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Evidence suggests the crucial role of dysfunctional default mode (DMN), salience and frontoparietal (FPN) networks, collectively termed the triple network model, in the pathophysiology of treatment-resistant depression (TRD).
Aims
Using the graph theory- and seed-based functional connectivity analyses, we attempted to elucidate the role of low-dose ketamine in the triple networks, namely the DMN, salience and FPN.
Method
Resting-state functional connectivity magnetic resonance imaging (rs–fcMRI) data derived from two previous clinical trials of a single, low-dose ketamine infusion were analysed. In clinical trial 1 (Trial 1), patients with TRD were randomised to either a ketamine or normal saline group, while in clinical trial 2 (Trial 2) those patients with TRD and pronounced suicidal symptoms received a single infusion of either 0.05 mg/kg ketamine or 0.045 mg/kg midazolam. All participants underwent rs–fcMRI pre and post infusion at Day 3. Both graph theory- and seed-based functional connectivity analyses were performed independently.
Results
Trial 1 demonstrated significant group-by-time effects on the degree centrality and cluster coefficient in the right posterior cingulate cortex (PCC) cortex ventral 23a and b (DMN) and the cluster coefficient in the right supramarginal gyrus perisylvian language (salience). Trial 2 found a significant group-by-time effect on the characteristic path length in the left PCC 7Am (DMN). In addition, both ketamine and normal saline infusions exerted a time effect on the cluster coefficient in the right dorsolateral prefrontal cortex a9-46v (FPN) in Trial 1.
Conclusions
These findings may support the utility of the triple-network model in elucidating ketamine’s antidepressant effect. Alterations in DMN, salience and FPN function may underlie this effect.
The vitamin K (VK) levels vary greatly among different populations and in different regions. Currently, there is a lack of reference intervals for VK levels in healthy individuals, The aim of this study is to establish and validate the reference intervals of serum vitamin K1 (VK1) and vitamin K2 (VK2, specifically including menaquinone-4 (MK4) and menaquinone-7 (MK7)) levels in some healthy populations in Beijing. Serum VK1, MK4, and MK7 were firstly measured by high-performance liquid chromatography and mass spectrometry in 434 subjects. The reference intervals for three indicators were established by calculating the data of 2.5 and 97.5 percentiles. Finally, preliminary clinical validation was conducted on 60 apparent healthy individuals undergoing physical examination. In the young, middle-aged, and elderly groups, the reference intervals of VK1 were 0.180 ng/mL ∼ 1.494 ng/mL, 0.247 ng/mL ∼ 1.446 ng/mL, and 0.167 ng/mL ∼ 1.445 ng/mL, respectively. The reference intervals of MK4 were 0.009 ng/mL ∼ 0.115 ng/mL, 0.002 ng/mL ∼ 0.103 ng/mL, and 0.003 ng/mL ∼ 0.106 ng/mL, respectively. The reference intervals of MK7 were 0.169 ng/mL ∼ 0.881 ng/mL, 0.238 ng/mL ∼ 0.936 ng/mL, and 0.213 ng/mL ∼ 1.012 ng/mL, respectively. The reference intervals had been validated by the samples of healthy individuals for physical examination. In conclusion, the reference intervals of VK established in this study with different age groups have certain clinical applicability, providing data support for further multicentre studies.
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.
Methods
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.
Results
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.
Conclusions
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 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).
Methods
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.
Results
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.
Conclusions
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.
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.
Methods
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.
Results
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%.
Conclusions
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.
The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.
Longitudinal studies on the variations of phenotypic and genotypic characteristics of K. pneumoniae across two decades are rare. We aimed to determine the antimicrobial susceptibility and virulence factors for K. pneumoniae isolated from patients with bacteraemia or urinary tract infection (UTI) from 1999 to 2022. A total of 699 and 1,267 K. pneumoniae isolates were isolated from bacteraemia and UTI patients, respectively, and their susceptibility to twenty antibiotics was determined; PCR was used to identify capsular serotypes and virulence-associated genes. K64 and K1 serotypes were most frequently observed in UTI and bacteraemia, respectively, with an increasing frequency of K20, K47, and K64 observed in recent years. entB and wabG predominated across all isolates and serotypes; the least frequent virulence gene was htrA. Most isolates were susceptible to carbapenems, amikacin, tigecycline, and colistin, with the exception of K20, K47, and K64 where resistance was widespread. The highest average number of virulence genes was observed in K1, followed by K2, K20, and K5 isolates, which suggest their contribution to the high virulence of K1. In conclusion, we found that the distribution of antimicrobial susceptibility, virulence gene profiles, and capsular types of K. pneumoniae over two decades were associated with their clinical source.
The discharged capillary plasma channel has been extensively studied as a high-gradient particle acceleration and transmission medium. A novel measurement method of plasma channel density profiles has been employed, where the role of plasma channels guiding the advantages of lasers has shown strong appeal. Here, we have studied the high-order transverse plasma density profile distribution using a channel-guided laser, and made detailed measurements of its evolution under various parameters. The paraxial wave equation in a plasma channel with high-order density profile components is analyzed, and the approximate propagation process based on the Gaussian profile laser is obtained on this basis, which agrees well with the simulation under phase conditions. In the experiments, by measuring the integrated transverse laser intensities at the outlet of the channels, the radial quartic density profiles of the plasma channels have been obtained. By precisely synchronizing the detection laser pulses and the plasma channels at various moments, the reconstructed density profile shows an evolution from the radial quartic profile to the quasi-parabolic profile, and the high-order component is indicated as an exponential decline tendency over time. Factors affecting the evolution rate were investigated by varying the incentive source and capillary parameters. It can be found that the discharge voltages and currents are positive factors quickening the evolution, while the electron-ion heating, capillary radii and pressures are negative ones. One plausible explanation is that quartic profile contributions may be linked to plasma heating. This work helps one to understand the mechanisms of the formation, the evolutions of the guiding channel electron-density profiles and their dependences on the external controllable parameters. It provides support and reflection for physical research on discharged capillary plasma and optimizing plasma channels in various applications.
Objectives: Over the past 2 years, many infection prevention and control (IPC) resources have been diverted to manage the COVID-19 pandemic. Its impact on the incidence of antimicrobial-resistant organisms has not been adequately studied. We investigated the impact of the pandemic on the incidence of carbapenem-resistant Enterobacterales (CRE) in Singapore. Methods: We extracted data on unique CRE isolates (clinical and/or surveillance cultures) and patient days for 6 public hospitals in Singapore from the carbapenemase-producing Enterobacteriaceae (CaPES) study group database, and we calculated the monthly incidence of CRE (per 10,000 patient days). Interrupted time-series (ITS) analysis was conducted with the pre–COVID-19 period defined as before February 2020, and the COVID-19 period defined as after February 2020. Statistical analyses were performed using Stata version 15 software. Results: From January 2017 to March 2021, 6,770 CRE isolates and 9,126,704 patient days were documented. The trend in CRE monthly incidence increased significantly during the pre–COVID-19 period (0.060; 95% CI, 0.033–0.094; P < .001) but decreased during the COVID-19 period (−0.183; 95% CI, −0.390 to 0.023; P = .080) without stepwise change in the incidence (−1.496; 95% CI, −3.477 to 0.485; P = .135). The trend in monthly incidence rate of CRE clinical cultures increased significantly during the pre–COVID-19 period (0.046; 95% CI, 0.028–0.064; P < .001) and decreased significantly during COVID-19 period (−0.148; 95% CI, −0.249 to −0.048; P = .048) with no stepwise change in the incidence (−0.063; 95% CI, −0.803 to 0.677; P = .864). The trend in monthly incidence rate of CRE surveillance cultures decreased during the pre–COVID-19 period (−0.020; 95% CI, −0.062 to 0.022; P = .341) and the COVID-19 period (−0.067; 95% CI, −0.291to 0.158; P = .552) without stepwise change in the incidence (−1.327; 95% CI, −3.535 to 0.881; P = .233). Conclusions: The rate of CRE in clinical cultures decreased during COVID-19 but not the rate in surveillance cultures. Further studies are warranted to study the impact of COVID-19 on CREs.
There was no previous meta-analysis investigating the efficacy/tolerability of psychostimulants for symptoms of attention-deficit hyperactivity disorder (ADHD) in preschool children.
Methods
Databases including PubMed, the Cochrane Library, EMBASE, ScienceDirect, and ClinicalTrials.gov were searched from inception to March 2022 for randomized controlled trials (RCTs) on therapeutic efficacy of psychostimulants against ADHD symptoms in preschool children (age ≤6 years) compared with placebos. Primary outcomes were (a) changes in ADHD symptoms evaluated by validated rating scales from parents’/teacher’s observation, or (b) post-intervention improvements in neuropsychological performance. Secondary outcomes were risks of adverse events.
Results
Meta-analysis of nine eligible trials including 544 preschool children (mean age=4.86 years, female=11.98%, median treatment duration=4.33 weeks) supported the efficacy of psychostimulants against global symptoms from observations of parents (Hedges’ g=0.6152, p<0.0001) and teachers (Hedges’ g=0.6563, p=0.0039). Efficacy of psychostimulants was also noted against symptoms of inattention and hyperactivity/impulsivity, especially the latter (i.e., main symptoms in preschool children). Moreover, male gender, older age, and longer treatment duration were associated with better efficacy. Regarding adverse events, only the risk of poor appetite was higher in the psychostimulant group (odds ratio [OR]=2.39). However, the qualities of evidence were low to very low, indicating potential discrepancy between the true and estimated effect.
Conclusions
Our results showed that psychostimulants might be beneficial for preschool children with ADHD, especially hyperactivity/impulsivity from teachers’ observation, with tolerable side effects. Nevertheless, the true magnitude of the effect needs to be confirmed with more research due to low to very low certainty of the evidence.
Everyone faces uncertainty on a daily basis. Two kinds of probability expressions, verbal and numerical, have been used to characterize the uncertainty that we face. Because our cognitive concept of living things differs from that of non-living things, and distinguishing cognitive concepts might have linguistic markers, we designed four studies to test whether people use different probability expressions when faced with animate or inanimate uncertainty. We found that verbal probability is the preferred way to express animate uncertainty, whereas numerical probability is the preferred way to express inanimate uncertainty. The “verbal-animate” and “numerical-inanimate” associations were robust enough to persist when tested with forced-choice response patterns regardless of the information (e.g., equally likely outcomes, frequencies, or personal beliefs) used to construct probabilities of events. When the response pattern was changed to free-responses, the associations were evident unless the subjects were asked to write their own probability predictions for vague uncertainty. Given that the world around us consists of both animate (i.e., living) and inanimate (i.e., non-living) things, “verbal-animate” and “numerical-inanimate” associations may play a major role in risk communication and may otherwise be useful for practitioners and consultants.
To compare the prevalence of overweight or obesity (ow/ob) with WHO BMI cut-off points, International Obesity Task Force (IOTF) cut-off points and Chinese BMI criteria and examine its potential factors among preschool children in Hunan Province.
Design:
A cross-sectional survey including anthropometric measurements and questionnaires about children’s information, caregivers’ socio-demographic characteristics and maternal characteristics. χ2 tests and univariate and multivariate binary logistic regression were performed to evaluate the possible factors of ow/ob.
Setting:
Hunan, China, from September to October 2019.
Participants:
In total, 7664 children 2 to 6 years of age.
Results:
According to Chinese BMI criteria, about 1 in 7–8 children aged 2–6 years had ow/ob in Hunan, China. The overall estimated prevalence of ow/ob among 2- to 6-year-old children was significantly higher when based on the Chinese BMI criteria compared with the WHO BMI cut-off points and IOTF cut-off points. According to Chinese BMI criteria, ow/ob was associated with residing in urban areas, older age, male sex, eating snacking food more frequently, macrosomia delivery, caesarean birth, heavier maternal prepregnancy weight and pre-delivery weight.
Conclusion:
The prevalence of ow/ob in preschool children in Hunan Province remains high. More ow/ob children could be screened out according to Chinese BMI cut-offs compared with WHO and IOTF BMI criteria. In the future, targeted intervention studies with matched controls will be needed to assess the long-term effects of intervention measures to provide more information for childhood obesity prevention and treatment.
Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.
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.
Methods
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.
Results
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.
Conclusions
Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.
The cost of recruitment and training of newcomers can be a burden for enterprises, causing adverse effects on human resources management. Although much research has addressed employee turnover, less attention has been paid to methods of improving the retention of new hires. This study is an empirical examination of the increase in predictive strength of antecedents of affective commitment for comparing newcomers’ workplace spirituality. The results of an employee survey completed by 237 newcomers with under two years of work experience indicate that socialization tactics have a direct impact on job embeddedness, which in turn has a direct effect on affective commitment. Workplace spirituality has a significant moderating effect on the relationship between socialization tactics and job embeddedness. Also, workplace spirituality has a significant moderating effect on the relationship between job embeddedness and affective commitment.
The aim of this study was to assess the current status of disease-related knowledge and to analyze the relationship among the general condition, illness perception, and psychological status of patients with coronavirus disease 2019 (COVID-19).
Methods:
A hospital-based cross-sectional study was conducted on 118 patients using convenience sampling. The general questionnaire, disease-related knowledge questionnaire of COVID-19, Illness Perception Questionnaire (IPQ), and Profile of Mood States (POMS) were used to measure the current status of participants.
Results:
The overall average score of the disease-related knowledge of patients with COVID-19 was (79.19 ± 14.25), the self-care situation was positively correlated with knowledge of prevention and control (r = 0.265; P = 0.004) and total score of disease-related knowledge (r = 0.206; P = 0.025); the degree of anxiety was negatively correlated with the knowledge of diagnosis and treatment (r = −0.182; P = 0.049). The score of disease-related knowledge was negatively correlated with negative cognition (volatility, consequences, emotional statements) and negative emotions (tension, fatigue, depression) (P < 0.05); positively correlated with positive cognition (disease coherence) and positive emotion (self-esteem) (P < 0.05).
Conclusions:
It was recommended that we should pay more attention to the elderly and low-income groups, and increase the knowledge about diagnosis and treatment of COVID-19 and self-care in the future health education for patients.
The East Asian winter monsoon (EAWM) is one of the most dynamic components of the global climate system. Although poorly understood, knowledge of long-term spatial differences in EAWM variability during the glacial–interglacial cycles is important for understanding the dynamic processes of the EAWM. We reconstructed the spatiotemporal characteristics of the EAWM since the last glacial maximum (LGM) using a comparison of proxy records and long-term transient simulations. A loess grain-size record from northern China (a sensitive EAWM proxy) and the sea surface temperature gradient of an EAWM index in sediments of the southern South China Sea were compared. The data–model comparison indicates pronounced spatial differences in EAWM evolution, with a weakened EAWM since the LGM in northern China but a strengthened EAWM from the LGM to the early Holocene, followed by a weakening trend, in southern China. The model results suggest that variations in the EAWM in northern China were driven mainly by changes in atmospheric carbon dioxide (CO2) concentration and Northern Hemisphere ice sheets, whereas orbital insolation and ice sheets were important drivers in southern China. We propose that the relative importance of insolation, ice sheets, and atmospheric CO2 for EAWM evolution varied spatially within East Asia.
Recent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR).
Methods
This study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders.
Results
The conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity.
Conclusions
These findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.
Studies have suggested an association between metabolic and cerebrocardiovascular diseases and major depressive disorder (MDD). However, the risk of metabolic and cerebrocardiovascular diseases in the unaffected siblings of patients with MDD remains uncertain. Using the Taiwan National Health Insurance Research Database, 22,438 unaffected siblings of patients with MDD and 89,752 age-/sex-matched controls were selected and followed up from 1996 to the end of 2011. Individuals who developed metabolic and cerebrocardiovascular diseases during the follow-up period were identified. Compared with the controls, the unaffected siblings of patients with MDD had a higher prevalence of metabolic diseases, such as hypertension (5.0% vs. 4.5%, p = 0.007), dyslipidemia (5.6% vs. 4.8%, p < 0.001), and obesity (1.7% vs. 1.5%, p = 0.028), and cerebrocardiovascular diseases, such as ischemic stroke (0.6% vs. 0.4%, p < 0.005) and ischemic heart disease (2.1% vs. 1.7%, p < 0.001). Logistic regression analyses revealed that the unaffected siblings of patients with MDD were more likely to develop hypertension, dyslipidemia, ischemic stroke, and ischemic heart diseases during the follow-up period than the controls. Our study revealed a familial coaggregation between MDD and metabolic and cerebrocardiovascular diseases. Additional studies are required to investigate the shared pathophysiology of MDD and metabolic and cerebrocardiovascular diseases.
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.
Methods
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).
Results
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.
Conclusions
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.