General Psychiatry最新文献

Background: Kabuki syndrome (KS) is a rare developmental disorder characterised by multiple congenital anomalies and intellectual disability. UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome), which encodes a histone demethylase, is one of the two major pathogenic risk genes for KS. Although intellectual disability is a key phenotype of KS, the role of UTX in cognitive function remains unclear. Currently, no targeted therapies are available for KS.

Aims: This study aimed to investigate how UTX regulates cognition, to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for treatment.

Methods: We generated UTX conditional knockout mice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3 (trimethylated histone H3 at lysine 27) demethylation.

Results: UTX-knockout mice showed decreased phosphorylation of calcium / calmodulin-dependent protein kinase II, impaired long-term potentiation and deficit in remote contextual fear memory. These effects were reversed by an Food and Drug Administration-approved drug desipramine.

Conclusions: Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function, and suggest that desipramine could be a potential treatment for KS.

Background: Depressive symptoms frequently occur in patients with heart failure (HF). However, research on the relationship between these symptoms and N-terminal pro-brain natriuretic peptide (NT-proBNP), a key biomarker for HF severity and treatment, is scarce and yields inconsistent results.

Aims: This study investigates the relationship among depressive symptomatology, NT-proBNP and health status in a cohort of patients with HF. Additionally, it assesses the impact of depressive symptoms on their clinical outcomes.

Methods: A cohort of 151 patients with HF was followed for 1 year. The Hospital Anxiety and Depression Scale-Depression (HADS-D) Score was used to assess anxiety and depressive symptoms, and NT-proBNP levels were measured. Health status was evaluated using the Kansas City Cardiomyopathy Questionnaire (KCCQ).

Results: Patients with HADS-D scores>5 points showed significantly higher NT-proBNP levels and lower KCCQ scores at baseline. Over the year, changes in HADS-D scores correlated positively with changes in NT-proBNP levels and negatively with changes in KCCQ scores. A baseline HADS-D score>5 points was significantly associated with an increased risk of the composite outcome of all-cause mortality and HF hospitalisation, even after adjusting for baseline characteristics (adjusted hazard ratio (HR): 2.17; 95% CI 1.05 to 4.48; p=0.036).

Conclusions: HADS-D scores are significantly correlated with NT-proBNP levels and health status in patients with HF. A baseline HADS-D score>5 points is significantly associated with an elevated risk for the composite outcome of all-cause mortality and hospitalisation due to HF.

Major depressive disorder (MDD) with suicidal ideation or behaviour (MDSI) is associated with an increased risk of future suicide. The timely identification of suicide risk in patients with MDD and the subsequent implementation of interventions are crucially important to reduce their suffering and save lives. However, the early diagnosis of MDSI remains challenging across the world, as no objective diagnostic method is currently available. In China, the challenge is greater due to the social stigma associated with mental health problems, leading many patients to avoid reporting their suicidal ideation. Additionally, the neural mechanisms underlying MDSI are still unclear, which may hamper the development of effective interventions. We thus conducted this narrative review to summarise the existing neuroimaging studies of MDSI in Chinese patients, including those involving structural magnetic resonance imaging (MRI), functional MRI, neuronal electrophysiological source imaging of the brain dynamics with electroencephalography and magnetoencephalography. By synthesising the current research efforts in neuroimaging studies of Chinese patients with MDSI, we identified potential objective neuroimaging biomarkers, which may aid in the early identification of patients with MDSI who are at high suicide-related risk. Our findings also offer insights into the complex neural mechanisms underlying MDSI and suggest promising therapeutic targets. Furthermore, we propose future directions to discover novel imaging signatures, improve patient care, as well as help psychiatrists and clinical investigators plan their future research.

Background: The research findings on the topological properties of functional connectomes (TP-FCs) in patients with schizophrenia (SZPs) exhibit inconsistencies and contradictions, which can be attributed to limitations such as small sample sizes and heterogeneous data processing techniques.

Aims: To address these limitations, we conducted a large-scale study. Uniform data processing flows were employed to investigate the aberrant TP-FCs and the associations between TP-FCs and symptoms or cognitions (A-TP-SCs) in SZPs.

Methods: The large-scale study included six datasets from four sites, involving 497 SZPs and 374 healthy controls (HCs). A uniform process for imaging data preprocessing and functional connectivity matrix configuration was used. ComBat was employed for data harmonisation, and various TPs were calculated. We explored between-group differences in brain functional integration (FI) and functional segregation (FS) measured with TP-FCs, and conducted partial correlation analyses, with adjustments for age, gender and educational level, to identify A-TP-SCs.

Results: Compared with random networks and HCs, SZPs maintained small-worldness and global FI capacity despite their compromised global FS capacity and resilience. A decline in nodal FI and FS capacity was observed in sensory areas, whereas an increase in nodal FI capacity was found in regions associated with cognition and information integration. In addition, associations between TP-FCs and positive symptoms, negative symptoms or cognitive functions including speed of processing, visual learning and the ability to inhibit cognitive interference were identified in SZPs.

Conclusions: The identified A-TP-SCs verified that reductions in FS and resilience indicated pathological impairments in schizophrenia. The A-TP-SCs or TP-FCs, which measured the same attributes of the functional connectomes, exhibited high internal consistency, robustly reinforcing these findings.

Background: The triple digital divide refers to the lack of internet access, use and knowledge among specific populations. In China, middle-aged and older adults and those living in rural areas or various regions of the country are more likely to have limited internet access and skills and, thus, have less accessibility to internet services. Few longitudinal studies have explored the association between the digital divide and the progression of depressive symptoms among middle-aged and older Chinese adults. Significantly, none of the existing studies have estimated this long-term relationship from a disparity perspective.

Aims: This study investigates the association between the triple digital divide and depressive symptom trajectories among middle-aged and older adults in China during a 10-year follow-up period from 2011 to 2020.

Methods: The sample for this secondary analysis comprises 3019 urban and 10 427 rural respondents selected from the China Health and Retirement Longitudinal Study baseline survey in 2011. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Employing longitudinal mixed-effects models, this study explored the association between the triple digital divide and depressive symptom trajectories among middle-aged and older Chinese adults by examining gender, rural-urban and regional disparities in this relationship.

Results: Our findings revealed a significant association between the triple digital divide and increasing trajectories of depressive symptoms, showing significant disparities based on gender, rural-urban dwelling and regional location. Notably, for both male and female participants who resided in urban areas or the central region of the country, their ability to use the internet, coupled with enhanced internet skills and greater access to internet services, was found to have a mitigating effect on the increasing trajectories of depressive symptoms.

Conclusions: To alleviate some of the confounding influences on the trajectory of depression in middle-aged and older adults, policymakers in China should continue to prioritise the development of internet technology, foster easy access to the internet to ensure it is 'elder-friendly', provide internet skill training platforms for this population and broaden access to various internet services appropriate for them. Additionally, the implementation of tailored interventions to address depression, especially targeting the more vulnerable cohorts, such as middle-aged and older women, those residing in rural areas and the western regions, is crucial. Such tailored approaches are essential for addressing the disparities and challenges associated with the triple digital divide.

Background: The associations between sugary beverages and genetic predisposition to depression risk remain unclear.

Aims: This study aimed to investigate the associations of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with depression and to assess whether these associations were modified by genetic predisposition.

Methods: We used data from the UK Biobank of 180 599 individuals aged 39-72 years who were depression-free at baseline. Dietary intake of SSBs, ASBs and NJs was accessed by a 24-hour dietary recall between 2009 and 2012. The Polygenic Risk Score for depression was estimated and categorised as low (lowest tertile), intermediate (tertile 2) and high (highest tertile). Cox proportional hazard and substitution models were conducted to evaluate hazard ratios (HRs) and 95% CIs.

Results: Over the 12-year follow-up, 4915 individuals developed depression. Higher consumption (>2 units/day) of SSBs (HR: 1.26, 95% CI 1.12 to 1.43) and ASBs (HR: 1.40, 95% CI 1.23 to 1.60) were both associated with an increased risk of depression. However, moderate consumption (>0-1 units/day) of NJs was associated with a lower risk of depression (HR: 0.89, 95% CI 0.83 to 0.95). Furthermore, genetic predisposition did not modify these associations (p interaction>0.05). In substitution models, the HRs for depression risk were 0.94 (95% CI 0.89 to 0.99) and 0.89 (95% CI 0.85 to 0.94), respectively, when 1 unit/day of SSBs or ASBs was replaced by an equivalent intake of NJs.

Conclusions: Higher consumption of SSBs and ASBs was associated with an increased risk of depression; in contrast, moderate consumption of NJs was inversely associated with a lower risk of depression. In theory, substituting SSBs and ASBs with NJs would suppose a reduction of depression risk.