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Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential for efficacy and safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, the current paper explored the experiences of 11 TRD patients (8 women, 3 men) participating in a double-blind randomized clinical trial with a single session of oral (1, 10 or 25 mg) psilocybin treatment. After qualitative analysis, three major themes were identified: (1) challenges with trust-building and expectation management; (2) navigating the experience; and (3) the need for a more comprehensive treatment. Subthemes of the first theme include a general distrust in mental healthcare, trust in study therapists, limited time for preparation, and managing expectations. The second theme included the following subthemes: trusting to surrender, profound and overwhelming experiences, and music as a guide. The third theme addressed a desire for multiple psilocybin sessions, and challenges with sensemaking. Patients' perspectives provided important insights into potential optimization of psilocybin treatment of TRD, including individualized preparation, investment in trust-building, offering additional psilocybin sessions, providing access to sustained (psycho)therapy with trusted therapists, and personalizing treatment approaches, which may also enhance real-world adaption of these treatments., (© 2024. The Author(s).)

Use of ED medication can be seen as a marker for ED. ED is associated with increasing age, exposure to traumatic events and physical injuries in military veterans. The objective of this study was to assess the prevalence of use of ED medication in Dutch military personnel in the period 2003-2012 and to assess its association with age and psychotropic medication use. Data on dispensing of ED medication, age and co-medication with psychotropic medication of all Dutch military personnel between 2003 and 2012 were collected. The prevalence of ED medication use in each year was estimated, stratified for age and use of psychotropic medication. The number of ED medication users increased a hundredfold from 0.09 to 9.29 per 1000 per year between 2003 and 2012. ED medication was more often used by men over 40 than under 40 (prevalence in 2012: 2.4% vs 0.2%, OR (2003-2012, adjusted for calendar year) 15.6, 95% CI 13.5-17.9) and by men using psychotropic medication (prevalence in 2012: 3.8% vs 0.9%, OR (2003-2012, adjusted for calendar year) 3.13, 95% CI 2.66-3.67). This study shows a strong increase between 2003 and 2012 in a number of ED medication users in male Dutch military personnel. ED medication use increases with age and with psychotropic medication use.

Genomic variation in the SKA2 gene has recently been identified as a promising suicide biomarker. In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD). Increased SKA2 methylation was significantly associated with lower cortisol stress reactivity in 85 healthy individuals exposed to the Trier Social Stress Test (B=-173.40, t=-2.324, p-value=0.023). Next, we observed that longitudinal decreases in SKA2 methylation after deployment were associated with the emergence of post-deployment PTSD symptoms in a Dutch military cohort (N=93; B=-0.054, t=-3.706, p-value=3.66 × 10(-4)). In contrast, exposure to traumatic stress during deployment by itself resulted in longitudinal increases in SKA2 methylation (B=0.037, t=4.173, p-value=6.98 × 10(-5)). Using pre-deployment SKA2 methylation levels and childhood trauma exposure, we found that the previously published suicide prediction rule significantly predicted post-deployment PTSD symptoms (AUC=0.66, 95% CI: 0.53-0.79) with an optimal sensitivity of 0.81 and specificity of 0.91. Permutation analysis using random methylation loci supported these findings. Together, these data establish the importance of SKA2 for cortisol stress responsivity and the development of PTSD and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD.

Post-traumatic stress disorder (PTSD) occurs in 5-10% of the population and is twice as common in women as in men. Although trauma exposure is the precipitating event for PTSD to develop, biological and psychosocial risk factors are increasingly viewed as predictors of symptom onset, severity and chronicity. PTSD affects multiple biological systems, such as brain circuitry and neurochemistry, and cellular, immune, endocrine and metabolic function. Treatment approaches involve a combination of medications and psychotherapy, with psychotherapy overall showing greatest efficacy. Studies of PTSD pathophysiology initially focused on the psychophysiology and neurobiology of stress responses, and the acquisition and the extinction of fear memories. However, increasing emphasis is being placed on identifying factors that explain individual differences in responses to trauma and promotion of resilience, such as genetic and social factors, brain developmental processes, cumulative biological and psychological effects of early childhood and other stressful lifetime events. The field of PTSD is currently challenged by fluctuations in diagnostic criteria, which have implications for epidemiological, biological, genetic and treatment studies. However, the advent of new biological methodologies offers the possibility of large-scale approaches to heterogeneous and genetically complex brain disorders, and provides optimism that individualized approaches to diagnosis and treatment will be discovered.

Animal studies have found that prior stressful events can result in increased reactivity in the HPA-axis. However, baseline function of the HPA-axis has typically been normal or decreased in post-traumatic stress disorder (PTSD). The first purpose of this study was to assess cortisol responsivity to traumatic reminders in women with PTSD related to childhood abuse. The second aim was to assess the relationship between stress-induced cortisol levels and neutral and emotional memory. Salivary cortisol levels were measured before, during and after exposure to personalized trauma scripts in abused women with (N=12) and without current PTSD (N=12). Memory for neutral and emotional material was assessed immediately after trauma scripts exposure and 3 days later. PTSD patients had 122% higher cortisol levels during script exposure, 69% higher cortisol levels during recovery, and 60% higher levels in the period leading up to the script exposure compared to controls. PTSD symptoms were highly predictive of cortisol levels during trauma script exposure (r=0.70), but not during periods of rest. Both in PTSD patients and controls, memory consolidation after the trauma scripts was impaired relative to baseline (P<0.001), with no differences between the two groups on memory performance. There was no association between memory performance and cortisol levels. These results are consistent with higher cortisol levels following exposure to traumatic stressors in PTSD.