Impact of COVID-19 pandemic on depression incidence and healthcare service use among patients with depression: an interrupted time-series analysis from a 9-year population-based study.

BACKGROUND: Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression. METHODS: Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression. RESULTS: We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10-1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period. CONCLUSIONS: During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises.

Projecting the 10-year costs of care and mortality burden of depression until 2032: a Markov modelling study developed from real-world data.

Background: Based on real-world data, we developed a 10-year prediction model to estimate the burden among patients with depression from the public healthcare system payer's perspective to inform early resource planning in Hong Kong. Methods: We developed a Markov cohort model with yearly cycles specifically capturing the pathway of treatment-resistant depression (TRD) and comorbidity development along the disease course. Projected from 2023 to 2032, primary outcomes included costs of all-cause and psychiatric care, and secondary outcomes were all-cause deaths, years of life lived, and quality-adjusted life-years. Using the territory-wide electronic medical records, we identified 25,190 patients aged ≥10 years with newly diagnosed depression from 2014 to 2016 with follow-up until 2020 to observe the real-world time-to-event pattern, based on which costs and time-varying transition inputs were derived using negative binomial modelling and parametric survival analysis. We applied the model as both closed cohort, which studied a fixed cohort of incident patients in 2023, and open cohort, which introduced incident patients by year from 2014 to 2032. Utilities and annual new patients were from published sources. Findings: With 9217 new patients in 2023, our closed cohort model projected the 10-year cumulative costs of all-cause and psychiatric care to reach US$309.0 million and US$58.3 million, respectively, with 899 deaths (case fatality rate: 9.8%) by 2032. In our open cohort model, 55,849-57,896 active prevalent cases would cost more than US$322.3 million and US$60.7 million, respectively, with more than 943 deaths annually from 2023 to 2032. Fewer than 20% of cases would live with TRD or comorbidities but contribute 31-54% of the costs. The greatest collective burden would occur in women aged above 40, but men aged above 65 and below 25 with medical history would have the highest costs per patient-year. The key cost drivers were relevant to the early disease stages. Interpretation: A limited proportion of patients would develop TRD and comorbidities but contribute to a high proportion of costs, which necessitates appropriate attention and resource allocation. Our projection also demonstrates the application of real-world data to model long-term costs and mortality, which aid policymakers anticipate foreseeable burden and undertake budget planning to prepare for the care need in alternative scenarios. Funding: Research Impact Fund from the University Grants Committee, Research Grants Council with matching fund from the Hong Kong Association of Pharmaceutical Industry (R7007-22).

Alterations in fecal virome and bacteriome virome interplay in children with autism spectrum disorder.

Emerging evidence suggests autism spectrum disorder (ASD) is associated with altered gut bacteria. However, less is known about the gut viral community and its role in shaping microbiota in neurodevelopmental disorders. Herein, we perform a metagenomic analysis of gut-DNA viruses in 60 children with ASD and 64 age- and gender-matched typically developing children to investigate the effect of the gut virome on host bacteria in children with ASD. ASD is associated with altered gut virome composition accompanied by the enrichment of Clostridium phage, Bacillus phage, and Enterobacteria phage. These ASD-enriched phages are largely associated with disrupted viral ecology in ASD. Importantly, changes in the interplay between the gut bacteriome and virome seen in ASD may influence the encoding capacity of microbial pathways for neuroactive metabolite biosynthesis. These findings suggest an impaired bacteriome-virome ecology in ASD, which sheds light on the importance of bacteriophages in pathogenesis and the development of microbial therapeutics in ASD.

Association between cumulative exposure periods of flupentixol or any antipsychotics and risk of lung cancer.

BACKGROUND: Preclinical evidence suggests that certain antipsychotic medications may inhibit the development of lung cancer. This study aims to investigate the association between incident lung cancer and different cumulative exposure periods of flupentixol or any antipsychotics. METHODS: Using electronic health records from the Hospital Authority in Hong Kong, this nested case-control study included case participants aged 18 years or older with newly diagnosed lung cancer after initiating antipsychotics between January 1, 2003, and August 31, 2022. Each case was matched to up to ten controls of the same sex and age, who were also antipsychotic users. Multivariable conditional logistic regression models were conducted to quantify the association between lung cancer and different cumulative exposure times of flupentixol (0-365 days [ref]; 366-1825 days; 1826+ days) and any antipsychotics (1-365 days [ref]; 366-1825 days; 1826+ days), separately. RESULTS: Here we show that among 6435 cases and 64,348 matched controls, 64.06% are males, and 52.98% are aged 65-84 years. Compared to patients with less than 365 days of exposure, those with 366-1825 days of exposure to flupentixol (OR = 0.65 [95% CI, 0.47-0.91]) and any antipsychotics (0.42 [0.38-0.45]) have a lower risk of lung cancer. A decreased risk is observed in patients who have 1826+ days of cumulative use of any antipsychotics (0.54 [0.47-0.60]). CONCLUSIONS: A reduced risk of lung cancer is observed in patients with more than one year of exposure to flupentixol or any antipsychotics. Further research on the association between lung cancer and other antipsychotic agents is warranted.

Antipsychotic drugs are mainly used to treat mental illnesses. Certain antipsychotic medications, such as flupentixol, may help protect patients against lung cancer. Here, we investigated whether prolonged use of flupentixol or other antipsychotics could reduce the occurrence of lung cancer among antipsychotic users. We demonstrated that a smaller proportion of patients with one to five years and more than five years of exposure to any antipsychotics develop lung cancer compared to those with less than one year of exposure. Specifically, for flupentixol, we observed a smaller proportion of patients with one to five years of exposure develop lung cancer compared to those with less than one year. To substantiate our current findings, further studies examining other populations and specific antipsychotic agents are necessary for developing effective lung cancer prevention strategies among this high-risk population.

Moment-to-moment affective dynamics in schizophrenia and bipolar disorder.

BACKGROUND: Affective disturbances in schizophrenia and bipolar disorder may represent a transdiagnostic etiological process as well as a target of intervention. Hypotheses on similarities and differences in various parameters of affective dynamics (intensity, successive/acute changes, variability, and reactivity to stress) between the two disorders were tested. METHODS: Experience sampling method was used to assess dynamics of positive and negative affect, 10 times a day over 6 consecutive days. Patients with schizophrenia (n = 46) and patients with bipolar disorder (n = 46) were compared against age-matched healthy controls (n = 46). RESULTS: Compared to controls, the schizophrenia group had significantly more intense momentary negative affect, a lower likelihood of acute changes in positive affect, and reduced within-person variability of positive affect. The bipolar disorder group was not significantly different from either the schizophrenia group or the healthy control group on any affect indexes. Within the schizophrenia group, level of depression was associated with weaker reactivity to stress for negative affect. Within the bipolar disorder group, level of depression was associated with lower positive affect. CONCLUSIONS: Patients with schizophrenia endured a more stable and negative affective state than healthy individuals, and were less likely to be uplifted in response to happenings in daily life. There is little evidence that these affective constructs characterize the psychopathology of bipolar disorder; such investigation may have been limited by the heterogeneity within group. Our findings supported the clinical importance of assessing multiple facets of affective dynamics beyond the mean levels of intensity.

Specificity of associations between parental psychopathology and offspring brain structure.

Multiple forms of parental psychopathology have been associated with differences in subcortical brain volume. However, few studies have considered the role of comorbidity. Here, we examine if alterations in child subcortical brain structure are specific to parental depression, anxiety, mania, or alcohol/substance use parental psychopathology, common across these disorders, or altered by a history of multiple disorders. We examined 6581 children aged 9 to 10 years old from the ABCD study with no history of mental disorders. We found several significant interactions such that the effects of a parental history of depression, anxiety, and substance use problems on amygdala and striatal volumes were moderated by comorbid parental history of another disorder. Interactions tended to suggest smaller volumes in the presence of a comorbid disorder. However, effect sizes were small, and no associations remained significant after correcting for multiple comparisons. Results suggest that associations between familial risk for psychopathology and offspring brain structure in 9-10-year-olds are modest, and relationships that do exist tend to implicate the amygdala and striatal regions and are moderated by a comorbid parental psychopathology history. Several methodological factors, including controlling for intracranial volume and other forms of parental psychopathology and excluding child psychopathology, likely contribute to inconsistencies in the literature.

Breast cancer risks following antipsychotic use in women with bipolar disorder versus schizophrenia: A territory-wide nested case-control study spanning two decades.

Accrued epidemiologic data largely support an association of antipsychotic use with breast cancer in women with schizophrenia. No studies have specifically investigated such risks in women with bipolar disorder. This study aims to examine the association between antipsychotics and breast cancer in women with bipolar disorder and compare it against schizophrenia. We conducted a nested case-control study using a territory-wide public healthcare database in Hong Kong examining women aged ≥18 years with bipolar disorder or schizophrenia. Using incidence density sampling, women with a breast cancer diagnosis were matched by up to 10 control participants. In total, 672 case participants (109 with bipolar disorder) and 6,450 control participants (931 with bipolar disorder) were included. Results show a significant association of first-generation antipsychotics with breast cancer in both women with schizophrenia [adjusted odds ratio (aOR) 1.49, 95% confidence interval (CI) 1.17-1.90] or bipolar disorder (aOR 1.80, 95% CI 1.11-2.93). Second-generation antipsychotics was associated with breast cancer only in women with bipolar disorder (aOR 2.49, 95% CI 1.29-4.79), with no significant association found in women with schizophrenia (aOR 1.10, 95% CI 0.88-1.36). In conclusion, further research on breast cancer risks is warranted for women with bipolar disorder on antipsychotics.

Sleep and academic performance among students in Hong Kong: Curvilinear relationship suggesting an optimal amount of sleep.

OBJECTIVES: This study aimed to elucidate the association between sleep and academic performance using standardized academic assessment in a large and representative sample of school children and adolescents in Hong Kong. METHODS: This school-based cross-sectional study was conducted in 2016. Students completed territory-wide standardized tests in Chinese, English, and Mathematics and a set of questionnaires covering sleep, academic anxiety and motivation. Parents provided additional information on socioeconomic status and children's study behaviors. Weekday proxy sleep duration was reflected by time-in-bed, the difference between bedtime and wakeup time. RESULTS: The study included 4262 Grade 3 (G.3) (mean age [SD], 9.2 [0.6] years; girls: 49.7%) and 3297 G.9 students (mean age [SD], 15.3 [0.74]; girls: 57.5%) from 77 schools. Apart from showing a general insufficiency of students' sleep in this metropolitan city, there was a significant quadratic relationship (G.3: ß = -0.05, p < .001; G.9: ß = -0.03, p < .01), indicating that students with an optimal level of sleep (9.5 h and 8.5 h in G.3 and G.9, respectively) tend to have better academic performance. The significant association remained after controlling for socioeconomic and study-related variables in that sleeping too little or too much was associated with poor academic performance. CONCLUSIONS: This is the first study to explore the curvilinear association between sleep duration and academic performance by using standardized test and simultaneously examining learning-related controls with a large representative sample in Hong Kong. The findings suggested that there is an inverted U-shaped relationship between sleep duration and academic performance in both school-aged children and adolescents. It is recommended that systematic sleep education and intervention is necessary to encourage the development of optimal sleep pattern, which might have beneficial effect on academic performance for students at both primary and secondary level.

Treatment-resistant depression and risk of autoimmune diseases: evidence from a population-based cohort and nested case-control study.

Recent literature indicates that patients with depression had increased immune activation. We hypothesised that treatment-resistant depression (TRD), an indicator of non-responsive depression with long-term dysregulated inflammation, could be an independent risk factor for subsequent autoimmune diseases. We performed a cohort study and a nested case-control study to examine the association between TRD and risk of autoimmune diseases, and to explore potential sex-specific difference. Using electronic medical records in Hong Kong, we identified 24,576 patients with incident depression between 2014 and 2016 without autoimmune history and followed up from diagnosis to death or December 2020 to identify TRD status and autoimmune incidence. TRD was defined as having at least two antidepressant regimens and the third regimen to confirm previous treatment failures. Based on age, sex and year of depression, we matched TRD patients 1:4 to the non-TRD in the cohort analysis using nearest-neighbour matching, and matched cases and controls 1:10 using incidence density sampling in the nested case-control analysis. We conducted survival analyses and conditional logistic regression respectively for risk estimation, adjusting for medical history. Across the study period, 4349 patients without autoimmune history (17.7%) developed TRD. With 71,163 person-years of follow-up, the cumulative incidence of 22 types of autoimmune diseases among the TRD patients was generally higher than the non-TRD (21.5 vs. 14.4 per 10,000 person-years). Cox model suggested a non-significant association (HR:1.48, 95% CI: 0.99-2.24, p = 0.059), whereas conditional logistic model showed a significant association (OR: 1.67, 95% CI: 1.10-2.53, p = 0.017) between TRD status and autoimmune diseases. Subgroup analysis showed that the association was significant in organ-specific diseases but not in systemic diseases. Risk magnitudes were generally higher among men compared to women. In conclusion, our findings provide evidence for an increased risk of autoimmune diseases in patients with TRD. Controlling chronic inflammation in hard-to-treat depression might play a role in preventing subsequent autoimmunity.

Decoding the radiomic features of dorsolateral prefrontal cortex in individuals with accelerated cortical changes: implications for personalized transcranial magnetic stimulation.

Purpose: Image-guided transcranial magnetic stimulation (TMS) is an emerging research field in neuroscience and rehabilitation medicine. Cortical morphometry, as a radiomic phenotype of aging, plays a vital role in developing personalized TMS model, yet few studies are afoot to examine the aging effects on region-specific morphometry and use it in the estimation of TMS-induced electric fields. Our study was aimed to investigate the radiomic features of bilateral dorsolateral prefrontal cortex (DLPFC) and quantify the TMS-induced electric fields during aging. Approach: Baseline, 1-year and 3-year structural magnetic resonance imaging (MRI) scans from normal aging (NA) adults ( n = 32 ) and mild cognitive impairment (MCI) converters ( n = 22 ) were drawn from the Open Access Series of Imaging Studies. The quantitative measures of radiomics included cortical thickness, folding, and scalp-to-cortex distance. Realistic head models were developed to simulate the impacts of radiomic features on TMS-induced E-fields using the finite-element method. Results: A pronounced aging-related decrease was found in the gyrification of left DLPFC in MCI converters ( t = 2.21 , p = 0.035 ), which could predict the decline of global cognition at 3-year follow up. Along with the decreased gyrification in left DLPFC, the magnitude of TMS-induced E-fields was rapidly decreased in MCI converters ( t = 2.56 , p = 0.018 ). Conclusions: MRI-informed radiomic features of the treatment targets have significant effects on the intensity and distribution of the stimulation-induced electric fields in prodromal dementia patients. Our findings highlight the importance of region-specific radiomics when conducting the transcranial brain stimulation in individuals with accelerated cortical changes, such as Alzheimer's disease.

A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic.

STUDY OBJECTIVES: The lifestyles change of children and adolescents during the COVID-19 pandemic due to antipandemic measures can affect their sleep health. Existing studies have used convenient samples and focused on the initial months of the pandemic, leaving a knowledge gap on changes in young people's sleep patterns under the "new normal" under COVID-19. METHODS: As part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. Sleep parameters were collected using the structured diagnostic interview for sleep patterns and disorders. We investigated the pandemic's effects on sleep parameters by comparing data of participants recruited pre-COVID and those recruited during COVID using multivariate regression, adjusting for age, sex, household income, seasonality, and presence of mental disorders, and the moderators and mediators of the effects. RESULTS: Between September 1, 2019 and June 2, 2021, 791 primary and 442 secondary school students were recruited and analyzed. Primary school and secondary school participants assessed before COVID had a longer sleep latency on school days (95% confidence interval [CI] = 1.0-5.2 minutes, adjusted P-value = .010; and 95% CI= 3.9-13.0 minutes, adjusted P-value = .004, respectively) and nonschool days (95% CI = 1.7-7.2 minutes, adjusted P-value = .005; 95% CI = 3.4-13.7 minutes, adjusted P-value = .014, respectively). Low household income was a moderator for later bedtime (adjusted P-value = .032) and later sleep onset (adjusted P-value = .043) during nonschool days among secondary school students. CONCLUSIONS: Changes associated with COVID have a widespread and enduring effect on the sleep health of school-aged students in Hong Kong. Household income plays a role in adolescent sleep health resilience, and the impact of antiepidemic measures on the health gaps of the youth should be considered. CITATION: Chau SWH, Hussain S, Chan SSM, et al. A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic. J Clin Sleep Med. 2023;19(4):749-757.

Executive function as a generalized determinant of psychopathology and functional outcome in school-aged autism spectrum disorder: a case-control study.

BACKGROUND: Individuals with autism spectrum disorder (ASD) are challenged not only by the defining features of social-communication deficits and restricted repetitive behaviors, but also by a myriad of psychopathology varying in severity. Different cognitive deficits underpin these psychopathologies, which could be subjected to intervention to alter the course of the disorder. Understanding domain-specific mediating effects of cognition is essential for developing targeted intervention strategies. However, the high degree of inter-correlation among different cognitive functions hinders elucidation of individual effects. METHODS: In the Philadelphia Neurodevelopmental Cohort, 218 individuals with ASD were matched with 872 non-ASD controls on sex, age, race, and socioeconomic status. Participants of this cohort were deeply and broadly phenotyped on neurocognitive abilities and dimensional psychopathology. Using structural equation modeling, inter-correlation among cognitive domains were adjusted before mediation analysis on outcomes of multi-domain psychopathology and functional level. RESULTS: While social cognition, complex cognition, and memory each had a unique pattern of mediating effect on psychopathology domains in ASD, none had significant effects on the functional level. In contrast, executive function was the only cognitive domain that exerted a generalized negative impact on every psychopathology domain (p factor, anxious-misery, psychosis, fear, and externalizing), as well as functional level. CONCLUSIONS: Executive function has a unique association with the severity of comorbid psychopathology in ASD, and could be a target of interventions. As executive dysfunction occurs variably in ASD, our result also supports the clinical utility of assessing executive function for prognostic purposes.

Clinical and radiomic features for predicting the treatment response of repetitive transcranial magnetic stimulation in major neurocognitive disorder: Results from a randomized controlled trial.

Image-guided repetitive transcranial magnetic stimulation (rTMS) has shown clinical effectiveness in senior adults with co-occurring depression and cognitive impairment, yet the imaging markers for predicting the treatment response are less investigated. In this clinical trial, we examined the efficacy and sustainability of 10 Hz rTMS for the treatment of depression and cognitive impairment in major neurocognitive disorder (NCD) patients and tested the predictive values of imaging-informed radiomic features in response to rTMS treatment. Fifty-five major NCD patients with depression were randomly assigned to receive a 3-week rTMS treatment of either active 10 Hz rTMS (n = 27) or sham rTMS (n = 28). Left dorsolateral prefrontal cortex (DLPFC) was the predefined treatment target. Based on individual structural magnetic resonance imaging scans, surface-based analysis was conducted to quantitatively measure the baseline radiomic features of left DLPFC. Severity of depression, global cognition and the serum brain-derived neurotrophic factor (BDNF) level were evaluated at baseline, 3-, 6- and 12-week follow-ups. Logistic regression analysis revealed that advanced age, higher baseline cognition and randomized group were associated with the remission of depression. Increased cortical thickness and gyrification in left DLPFC were the significant predictors of clinical remission and cognitive enhancement. A 3-week course of 10 Hz rTMS is an effective adjuvant treatment for rapid ameliorating depressive symptoms and enhancing cognitive function. Pre-treatment radiomic features of the stimulation target can predict the response to rTMS treatment in major NCD. Cortical thickness and folding of treatment target may serve as imaging markers to detect the responders. ChiCTR-IOR-16008191, registered on March 30, 2016.

Disentangling the relationship of gut microbiota, functional gastrointestinal disorders and autism: a case-control study on prepubertal Chinese boys.

Emerging evidence of an altered gut microbiome in autism spectrum disorder (ASD) suggests a pathomechanism through the gut-brain axis despite the inconsistent microbiome profile reported across studies. One of the knowledge gaps in the existing ASD microbiota studies is the lack of systematic exploration of the role of comorbid functional gastrointestinal disorder (FGID) in the association of ASD and altered gut microbiome. Consequently, 92 ASD and 112 age-matched typically developing (TD) boys were profiled on general psychopathology, FGID status by Rome IV classification, and gut microbiota using 16S ribosomal RNA amplicon sequencing at the V4 hypervariable region. Compared to TD, a significant decrease in the within-sample abundance of taxa was observed in ASD, regardless of FGID status. The microbiota of ASD FGID+ and ASD FGID- clustered apart from the TD groups. The microbiota of ASD FGID+ also showed qualitative differences from that of ASD FGID- and had the highest-level Firmicutes: Bacteroidetes ratio, which was paralleled by elevated levels of anxiety and overall psychopathology. The altered gastrointestinal microbiota composition in ASD appeared to be independent of comorbid FGID. Further studies should address how FGID may mediate neuropsychiatric symptoms in ASD through inflammation along the microbiota-gut-brain axis.

Mortality-causing mechanisms and healthcare resource utilisation of treatment-resistant depression: A six-year population-based cohort study.

Background: Few studies investigated the mechanisms of treatment-resistant depression (TRD) leading to the worsened survival outcome, and economic evidence was mostly restricted to short follow-ups. We aimed to examine the association and potential mediators between TRD and all-cause mortality, and estimate a longer-term associated health resource utilisation pattern. Methods: This was a population-based cohort study using territory-wide electronic medical records in Hong Kong. Incident depression patients diagnosed in 2014 were followed up from the first diagnosis to death or December 2019 for TRD identification. We matched the TRD cohort 1:4 to the non-TRD cohort on propensity scores estimated by age, sex, history of physical disorders, and history of psychiatric conditions before depression diagnoses. Findings: 18% of incident patients developed TRD within six years of follow-up. Cox model showed that patients with TRD had 1⋅52-fold (95% CI: 1⋅14-2⋅02) greater risk of all-cause mortality, compared with non-TRD patients. Path analysis suggested that post-TRD psychiatric conditions significantly mediated 41⋅6% of mortality in patients with TRD (p=0.003). TRD was associated with 1⋅8-fold (95%CI: 1⋅63-2⋅00) higher healthcare costs compared to non-TRD patients over six years in negative binomial regression, with higher costs for both psychiatric and non-psychiatric services utilisation in all settings. Interpretation: Identifying patients with TRD and subsequent monitoring for post-TRD psychiatric diagnoses could be a way to reduce premature mortality. Multidisciplinary care involving both psychiatric and general medical professionals is also warranted to relieve the multifaceted impacts on healthcare resources and overall cost. Funding: Unconditional educational grant from Janssen.

Depression duration and risk of incident cardiovascular disease: A population-based six-year cohort study.

BACKGROUND: Depression symptoms are significantly associated with an increased risk of cardiovascular disease (CVD). However, understanding of the magnitude of the association between depression duration and risk of CVD is limited. Therefore, we aimed to assess whether a longer duration of exposure to depression is associated with a higher risk of new-onset CVD. METHODS: We conducted a territory-wide retrospective cohort study among patients (≥ 10 years old) with depression diagnosed between January and December 2014 in Hong Kong. The observation period spanned January 1, 2014, to December 31, 2019, and all participants had no CVD at baseline. Incidence of CVD was calculated. We used Cox proportional hazard regression to adjust confounders and estimate hazard ratios of CVD risk. RESULTS: Among 11,651 participants with depression, 1306 (11.2%) individuals developed CVD. Multi-adjusted models showed individuals with depression duration of 2-5 years (Hazard Ratios [HRs]: 1.38 [95% confidence interval (CI): 1.19-1.60]) and ≥6 years (1.45 [1.25-1.68]) had a significantly escalated risk of developing CVD, compared to those with depression within one year. Stratified analyses indicated that the association was prominent in women and those under 65 years old. LIMITATIONS: Lack of depression severity information and the small sample size in some subgroup analyses. CONCLUSIONS: Longer exposure to depression is associated with significant increased risk of CVD. The interplay between mental and vascular health emphasizes the need for CVD prevention in patients with long-term depression.

Antidepressant efficacy of low-frequency repetitive transcranial magnetic stimulation in antidepressant-nonresponding bipolar depression: a single-blind randomized sham-controlled trial.

BACKGROUND: To examine the antidepressant efficacy and response predictors of R-DLPFC-LF rTMS for antidepressant-nonresponding BD. METHODS: We conducted a single-blind randomized sham-controlled trial for 54 (28 sham, 26 active) patients with antidepressant-nonresponding BD (baseline MADRS ≥ 20). Patients received 15 daily sessions of active or sham neuronavigated rTMS (Figure-of-8 coil, five 1 Hz 60 s 110% RMT trains). Outcome measures included depressive response (≥ 50% MADRS reduction, CGI ≤ 2) and remission (MADRS < 7, CGI = 1) rates, treatment emergent hypo/mania (YMRS), depressive and anxiety symptoms (HAM-A). RESULTS: 48 patients (25 sham, 23 active) completed treatment, with 3 drop-outs each in active and sham groups. Active rTMS did not produce superior response or remission rates at endpoint or 6 or 12 weeks (ps > 0.05). There was no significant group * time interaction (ps > 0.05) in a multivariate ANOVA with MADRS, HAMA and YMRS as dependent variables. Exploratory analysis found MADRS improvement to be moderated by baseline anxiety (p = 0.02) and melancholia (p = 0.03) at week 3, and depressive onset at weeks 6 (p = 0.03) and 12 (p = 0.04). In subjects with below-mean anxiety (HAMA < 20.7, n = 24), MADRS improvement from active rTMS was superior to sham at week 3 (ITT, t = 2.49, p = 0.04, Cohen's d = 1.05). No seizures were observed. Groups did not differ in treatment-emergent hypomania (p = 0.1). LIMITATIONS: Larger sample size might be needed to power subgroup analyses. Moderation analyses were exploratory. Single-blind design. Unblinding before follow-up assessments due to ethical reasons. CONCLUSIONS: 1-Hz 110% RMT (5 × 60 s trains) R-DLPFC-LF rTMS was not effective for antidepressant non-responding BD but may be further investigated at increased dosage and/or in BD patients with low anxiety. Trial registration CCRB Clinical Trials Registry, CUHK, CUHK_CCT00440. Registered 04 December 2014, https://www2.ccrb.cuhk.edu.hk/registry/public/279.

Personalized prediction of repetitive transcranial magnetic stimulation clinical response in medication-refractory depression data.

This article describes a dataset that was generated as part of the article: Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning (DOI: 10.1016/j.jad.2021.04.081). We collected resting-state functional Magnetic Resonance Imaging data from 70 medication-refractory depressed subjects before undergoing four weeks of repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex. The data presented here include information about the seed-based analyses such as regions of interest, individual/group functional connectivity maps and contrast maps. The contrast maps are controlled for age, gender, duration of the current depressive episode, duration since the first depressive episode, and symptom scores. Demographics, clinical characteristics, and categorical treatment response variables are reported as well. Further, the individual connectivity values of the identified neuroimaging biomarkers of long-term clinical response were used as features in the support vector machine models are presented in combination with the trained classifiers of the support vector machine models. Post hoc analyses that were not published in the original analyses are presented as well. Finally, the R or MATLAB code scripts for all figures published in the co-submitted paper are included.