Schizophrenia progresses through high-risk, first-episode, and chronic stages, each associated with altered spontaneous brain activity. Resting state functional MRI studies highlight these changes, but inconsistencies persist, and the genetic basis remains unclear.

A neuroimaging meta-analysis was conducted to assess spontaneous brain activity alterations in each schizophrenia stage. The largest available genome-wide association study (GWAS) summary statistics for schizophrenia (N = 53,386 cases, 77,258 controls) were used, followed by Hi-C-coupled multimarker analysis of genomic annotation (H-MAGMA) to identify schizophrenia-associated genes. Transcriptome-neuroimaging association and gene prioritization analyses were performed to identify genes consistently linked to brain activity alterations. Biological relevance was explored by functional enrichment.

Fifty-two studies met the inclusion criteria, covering the high-risk (Nhigh-risk = 409, Ncontrol = 475), first-episode (Ncase = 1842, Ncontrol = 1735), and chronic (Ncase = 1242, Ncontrol = 1300) stages. High-risk stage showed reduced brain activity in the right median cingulate and paracingulate gyri. First-episode stage revealed increased activity in the right putamen and decreased activity in the left gyrus rectus and right postcentral gyrus. Chronic stage showed heightened activity in the right inferior frontal gyrus and reduced activity in the superior occipital gyrus and right postcentral gyrus. Across all stages, 199 genes were consistently linked to brain activity changes, involved in biological processes such as nervous system development, synaptic transmission, and synaptic plasticity.

Brain activity alterations across schizophrenia stages and genes consistently associated with these changes highlight their potential as universal biomarkers and therapeutic targets for schizophrenia.

Little is known regarding the shared genetic architecture underlying the phenotypic associations between depression and preterm birth (PTB). We aim to investigate the genetic overlap and causality of depression with PTB.

Leveraging summary statistics from the largest genome-wide association studies for broad depression (Ntotal = 807,533), major depression (Ntotal = 173,005), bipolar disorder (Ntotal = 414,466), and PTB (Ntotal = 226,330), we conducted a large-scale genome-wide cross-trait analysis to assess global and local genetic correlations, identify pleiotropic loci, and infer potential causal relationships

Positive genetic correlations were observed between PTB and broad depression (rg = 0.242), major depression (rg = 0.236), and bipolar disorder (rg = 0.133) using the linkage disequilibrium score regression, which were further verified by the genetic covariance analyzer. Local genetic correlation was identified at chromosome 11q22.3 (harbors NCAM1-TTC12-ANKK1-DRD2) for PTB with depression. Cross-trait meta-analysis identified two loci shared between PTB and broad depression, two loci shared with major depression, and five loci shared with bipolar disorder, among which three were novel (rs7813444, rs3132948 and rs9273363). Mendelian randomization demonstrated a significantly increased risk of PTB for genetic liability to broad depression (odds ratio [OR]=1.30; 95% confidence interval [CI]: 1.11-1.52) and major depression (OR=1.27; 95%CI: 1.08-1.49), and the estimates remained significant across the sensitivity analyses.

Our findings demonstrate an intrinsic link underlying depression and PTB and shed novel light on the biological mechanisms, highlighting an important role of early screening and effective intervention of depression in PTB prevention, and may provide novel treatment strategies for both diseases.

MicroRNAs (miRNAs) alterations in patients with bipolar disorder (BD) are pivotal to the disease’s pathogenesis. Since obtaining brain tissue is challenging, most research has shifted to analyzing miRNAs in peripheral blood. One innovative solution is sequencing miRNAs in plasma extracellular vesicles (EVs), particularly those neural-derived EVs emanating from the brain.

We isolated plasma neural-derived EVs from 85 patients with BD and 39 healthy controls (HC) using biotinylated antibodies targeting a neural tissue marker, followed by miRNA sequencing and expression analysis. Furthermore, we conducted bioinformatic analyses and functional experiments to delve deeper into the underlying pathological mechanisms of BD.

Out of the 2,656 neural-derived miRNAs in EVs identified, 14 were differentially expressed between BD patients and HC. Moreover, the target genes of miR-143-3p displayed distinct expression patterns in the prefrontal cortex of BD patients versus HC, as sourced from the PsychENCODE database. The functional experiments demonstrated that the abnormal expression of miR-143-3p promoted the proliferation and activation of microglia and upregulated the expression of proinflammatory factors, including IL-1β, IL-6, and NLRP3. Through weighted gene co-expression network analysis, a module linking to the clinical symptoms of BD patients was discerned. Enrichment analyses unveiled these miRNAs’ role in modulating the axon guidance, the Ras signaling pathway, and ErbB signaling pathway.

Our findings provide the first evidence of dysregulated plasma miRNAs within neural-derived EVs in BD patients and suggest that neural-derived EVs might be involved in the pathophysiology of BD through related biological pathways, such as neurogenesis and neuroinflammation.

To examine how the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) online food benefit ordering could influence WIC benefit redemptions.

A cross-sectional study. We compare the average redemption rates between online ordering early adopters and non-adopters among WIC customers before and after implementing WIC online ordering. A propensity score-weighted difference-in-difference model was used to estimate the coefficients.

The Oklahoma WIC programme and a grocery store chain in Oklahoma.

12743 Oklahoma WIC households that had redeemed their food benefits at the grocery store chain in 2020.

WIC online ordering significantly positively affected redemption rates for eight of the fifteen food categories. For example, the difference-in-difference coefficients (P–values) of these food categories were cheese or tofu (0·077, <0·01), yogurt (0·092, <0·01), whole milk (0·082, 0·022), low-fat milk (0·060, <0·01), eggs (0·049, 0·033), breakfast cereal (0·085, <0·01) and infant formula (0·073, 0·039). Two food categories with significantly negative difference-in-difference coefficients had relatively lower redemption rates overall: canned fish (Coefficient = –0·209, P < 0·01) and infant cereal (Coefficient = –0·138, P = 0·015). There were no significant changes in the redemption of fruits and vegetables (Coefficient = 0·031, P = 0·121).

Adopting WIC online ordering was positively associated with benefit redemption rates among most food benefit categories. Our findings provide preliminary but important evidence regarding online food benefit redemption among low-income consumers.

Social determinants of health (SDHs) exert a significant influence on various health outcomes and disparities. This study aimed to explore the associations between combined SDHs and mortality, as well as adverse health outcomes among adults with depression.

The research included 48,897 participants with depression from the UK Biobank and 7,771 from the US National Health and Nutrition Examination Survey (NHANES). By calculating combined SDH scores based on 14 SDHs in the UK Biobank and 9 in the US NHANES, participants were categorized into favourable, medium and unfavourable SDH groups through tertiles. Cox regression models were used to evaluate the impact of combined SDHs on mortality (all-cause, cardiovascular disease [CVD] and cancer) in both cohorts, as well as incidences of CVD, cancer and dementia in the UK Biobank.

In the fully adjusted models, compared to the favourable SDH group, the hazard ratios for all-cause mortality were 1.81 (95% CI: 1.60–2.04) in the unfavourable SDH group in the UK Biobank cohort; 1.61 (95% CI: 1.31–1.98) in the medium SDH group and 2.19 (95% CI: 1.78–2.68) in the unfavourable SDH group in the US NHANES cohort. Moreover, higher levels of unfavourable SDHs were associated with increased mortality risk from CVD and cancer. Regarding disease incidence, they were significantly linked to higher incidences of CVD and dementia but not cancer in the UK Biobank.

Combined unfavourable SDHs were associated with elevated risks of mortality and adverse health outcomes among adults with depression, which suggested that assessing the combined impact of SDHs could serve as a key strategy in preventing and managing depression, ultimately helping to reduce the burden of disease.

Fall from height is common in all age groups. In 2020 alone, over 6000 people in Canada died from fall-related injuries. Most of the published literature investigating fall-related injuries are often focused on fracture patterns, survival and recovery. Fatal falls are not well studied. The objective of this study is to characterize the demographics and craniocerebral and vertebrospinal injury patterns related to fatal falls within Southwestern Ontario.

A retrospective case review was conducted at the Department of Pathology, London Health Sciences Centre, for deaths attributed to falls from 2000 to 2020. Only cases with complete autopsy and detailed neuropathology reports were included. Demographic data, comorbidity profiles and craniocerebral and vertebrospinal injuries, along with scene details, were collected and analyzed.

45 cases were included, with a male sex predominance and a mean age of 60.3 ± 18.1 years. The most common head injuries were hematoma, cerebral contusions and skull base fractures. Falls from stairs were the most common. Low fall (<3 m) was associated with subfalcine herniation and was more commonly seen in older individuals (>65 years). Younger individuals were more prone to falls from a high height (>3 m), with frontotemporal lobe contusions as the most common finding.

This study provides a detailed depiction of craniocerebral and vertebrospinal injury patterns of the fatal falls in Southwestern Ontario. Our findings show low falls are a more common cause of fatalities in individuals 65 years and older, and age is a significant predictor of frontal contusions and subdural hematomas.