In contemporary neuroimaging studies, it has been observed that patients with major depressive disorder (MDD) exhibit aberrant spontaneous neural activity, commonly quantified through the amplitude of low-frequency fluctuations (ALFF). However, the substantial individual heterogeneity among patients poses a challenge to reaching a unified conclusion.

To address this variability, our study adopts a novel framework to parse individualized ALFF abnormalities. We hypothesize that individualized ALFF abnormalities can be portrayed as a unique linear combination of shared differential factors. Our study involved two large multi-center datasets, comprising 2424 patients with MDD and 2183 healthy controls. In patients, individualized ALFF abnormalities were derived through normative modeling and further deconstructed into differential factors using non-negative matrix factorization.

Two positive and two negative factors were identified. These factors were closely linked to clinical characteristics and explained group-level ALFF abnormalities in the two datasets. Moreover, these factors exhibited distinct associations with the distribution of neurotransmitter receptors/transporters, transcriptional profiles of inflammation-related genes, and connectome-informed epicenters, underscoring their neurobiological relevance. Additionally, factor compositions facilitated the identification of four distinct depressive subtypes, each characterized by unique abnormal ALFF patterns and clinical features. Importantly, these findings were successfully replicated in another dataset with different acquisition equipment, protocols, preprocessing strategies, and medication statuses, validating their robustness and generalizability.

This research identifies shared differential factors underlying individual spontaneous neural activity abnormalities in MDD and contributes novel insights into the heterogeneity of spontaneous neural activity abnormalities in MDD.

Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.

A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC–MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.

A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.

The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Randomized clinical trials (RCT) are the foundation for medical advances, but participant recruitment remains a persistent barrier to their success. This retrospective data analysis aims to (1) identify clinical trial features associated with successful participant recruitment measured by accrual percentage and (2) compare the characteristics of the RCTs by assessing the most and least successful recruitment, which are indicated by varying thresholds of accrual percentage such as ≥ 90% vs ≤ 10%, ≥ 80% vs ≤ 20%, and ≥ 70% vs ≤ 30%.

Data from the internal research registry at Columbia University Irving Medical Center and Aggregated Analysis of ClinicalTrials.gov were collected for 393 randomized interventional treatment studies closed to further enrollment. We compared two regularized linear regression and six tree-based machine learning models for accrual percentage (i.e., reported accrual to date divided by the target accrual) prediction. The outperforming model and Tree SHapley Additive exPlanations were used for feature importance analysis for participant recruitment. The identified features were compared between the two subgroups.

CatBoost regressor outperformed the others. Key features positively associated with recruitment success, as measured by accrual percentage, include government funding and compensation. Meanwhile, cancer research and non-conventional recruitment methods (e.g., websites) are negatively associated with recruitment success. Statistically significant subgroup differences (corrected p-value < .05) were found in 15 of the top 30 most important features.

This multi-source retrospective study highlighted key features influencing RCT participant recruitment, offering actionable steps for improvement, including flexible recruitment infrastructure and appropriate participant compensation.

Patients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns.

A 2-year open-label randomized prospective comparative trial from August 2017 to September 2022 in Taiwan. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomizing a proportion to conduct guided dose reduction. We depicted the trajectories of individual patients and named subgroups based on dose-tapering patterns. Predictors of baseline characteristics for designated subgroups were examined by logistic regression analysis; changes in outcomes were compared by paired t-test.

Fifty-one patients undergoing guided dose reduction, 18 (35.3%) reduced 4 steps consecutively (sequential reducers, SR), 14 (27.5%) reduced 1 to 3 steps (modest reducers, MR), 3 (5.9%) re-escalated to previous level (alert reducers, AR), 7 (13.7%) returned to baseline level (baseline returners, BR), 6 (11.7%) relapsed (failed reducers, FR) and 3 (5.9%) withdrew without relapse (early exits, EE). Patients with a history of relapse assumed a conservative dose-tapering pace; only the SR subgroup exhibited significant improvements in functioning and quality of life while failing to identify variables for predicting who would become SR or FR.

Guided dose reduction comprises dynamic processes with differences between individual trajectories. The proposed naming of dose-tapering patterns/subgroups provides a framework depicting patients undergoing dose-tapering. Longer-term observation and more flexible tapering approaches are anticipated to reveal favorable outcomes.

Patients with remitted psychosis face a dilemma between the wish to discontinue antipsychotics and the risk of relapse. We test if an operationalized guided-dose-reduction algorithm can help reach a lower effective dose without increased risks of relapse.

A 2-year open-label randomized prospective comparative cohort trial from Aug 2017 to Sep 2022. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomized 2:1 into guided dose reduction group (GDR) v. maintenance treatment group (MT1), together with a group of naturalistic maintenance controls (MT2). We observed if the relapse rates would be different between 3 groups, to what extent the dose could be reduced, and if GDR patients could have improved functioning and quality of life.

A total of 96 patients, comprised 51, 24, and 21 patients in GDR, MT1, and MT2 groups, respectively. During follow-up, 14 patients (14.6%) relapsed, including 6, 4, and 4 from GDR, MT1, and MT2, statistically no difference between groups. In total, 74.5% of GDR patients could stay well under a lower dose, including 18 patients (35.3%) conducting 4 consecutive dose-tapering and staying well after reducing 58.5% of their baseline dose. The GDR group exhibited improved clinical outcomes and endorsed better quality of life.

GDR is a feasible approach as the majority of patients had a chance to taper antipsychotics to certain extents. Still, 25.5% of GDR patients could not successfully decrease any dose, including 11.8% experienced relapse, a risk comparable to their maintenance counterparts.

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global health crisis that may cause mental health problems and heighten suicide risk. We investigated the impact of the COVID-19 pandemic on trends in suicide attempts and suicide deaths in New Taipei City, Taiwan.

The current study used the official daily data on suicide attempts and deaths in New Taipei City, Taiwan (4 million inhabitants) between 2015 and 2020 from the Taiwan National Suicide Prevention Reporting System. Interrupted time-series (ITS) analyses with parameters corrected by the estimated autocorrelations were applied on weekly aggregated data to examine whether the suicide trends during the early COVID-19 pandemic (late January to July 2020) deviated from previous trends (January 2015 to late January 2020). The impact due to the suicide prevention policy change was also examined (since August 2020).

ITS analyses revealed no significant increases in both mean and trend on weekly suicide deaths during the COVID-19 pandemic and after the policy change. In contrast, there was a significant increasing trend in weekly suicide attempts since the COVID-19 outbreak at the rate of 1.54 attempts per week (95% confidence interval 0.49–2.60; p = 0.004). Sex difference analysis revealed that, however, this increasing trend was observed only in females not in males.

The COVID-19 pandemic has different impacts on suicides attempts and deaths during the early pandemic in New Taipei City, Taiwan. The COVID-19 outbreak drastically increased the trend of suicide attempts. In contrast, the number of suicide deaths had remained constant in the investigated periods.

The Brain Health Test-7 (BHT-7) is a revised tool from the original BHT, containing more tests about frontal lobe function. It was developed with theaim of identifying patients with mild cognitive impairment (MCI) and early dementia.

Here we report the validity of the BHT-7 versus the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in differentpsychiatry or neurology clinics.

Patients with memory complaints were recruited in this study from the outpatient clinic of psychiatry or neurology in 3 different kinds of hospitals. Allpatients underwent the evaluation of the BHT-7, MMSE, MoCA, and clinical dementia rating (CDR). The clinical diagnosis (normal, MCI, dementia) was made by consensus meeting, taking into account all available data.

Demographic data and the scores of the MMSE, MoCA, and BHT-7 between groups were compared. Logistic regression was adopted for analysis of optimal cutoff values, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating characteristic (ROC) curve,and the area under the ROC curve (AUC).

We enrolled a total of 1090 subjects (normal 402, MCI 317, dementia 371); of them, 705 (64.7%) were female. There was a statistically significant differencein age, years of education, and 3 cognitive test scores among the 3 groups.

Compared with the MMSE and MoCA, the BHT-7 performed slightly betterthan MMSE and MoCA in differentiating MCI or dementia from the normalcontrols (Table 1). For BHT- 7, the cutoff point was 17 between normal andMCI, and 14 between normal and dementia. These cutoff points for BHT-7were consistent through 3 different clinical settings, but inconsistent for MMSE and MoCA. The testing time for the BHT-7 was about 5-7 minutes, shorter than that of the MMSE and MoCA.

Compared with MMSE and MoCA, the BHT-7 showed slightly better performance in differentiating normal from MCI or dementia subjects. The testing time for the BHT-7 was shorter, and its cutoff points were consistent through different outpatient clinic settings. The results support that BHT-7 is auseful cognitive screening tool for MCI or early dementia in various hospital settings.

Table 1

Comparisons of the performance of BHT-7, MMSE, MoCA

Unawareness of deficits is common and is associated with poor outcomes in Alzheimer's disease (AD); however, little is known about correlated neurobiochemical changes.

Proton magnetic resonance spectroscopy was used to examine neurobiochemical correlates of unawareness of deficits as assessed by the Dementia Deficit Scale in 36 patients with AD. Magnetic resonance spectroscopy spectra were acquired from the anterior cingulate area and right orbitofrontal area. Concentrations of N-acetyl-aspartate (NAA), total creatine, and other neurometabolites were calculated.

Nineteen (52.8%) participants had relative unawareness of deficits. This condition was negatively correlated with NAA/creatine in the anterior cingulate area (β = −0.36, p = 0.025) and positively correlated with NAA/creatine in the right orbitofrontal area (β = 0.41, p = 0.009) after controlling for dementia severity.

These findings suggest unawareness of deficits in AD was associated with the altered neurochemical metabolites in the anterior cingulate area and right orbitofrontal area. However, the two areas might have opposite neuronal functions in unawareness of deficits.

To rapidly establish a temporary isolation ward to handle an unexpected sudden outbreak of severe acute respiratory syndrome (SARS) and to evaluate the implementation of exposure control measures by healthcare workers (HCWs) for SARS patients.

Rapid creation of 60 relatively negative pressure isolation rooms for 196 suspected SARS patients transferred from 19 hospitals and daily temperature recordings of 180 volunteer HCWs from 6 medical centers.

A military hospital.

Of the 196 patients, 34 (17.3%) met the World Health Organization criteria for probable SARS with positive results of serologic testing for SARS-associated coronavirus (SARS-CoV), reverse transcriptase polymerase chain reaction (RT-PCR) from nasopharyngeal or throat swabs for SARS-CoV, or both. Seventy-four patients had suspected SARS based on unprotected exposure to SARS patients; three of them had positive results on RT-PCR but negative serologic results. The remaining 88 patients did not meet the criteria for a probable or suspected SARS diagnosis. Of the 34 patients with probable SARS, 13 were transferred to medical centers to receive mechanical ventilation due to rapid deterioration of chest x-ray results, and three patients died of SARS despite intensive therapy in medical centers. During the study period, one nurse developed probable SARS due to violation of infection control measures, but there was no evidence of cross-transmission to other HCWs.

Despite the use of full personal protection equipment, the facility failed to totally prevent exposures of HCWs to SARS but minimized the risk of nosocomial transmission. Better training and improvements in infection control infrastructure may limit the impact of SARS.