BackgroundThyroid function and glycolipid metabolic alterations are often associated with major depressive disorder (MDD), yet their roles in suicide risk among adolescents with MDD remain unclear. This study aimed to investigate thyroid-stimulating hormone (TSH) levels, glycolipid metabolism parameters, and their associations with suicidal ideation (SI) in adolescents with MDD.MethodsThis cross-sectional study was conducted at one general hospital and one psychiatric hospital in Anhui Province, China. Socio-demographic data and laboratory parameters were collected from participants, and the patients’ depressive symptoms and SI severity were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24) and the Positive and Negative Suicide Ideation Inventory (PANSI), respectively. TSH levels and glycolipid metabolism parameters were also measured.ResultsA total of 146 adolescents with MDD and 70 healthy controls (HCs) were enrolled in this study. Compared with HCs, patients had lower fasting blood glucose (FBG) levels (P < 0.001). Logistic regression analyses showed that a worse relationship with family, a higher HAMD-24 total score, and higher TSH and FBG levels were independently associated with concurrent SI in adolescents with MDD (all P < 0.05). Furthermore, receiver operating characteristic (ROC) curve analysis showed that the combination of these four factors had a good discriminatory ability for SI, with an area under the curve (AUC) of 0.851.ConclusionIn this cross-sectional study, TSH and FBG levels were associated with SI in adolescents with MDD. Nevertheless, whether these parameters can serve as clinically useful biomarkers requires further validation in larger prospective studies.
StockWatch: Lilly’s Up-to-$3.8B Deal for AtaiBeckley a Good Trip for Psychedelic Drugs, Analysts and Investors Agree
It wasn’t too long ago that biopharma giants stayed away from developing psychedelic drugs—but positive clinical data plus a friendlier regulatory climate in Washington have prompted the largest drug developers to embrace the field.
The latest and most telling example of pharma embracing psych drugs came when Eli Lilly (NYSE: LLY) announced that it agreed to acquire AtaiBeckley (Nasdaq: ATAI) for up to $3.8 billion—of which Lilly will pay $2.8 billion upfront. The deal, set to close in the third quarter, expands Lilly’s neuroscience portfolio by adding the pipeline of AtaiBeckley led by BPL-003 (mebufotenin benzoate), a Phase III candidate for treatment-resistant depression (TRD) that is a synthetic form of 5-MeO-DMT administered intranasally. BPL-003 has been granted the FDA’s Breakthrough Therapy designation.
BPL-003 wowed analysts and others back in April after AtaiBeckley published positive data from a Phase IIa trial (NCT05660642) showing that a single intranasal dose of BPL-003 led to rapid and sustained reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline in 12 TRD patients who remained on stable SSRI therapy throughout the study. Both the six patients dosed at 10 mg and six at 12 mg showed a 66.7% antidepressant response rate (defined as ≥50% reduction from baseline MADRS score) at Day 2, with five of six participants in the 10 mg cohort (83%) and four of six in the 12 mg cohort (66.7%) maintaining their response at Week 12.
“Especially with progress on BPL-003, we see the company as positioning itself well to becoming a significant player in the mental health therapeutics space,” Sumant Kulkarni, a senior analyst covering biotechnology with Canaccord Genuity, wrote on news of the positive data, adding: “We also still see this space as large enough to accommodate multiple approaches/competitors.”
$3.7B in projected peak sales
Kulkarni also raised Canaccord Genuity’s peak unadjusted U.S. sales forecast for BPL-003 to $3.7 billion by 2036 from $2 billion, after revising the firm’s model by raising the list price from $20,000 to $30,000 per annual treatment course (not accounting for insurance coverage), about the same price as Spravato® (esketamine), also a nasal spray marketed by Johnson & Johnson (NYSE: JNJ) for TRD plus some depressive symptoms in adults with major depressive disorder (MDD).
Spravato, a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, crossed the $1 billion sales threshold during the second quarter, as it generated $584 million, up 25% quarter-over-quarter from $464 million in Q1—and up 43% from $734 million in the first half of 2025.
“Sales are tracking to reach annual sales guidance of $3-3.5B+ by 2027–28,” Jefferies equity analyst Andrew Tsai wrote in a research note focused on J&J’s second-quarter results. “Spravato’s trajectory supports the notion psychedelics can be commercially viable in hard-to-treat mental health disorders, by leveraging JNJ’s infrastructure.”
Given the data for BPL-003, Lilly got a bargain, Tsai wrote in a separate note on the Lilly-AtaiBeckley acquisition.
“We think the deal heavily favors LLY, as ATAI’s lead asset BPL-003 (intranasal 5-MeO-DMT) should have multibillion dollar peak sales potential,” Tsai wrote, rather than the $1 billion-plus that he thinks was implied by the deal price.
Tsai and Jefferies had previously forecast peak sales of between $1 billion and $2 billion—a range he said was “arguably conservative” since BPL-003 could, if it aces its Phase III trial, show superiority to Spravato, which is on track to reach up to $5 billion-plus in peak sales.
Positive implications
“At the same time, we appreciate LLY has significantly more resources to maximize the long-term value of ATAI’s psychedelic assets. In any case, the deal has (+) [positive] implications for the entire psychedelic space,” Tsai added.
Among pharma giants joining J&J in embracing psychedelic drug development in recent years:
- AbbVie (NYSE: ABBV), which last year acquired the lead pipeline program of privately held Gilgamesh Pharmaceuticals, the moderate-to-severe MDD candidate bretisilocin (GM-2505), for up to $1.2 billion.
- Otsuka Holdings (Tokyo Stock Exchange: 4578), which in 2023 acquired Mindset Pharma, a Canadian psych drug developer focused on psychiatric and neurological disorders, for C$80 million ($56 million).
With its deal for AtaiBeckley, Lilly becomes the latest pharma giant to perceive the positive implications Tsai cited.
“Treatment-resistant depression persists even after multiple treatments have failed. Millions of people are still searching for relief and desperately need a therapy that works,” Carole Ho, executive vice president and president, Lilly Neuroscience, said in a statement. “Advancing AtaiBeckley’s investigational therapies gives us a real chance to change that.”
Investors agreed with Lilly, giving the pharma a 1% increase Thursday, the day the acquisition was announced, from $1,156.63 to $1,169.17—no small feat since buyers typically stay flat or see their shares slide after announcing an acquisition. And not surprisingly, AtaiBeckley investors were enthusiastic about the deal, as its stock leaped 33% from $5.36 to $7.15. On Friday, Lilly inched up 0.8% to $1,178.58 while AtaiBeckley rose 1% to $7.22.
The AtaiBeckley buyout is Lilly’s eighth announced acquisition of a smaller biopharma this year.
Lilly is acquiring three infectious diseases vaccine developers—Vaccine Company for up to $1.55 billion, Curevo for up to $1.5 billion, and LimmaTech Biologics for up to $780 million—as well as in vivo chimeric antigen receptor T-cell (CAR T) developer Kelonia Therapeutics for up to $7 billion); JAK inhibitor developer Ajax Therapeutics for up to $2.3 billion; next-generation dual-payload antibody-drug conjugate (ADC) developer CrossBridge Bio for up to $300 million; and nonviral DNA delivery-focused drug developer Engage Biologics for up to $202 million cash.
The deal spree reflects Lilly’s desire to capitalize on the billions of dollars it is generating from sales of its obesity and diabetes drugs based on glucagon-like peptide 1 (GLP-1) receptor agonists alone or in tandem with a glucose-dependent insulinotropic polypeptide (GIP).
“If we see great ideas that we think we can use to help people that need them, of course we’ll do deals,” Daniel M. Skovronsky, MD, PhD, Lilly’s chief scientific and product officer and president of Lilly Research Laboratories, said on CNBC.
“Positive development”
David Risinger, a senior managing director and senior research analyst covering diversified biopharmaceuticals at Leerink Partners, said his firm viewed Lilly’s buyout of AtaiBeckley “as a positive development because it enhances LLY’s pipeline of potential neuroscience blockbuster candidates.”
That pipeline is led by five Phase III programs involving four drugs, none of them a psychedelic. Two of the programs belong to brenipatide, a dual agonist of both the GIP and GLP-1 receptors. Brenipatide is being developed for both MDD and alcohol use disorder.
Also in Lilly’s late-stage neuroscience pipeline are:
- Donanemab, which binds to deposited amyloid plaque in the brain and is being studied for the treatment of cognitively unimpaired Alzheimer’s disease.
- Ixoberogene Soroparvovec (Ixo-Vec), an intravitreal gene therapy being studied as a single one-time treatment for vision loss associated with neovascular (wet) age-related macular degeneration (AMD).
- Remternetug (LY3372993), which also binds to deposited amyloid plaque in the brain and is under study as a treatment of cognitively unimpaired/mild cognitive impairment due to Alzheimer’s disease, with potential for subcutaneous delivery.
In addition, AtaiBeckley “would provide differentiated exposure in psychiatry and reinforce [Lilly’s] broader effort to diversify beyond its cornerstone cardiometabolic franchise,” observed Evan David Seigerman, a managing director and head of healthcare research at BMO Capital Markets, as reported by Reuters.
AtaiBeckley was formed last November by the merger of atai Life Sciences and Beckley Psytech. The company’s stock has nearly doubled, soaring 98% over the past six months from $3.64 on January 16.
“Going mainstream”
“Psychedelic Medicine is going mainstream,” declared Steve Jurvetson, co-founder of Future Ventures, in a post on X. Jurvetson and Future were among early investors, along with Peter Thiel in atai Life Sciences.
AtaiBeckley is one of numerous psychedelic drug developers to show significant six-month gains since January: As of Friday’s closing bell, Compass Pathways (Nasdaq: CMPS) shares jumped 68% to $12.35, GH Research ballooned 69% to $28.71, while Definium Therapeutics (Nasdaq: DFTX) nearly tripled, zooming 194% to $44.29.
Interestingly, those three companies did not get a solid bounce from AtaiBeckley’s acquisition by Lilly. Since the deal was announced Thursday, Compass fell 7% from $13.31 pre-announcement, Definium dipped 3% from $45.66. GH rose 8% Thursday from $26.92 to $29.13, before sliding 1.4% the following day.
Bucking the trend was Cybin, d/b/a Helus Pharma (Nasdaq: HELP), which has climbed 11% since the Lilly-AtaiBeckley announcement, from $6.51 to $7.25. Its shares have slumped 6% since January—but soared 58% over the past month on positive news, such as the 88%+ enrollment rate of patients in Helus’ Phase III APPROACH pivotal trial (NCT06564818) of HLP003 in MDD, on track for topline data readout in Q4 2026.
“We see the potential for 150–200% upside [jump in stock price] if Phase III data in 4Q26 are positive,” Kulkarni wrote, making it the largest potential jump among psychedelic drug developers.
In addition to favorable data, the stock surges also reflect actions by President Donald J. Trump’s administration to encourage psychedelic drug development. In April, President Trump signed Executive Order 14401, directing the FDA and other federal agencies to accelerate research and improve access to psychedelic drugs, citing their potential as promising treatments for serious mental illnesses.
And on July 13, the FDA published “Psychedelic Drugs: Considerations for Clinical Investigations,” a final guidance designed to provide general considerations for developers of psych drugs, with recommendations for how to conduct clinical trials for the treatments.
“Rather than providing specific recommendations on study design, this guidance will present foundational constructs that all sponsors studying the therapeutic potential of psychedelic drugs, including sponsors without commercial drug development as primary interest (e.g., academic researchers), should consider,” the FDA wrote in the final guidance. “Sponsors are encouraged to request meetings with FDA for advice on a specific drug development program.”
Leaders and laggards
- Q32 Bio (Nasdaq: QTTB) shares nearly doubled, leaping 91% from $11.21 to $21.38 July 13 after the autoimmune and inflammatory disease drug developer announced positive 36-week topline results from Part B of the Phase IIa SIGNAL-AA trial (NCT06018428) assessing bempikibart in patients with severe or very severe alopecia areata. Q32 said it saw clinically meaningful efficacy data on the primary endpoint of mean percent change from baseline in SALT score, with a reduction from baseline of 35.3% in the prespecified modified intent to treat (mITT) analysis. The company also reported that 40.0% of patients (10/25) achieved SALT-20 response at Week 36 in the mITT analysis, while 30.3% of patients (10/33) achieved SALT-20 response at Week 36 in the ITT analysis of all enrolled patients.
- Veradermics (NYSE: MANE) shares yo-yoed this past week, climbing 12% from $110.17 to $123.70 Wednesday after the pattern hair loss drug developer announced positive topline results from its open-label Phase II Study 207 trial (NCT06527365) assessing VDPHL01, an extended-release oral minoxidil formulation, in women with mild-to-moderate pattern hair loss. Veradermics said most study participants reported improved hair coverage at Month 2, with approximately 88.9% of patients dosed once daily and 90.0% dosed twice daily reporting “improved” or “much improved” outcomes at Month 6. Participants dosed once daily showed a mean increase in non-vellus target area hair count (TAHC) of 22.7 hairs/cm² at Month 6, an average that rose to 23.3 hairs/cm² in twice daily dosed patients. The mini surge was short-lived, however, as investors more than gave back the gain, selling off shares to send them tumbling 14% to $105.83 Thursday amid possible investor questions about whether the good clinical news was already reflected in the stock price.
The post StockWatch: Lilly’s Up-to-$3.8B Deal for AtaiBeckley a Good Trip for Psychedelic Drugs, Analysts and Investors Agree appeared first on GEN – Genetic Engineering and Biotechnology News.
Genetic Study Links Excessive Sweating to Neurological Dysfunction
Data from a new study suggest that a form of hyperhidrosis, or excessive sweating, may be due to genetic mutations that result in the overstimulation of the nerves that control the sweat glands. These findings, which are reported in Science Advances, could open a door to targeted treatments for the condition using existing medicines. Full details of the findings are provided in the paper titled “A neurocutaneous NaV1.8 channelopathy underlies a genetic subtype of primary idiopathic hyperhidrosis.” The international study is led by scientists at Vrije Universiteit Brussel.
Excessive sweating, which affects roughly two to five percent of the population, causes more than just discomfort. The impact of the condition on the daily lives of people living with it can be very severe. Patients often sweat so profusely that they have to change clothes several times a day. Many avoid social contact, experience shame, and develop depression. Yet the condition is often seen as a superficial skin problem and patients often do not receive appropriate care.
That could change thanks to the findings from this study which is the culmination of 10 years of research done by scientists in the lab of Frank Bosmanbs, PhD, at Vrije Universiteit Brussel and their collaborators at Johns Hopkins University. To pinpoint a genetic basis for hyperhidrosis, the scientists analyzed the DNA of more than 180 patients. They discovered defects in the Nav1.8 ion channel, which normally functions as a biological gate that regulates electrical signals in the nervous system.
Specifically, in patients with hyperhidrosis, the gate is left too wide open due to a genetic predisposition. As a result of this, the nerves are constantly overstimulated and in a state of activity, which results in excessive sweating often triggered by emotional or stress-related stimuli. To dig deeper into their theory, the scientists developed an experimental mouse model. Because mice only sweat from their paws, the team developed a microscopic measurement method to count sweat droplets using an iodine-starch mixture.
They found that mice that had the same genetic defect as hyperhidrosis patients also sweated excessively. Furthermore, once the scientists administered a substance that blocked the overactive nerve signals, their symptoms decreased significantly and reversibly. However the genetic picture is more complex. Bosmanbs and his team found a patient who had inherited an inhibitory nerve mutation but still sweated excessively due to a separate mutation in a local water channel within the sweat gland. It suggests that there are different biological pathways that can lead to the same overstimulation that results in hyperhidrosis.
Though the genetic picture is a complex one, the scientists believe that their findings offer the prospect of better treatments for this condition. Currently, some severe forms of hyperhidrosis are treated by severing the sympathetic nerve pathways in the chest. While effective, this treatment is both invasive and can have unwanted side effects. With a deeper understanding of the genetic basis of the condition, scientists may be able to better predict which patients are likely to get the most benefit from localized treatment of the sweat glands, systemic medication or nerve-targeted therapies. Another potential treatment avenue is drug repurposing, which is supported by the evidence from the mouse studies. However, further testing via controlled clinical trials is required.
The post Genetic Study Links Excessive Sweating to Neurological Dysfunction appeared first on GEN – Genetic Engineering and Biotechnology News.
Altered tryptophan metabolism as a contributor to cognitive impairment in chronic kidney disease: a narrative review
Approximately 40% of patients with chronic kidney disease (CKD) experience cognitive impairment (CI), which is strongly associated with increased mortality. CI is driven by multiple factors, including vascular injury, accumulation of uremic toxins, disruption of the blood–brain barrier, and chronic inflammation. Recent evidence suggests that kidney disease and neurocognitive decline are mechanistically linked through dysregulated tryptophan metabolism. Tryptophan is metabolised through three main pathways: the kynurenine, indole, and serotonin pathways, each producing bioactive metabolites with distinct neurophysiological effects. The hallmarks of CKD include chronic inflammation, gut microbial dysbiosis, and impaired renal clearance, all of which alter tryptophan metabolism. Inflammation drives tryptophan metabolism towards the kynurenine pathway, increasing the formation of neurotoxic compounds that promote oxidative stress, excitotoxicity, and neuronal injury. However, reduced availability of tryptophan for serotonin synthesis impairs serotonergic signalling and neurotransmission, as well as melatonin biosynthesis, thereby contributing to circadian rhythm disturbances and impaired glymphatic clearance. Concurrently, gut dysbiosis and reduced renal clearance promote the accumulation of indole-derived uremic toxins, leading to endothelial dysfunction, neuroinflammation, and disruption of the blood–brain barrier. This review highlights the current evidence of dysregulated tryptophan metabolism in CKD and its impact on the pathogenesis of neurocognitive complications. The review also discusses potential biomarkers and therapeutic strategies, including kynurenine pathway inhibitors, gut microbiota modulation, uremic toxin adsorption, melatonin supplementation and personalised medicine to mitigate cognitive impairment in CKD.
Pharmacotherapy, acupoint stimulation, and psychotherapy for perimenopausal women with anxiety, depression, and panic disorder: a systematic review and network meta-analysis of randomized controlled trials
BackgroundPerimenopausal women frequently experience physiological and psychological symptoms, including anxiety, depression, and panic disorders, mainly due to declining ovarian function and hormonal changes. Current options include pharmacotherapy, acupoint stimulation (AcuStim), and psychotherapy (psych), but their comparative efficacy and safety remain controversial.ObjectiveThis network meta-analysis (NMA) systematically compared pharmacotherapy, AcuStim, and psychotherapy for perimenopausal anxiety, depression, and panic disorder, assessing clinical efficacy, adverse events (AEs), and changes in the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Kupperman Index (KI), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Index (PSQI), and serum hormone levels.MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed from inception to June 14, 2026, for randomized controlled trials (RCTs). A Bayesian NMA was performed, and the Surface Under the Cumulative Ranking Curve (SUCRA) was calculated.ResultsThe study included 131 RCTs, encompassing 11457 perimenopausal women diagnosed with emotional disorders. These trials evaluated three distinct treatment strategies. The NMA showed that the highest SUCRA probabilities were observed for drug_psych across HAMD (SUCRA = 92.4%), KI (SUCRA = 97.9%), SDS (SUCRA = 94.5%), PSQI (SUCRA = 98.1%), and follicle-stimulating hormone (FSH) (SUCRA = 96.1%) reduction and estradiol (E2) (SUCRA = 0.1%) elevation; for AcuStim_psych (SUCRA = 93.7%) in HAMA reduction; for psych (SUCRA = 98.9%) in SAS reduction; for drug_AcuStim in clinical efficacy (SUCRA = 9.0%) and luteinizing hormone (LH) reduction (SUCRA = 100%); and for control (SUCRA = 65.5%) in safety outcomes. In pharmacotherapy subgroup analyses, antidepressants (ADs)_Traditional Chinese medicine (TCM) ranked highest for HAMD (SUCRA = 87.2%) and safety (SUCRA = 82%), ADs_antipsychotics (AP) (SUCRA = 97.5%) for HAMA, and ADs_hormone replacement therapy (HRT) (SUCRA = 10.2%) for clinical efficacy.ConclusionPharmacological, acupoint stimulation, and psychological interventions each demonstrated therapeutic benefits for perimenopausal women with emotional disorders. Combination therapies generally showed more favorable efficacy across multiple psychological and endocrine outcomes than single-modality interventions, while no single treatment strategy was consistently superior across all outcomes. These findings may provide evidence to support individualized treatment selection according to patients’ clinical characteristics and therapeutic goals.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261340530.
<![CDATA[COMP360 psilocybin shows rapid, durable gains in treatment‑resistant depression, as psychedelics continue to grow.]]>
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Fragile self, mechanical world: mechanistic delusions and ego fragility in schizotypal–affective spectrum disorder—a CARE case report
Categorical nosological systems frequently fall short when confronted with patients whose presentations cross established diagnostic boundaries. We report M.S., a 44-year-old Brazilian man involuntarily admitted to a psychiatric inpatient unit who presented with systematized persecutory ideation of mechanistic–technological content (chip implantation, satellite-based surveillance), structural ego fragility, absent insight, and progressive social and occupational deterioration. While prior diagnoses of bipolar disorder and provisional schizophrenia had been considered, neither fully captured the clinical complexity. Psychopathological-dimensional analysis, grounded in phenomenological observation and contemporary psychopathological theory, suggests three potentially interacting axes: (1) structural ego fragility (Ich-Schwäche), potentially arising from impaired early attachment and deficient relational learning; (2) a relational causality deficit replaced by concrete–mechanistic reasoning; and (3) limbic hyperactivation that appears to sustain an anxiety–perplexity–paranoia feedback loop. These converge on a schizotypal–affective spectrum formulation. Laboratory investigations identified severe dyslipidemia and marked hyperandrogenism (total testosterone 1,367 ng/dL), the latter potentially associated with limbic hyperactivation, though causality cannot be established from a single cross-sectional measurement. Psychometric assessment (BPRS-18) at admission yielded a total score of 43, with suspiciousness (5) and unusual thought content (5) as dominant items. During a seven-day inpatient course, a multimodal thymic strategy—risperidone, lithium carbonate, and structured psychotherapy—produced attenuation of paranoid reactivity, improved family engagement, and the spontaneous resumption of guitar playing from day 3, as a functional correlate of behavioral stabilization. The patient was discharged with a referral for a three-monthly paliperidone palmitate long-acting injectable. The pharmacological response retrospectively supports the dimensional formulation and illustrates the heuristic value of psychopathological analysis grounded in ego structure, causal reasoning, and affective dysregulation as a complementary approach to categorical nosology in complex psychotic–affective presentations.
Retraction: Metoprolol, N-Acetylcysteine, and Escitalopram Prevents Chronic Unpredictable Mild Stress-Induced Depression by Inhibition of Endoplasmic Reticulum Stress
A Self-Guided Mobile Mindfulness Intervention Embedded in Daily Routines for Adults With Mild to Moderate Psychological Distress: Randomized Controlled Trial
Background: Mobile mindfulness interventions have shown promise for reducing anxiety and depressive symptoms, but sustaining engagement remains a persistent challenge. Many digital programs still rely on formal practice that requires dedicated time, which may be difficult to integrate into daily life. Objective: This randomized controlled trial evaluated Habitual Mindfulness Practice (HMP), a self-guided mobile mindfulness intervention that embeds brief practices into recurring daily routines, among adults with mild to moderate psychological distress. Outcomes were compared with those of Traditional Mindfulness (TM), Mindfulness-Based Psychoeducation (MBP), and a waitlist control (WL). Methods: Adults aged 18 to 65 years with mild to moderate symptoms of anxiety or depression were randomly assigned in a 1:1:1:1 ratio to HMP, TM, MBP, or WL (N=686). All procedures were conducted online, and the intervention was fully self-guided, with outcomes assessed using self-report measures. The intervention lasted 21 days, with assessments conducted at baseline, postintervention, and 3-month follow-up. Primary outcomes were depressive and anxiety symptoms. Secondary outcomes included mindfulness, cognitive emotion regulation, affective balance, and interpersonal difficulties. Postintervention group differences were examined, controlling for baseline scores, and longitudinal trajectories were evaluated across the active intervention conditions. Results: At postintervention, significant group effects were observed for depressive symptoms (=28.67, <.001, ηp²=0.11) and anxiety symptoms (=30.11, <.001, ηp²=0.12). Both HMP and TM showed lower depressive and anxiety symptom scores than MBP and WL. TM showed lower postintervention anxiety than HMP (=.04), whereas depressive symptoms did not differ significantly between HMP and TM (=.63). The mindfulness practice conditions also showed more favorable postintervention outcomes for mindfulness, affective balance, interpersonal difficulties, and emotion regulation. Improvements in depressive and anxiety symptoms were generally maintained at follow-up among the active intervention conditions, although maintenance of secondary outcomes varied across measures. Postintervention outcome data were available for 55.2% (379/686) of randomized participants, and follow-up outcome data were available for 24.1% (124/515) of participants in the active intervention conditions. HMP and TM did not differ significantly in practice duration, engagement, or satisfaction. Conclusions: A routine-embedded, self-guided mobile mindfulness intervention may be a feasible approach for reducing mild to moderate psychological distress. HMP produced benefits broadly comparable to those of traditional app-delivered mindfulness, but it did not confer advantages in engagement or short-term efficacy. Trial Registration: Chinese Clinical Trial Registry ChiCTR2400093771; https://tinyurl.com/3d6tky8v
