IntroductionIn the treatment of schizophrenia, antipsychotics used during acute inpatient care must control acute symptoms while remaining sufficiently tolerable to support treatment beyond the acute phase. Brexpiprazole, a serotonin-dopamine activity modulator may be one such option; however, its real-world use and short-term continuation in acute inpatient settings remain insufficiently characterized.MethodsWe conducted a retrospective observational study of inpatients with DSM-5 schizophrenia treated with brexpiprazole at a university hospital in Japan between June 2018 and July 2024. The index date (week 0) was defined as the date of brexpiprazole initiation during the index hospitalization. The primary outcome was brexpiprazole continuation at week 8. We compared baseline demographic and treatment-related variables between the continuation and discontinuation groups and summarized reasons for discontinuation from electronic medical records. As a secondary exploratory analysis, we examined longitudinal changes in Clinical Global Impressions–Severity scale (CGI-S) and Brief Psychiatric Rating Scale (BPRS) total scores (weeks 0/4/8) in the continuation group using a linear mixed-effects model including time, concomitant psychotropic medication status, and their interaction.ResultsSixty-seven patients were included. Baseline illness severity was substantial (median CGI-S 5.0 [IQR 5.0–6.0]; mean BPRS total 58.5 ± 9.6). Concomitant psychotropic medications were common. Thirty-six patients continued brexpiprazole to week 8 (53.7%). In unadjusted exploratory comparisons, continuation was associated with the female sex (p = 0.036), lower prior chlorpromazine-equivalent dose (p = 0.015), and shorter duration of untreated psychosis (p = 0.003), with a trend toward shorter duration since onset (p = 0.073). The most frequent reason for discontinuation was adverse events (n = 10, 32.3%), most commonly akathisia (n = 6), followed by insufficient efficacy (n = 9, 29.0%) and patient preference/refusal (n = 7, 22.6%). In exploratory mixed-effects analyses within the continuation group, CGI-S and BPRS total scores decreased over time, with significant group-by-time interactions by concomitant medication status. However, between-group differences should be interpreted cautiously.DiscussionThis study describes 8-week continuation and reasons for discontinuation of brexpiprazole in acute inpatient schizophrenia care. Given the retrospective single-center design and potential selection/information bias and unmeasured confounding, further studies are warranted to clarify its clinical positioning in real-world practice.
THE EFFECTS OF AN ONLINE FAMILY PSYCHOEDUCATION PROGRAM ON EXPRESSED EMOTION OF FAMILY MEMBERS AND MEDICATION ADHERENCE OF PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA
Conditions: First- Episode Schizophrenia
Interventions: Behavioral: Mobile based family psychoeducation program
Sponsors: Mahidol University
Completed
Interventions: Behavioral: Mobile based family psychoeducation program
Sponsors: Mahidol University
Completed
Opportunities for Digital Health to Support Early Psychosis Care in Ghana: Qualitative Study Among Patients, Caregivers, and Clinicians
Background: Youth experiencing early psychosis in West Africa often face delays in accessing evidence-based treatment. Digital mental health interventions may offer an acceptable and scalable approach to improve access to early psychosis care in West Africa; however, few data exist on the experiences and perspectives of patients with early psychosis and their caregivers to inform digital intervention development. Objective: This study aims to explore current experiences of early psychosis care, identify barriers and facilitators to in-person early psychosis care within health facilities, and identify opportunities for digital interventions to support patients with early psychosis and caregivers in Ghana. Methods: We conducted qualitative focus group discussions among patients with early psychosis, their caregivers, and their mental health care providers recruited at Accra Psychiatric Hospital in Accra, Ghana. Trained qualitative researchers facilitated discussions using a structured qualitative interview guide, exploring current care practices for early psychosis in Ghana, barriers and facilitators to facility-based care, and perceptions of digital mental health interventions. Transcripts were translated, transcribed, and analyzed thematically using a hybrid inductive and deductive approach grounded in the theoretical framework of acceptability. Results: Overall, we conducted 4 focus group discussions (N=31) among 7 patients with early psychosis (median age 28, IQR 21‐41 years), 6 caregivers (median age 58, IQR 29‐34 years), and 18 clinicians (median age 30, IQR 29‐34 years). Participants described current early psychosis care practices in Ghana, including seeking spiritual and traditional healing, the dearth of information and resources about psychosis, and the integral role of caregivers in facilitating treatment engagement and continuation (often at the cost of caregiver mental distress and burnout). Common barriers to facility-based mental health care included stigma associated with mental illness, lack of prior knowledge about early psychosis and treatment options, and practical constraints (eg, financial, logistical, and health care system limitations). Motivating factors for facility-based care included success stories from community members and strong rapport and trust in mental health clinicians. Technology (eg, mobile phones, laptops, radio, and television) was commonly used among participants in typical daily tasks, health information seeking, and stress reduction. Participants expressed support for digital tools that could deliver psychoeducation about early psychosis, support treatment adherence, and extend patient-provider communication between clinic visits. Conclusions: Digital mental health interventions have the potential to complement facility-based early psychosis services in Ghana by addressing misinformation, reducing access barriers, and supporting caregiver roles. These qualitative findings inform potential integration points, content, attributes, and strengths of digital modalities that could be leveraged to support patients with early psychosis and their caregivers in Ghana.
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Machine learning for oral frailty factors in hospitalized schizophrenia patients: two-stage feature selection and SHAP analysis
BackgroundLong-term hospitalized patients with schizophrenia (SZ) often experience significant oral health problems, and oral frailty (OF) can further exacerbate the decline in their quality of life. However, the status and key influencing factors contributing to OF in this population remain insufficiently explored. Most existing studies rely on traditional regression models, which are prone to overfitting when processing high-dimensional data, making accurate risk identification difficult. This study aims to clarify the current status of OF in this population in Southwest China, identify the influencing factors, and optimize the predictive model using machine learning (ML), thereby providing a basis for clinical practice.MethodsA total of 404 long-term hospitalized patients with SZ from three psychiatric hospitals in Southwest China were enrolled in this study. The Oral Frailty Index-8 was employed to assess OF. Nine feature selection methods and five ML models were employed to optimize the model through two-stage feature selection, while Shapley Additive Explanations (SHAP) were used to analyze the model’s predictive logic.ResultsThe prevalence of OF in this population was determined to be 69.3%. The optimal model identified was the random forest, with the Area Under the Curve increasing to 0.779 following two-stage optimization. Compared to non-feature selection, performance improved by approximately 6.57%. SHAP analysis revealed that the Number of Teeth, Number of Psychiatric Hospitalizations, Self-discontinuation of Medication, Marital Status, and Age were core risk factors for OF.ConclusionThe prevalence of OF in long-term hospitalized patients with SZ is notably high. Two-stage feature selection enhances the accuracy of the predictive model, and the identified core factors can serve as a reference for developing individualized oral intervention programs in clinical practice.
Postmarketing surveillance of elobixibat for patients with chronic constipation and concomitant schizophrenia or depression in Japan
BackgroundLittle is known about the optimal treatment for constipation in patients with schizophrenia or depression. Elobixibat is a laxative with a novel mechanism of action that inhibits the ileal bile acid transporter, acting as both an osmotic and a stimulant agent.MethodsWe conducted a prospective, multicenter, postmarketing surveillance study to assess the safety and effectiveness of elobixibat for patients with chronic constipation in Japan (jRCT1080223950). The surveillance period was between June 2018 and May 2022. Patients were observed from the date of initial administration of elobixibat to 55 days thereafter (4-week treatment groups) or to 419 days thereafter (52-week treatment groups). Safety outcomes included adverse drug reactions (ADRs). Effectiveness outcomes included defecation frequency, Bristol Stool Form Scale (BSFS) scores, and constipation-related symptoms.ResultsIn the safety analysis set, the 4-week treatment groups comprised 105 patients with schizophrenia and 129 with depression; the 52-week treatment groups included 43 patients with schizophrenia and 55 with depression. Approximately 85% to 95% of patients used antipsychotics, and 40% to 55% used anxiolytics or sedative-hypnotics. The proportions of patients who experienced ADRs were 4.76% in the 4-week treatment group and 2.33% in the 52-week treatment group of patients with schizophrenia, and 3.88% and 9.09% of patients with depression. Diarrhea was the most common ADR in each group. There were no serious ADRs. In the 4-week treatment groups, the mean defecation frequency per week at baseline was 3.3 among patients with schizophrenia and 3.0 among patients with depression, which increased to 5.3 and 4.9, respectively, at week 4. In the 52-week treatment groups, the mean defecation frequency per week at week 52 was higher than that at baseline. After treatment, the proportion of patients with an ideal BSFS score of 4 increased in all groups by week 2 and reached approximately 60% by week 52. All constipation-related symptoms also improved by week 2 in all groups.ConclusionsElobixibat improved chronic constipation with no new safety signal identified in patients with schizophrenia or depression and with available follow-up in real-world settings.Clinical trial registrationhttps://jrct.mhlw.go.jp/latest-detail/jRCT1080223950, identifier jRCT1080223950.
Interoceptive dysfunction and its neural correlates in schizophrenia: protocol for a cross-sectional multimodal MRI study
BackgroundInteroception—the perception and integration of internal bodily signals—is fundamental to emotion regulation, bodily self-awareness, and predictive coding. Emerging evidence suggests that interoceptive disturbances may contribute to core psychopathological features of schizophrenia. Our research group recently conducted a systematic review and meta-analysis demonstrating significant impairments in interoceptive accuracy and sensitivity among individuals with schizophrenia. However, the neural mechanisms underlying these deficits remain unclear.MethodsThis cross-sectional protocol will recruit 30 individuals with schizophrenia and 30 age- and sex-matched healthy controls. Participants will complete (1) behavioral interoceptive assessment using the heartbeat counting task; (2) subjective interoceptive questionnaires, including the Multidimensional Assessment of Interoceptive Awareness (MAIA) and the Body Perception Questionnaire (BPQ); (3) clinical symptom ratings (PANSS, HAM-A, HAM-D); and (4) cognitive testing (TMT, animal fluency, DSST). All participants will undergo multimodal MRI scanning, including structural T1-weighted imaging, resting-state fMRI, and diffusion tensor imaging. Neuroimaging data will be preprocessed and analyzed using DPABISurf, SPM12, and GRETNA. Expected Results: We anticipate that individuals with schizophrenia will show reduced interoceptive accuracy, altered subjective interoceptive awareness, and abnormal intrinsic neural activity and connectivity within interoception-related circuits, including the anterior insula, anterior cingulate cortex, amygdala, and thalamus. Structural abnormalities within thalamo-cortical pathways are also expected. Interoceptive deficits are hypothesized to correlate with symptom severity and cognitive performance.ConclusionsThis study will provide an integrated characterization of interoceptive dysfunction and its neural correlates in schizophrenia. Findings may advance understanding of bodily self-disturbance and emotional dysregulation and support the development of future interoception-focused therapeutic approaches.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2500110551.
Brain Gene Variations Help Explain Neurological and Psychiatric Sex Differences
Thousands of genes are expressed differently in the brains of men and women, researchers have discovered.
The findings could help explain differences in neurodevelopmental, psychiatric, and neurodegenerative disorders between the sexes.
While men are more likely to experience schizophrenia, attention deficit hyperactivity disorder, and Parkinson’s disease, women are more prone to mood disorders and Alzheimer’s disease.
The U.S. study, in Science, is the first systemic single-cell survey of sex differences in gene expression across multiple regions of the human brain.
“Together, these findings provide a comprehensive map of molecular sex differences in the human brain and offer initial insight into their underlying mechanisms and potential functional consequences,” Alex DeCasien, PhD, from the National Institute of Mental Health in Bethesda, Maryland, told Inside Precision Medicine.
DeCasien and co-workers conducted a high-resolution analysis of gene expression in tissue samples from the brains of 15 men and 15 women using single-nucleus RNA sequencing.
They then used data from earlier large neuroimaging studies to select six cortical regions to sample, four of which showed sex-related differences in grey matter volume and two in which no such differences were found.
The team found subtle but widespread differences in gene activity between men and women. Biological sex explained very little of the variance in gene expression across the brain, at less than 1%, but differences were widespread—with more than 3000 genes showing different expression according to sex in at least one cortical region.
The greatest sex-related differences in gene expression were on the sex chromosomes. However, most of the genes showing sex-related variations in expression were autosomal—carried on one of the 22 numbered non-sex chromosomes.
The predominant driver for sex-biased expression of genes on these autosomal chromosomes were sex steroid hormones such as estrogen and testosterone.
Surprisingly, more than half the X chromosome genes in women were expressed in both alleles for at least one cell type. This indicated that many had escaped X chromosome inactivation—a female phenomenon in which one of the two X chromosomes is switched off early in development to stop women producing double the number of X-linked gene products to men.
“That finding has implications for understanding sex-biased disease susceptibility because several genes implicated in neurodevelopmental disorders reside on the X chromosome,” commented Jessica Tollkuhn, PhD, from Cold Spring Harbor Laboratory, and S Marc Breedlove, from Michigan State University, in an accompanying Perspective article.
They noted that autosomal genes showing sex-biased expression were substantially enriched for extracellular matrix components, hormone signaling pathways, and metabolic processes. “Genes with greater expression in women were enriched for mitochondrial and synaptic functions, whereas male-biased genes were associated with metabolic and structural pathways,” the editorialists added.
“By pinpointing these sexually differentiated processes, the data provide a treasure trove for the discovery of biomarkers of and/or therapeutic targets for differential disease risk in men and women.”
DeCasien and team added: “These findings raise the possibility that sex differences in gene expression modulate the magnitude of genetic effects at risk loci, contributing to differences in disease vulnerability and to reduced portability of polygenic risk prediction across sexes.”
The post Brain Gene Variations Help Explain Neurological and Psychiatric Sex Differences appeared first on Inside Precision Medicine.
Baseline Mismatch Negativity Amplitude Predicts Direction and Magnitude of Ketamine Effect in Healthy Volunteers — A “Disordinal” Effect
Mismatch negativity (MMN) is a component of the auditory event-related potential (ERP) that is elicited during a passive oddball paradigm where task-irrelevant infrequent deviants are presented in a stream of more frequent standard stimuli. MMN is believed to index a pre-attentive stage of auditory information processing closely linked to N-methyl-D-aspartate receptors (NMDAR) function. Ketamine is thought to act primarily as an NMDAR antagonist, has been used in clinical trials to model the symptoms of schizophrenia and is increasingly used in the clinic to treat depression.
Medical evaluation of first presentation of psychotic symptoms in children and adolescents
IntroductionPsychotic symptoms in children and adolescents may represent either normative developmental phenomena or severe psychiatric and medical conditions, requiring careful differential diagnosis.MethodsThis retrospective study aimed to evaluate the medical workup of children and adolescents admitted for a first presentation of psychotic symptoms at a tertiary pediatric center over a 10-year period. The sample included 68 patients (mean age 13.7 ± 3.7 years) who underwent clinician-directed evaluations including physical exams, laboratory tests, toxicology screens, neuroimaging, and lumbar puncture when indicated.ResultsSixteen patients (23.5%) were diagnosed with substance-/medication-induced or medically-associated psychosis. In this cohort, younger age, very early onset psychosis (<13 years), and catatonia at first presentation were more frequently observed among patients with secondary etiologies, whereas documented prior subthreshold symptoms were more frequently documented among those diagnosed with primary psychiatric disorders. Most investigations did not identify a secondary cause, reflecting clinician-directed evaluation in routine practice; however, selected cases (e.g., autoimmune encephalitis, multiple sclerosis) illustrate the clinical importance of careful assessment when specific suspicion is present.ConclusionThese findings suggest that targeted medical evaluation may be useful in pediatric psychosis, particularly when clinical features raise suspicion for secondary etiologies, and may help inform clinical decision-making in tertiary pediatric settings.
The associations of systemic inflammation and insulin resistance-related indicators with psychopathology and BDNF in patients with chronic schizophrenia
BackgroundThe triglyceride-glucose (TyG) index and C-reactive protein-triglyceride-glucose index (CTI) are innovative indicators for assessing insulin resistance (IR) and inflammation, yet research on them in patients with schizophrenia remains limited. This study aimed to explore TyG index and CTI levels and their associations with psychopathology and brain-derived neurotrophic factor (BDNF) in patients with chronic schizophrenia (CS).MethodsThis cross-sectional study was conducted across one general hospital and two psychiatric hospitals in Anhui Province, China. Socio-demographic information and hematological parameters were collected from participants, and their psychiatric and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS), respectively.ResultsA total of 324 patients with CS and 150 healthy controls (HCs) were enrolled in the study. Compared with HCs, patients had higher TyG index and CTI levels (all P < 0.001). Binary logistic regression analyses revealed that among patients, a high TyG index level was significantly associated with higher BDNF levels and lower negative factor scores of the PANSS, while a high CTI level was significantly associated with higher depression-hopelessness factor scores of the CDSS and lower negative factor scores of the PANSS (all P < 0.05).ConclusionPatients with CS had higher levels of TyG index and CTI, which were significantly associated with the severity of negative and depressive symptoms, as well as BDNF levels. It is suggested that the integration of the TyG index and CTI into clinical monitoring for patients with CS is necessary.