities on self-reported overall health. We used a linear model to estimate the effects of individual and pairwise stigmas on self-ratings of overall health. Results: We began by aiming to create cohorts for all 93 stigmatized identities previously found to affect health, of which 47 (51%) could be practicably examined. We first modeled individual stigmas alone to contrast the results with those that included both individual and pairwise stigmas. After using the false discovery rate to adjust for testing multiple hypotheses in the collective model, 29 individual and 116 pairs of stigmas had statistically significant effects on self-reported overall health. All significant individual effects were negative or neutral except for skin cancer. Those with the largest negative effect on self-rated overall health were difficulty walking or climbing stairs, unemployed or unable to work, difficulty with errands, and low educational attainment. Pairs of intersecting stigmas had a mix of negative and positive incremental effects, indicating that some stigmatized identities are negative modifiers, such as depression, and other combinations are less negative than the sum of their individual negative effects, such as having difficulty with multiple types of activities of daily living. The individual stigmas with the largest number of statistically significant stigma pairs were unemployed or unable to work (14/47, 30%); depression and low income (11/47 each, 24%); and difficulty walking or climbing stairs, cognitive difficulties, obesity, and skin cancer (8/47 each, 17%). Conclusions: Taken together, numerous pairs of stigmatized identities significantly affect self-reported overall health. While each stigmatization has both direct and indirect effects on health, the relative importance of direct and indirect effects will vary. Many of these are aligned with prior literature, and others warrant further exploration. While the large sample size of this study is a strength, we were unable to model higher-order intersectionality and encourage future research exploring this. The individual and pairwise identities with significant negative effects should be incorporated into research and clinical care by considering the multidimensionality of individuals and how that affects their overall health.
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AI Chatbots for Mental Health Self-Management: Lived Experience–Centered Qualitative Study

Background: Large language models (LLMs) now enable chatbots to engage in sensitive mental health conversations, including depression self-management. Yet their rapid deployment often overlooks how well these tools align with the priorities of people with lived experiences, which can introduce harms such as inaccurate information, lack of empathy, or inadequate crisis support. Objective: This study explores how people with lived experience of depression experience an LLM-based mental health chatbot in self-management contexts, and what perceived benefits, limitations, and concerns inform harm-mitigating design implications. Methods: We developed a technology probe (a GPT-4o–based chatbot named Zenny) designed to simulate depression self-management scenarios grounded in prior research. We conducted interviews with 17 individuals with lived experiences of depression, who interacted with Zenny during the session. We applied qualitative content analysis to interview transcripts, notes, and chat logs using sensitizing concepts related to values and harms. Results: We identified 3 themes shaping participants’ evaluations: (1) informational accuracy and applicability, including concerns about incorrect or misleading information, vagueness, and fit with personal constraints; (2) emotional support vs need for human connection, including validation and a judgment-free space alongside perceived limits of machine empathy; and (3) a personalization-privacy dilemma, where participants wanted more tailored guidance while withholding sensitive information and using privacy-preserving tactics. Conclusions: People with lived experience of depression evaluated LLM-based mental health chatbots through intertwined priorities of actionable information, emotional validation with clear limits, and personalization that does not require unsafe data disclosure. These findings suggest concrete design strategies to mitigate harms and support LLM-based tools as complements to, rather than replacements for, human support and recovery.
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<![CDATA[Lipocine’s oral brexanolone (LPCN 1154) for the treatment of postpartum depression failed to meet the primary endpoint in a phase 3 placebo-controlled trial.]]>

Attenuation of mGluR1/5-dependent synaptic plasticity and ERK pathway dysfunction in the hippocampus of diabetic rats

Streptozotocin-induced diabetic rats (STZ rats), an established animal model of type 1 diabetes mellitus, develop cognitive decline, which has been linked to impairments in hippocampal synaptic plasticity. Long-term depression (LTD) in the hippocampus may be induced by the activation of different types of G protein-coupled receptors, particularly metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. We previously demonstrated that acetylcholine receptor activation-dependent LTD was impaired in STZ rats, and herein investigated group I mGluR (mGluR1/5)-dependent LTD in the Schaffer collateral-CA1 synapses of STZ rats. Extracellular field recordings revealed that the chemical activation of mGluR1/5 with (S)-3,5-dihydroxyphenylglycine (DHPG, 50 μM, 10 min) induced sustained LTD in both control and STZ rats; however, the magnitude of DHPG-LTD was significantly smaller in STZ rats. Moreover, the paired-pulse ratio between before and 80 min after the application of DHPG increased in both control and STZ rats, and DHPG-LTD was independent of NMDA receptor activation. A Western blot analysis showed that DHPG-induced extracellular signal-regulated kinase (ERK) phosphorylation was reduced in STZ rats, whereas DHPG-induced phosphoinositide-dependent kinase 1 phosphorylation and the expression level of the scaffold protein, Homer1, were unchanged. Collectively, these results suggest that impaired ERK/MAPK signaling affected hippocampal mGluR1/5-dependent LTD in STZ rats, and the dysregulation of ERK may contribute to diabetes-associated cognitive decline because of its crucial role in protein synthesis-dependent synaptic plasticity.

Asking for help: the development of a simulation-based mental health application to enhance depression literacy, mental health communication, and help-seeking among Black autistic youth

Black autistic youth experience disproportionately high rates of depression and face intersecting barriers such as racial discrimination, stigma, and limited access to care, yet few interventions address their needs. This study introduces Asking for Help (A4H), a culturally responsive, simulation-based intervention designed to improve depression literacy and help-seeking skills through an e-learning module and interactive conversation practice. Guided by mental health literacy theory, the Theory of Help-Seeking Behavior, the Theory of Planned Behavior, and Disability Critical Theory, A4H was developed using community-engaged and user-centered design principles. Usability testing employed a mixed-methods design with 32 participants (12 youth, 10 caregivers, 8 specialists) using the System Usability Scale (SUS), Patient Health Questionnaire-9 (PHQ-9), and semi-structured interviews. Black autistic youth reported moderate depressive symptoms (mean PHQ-9 = 14.7) and rated usability slightly below benchmark (mean SUS = 66.2), while caregivers and specialists scored higher (73.5 and 71.0). Qualitative feedback highlighted cultural relevance and immediate feedback as strengths, with recommendations for simplified language, improved navigation, and multimodal supports; emotional safety and trust were critical for engagement. No short-term symptom change was observed, consistent with the formative design. Findings indicate A4H is feasible and culturally responsive but requires refinements before efficacy testing to assess impacts on literacy, help-seeking intentions, and communication skills.