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.

The aim of this 4-year follow-up study was to examine the predictive effects of demographics, three types of sexual stigma, three types of self-identity confusion, anxiety, depression, family support and problematic Internet use before the coronavirus disease 2019 (COVID-19) pandemic on new-onset suicide risk and persistent suicide risk in young adult lesbian, gay and bisexual individuals who experienced the COVID-19 pandemic in Taiwan.

Baseline data were collected from 1,000 lesbian, gay and bisexual individuals in 2018 and 2019. Outcome data on suicide risk were collected again in 2023. The suicide module of the Mini International Neuropsychiatric Interview was used to assess suicide risk in terms of thoughts of death, desire to self-harm, thoughts of suicide, plans for suicide and suicide attempts in the preceding month at the initial and follow-up assessments. Baseline three types of sexual stigma, self-identity disturbance, depression, anxiety and problematic Internet use were used to examine their prediction of new-onset suicide risk and persistent suicide risk at follow-up.

In total, 673 individuals participated in the follow-up survey. Notably, 16.5% of the participants who had no suicide risk at baseline had new-onset suicide risk at follow-up; 46.4% of the participants who had suicide risk at baseline also had suicide risk at follow-up. Participants who were transgender (p = .003), who perceived greater levels of microaggression (p < .001), and who had greater levels of problematic Internet use at baseline (p = .024) were more likely to have new-onset suicide risk at follow-up. Participants who had greater levels of self-identity confusion were more likely to have persistent suicide risk at follow-up (p = .023).

Intervention strategies for reducing suicide risk in lesbian, gay and bisexual individuals should be developed with consideration of the predictors identified in this study.

Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear.

In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done.

Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend <0.001). Participants with one point increment in CSD and ACE had higher GDS score by 0.11 (95% confidence interval [CI], 0.09–0.14) and 0.41 (95% CI, 0.35–0.47), respectively. The association of CSD with GDS score was significant in women only (P for sex interaction <0.001; women: β (95% CI)=0.14 (0.11–0.17), men: 0.04 (−0.01 to 0.08)). The association between ACE and GDS score was stronger in participants with high social deprivation index (SDI) (P for interaction = 0.01; low SDI: β (95% CI)=0.36 (0.29–0.43), high SDI: 0.64 (0.48–0.80)). The proportion of association of CSD and ACE scores with GDS score mediated via education was 20.11% and 2.28%.

CSD and ACE were associated with late-life depressive symptoms with dose-response patterns, especially in women and those with low adulthood socio-economic status. Education was a major mediator for CSD but not ACE. Eliminating ACE should be a top priority.

We explored long-term employment status and income before and after depression diagnosis among men and women and at different working ages in Taiwan.

Data from 2006 to 2019 were obtained from the National Health Insurance Research Database (NHIRD). Individuals with newly diagnosed depressive disorder aged 15 to 64 years during the study period were identified. An equal number of individuals without depression were matched for their demographic and clinical characteristics. Employment outcomes included employment status, which was categorized into employed or unemployed, and annual income. Based on the occupation categories and monthly insurance salary recorded in the Registry for Beneficiaries of the NHIRD, a subject was defined as unemployed if he or she differed from the income earner or the occupation category was unemployed. Monthly income was defined as zero for unemployed subjects and proxied as monthly insurance salary for others. Annual income was the sum of monthly income in each observation year.

A total of 420,935 individuals with depressive disorder were included in the study, and an equal number of individuals with not diagnosed depression served as controls. Employment rate and income were lower in the depression group than in the control group before the year of diagnosis, with a difference of 5.7% in employment rate and USD 1,173 in annual income. This gap increased considerably after the year of diagnosis (7.3% in employment rate and USD 1,573 in annual incomes) and further widened in the subsequent years (8.1% in employment rate and USD 2,006 in annual incomes in the 5th following year). The drops in the employment rate and income caused by depression were more evident in men and older age groups than in women and younger age groups, respectively. However, the reduction in employment rate and income in the following years after the diagnosis was more considerable among younger age groups.

The effect of depression on employment status and income was significant during the year of diagnosis and continued afterwards. The effect on employment outcomes varied between genders and across all age groups.

To propose a scoring system based on laryngoscopic characteristics for the differential diagnosis of benign and malignant vocal fold leukoplakia.

Laryngoscopic images from 200 vocal fold leukoplakia cases were retrospectively analysed. The laryngoscopic signs of benign and malignant vocal fold leukoplakia were compared, and statistically significant features were assigned and accumulated to establish the leukoplakia finding score.

A total of five indicators associated with malignant vocal fold leukoplakia were included to construct the leukoplakia finding score, with a possible range of 0–10 points. A score of 6 points or more was indicative of a diagnosis of malignant vocal fold leukoplakia. The sensitivity, specificity and accuracy values of the leukoplakia finding score were 93.8 per cent, 83.6 per cent and 86.0 per cent, respectively. The consistency in the leukoplakia finding score obtained by different laryngologists was strong (kappa = 0.809).

This scoring system based on laryngoscopic characteristics has high diagnostic value for distinguishing benign and malignant vocal fold leukoplakia.

Caregiver-mediated intervention (CMI), based on parent skills training, is a family-mediated intervention model for children with neurodevelopmental disorders, in particular autism spectrum disorder. This study aimed to evaluate the effectiveness of CMI.

Thirty-three children (aged 22–69 months from our department) and their caregivers participated in a two-week training course of ten 90-minute lessons. Caregivers were encouraged to try their best to apply intervention skills in both home routines and play routines to encourage the development of cognition, motion, social adaptability, and behavior of children. Demographic information, video-recorded data, and diagnostic scales were collected at two key time points: baseline and post-training (PT – within six months).

Three aspects were assessed – primary variables, secondary variables, and correlation analyses. Results showed an improvement in PT in (1) Adult/Child Interaction Fidelity Rating (P < 0.01) and (2) adaptability of Gesell Developmental Scale and stereotyped behaviors and limited interests of Autism Diagnostic Observation Schedule (P < 0.05, P < 0.01). Moreover, a negative correlation occurred between caregiver skill improvement and parent education (P < 0.05), but without correlations with other demographics.

As an efficacious family intervention for both children and their caregivers, CMI is worth being generalized widely.

As a neuroprogressive illness, depression is accompanied by brain structural abnormality that extends to many brain regions. However, the progressive structural alteration pattern remains unknown.

To elaborate the progressive structural alteration of depression according to illness duration, we recruited 195 never-treated first-episode patients with depression and 130 healthy controls (HCs) undergoing T1-weighted MRI scans. Voxel-based morphometry method was adopted to measure gray matter volume (GMV) for each participant. Patients were first divided into three stages according to the length of illness duration, then we explored stage-specific GMV alterations and the causal effect relationship between them using causal structural covariance network (CaSCN) analysis.

Overall, patients with depression presented stage-specific GMV alterations compared with HCs. Regions including the hippocampus, the thalamus and the ventral medial prefrontal cortex (vmPFC) presented GMV alteration at onset of illness. Then as the illness advanced, others regions began to present GMV alterations. These results suggested that GMV alteration originated from the hippocampus, the thalamus and vmPFC then expanded to other brain regions. The results of CaSCN analysis revealed that the hippocampus and the vmPFC corporately exerted causal effect on regions such as nucleus accumbens, the precuneus and the cerebellum. In addition, GMV alteration in the hippocampus was also potentially causally related to that in the dorsolateral frontal gyrus.

Consistent with the neuroprogressive hypothesis, our results reveal progressive morphological alteration originating from the vmPFC and the hippocampus and further elucidate possible details about disease progression of depression.

The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration.

A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012–2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1–364 and ⩾365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve.

The mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67; 95% confidence interval 0.60–0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury.

Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.

Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.

This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).

FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.

The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.