The right inferior frontal gyrus (RIFG) is a potential beneficial brain stimulation target for autism. This randomized, double-blind, two-arm, parallel-group, sham-controlled clinical trial assessed the efficacy of intermittent theta burst stimulation (iTBS) over the RIFG in reducing autistic symptoms (NCT04987749).

Conducted at a single medical center, the trial enrolled 60 intellectually able autistic individuals (aged 8–30 years; 30 active iTBS). The intervention comprised 16 sessions (two stimulations per week for eight weeks) of neuro-navigated iTBS or sham over the RIFG. Fifty-seven participants (28 active) completed the intervention and assessments at Week 8 (the primary endpoint) and follow-up at Week 12.

Autistic symptoms (primary outcome) based on the Social Responsiveness Scale decreased in both groups (significant time effect), but there was no significant difference between groups (null time-by-treatment interaction). Likewise, there was no significant between-group difference in changes in repetitive behaviors and exploratory outcomes of adaptive function and emotion dysregulation. Changes in social cognition (secondary outcome) differed between groups in feeling scores on the Frith-Happe Animations (Week 8, p = 0.026; Week 12, p = 0.025). Post-hoc analysis showed that the active group improved better on this social cognition than the sham group. Dropout rates did not vary between groups; the most common adverse event in both groups was local pain. Notably, our findings would not survive stringent multiple comparison corrections.

Our findings suggest that iTBS over the RIFG is not different from sham in reducing autistic symptoms and emotion dysregulation. Nonetheless, RIFG iTBS may improve social cognition of mentalizing others' feelings in autistic individuals.

Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD).

Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test.

euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068).

Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

Few previous studies have established Snaith–Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups.

To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan.

This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses.

The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values.

Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

Divergent thinking is a critical creative cognitive process. Its neural mechanisms have been well-studied through structural and functional imaging in healthy individuals but are less explored in patients with bipolar disorder (BD). Because of the traditional link between creativity and BD, this study investigated the structural correlates of divergent thinking in patients with BD through surface-based morphometry.

Fifty-nine patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched controls (33.9 ± 7.4 years) were recruited. The participants underwent structural magnetic resonance imaging and an evaluation of divergent thinking by using the Chinese version of the Abbreviated Torrance Test for Adults (ATTA). FreeSurfer 7.0 was used to generate thickness and surface area maps for each participant. Brainwise regression of the association between cortical thickness or surface area and ATTA performance was conducted using general linear models.

Divergent thinking performance did not differ significantly between the patients with BD and the healthy controls. In these patients, total ATTA score was negatively correlated with cortical thickness in the right middle frontal gyrus, right occipital, and left precuneus but positively correlated with the surface area of the right superior frontal gyrus. By contrast, total ATTA scores and cortical thickness or surface area were not significantly correlated among the controls.

The findings indicate that divergent thinking involves cerebral structures for executive control, mental imagery, and visual processing in patients with BD, and the right prefrontal cortex might be the most crucial of these structures.

Cognitive impairment is a growing problem with increasing burden in ageing global population. Older adults with major depressive disorder (MDD) have higher risk of dementia during ageing. Neurofilament light chain (NfL) has been proven as a potential biomarker related to dementia. The present study aims to assess the cognitive deficits in older adults with MDD and investigate their association with peripheral blood levels of NfL.

We enrolled 39 individuals with MDD and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer’s type. Both groups were over age 65 and with restricted Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and cognitive impairment in each domain.

In the MDD group, participants have higher rate of family psychiatry history and higher rate of current alcohol use habit compared with patients with neurocognitive disorders. In the neurocognitive disorders group, participants showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits similar to that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster.

We noted the negative correlation between NfL levels and cognitive performance in MDD patients whose cognitive manifestation were more similar to that of degenerative neurocognitive disorders. NfL might be a potential marker to predict patients with MDD to develop cognitive decline especially in domains typically found in Alzheimer’s disease. Further longitudinal studies are required to validate our findings for clinical implications.

Social support may protect against Alzheimer’s disease and related dementias (ADRD), potentially through emotional or instrumental support elements. Black and Hispanic/Latinx older adults bear a disproportionate burden of ADRD. However, independent effects of emotional and instrumental support on cognition, a primary indicator of ADRD risk, are largely understudied in these groups. Guided by the differential vulnerability hypothesis – the theoretical framework which posits that systemic racism disadvantages Black and Hispanic/Latinx individuals’ health – we hypothesize that emotional and instrumental support may be particularly important to protect against worse cognition for Black and Hispanic/Latinx older adults, who often have fewer resources due to these inequalities (e.g., wealth, educational opportunities) to otherwise maintain health. Using the NIH Toolbox Emotion Module measures of emotional (e.g., the extent to which individuals can rely on others in challenging times) and instrumental support (e.g., the extent to which individuals can rely on others for assistance in daily activities), we aimed to identify positive social support factors (i.e., emotional and instrumental support) that may protect against ADRD risk (i.e., longitudinal executive function and memory performance) among Black and Hispanic/Latinx older adults.

Participants were 362 Black and 265 Hispanic/Latinx adults aged 65-89 (63% female, average age=75) from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study who completed baseline and up to two additional waves of assessments (every 1.5 years), including questionnaires, neuropsychological evaluations, and the NIH toolbox. Predictors included baseline covariates (i.e., age, language of test administration, gender, education, income, self-rated health) and NIH toolbox emotional and instrumental support variables. Outcomes were baseline and longitudinal memory (visual and verbal episodic memory) and executive functioning (verbal fluency and working memory) composites from the Spanish and English Neuropsychological Assessment Scales (SENAS). Latent growth curve models were conducted separately in Black and Hispanic/Latinx participants to estimate effects of emotional and instrumental support on baseline cognition and subsequent change in each domain.

Black participants reported greater emotional support. There were no group differences in levels of instrumental support. Greater instrumental support was associated with better initial memory (standardized β= .194, 95%CI: [.063, .325]) among Black participants but not among Hispanic/Latinx participants. In Hispanic/Latinx participants, greater emotional support was associated with better initial executive functioning (standardized β= .215, 95%CI: [.079, .350]. Emotional support was not associated with either cognitive domain in Black participants. There were no associations between emotional or instrumental support on cognitive change in either group.

Results point to differences between Black and Hispanic/Latinx older adults in the impact of specific aspects of social support on different cognitive domains. Positive associations between instrumental support and baseline memory in Black participants and between emotional support and executive functioning in Hispanic/Latinx participants suggest unique cognitive consequences of social support across groups. Differences in the role of specific types of social supports may be useful in identifying intervention targets specifically for Black and Hispanic/Latinx older adults, who are disproportionately affected by ADRD. Future research will examine these constructs using multiple group models to test these associations more rigorously.

Expertise in social perception, defined as the ability to decode another person's mental states based on basic behavioral signals (Allison et al., 2000; Beauchamp et al., 2008). The Reading the Mind in the Eyes Test (RMET) is a social-perception task of theory of mind (ToM, Meinhardt-Injac et al., 2020) and used to test different clinical disorders, like autism spectrum disorders (ASD, Peñuelas-Calvo et al., 2019). RMET has been used to demonstrate gender, cultural, genetic, and personality trait influences on ToM and elucidate its neurobiological mechanisms (Adams et al., 2010). In Taiwan, there has few sensitive tools to evaluate children's social perception, thus the purpose of this study is to examine psychometric properties of child's version of RMET in Taiwan (RMET-C-TW) and cross-cultural comparisons.

RMET-C (Baron-Cohen et al., 2001) was used to assess mental state/emotion recognition (Vellante et al., 2013). It consists of photographs of the eye regions of 28 faces. Participants were asked to make a choice between four words presented, choose the one that best described for feel or think. One point was given to each correctly response. RMET-C-TW was double-translation of words to ensure cultural applicability in Taiwan. This study included both a normative sample and criteria sample. The normative sample consisted of 769 (385 male, 384 female) 3 to 9 grades students from northern Taiwan. The normative sample completed both the RMET-C-TW and Chinese Vocabulary Test (CVT) in groups at their own schools, the CVT was to ensure that participants had sufficient vocabulary skills to understand the options provided in REMT-C-TW. The criteria sample were collected from 46 matched, school-aged children with ASD (age mean = 10.52, SD = 1.62; IQ = 108.39, SD = 11.75), and normally developing controls (age mean = 10.66, SD=1.68; IQ = 109.70, SD = 12.12). These two groups were administered the (1) WISC-III (2) CVT (3) RMET-C-TW and (4) ToM Test.

The results showed that RMET-C-TW had acceptable test-retest reliability and internal consistency (test-retest reliability = .71, Cronbach α= .40). There were significant gender and age difference in the performance of RMET-C-TW, example female, older participants performed better. Item analysis showed 93% of items in the RMET-C-TW had cross- cultural consistency in the distribution of respondents' choices. In criteria sample, the control group's RMET-C-TW scores significantly better than ASD group. Physician diagnosis (r = .49, p < .01) and high-order ToM's scores (r = .33, p < .01) were significantly associated with RMET-C-TW scores.

RMET-C-TW has acceptable reliability and good developmental validity (age-related growth) in three to nine grades, and future can be extended to different age and clinicians to understand the development of social perception. Therefore, RMET-C-TW can be used as an initial screening and cross-cultural tool for ASD. In addition, EF is divided into cold and hot, and hot EF makes a unique contribution to ToM in ASD (Kouklari et al., 2017), thus this tool may also be used in the future to understand the association of hot EF with social perception.

Treatment with atezolizumab plus standard chemotherapy can prolong the overall survival of patients with metastatic non-squamous non-small cell lung cancer (NSCLC). However, the economic value of this treatment regimen is unknown. This study aimed to estimate the cost effectiveness of atezolizumab plus chemotherapy in the first-line treatment of metastatic non-squamous NSCLC from a healthcare system perspective in China.

A partitioned survival model consisting of three discrete health states was developed to estimate the cost and effectiveness of atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) versus carboplatin or cisplatin plus pemetrexed (PP) in the first-line treatment of metastatic non-squamous NSCLC over a 12-year lifetime horizon. Key clinical data were generated from the IMpower132 trial. Local direct medical and non-medical costs were used and health preference data were collected from patients with NSCLC in 13 tertiary hospitals across five provinces in China. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model.

Compared with the PP regimen, APP therapy yielded a gain of 0.21 QALYs at an increased cost of CNY145,602 (USD22,574), resulting in an ICER of CNY684,894 (USD106,185) per QALY gained. The ICER was significantly higher than three times the gross domestic product per capita for China in 2021 (USD37,663). One-way sensitivity analyses revealed that one of the most influential factors in this model was the cost of atezolizumab. Probabilistic sensitivity analysis showed that there was 14.7% probability that atezolizumab plus chemotherapy was cost effective at a willingness-to-pay value of CNY242,928 (USD37,663) per QALY gained.

The APP regimen could prolong survival and improve health benefits over standard chemotherapy in the first-line treatment of patients with metastatic non-squamous NSCLC, but it is unlikely to be a cost-effective treatment option in China.

National health insurance (NHI) Taiwan has provided additional markups on dental service fees for people with specific disabilities, and the expenditure has increased significantly from TWD473 million (USD15 million) in 2016 to TWD722 million (USD24 million) in 2022. The purpose of this study was to determine oral health risk and to develop a risk assessment model for capitation outpatient dental payments in children with Autism.

Based on the literature and expert opinion, we developed a level of oral health risk model from the claim records of 2019. The model uses oral outpatient claim data to analyze: (i) the degree of caries disease; (ii) the level of dental fear or cooperation; and (iii) the level of tooth structure. Each factor was given a score from zero to four and a total score was calculated. Low-, medium-, and high-risk groups were formed based on the total points. The oral health risk capitation models are estimated by ordinary least squares using an individual’s annual outpatient dental expenditure in 2019 as the dependent variable. For subgroups based on age group and level of disability, expenditures predicted by the models are compared with actual outpatient dental expenditures. Predictive R-squared and predictive ratios were used to evaluate the model’s predictability.

The demographic variables, level of oral health risk, preventive dental care, and the type of dental health care predicted 30 percent of subsequent outpatient dental expenditure in children with autism. For subgroups (age group and disability level) of high-risk patients, the model substantially overpredicted the expenditure, whereas underprediction occurred in the low-risk group.

The risk-adjusted model based on principal oral health was more accurate in predicting an individual’s future expenditure than the relevant study in Taiwan. The finding provides insight into the important risk factor in the outpatient dental expenditure of children with autism and the fund planning of dental services for people with specific disabilities.