BackgroundThis study aimed to quantify prefrontal cortex (PFC) activation and postural control complexity in older adults with mild cognitive impairment (MCI) during single-task standing and dual-task standing balance conditions and to investigate the associations between these measures.MethodsThis secondary analysis included 21 older adults with MCI (71.19 ± 3.36 years) and 19 cognitively intact controls (70.16 ± 4.54 years) from a previously reported cohort. Outcomes included cognitive performance, sample entropy of COP displacement (SampEn-COP), PFC activation across four bilateral functional regions, and exploratory correlations between PFC activation and SampEn-COP.ResultsA significant group effect was observed for SampEn-COPml, with lower values in the MCI group than in the control group (p = 0.002, η2p = 0.217, q = 0.007). SampEn-COPap was significantly higher under the dual-task condition than under the single-task condition (p = 0.005, η2p = 0.187, q = 0.016). Group × Task interactions were observed at the uncorrected level in the dorsolateral prefrontal cortex (DLPFC; p = 0.041, η2p = 0.106, q = 0.073) and orbitofrontal cortex (OFC; p = 0.039, η2p = 0.107, q = 0.073). The MCI group also showed lower cognitive accuracy and response rates than the control group across task conditions (both q < 0.01). An exploratory negative correlation between OFC activation and SampEn-COPap was observed in the MCI group under the single-task condition (r = −0.469, p = 0.032, q = 0.256).ConclusionOlder adults with MCI showed a less complex medial–lateral postural control pattern than cognitively intact older adults. During dual-task standing, changes in postural complexity were accompanied by preliminary evidence of task-related increases in DLPFC and OFC activation in the MCI group, suggesting greater prefrontal involvement in managing concurrent cognitive and postural demands.
Daytime lighting conditions alter home-cage behavior across both sexes in diurnal grass rats
Circadian rhythms are crucial to biological functions, and cognitive functions such as attention, choice, and preference-related behaviors are modulated by circadian rhythms and disrupted in mood disorders such as Seasonal Affective Disorder (SAD) and Major Depressive Disorder (MDD). These neuropsychiatric diseases can be induced or worsened by alterations to daily light patterns and can also be treated with circadian-timed bright-light therapy, suggesting modulatory effects of light brightness on mood and behavior. While most laboratory rodents are nocturnal, the Nile grass rat (Arvicanthis niloticus) is diurnal, offering a unique model to study light modulation effects relevant to humans. In this work, we track daily activity in male and female grass rats under varied lighting for several weeks, revealing sex-specific circadian patterns and responses. These findings establish a foundation for mechanistic studies of light effects on mood-related brain circuits in diurnal animals.
Exploratory cluster analysis of self-reported adverse events associated with antidepressants using Gower distance and partitioning around medoids: a single-center cross-sectional study
BackgroundAntidepressants are first-line pharmacological interventions for depressive disorders, with globally increasing prescription volumes. Associated adverse events (AEs) represent the primary reason for treatment discontinuation. Existing studies mostly limit analysis to simple stratification by organ system or severity, while exploratory subtyping grounded in multidimensional clinical features of AEs remains scarce.ObjectiveThis study aims to overcome the limitations of traditional single-dimensional analyses by integrating multidimensional data—including demographic and sociological characteristics, clinical disease severity, and AE-related information—to conduct exploratory cluster subtyping at the patient level.MethodsThis study is an exploratory secondary analysis of a single-center, retrospective, recall-based cross-sectional survey on antidepressant adverse events registered with the Chinese Clinical Trial Registry (ChiCTR2500111836). It included 500 patients (905 AE episodes) self-reporting AEs within the past year at Beijing Anding Hospital (April 2025–January 2026). Unlike the original survey’s descriptive aim, this analysis identified heterogeneous patient subtypes: one AE per patient ID ensured independence; the Gower-PAM algorithm clustered 23 variables; and bootstrap-derived Adjusted Rand Index (ARI) values plus an all-event sensitivity analysis confirmed robust subtyping stability.ResultsK = 2 was the optimal clustering solution (silhouette coefficient = 0.219; mean ARI = 0.916). Cluster 1 (42.2%) was characterized by early onset, high burden, and discontinuation-prone features, with moderate-to-severe AEs in 65.9% and a discontinuation rate of 75.8%. Cluster 2 (57.8%) was late-onset, low-burden, and high-tolerance, with mild AEs in 75.4% and a discontinuation rate of 16.6%. Significant differences were observed between groups in social support, work stress, and improvement of depressive symptoms.ConclusionsThis study identified two AE subtypes, revealing a concomitant pattern of “disease burden–psychosocial resources–AE tolerance,” providing exploratory evidence for risk stratification. Limited by the single-center retrospective design and self-report bias, validation in future prospective multicenter studies is needed.Clinical trial registrationhttps://www.chictr.org.cn/bin/home, identifier ChiCTR2500111836.
PROMATER: protocol for a randomized controlled trial of a digital self-guided intervention to promote perinatal mental health and reduce self-criticism
BackgroundPerinatal mental health represents a significant public health concern given the high prevalence of mental disorders during pregnancy and the postpartum period and their impact on maternal well-being, mother-infant bonding, and child development. Emerging evidence identifies self-criticism as a transdiagnostic vulnerability factor associated with psychological distress in this period, while self-compassion has been recognized as an important protective factor. In Brazil, access to preventive perinatal mental health interventions remains limited. This paper describes the protocol of a randomized controlled trial (RCT) evaluating PROMATER – an online program designed to promote perinatal mental health by targeting self-criticism and self-compassion.MethodsA total of 130 pregnant women between 28 and 34 weeks of gestation will enroll in a two-arm RCT with a dismantling design. Participants will be randomized (1:1 ratio) to either the PROMATER intervention or to an active control group. Participants and data analysts will be blinded to group allocation. PROMATER consists of a 3-week program (6 modules) addressing maternal expectations, self-criticism, perinatal mental health, social support, self-compassion, and mindfulness and mother-infant bonding. The active control offers a structurally equivalent program covering the same topics, except for the modules specifically targeting these transdiagnostic processes. Primary outcomes are self-compassion, assessed via the compassionate self-responding (CSR) score of the Self-Compassion Scale, and self-criticism, operationalized through the uncompassionate self-responding (USR) score. Secondary outcomes include postpartum depression, anxiety, quality of life, social support, and mother-infant bonding. Assessments occur at baseline (T1), post-intervention (T2), and 3-month postpartum follow-up (T3). Data will be analyzed using Linear Mixed Models (LMM) following the Intention-to-Treat (ITT) principle.DiscussionEvaluating the effectiveness of a brief, accessible, online intervention has the potential to address the need for an evidence-based approach designed to promote maternal well-being during pregnancy and the postpartum period. The intervention is designed to maximize reach and minimize cost, with the potential to scale up and incorporate in routine perinatal care. The active control condition will allow examination of whether directly targeting self-criticism and self-compassion confers incremental benefit over structured perinatal psychoeducation alone.Systematic review registrationhttps://ensaiosclinicos.gov.br/, identifier RBR-99tjfz5.
Association between first-trimester serum 25(OH)D and EPDS-positive postpartum depressive symptoms in women with gestational diabetes mellitus: a retrospective cohort study
IntroductionGestational diabetes mellitus (GDM) has been associated with an increased risk of postpartum depressive symptoms, while maternal vitamin D status may also be related to perinatal mood disturbances. This study investigated the association between first-trimester serum 25-hydroxyvitamin D [25(OH)D] concentrations and Edinburgh Postnatal Depression Scale (EPDS)-positive postpartum depressive symptoms in women with GDM.MethodsThis retrospective cohort study included 242 women with GDM. Prenatal depressive and anxiety symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Sequential logistic regression models were adjusted for baseline maternal characteristics, prenatal PHQ-9 and GAD-7 scores, and glycated hemoglobin A1c (HbA1c).ResultsAmong 242 women, 69 had EPDS-positive postpartum depressive symptoms. Each 5-ng/mL increase in 25(OH)D was associated with lower odds of EPDS-positive symptoms in the crude model (OR 0.35, 95% CI 0.25–0.48) and after adjustment for baseline characteristics (adjusted OR 0.36, 95% CI 0.25–0.50). After additional adjustment for prenatal PHQ-9 and GAD-7 scores, the association was attenuated and was no longer statistically significant overall (adjusted OR 0.69, 95% CI 0.43–1.12; P = 0.134). Additional adjustment for HbA1c produced similar results. Exploratory stratified analyses using the full Model 2 covariate set showed no statistically significant associations within strata defined by pre-pregnancy BMI, hypertensive disorders of pregnancy, or insulin use, and no significant interactions were detected.DiscussionThese findings suggest that the overall association between first-trimester 25(OH)D and postpartum depressive symptoms was substantially influenced by prenatal mental health status and was not consistently demonstrated after comprehensive covariate adjustment.
Body-based therapies and transcranial magnetic stimulation for posttraumatic stress disorder: a proposed integrative approach
Posttraumatic stress disorder (PTSD) remains difficult to treat, with 30–50% of patients retaining their diagnosis after first-line trauma-focused psychotherapies. Body-based therapies (BBTs) and transcranial magnetic stimulation (TMS) have each shown preliminary benefit for PTSD but have not yet been studied in combination. To our knowledge, this is the first proposal to integrate these modalities as a combined therapeutic approach. PTSD involves disrupted coordination across multiple levels of neural organization, from cortical regulatory networks to limbic threat circuits and autonomic systems. BBTs are theorized to engage bottom-up processes, including autonomic regulation and interoceptive recalibration, while TMS operates through top-down modulation of prefrontal-limbic circuitry and large-scale network connectivity. This complementarity suggests that a combined approach could engage a broader range of PTSD-related dysfunction than either intervention alone. This article reviews the evidence and proposed mechanisms for each modality, places both within current models of PTSD neurocircuitry, and examines potential pathways of interaction including neuroplasticity priming and autonomic stabilization. Important risks are also addressed, including autonomic destabilization, unknown optimal sequencing, and the open question of whether mechanistically distinct treatments produce additive benefits. The case for combining BBTs and TMS is presented as a hypothesis warranting further investigation.
Perinatal mental health equity: patient perspectives on virtual collaborative care providing what women need now in the post-COVID era
IntroductionThe COVID-19 pandemic increased perinatal mental health needs and disrupted routine obstetric care, disproportionately affecting Black and economically disadvantaged communities. Michigan’s Perinatal Collaborative Care Model (Peri CoCM), a publicly funded virtual program, launched during the pandemic and continued after the public health emergency. This qualitative study examined participant experiences with Peri CoCM, including perceived usefulness, acceptability, and barriers/facilitators to engagement, particularly among marginalized perinatal people to inform post-COVID service delivery.MethodsEligible participants were pregnant or up to one year postpartum Peri CoCM patients recruited from a May–July 2025 referral cohort. Nine women ages 27–42 completed one-hour, semi-structured Zoom interviews between August and September 2025; the sample intentionally overrepresented self-identified Black women. Interviews were recorded, transcribed, verified against audio, and analyzed by a coding team using grounded-theory–informed thematic analysis with constant comparison.ResultsParticipants reported positive experiences with Peri CoCM across four thematic areas: (1) Pathways to care, (2) Perceived impacts of program, (3) Importance of culturally responsive care, and (4) Recommendations for program optimization. Trusted referrals from obstetric and other providers facilitated entry into care, often for anxiety, depression, grief, or first-time mental health support. Participants described Peri CoCM as accessible, supportive, and valuable during pregnancy and postpartum. Virtual options, flexible scheduling, compassionate behavioral health clinicians, and consistent follow-up reduced barriers and promoted openness. The short-term model helped some transition to longer-term therapy, while clinicians supported insurance navigation, medication decisions, and community resource connections. Participants gained coping skills, validation, and self-understanding. They emphasized culturally responsive provider fit and recommended longer continuity, broader wraparound services, and sustained no-cost access to reduce stress and improve engagement.ConclusionMichigan’s Peri CoCM was perceived as a low-barrier, relationship-centered, culturally responsive virtual pathway supporting perinatal wellbeing and systems navigation in the post-COVID era. Cost transparency and flexible delivery were central to acceptability and expanded access to equitable care.
Problematic Reliance on Generative AI in an Anxious Young Adult: Case Report
Generative Artificial Intelligence (AI) tools are increasingly integrated into daily life, offering cognitive support across domains such as writing, decision-making, and social interpretation. While beneficial, excessive reliance may contribute to diminished confidence in one’s own thinking. This report describes a woman in her mid-20s with Generalized Anxiety Disorder and Major Depressive Disorder who developed a pattern of functional dependence on generative AI tools- specifically ChatGPT. She historically had strong social, academic and occupational functioning. Psychiatric consultation did not suggest the presence of a personality disorder, and although she was a high-achieving individual, clinically significant perfectionistic traits were not evident. Despite this, she increasingly relied on AI for routine cognitive and interpersonal tasks including composing emails, interpreting social interactions, predicting the future and making decisions and felt increasingly uncomfortable completing such tasks independently. This case highlights the potential danger of generative AI tools in reassurance seeking behavior and how it might compound anxiety. These behaviors were observed across both professional and personal contexts, suggesting that AI use was not limited to task-specific assistance but reflected a generalized strategy for managing uncertainty and self-doubt. This behavioral pattern is characterized in this case by cognitive offloading, reduced confidence in independent judgment, and reinforcement of externalized thinking processes. This led to the subjective belief of declining skill and compromised functional autonomy. The Interaction of Person-Affect-Cognition-Execution (I-PACE) model was used to describe this pattern of behavior. While repeatedly turning to a family member or friend for validation and reassurance might lead to interpersonal fatigue, AI tools have no such limits and are infinitely accessible. This might ultimately worsen a patient’s ability to tolerate uncertainty. Given the ubiquity of AI tools and the prevalence of anxiety disorders, clinicians may need to be aware of the role AI tools potentially play in reassurance seeking and thus perpetuation of anxiety.
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Caregiver Challenges and Functional Requirements for an mHealth App Supporting Home-Based Dementia Care: Qualitative Interview Study
<strong>Background:</strong> The growth of the older adult population in Indonesia since 2019 has contributed to a 2.46% increase in dementia cases, with the number of cases projected to increase 2.5-fold by 2050. This trend is exerting a major impact on older adults and increasing the burden on caregivers. The current lack of systemic health support suggests that digital solutions—such as mobile health (mHealth) apps—have the potential to support caregivers and people living with dementia. However, to date, no mHealth initiatives have been developed through a participatory approach that involves users in the design process in accordance with the sociocultural conditions in Indonesia. <strong>Objective:</strong> This study aimed to identify the challenges faced by dementia caregivers in home care settings and to determine the functional requirements for an mHealth app to support them. <strong>Methods:</strong> The study adopted a qualitative participatory design, interviewing 12 health care workers, 2 employees of nongovernmental organizations, and 35 dementia caregivers. The qualitative data were analyzed using content analysis. The challenges identified by the interviewees were mapped onto the app design process as functional requirements. <strong>Results:</strong> The challenges identified in this study include a lack of education and awareness regarding the symptoms and treatment of dementia, the stress and mental strain experienced by caregivers, difficulties in monitoring the health and daily lives of people with dementia, barriers to access to health services, and declining cognitive function among older adults with dementia. To overcome these challenges, we identified corresponding functional requirements for the mHealth app, including diaries, music playlists, community forums, and quizzes and games for people with dementia, as well as dementia education videos and psychological assessments for caregivers. Aspects such as ease of use and the quality of information influenced the acceptance of the app by people with dementia and their caregivers. Educational materials, such as short videos, articles, and infographics, addressed dementia symptoms and steps that can be taken at home to care for people with dementia. Psychological assessments were developed using a validated tool. Quizzes and games helped caregivers design fun, relevant questions based on the personal experiences of adults with dementia. Music playlists highlighted songs that suited the mood of people with dementia, enhancing their personalized experiences without needing explicit guidance from the app. Community forums encouraged caregivers to voluntarily share their experiences and support others, strengthening their sense of belonging and emotional involvement in the caregiving process. Diaries could be used by caregivers to record the daily condition of people with dementia and their care. <strong>Conclusions:</strong> The challenges and functional requirements identified in this study provide a practical foundation for organizations and facilities to develop culturally appropriate health apps for dementia home care in Indonesia.
Brain Protein in Mice Offers Insights Into Brain Development and ADHD
Attention-deficit/hyperactivity disorder (ADHD), marked by excessive activity and impulsivity, is linked to changes in the brain’s dopamine system, though the mechanisms remain unclear. Researchers at the University of Fukui have now found that in genetically modified, conditional knockout mice, loss of a protein called N-ethylmaleimide-sensitive factor (NSF)—which is linked to dopamine receptors—in D2 receptor-expressing cells led to lower dopamine levels and ADHD-like behaviors. Their results also pointed to a potential therapeutic strategy.
The team, headed by assistant professor Min-Jue Xie, PhD, at the Division of Development of Mental Functions, Research Centre for Child Mental Development, suggests that the results offer insight into how brain changes may contribute to ADHD and informing future treatments.
“This is basic research and will not immediately lead to a new treatment,” Xie acknowledged. “However, it provides important clues for understanding how dopaminergic dysfunction may contribute to ADHD. In the future, these findings may help develop new therapeutic strategies targeting D2R function and striatal dopamine signaling, especially for treatment-resistant ADHD.”
Xie is first and corresponding author of the researchers’ published paper in Neuropsychopharmacology, titled “Deletion of N-ethylmaleimide-sensitive factor in dopamine D2 receptor-expressing cells impairs striatal development and dopaminergic function and induces ADHD-like behaviors in mice.”
ADHD is a neurodevelopmental disorder that can affect attention, activity levels, and impulse control, with symptoms often beginning in childhood and sometimes continuing into adulthood. Although the exact causes of ADHD are not fully understood, changes in the brain’s dopamine system have long been linked to the condition. Dopamine is a chemical messenger that helps brain cells communicate and plays an important role in movement, motivation, and behavior.
While dopamine-related changes have been associated with ADHD, it remains unclear how the brain cells that respond to dopamine are maintained and how their disruption may contribute to ADHD-related behaviors. This is particularly relevant to dopamine D2 receptor (D2R)-expressing cells, which are found in the striatum, a brain region involved in movement and behavioral control. Understanding what helps these cells develop and function normally could provide new insights into the biological processes involved in ADHD. “Although D2R has been extensively studied, the upstream mechanisms regulating its function and localization remain unclear,” the authors wrote.
Against this backdrop, a research team from Japan, led by Xie, set out to investigate the role of NSF in these dopamine-related brain cells. NSF regulates membrane fusion, helping brain cells release chemical messengers and move proteins within their membranes. “NSF dysfunction is implicated in neuropsychiatric disorders, with reduced expression in autism spectrum disorder (ASD) and schizophrenia and aggregates in Parkinson’s disease,” the investigators noted.
“The motivation for this study came from previous findings suggesting that NSF may be involved in neurodevelopmental and neuropsychiatric disorders,” Xie explained. “NSF was known to interact with D2R; however, the role of this interaction in vivo remained unclear. Because ADHD is thought to involve reduced striatal dopaminergic function and D2R dysfunction, we hypothesized that NSF may be important for maintaining D2R-expressing neurons and dopaminergic function. This led us to initiate the present study.”
For their study the team created knockout mice in which NSF was removed specifically from D2R-expressing neurons. “… we generated D2R-specific Nsf conditional knockout (Nsf f/f;D2R-Cre) mice to examine NSF function in D2R-expressing cells in vivo,” they explained. They then studied the animals’ brain development, dopamine levels, and behavior. The team also tested whether drugs that affect dopamine signaling could reduce the behavioral changes seen in the modified mice.
The loss of NSF affected the developing brain, resulting in fewer dopamine D2R-expressing cells, increased early developmental cell death, and a smaller striatum. The mice also had markedly lower dopamine levels in this brain region. Together, these findings suggest that NSF helps maintain dopamine-related cells and supports normal development and dopamine function.
The brain changes were accompanied by ADHD-like behaviors. “Nsf f/f;D2R-Cre mice exhibited attention-deficit/hyperactivity disorder (ADHD)-like behaviors, including hyperactivity and impulsivity,” the team reported. The knockout mice were more hyperactive than control mice and showed more impulsive-like behavior in a test that measured how quickly they jumped from an elevated platform. By the end of the seven-minute test, 86% of the experimental group mice had jumped, compared with 31% of the control group mice. “These findings indicate that a reduction in D2R-expressing cells coincides with ADHD-like behaviors, suggesting a link between D2R dysfunction and these abnormalities.”
The researchers then explored whether these behaviors could be reduced by changing dopamine signaling. Methylphenidate, a medicine commonly used to treat ADHD, did not significantly reduce hyperactivity when given alone to the modified mice. However, when it was given together with quinpirole, a drug that activates D2R, the mice became less hyperactive and showed less impulsive-like behavior. During the seven-minute test, the proportion of knockout mice that jumped fell from 78% without treatment to 11% after the two drugs were given together. “Combined administration of methylphenidate and a D2R agonist, quinpirole, alleviated both behaviors, suggesting a potential complementary approach for ADHD treatment,” the investigators wrote.
“This study supports the translational relevance of the Nsf f/f;D2R-Cre model for ADHD and indicates that targeting D2R dysfunction, particularly in treatment-resistant ADHD, may be a promising therapeutic strategy.”
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