PurposePromoting continuum beliefs has been discussed as a strategy for stigma reduction. The current study examines associations of continuum beliefs with stigma aspects (stereotypes, emotions, and social distance) and mental health literacy (illness recognition and treatment recommendations).MethodsIn 2011, a sample of the German population (N = 3,642) completed a vignette-based interview on attitudes regarding schizophrenia, depression, or alcohol dependence. Logistic regression analyses were performed and predicted probabilities were used to calculate prevalence estimates and depict direct effect sizes.ResultsIncreased continuum beliefs were strongly related to a decreased likelihood of social distance and endorsement of some negative stereotypes (e.g., being alien for schizophrenia) and an increased likelihood for endorsement of other negative stereotypes (e.g., lack of willpower for schizophrenia and depression) and emotions (e.g., anger for schizophrenia). Effect sizes indicated a greater reduction in negative stereotypes and desired social distance than increases in negative stereotypes or emotions. Furthermore, continuum beliefs were associated with a decreased probability of illness recognition for schizophrenia and recommending treatment for schizophrenia and depression, but an increased likelihood for illness recognition and recommending treatment for alcohol dependence.ConclusionPotentially harmful associations of continuum beliefs were found for schizophrenia and depression and should be considered by future studies and intervention designs. These potentially harmful associations are likely outweighed by helpful associations based on prevalence estimates and effect sizes. Associations between continuum beliefs and mental health literacy seem to be illness-dependent. Because of the sociocultural context and the time gap between the study and publication, representativeness for current public attitudes is limited.
MapLight’s Schizophrenia Candidate Has Mixed Results at Phase II
MapLight Therapeutics announced this week that its candidate drug for treatment of schizophrenia had achieved its primary endpoint in a Phase II trial, but only at the twice daily dose tested in the trial.
As reported by the California-based company, while participants of the trial who were given the candidate drug, ML-007C-MA, once a day did show some signs of improvement it was not statistically significant.
ML-007C-MA is a combined muscarinic agonist (betovumeline) and peripherally acting anticholinergic (fesoterodine). It acts by turning on two receptors in the brain, M1 and M4.
M1 is the main receptor the drug is trying to stimulate in the brain cortex and hippocampus, where it is linked to cognition, attention, and possibly some aspects of psychosis. Turning on M4 also helps by acting like a brake on the overactive signaling that contributes to hallucinations and delusions. Betovumeline activates both M1 and M4 centrally, while fesoterodine is there mainly to block unwanted side effects outside the brain, like gastrointestinal issues.
In this study, MapLight randomized 307 adults with an acute exacerbation of schizophrenia to treatment with either a twice daily or once daily treatment with ML-007C-MA or placebo for five weeks.
At five weeks, patients given the twice daily dose had a statistically significant and clinically meaningful reduction in Positive and Negative Syndrome Scale (PANSS) total score of 4.5 points compared to placebo. Cognitive scores were also better in the twice daily group versus placebo.
While this result is positive overall, the non-statistically significant result for the once daily dose proved unpopular with investors and company shares on the Nasdaq fell 40% after the announcement.
In September 2024, Cobenfy, the first muscarinic M1/M4 agonist drug for treatment of schizophrenia was approved by the FDA. Now owned by BMS, Cobenfy will be the main competitor for ML-007C-MA if approved.
Cobenfy was groundbreaking because it was the first new mechanism of action for schizophrenia in decades, moving beyond dopamine blockade to a muscarinic approach and targeting both hallucinations and delusions as well as the more cognitive aspects of the disease, which are not well treated with other drugs.
Despite the approval of Cobenfy, a number of other competitors developing treatments for schizophrenia have failed in recent years. Whether MapLight can succeed at Phase III with ML-007C-MA—which is also being tested as a treatment for psychosis linked to Alzheimer’s disease—and compete with Cobenfy, remains to be seen.
The post MapLight’s Schizophrenia Candidate Has Mixed Results at Phase II appeared first on Inside Precision Medicine.
Latest developments in the use of e-cigarettes by people with schizophrenia spectrum disorders who smoke: a scoping review
BackgroundTobacco use is significantly more prevalent among individuals with schizophrenia spectrum disorders (SSD) compared to the general population, contributing to elevated rates of premature mortality from smoking-related diseases. Despite a decline in smoking prevalence in the general population, individuals with SSD continue to smoke at persistently high rates, driven by biological, psychological, and social factors. Standard smoking cessation approaches yield markedly poorer outcomes in this group compared to non-psychiatric populations. This scoping review aimed to map the emerging evidence on the use of e-cigarettes among individuals with SSD or serious mental illness (SMI).MethodsThis scoping review was conducted in accordance with the Population–Concept–Context (PCC) framework and reported following the PRISMA extension for Scoping Reviews (PRISMA-ScR) guidelines. The review focused on studies published between January 2020 and February 2026, searched on PubMed and EMBASE, providing an up-to-date synthesis of emerging evidence on e-cigarette use in this vulnerable population.ResultsThree studies reported across four publications were included (total N = 323); one research group (Pratt et al.) contributed two separate publications reporting distinct outcomes from the same study cohort. Findings suggest that e-cigarette-based interventions are feasible and acceptable in individuals with SSD and SMI, with preliminary evidence of smoking reduction and decreased exposure to tobacco-related carcinogens. However, sustained harm reduction appeared dependent on a combined approach considering that device provision was empowered in its efficacy to sustain harm reduction over time when integrated with behavioral support.ConclusionsThe available evidence, while preliminary and limited by the small number of included studies, should be interpreted with caution regarding generalizability to patients with Schizophrenia Spectrum Disorders exclusively, as three of the four included publications recruited participants with broader SMI diagnoses of which SSD represents only a subset. Further research, including larger adequately powered trials with standardized outcome measures and longer follow-up, is needed to establish the generalizability and long-term impact of these interventions.
Transition Care for FEP
Conditions: Schizoaffective Disorders; Bipolar Disorder With Psychotic Features; Schizophrenia Disorders; Major Depressive Disorder With Psychotic Features; Psychosis NOS
Interventions: Behavioral: Transition Care Team
Sponsors: University of Chicago; Sidney R. Baer, Jr. Foundation
Recruiting
Interventions: Behavioral: Transition Care Team
Sponsors: University of Chicago; Sidney R. Baer, Jr. Foundation
Recruiting
CD163+ perivascular macrophages in schizophrenia: a research framework for testing macrophage-related mechanisms
Elevated densities of CD163+ perivascular macrophages have been reported in schizophrenia post-mortem brain tissue, particularly in regions involved in neurodevelopment, dopaminergic signaling, and blood–brain barrier (BBB) regulation. However, the biological significance and developmental lineage of these findings remain unclear. While CD163 is linked to regulatory and scavenging functions, macrophage activation states form a continuum and cannot be inferred from any single marker. This Perspective outlines a structured, testable research framework to determine whether this accumulation reflects altered responsiveness to persistent intracellular, inflammatory, systemic, or treatment-related signals. To test this, we propose sequential methodological aims, including defining CD163+ cell localization and phenotypes in predefined brain regions, and assessing viral and non-viral molecular signals using spatial transcriptomic and cell-specific methods. This framework also involves comparing macrophage activation states across schizophrenia and other psychiatric and non-psychiatric control groups, using single-cell and single-nucleus sequencing. By not presuming a specific infectious aetiology, this approach will provide a general methodology to investigate macrophage-related mechanisms across diverse potential triggers. Within this model, HSV-1 is evaluated strictly as an illustrative proof-of-concept candidate for testing intracellular pathogen responses, rather than an exclusive cause, as epidemiological associations have been inconsistent and localization of viral materials within these cells has not been demonstrated. Similarly, Bacille Calmette–Guérin (BCG)-associated trained immunity is introduced strictly as a preliminary, ex vivo/in vitro approach to probe macrophage reprogramming and plasticity. Ultimately, this framework provides a systematic approach for investigating macrophage-related mechanisms and their potential drivers in schizophrenia without presupposing a specific underlying aetiology.
Perception and willingness toward second-generation long-acting antipsychotics among patients with schizophrenia: a cross-sectional survey in Fujian, China
ObjectiveTo assess perceptions and willingness toward second-generation antipsychotic long-acting injectables (SGA-LAIs) among patients with schizophrenia, to identify the influencing factors, and to provide evidence for optimizing clinical implementation strategies.MethodsA cross-sectional survey was conducted in which patients with schizophrenia who attended outpatient follow-up visits at a tertiary psychiatric hospital were recruited via convenience sampling. A validated, expert-reviewed questionnaire was administered. Data were analyzed using descriptive statistics and chi-square tests, with binary logistic regression models employed to explore the determinants of patients’ willingness to accept SGA-LAIs.ResultsThe sample characteristics included 126 males (55.5%), 114 patients (50.2%) aged 31–50 years, 140 patients (61.7%) with an illness course exceeding 5 years, and 126 patients (55.5%) with experience with SGA-LAIs. Overall, 155 participants (68.3%) expressed positive willingness to use SGA-LAIs, whereas 72 participants (31.7%) expressed negative willingness. Univariate analysis revealed significant differences between the willingness-positive and willingness-negative groups in terms of disease course (χ² = 12.314, P = 0.006) and prior SGA-LAI experience (χ² = 55.525, P < 0.001). Binary logistic regression analysis revealed that patients with prior SGA-LAI experience (OR = 11.11, 95% CI: 5.41~23.26, P < 0.001), a disease course of 5–10 years (OR = 2.898, 95% CI: 1.134-7.407, P = 0.026), and a disease course of > 10 years (OR = 3.282, 95% CI: 1.300-8.288, P = 0.012) demonstrated significantly greater willingness to accept SGA-LAIs. Among the willingness-positive group, the most endorsed advantages of SGA-LAIs were “avoiding daily medication” (80.7%) and “increased effectiveness” (68.4%), and the primary concern was “injection pain” (56.8%). In the willingness-negative group, the predominant reasons for refusal were “rejection of needles” (93.1%) and “rejection of changing therapeutic regimens” (79.2%).ConclusionThe overall acceptance of and willingness to use SGA-LAIs among patients with schizophrenia followed up in psychiatric hospitals are high. Experience with SGA-LAIs and disease course were identified as independent factors influencing patients’ willingness to use SGA-LAIs. In clinical practice, patient acceptance can be enhanced by strengthening doctor-patient communication, prioritizing medication education for patients with a long disease course, and improving patients’ initial experience with SGA-LAIs, thereby supporting broader clinical adoption of SGA-LAIs.
Family caregivers’ involvement in home-based recovery for patients with schizophrenia: a qualitative study in Beijing, China
BackgroundFamily caregivers play critical roles in supporting the home-based recovery of patients with schizophrenia, but they often encounter substantial challenges and receive insufficient systemic support. Understanding caregivers’ involvement in home-based recovery is essential for aligning community mental health services with families’ capacities and needs. This study aimed to explore family caregivers’ involvement and adaptive processes in supporting home-based recovery of patients with schizophrenia in China.MethodsA qualitative study using interpretative phenomenological analysis was conducted through semi-structured interviews. Family caregivers were purposively recruited from four community health service centers (CHSCs) across urban and rural areas of Beijing. All interviews were audio-recorded, transcribed verbatim, anonymized, and analyzed iteratively to identify themes and subthemes.ResultsA total of 20 family caregivers were recruited, including 11 from two urban districts and 9 from a rural district in Beijing. Five themes were identified: Caregivers’ redefinition of recovery as stability rather than cure; Routine recovery involvement in medication management and symptom monitoring; Experienced tensions between the patient’s independence and relapse prevention; Bearing family obligation and personal strain in sustained caregiving involvement; and Uncertainty in sustaining caregiving and the patients’ future stability. Caregivers reported persistent challenges in supporting patients’ independent living, participation in family activities, communication, and social interaction.ConclusionFamily caregivers gradually develop their capacity to support home-based recovery, but continue to encounter complex challenges while receiving limited support from CHSCs. Strengthening recovery-oriented family support within community mental health services, particularly through accessible psychoeducation and rehabilitation guidance, may enhance caregivers’ capacity to support patients’ independence and social participation, thereby promoting sustainable home-based care and long-term functional recovery.
The ECHO study: compassion-focused therapy for young voice hearers and their caregivers. A pilot study
BackgroundVoice hearing can occur in healthy people without a trigger, be caused by a traumatic event, or occur as part of a psychiatric disorder. There are still many gaps in our understanding of voice hearing, and research in this field can be challenging, maybe because it is associated with shame and stigma. Those who experience distress by voice hearing could benefit from a treatment, aimed directly at that. The ECHO manualized treatment is based on the principles of compassion-focused therapy (CFT).MethodsTreatment will take place on several different psychiatric hospitals in the Region of Southern Denmark. Treatment consists of a 10-session, manualized CFT for voice hearing. Caregivers participate in half of the sessions, and a recording of the voice content is made, which the caregivers are encouraged to listen to. The study is designed as a prospective single-arm pre–post intervention study using a mirror-image approach, in which participants serve as their own controls over time. The intervention group consists of (N = 60) voice-hearing adolescents aged 13–18 years. Additionally, a clinical comparison group (who also receive the intervention) of (N = 20) individuals aged 18–20 years with first-episode schizophrenia and voice hearing is included for descriptive and exploratory analyses. Data are collected 3 months prior to CFT treatment, immediately before the start of treatment, immediately after treatment is completed, and at 1 month follow-up. Data will be centered around social cognition, perceived social safeness, social connectedness, general well being, auditory hallucinations and compassion.DiscussionThe ECHO study addresses the wellbeing and thriving of an overlooked group of young people. The results of this study will provide information about who the voice hearers are, what challenges they face, and how they perceive them. The results will also provide information about the feasibility and efficacy of the treatment manual and, thus, its potential further implementability. Caregivers participate in half of the sessions, to facilitate a common language about mental states and voice hearing. To support their understanding, a recording of the voice content is made and the caregivers are encouraged to listen to it. We suggest that when caregivers understand the young voice hearers’ experiences, they can adjust their expectations and approach accordingly. We also suggest that by sharing the voice content, the young voice hearer will feel less isolated.Study protocol registrationhttps://clinicaltrials.gov/study/NCT07314515, identifier NCT07314515.
A novel mutation in SETD1A is associated with early-onset epilepsy—a rare case report
SET Domain Containing 1A (SETD1A) is a histone H3K4 methyltransferase implicated in neurodevelopmental disorders. Pathogenic variants in this gene are associated with schizophrenia, intellectual disability, and epilepsy. Here, whole-exome sequencing and Sanger sequencing were performed on a 4-year-old Chinese girl with early-onset epilepsy and her unaffected parents. A novel de novo heterozygous variant in SETD1A (NM_014712.3: c.1067C > T/p.Ser356Phe) was identified in a patient presenting with focal-to-bilateral tonic–clonic seizures, beginning at 3 months of age. Neuroimaging revealed a normal brain MRI, and comprehensive neuropsychological assessment indicated preserved cognitive function. The variant was absent in 200 local controls and classified as likely pathogenic per ACMG criteria. This study may expand the mutation and phenotypic spectrum of SETD1A-related disorders, establishing the relationship between SETD1A variants and isolated early-onset epilepsy without accompanying severe neurodevelopmental deficits, highlighting the value of genetic testing in infants with unexplained epilepsy.
Evaluating Wearable Devices for Remote Monitoring in Psychosis: Pilot Study Nested Within the CONNECT Cohort Study
Background: Digital remote monitoring technologies, including smartphones and wearables, offer promising avenues for early detection of psychosis relapse. However, selecting devices that are acceptable to participants and produce high-quality data remains challenging. Objective: The aim of this nested pilot study was to assess the acceptability and data quality of 3 commercially available wearable devices in people with psychosis recruited to the CONNECT cohort study. Methods: Participants recruited to the CONNECT study before July 31, 2024, were included in the pilot study and selected 1 of 3 wearable devices: a Fitbit Charge 5, Samsung Galaxy Watch 5, or Apple Watch SE. Baseline demographics were compared between device groups. Acceptability of devices to participants was assessed through a Wearable Device Satisfaction Questionnaire after 3 months of use, with the proportion of positive responses to each question calculated and compared. Data completeness was also assessed by calculating the number (and percentage) of valid days of step count, heart rate, and sleep data, and comparing between groups. Data quality was assessed through summarizing the amount of troubleshooting required, additional metrics available from the wearables, and continuity of data completeness by calculating the proportion of participants with at least 3 days of heart rate data per week for the first 20 weeks of follow-up. Predefined criteria were used to determine the next steps for the wider CONNECT study: if one device was superior, this would be selected; if none were found to be superior and the Fitbit was found to be noninferior, then Fitbit would be retained. Results: Of the first 107 participants recruited to CONNECT, 105 were included in the pilot study evaluation. The Samsung Galaxy Watch was selected most frequently by participants (46/105, 43.8%), followed by the Apple Watch (27/105, 25.7%), and Fitbit Charge (23/105, 21.9%). Differences in participant demographics were observed across device groups. Self-reported acceptability after use did not differ substantially between devices. However, in terms of data completeness, the median proportion of valid heart rate data days was significantly lower for Samsung Galaxy (median 31.2%, IQR 8.5%-46.0%) compared to Fitbit (median 80.1%, IQR 26.7%-95.0%; =.003) and Apple Watch (median 49.3%, IQR 21.5%-86.0%; =.02). There was no significant difference between Fitbit and Apple Watch. Similar patterns were observed for step count and sleep data. The Samsung Galaxy Watch required more frequent troubleshooting for data flow issues and lacked additional physiological metrics, available from the other devices. Conclusions: Due to comparatively lower data quality and technical performance, the Samsung Galaxy Watch was discontinued for use in the subsequent phase of the CONNECT study. The study highlights the importance of incorporating nested evaluations of devices in long-term research.
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