Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Physical health checks in primary care for people with severe mental illness ((SMI) defined as schizophrenia, bipolar disorders and non-organic psychosis) aim to reduce health inequalities. Patients who decline or are deemed unsuitable for screening are removed from the denominator used to calculate incentivisation, termed exception reporting.

To describe the prevalence of, and patient characteristics associated with, exception reporting in patients with SMI.

We identified adult patients with SMI from the UK Clinical Practice Research Datalink (CPRD), registered with a general practice between 2004 and 2018. We calculated the annual prevalence of exception reporting and investigated patient characteristics associated with exception reporting, using logistic regression.

Of 193 850 patients with SMI, 27.7% were exception reported from physical health checks at least once. Exception reporting owing to non-response or declining screening increased over the study period. Patients of Asian or Black ethnicity (Asian: odds ratio 0.72, 95% CI 0.65–0.80; Black: odds ratio 0.86, 95% CI 0.76–0.97; compared with White) and women (odds ratio 0.90, 95% CI 0.88–0.92) had a reduced odds of being exception reported, whereas patients diagnosed with ‘other psychoses’ (odds ratio 1.19, 95% CI 1.15–1.23; compared with bipolar disorder) had increased odds. Younger patients and those diagnosed with schizophrenia were more likely to be exception reported owing to informed dissent.

Exception reporting was common in people with SMI. Interventions are required to improve accessibility and uptake of physical health checks to improve physical health in people with SMI.

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.

Understanding the effects of ketamine on depressive symptoms could help identify which patients might benefit and clarify its mechanism of action in both the early (≤1 day post-infusion) and late (e.g. 2–30 days post-infusion) post-infusion periods. Symptom network analyses could provide complementary information regarding relationships between symptoms.

To identify the effects of ketamine on symptom-level changes in depression across both the early and late post-infusion periods and on depressive symptom network changes.

In this secondary analysis of 152 adults with treatment-resistant depression (with 38.8% reporting suicidal ideation at baseline), we compared symptom changes in the early and late post-infusion periods between individuals randomised to a single 40 min infusion of intravenous ketamine 0.5 mg/kg (n = 103) or saline (n = 49) and identified changes in symptom networks between pre- and post-ketamine treatment using network analyses.

In the early post-infusion period, the greatest improvement (comparing ketamine with saline) was in depressive symptoms related to sadness. In network analyses, symptom network connectivity increased following ketamine infusion. Symptoms of sadness and lassitude showed persistent improvement in the first week post-infusion, whereas improvements in suicidal thoughts first emerged 3–4 weeks post-infusion.

Ketamine improved all symptoms but showed the greatest effect on symptoms of sadness, both immediately and in the initial week after treatment. Ketamine also rapidly altered the topology of symptom networks, strengthening interrelationships between residual symptoms. The efficacy of ketamine (compared with saline) regarding suicidal symptoms emerged later. Our findings suggest potentially divergent efficacy, time courses and mechanisms for different symptoms of depression.

Late-life affective disorders (LLADs) are common and are projected to increase by 2050. There have been several studies linking late-life depression to an increased risk of dementia, but it is unclear if bipolar affective disorder or anxiety disorders pose a similar risk.

We aimed to compare the risk of LLADs progressing to all-cause dementia, and the demographic and clinical variables mediating the risk.

We used the South London and Maudsley National Health Service Foundation Trust Clinical Records Interactive Search system to identify patients aged 60 years or older with a diagnosis of any affective disorder. Cox proportional hazard models were used to determine differences in dementia risk between late-life anxiety disorders versus late-life depression, and late-life bipolar disorder versus late-life depression. Demographic and clinical characteristics associated with the risk of dementia were investigated.

Some 5695 patients were identified and included in the final analysis. Of these, 388 had a diagnosis of bipolar affective disorder, 1365 had a diagnosis of an anxiety disorder and 3942 had a diagnosis of a depressive disorder. Bipolar affective disorder was associated with a lower hazard of developing dementia compared to depression (adjusted model including demographics and baseline cognition, hazard ratio: 0.60; 95% CI: 0.41–0.87). Anxiety disorders had a similar hazard of developing dementia (adjusted hazard ratio: 1.05; 95% CI: 0.90–1.22). A prior history of a depressive disorder reduced the risk of late-life depression progressing to dementia – suggesting the new onset of a depressive disorder in later life is associated with higher risk – but a prior history of anxiety disorders or bipolar affective disorder did not alter risk.

LLADs have a differential risk of developing all-cause dementia, with demographic- and illness-related factors influencing the risk. Further prospective cohort studies are needed to explore the link between LLADs and dementia development, and mediators of the lower risk of dementia associated with late-life bipolar disorder compared to late-life depression.

Health technology assessment (HTA) is a form of policy analysis that informs decisions about funding and scaling up health technologies to improve health outcomes. An equity-focused HTA recommendation explicitly addresses the impact of health technologies on individuals disadvantaged in society because of specific health needs or social conditions. However, more evidence is needed on the relationships between patient engagement processes and the development of equity-focused HTA recommendations.

The objective of this study is to assess relationships between patient engagement processes and the development of equity-focused HTA recommendations.

We analyzed sixty HTA reports published between 2013 and 2021 from two Canadian organizations: Canada’s Drug Agency and Ontario Health.

Quantitative analysis of the HTA reports showed that direct patient engagement (odds ratio (OR): 3.85; 95 percent confidence interval (CI): 2.40–6.20) and consensus in decision-making (OR: 2.27; 95 percent CI: 1.35–3.84) were more likely to be associated with the development of equity-focused HTA recommendations than indirect patient engagement (OR: .26; 95 percent CI: .16–.41) and voting (OR: .44; 95 percent CI: .26–.73).

The results can inform the development of patient engagement strategies in HTA. These findings have implications for practice, research, and policy. They provide valuable insights into HTA.