Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.

We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).

Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.

Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) trial demonstrated that minimally invasive surgery to treat spontaneous lobar intracerebral hemorrhage (ICH) improved functional outcomes. We aimed to explore current management trends for spontaneous lobar ICH in Canada to assess practice patterns and determine whether further randomized controlled trials are needed to clarify the role of surgical intervention.

Neurologists, neurosurgeons, physiatrists and trainees in these specialties were invited to complete a 16-question survey exploring three areas: (1) current management for spontaneous lobar ICH at their institution, (2) perceived influence of ENRICH on their practice and (3) perceived need for additional clinical trial data. Standard descriptive statistics were used to report categorical variables. The χ2 test was used to compare responses across specialties and career stages.

The survey was sent to 433 physicians, and 101 (23.3%) responded. Sixty-eight percent of participants reported that prior to publication of the ENRICH trial, spontaneous lobar ICH was primarily managed conservatively, with surgery reserved for life-threatening situations. Forty-three percent of participants did not foresee a significant increase in surgical intervention at their institution. Of neurosurgical respondents, 33% remained hesitant to offer surgical intervention beyond lifesaving operations. Only 5% reported routinely using specifically designed technologies to evacuate ICH. Seventy percent reported that another randomized controlled trial comparing nonsurgical to surgical management for spontaneous lobar ICH is needed.

There is significant practice variability in the management of spontaneous lobar ICH across Canadian institutions, stressing the need for additional clinical trial data to determine the role of surgical intervention.

The prevalence of youth anxiety and depression has increased globally, with limited causal explanations. Long-term physical health conditions (LTCs) affect 20–40% of youth, with rates also rising. LTCs are associated with higher rates of youth depression and anxiety; however, it is uncertain whether observed associations are causal or explained by unmeasured confounding or reverse causation.

Using data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and Norwegian National Patient Registry, we investigated phenotypic associations between childhood LTCs, and depression and anxiety diagnoses in youth (<19 years), defined using ICD-10 diagnoses and self-rated measures. We then conducted two-sample Mendelian Randomization (MR) analyses using SNPs associated with childhood LTCs from existing genome-wide association studies (GWAS) as instrumental variables. Outcomes were: (i) diagnoses of major depressive disorder (MDD) and anxiety disorders or elevated symptoms in MoBa, and (ii) youth-onset MDD using summary statistics from a GWAS in iPSYCH2015 cohort.

Having any childhood LTC phenotype was associated with elevated youth MDD (OR = 1.48 [95% CIs 1.19, 1.85], p = 4.2×10−4) and anxiety disorder risk (OR = 1.44 [1.20, 1.73], p = 7.9×10−5). Observational and MR analyses in MoBa were consistent with a causal relationship between migraine and depression (IVW OR = 1.38 [1.19, 1.60], pFDR = 1.8x10−4). MR analyses using iPSYCH2015 did not support a causal link between LTC genetic liabilities and youth-onset depression or in the reverse direction.

Childhood LTCs are associated with depression and anxiety in youth, however, little evidence of causation between LTCs genetic liability and youth depression/anxiety was identified from MR analyses, except for migraine.

Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Operative cancellations adversely affect patient health and impose resource strain on the healthcare system. Here, our objective was to describe neurosurgical cancellations at five Canadian academic institutions.

The Canadian Neurosurgery Research Collaborative performed a retrospective cohort study capturing neurosurgical procedure cancellation data at five Canadian academic centres, during the period between January 1, 2014 and December 31, 2018. Demographics, procedure type, reason for cancellation, admission status and case acuity were collected. Cancellation rates were compared on the basis of demographic data, procedural data and between centres.

Overall, 7,734 cancellations were captured across five sites. Mean age of the aggregate cohort was 57.1 ± 17.2 years. The overall procedure cancellation rate was 18.2%. The five-year neurosurgical operative cancellation rate differed between Centre 1 and 2 (Centre 1: 25.9%; Centre 2: 13.0%, p = 0.008). Female patients less frequently experienced procedural cancellation. Elective, outpatient and spine procedures were more often cancelled. Reasons for cancellation included surgeon-related factors (28.2%), cancellation for a higher acuity case (23.9%), patient condition (17.2%), other factors (17.0%), resource availability (7.0%), operating room running late (6.4%) and anaesthesia-related (0.3%). When clustered, the reason for cancellation was patient-related in 17.2%, staffing-related in 28.5% and operational or resource-related in 54.3% of cases.

Neurosurgical operative cancellations were common and most often related to operational or resource-related factors. Elective, outpatient and spine procedures were more often cancelled. These findings highlight areas for optimizing efficiency and targeted quality improvement initiatives.

The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.

We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case–control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.

In UKB, reductions in network efficiency were observed in MDD cases globally (d = −0.076, pFDR = 0.033), across all tiers (d = −0.069 to −0.079, pFDR = 0.020), and in hubs (d = −0.080 to −0.113, pFDR = 0.013–0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.

Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.