Serotonin 4 receptor brain binding and oxytocin-promoted affective and social cognition in healthy women - A randomized controlled trial.

Background: Oxytocin is a neuropeptide known for its prosocial properties and role in social bonding, and intervention with intranasal oxytocin is posited to modulate affective and social cognition (i.e., hot cognition). Serotonin (5-HT) neurotransmission is also involved in emotional and social behaviors and appear to work in concert with oxytocin. However, this interaction so far remains elusive in humans. Therefore, we here investigate the relation between brain 5-HT 4 receptor (5-HT4R) levels and oxytocin-modulated hot cognition. Methods: Using a double blind, placebo-controlled, randomized crossover design, 35 healthy women received a dose of 24 IU intranasal oxytocin or placebo one month apart. The women were naturally cycling and to control for hormonal fluctuations across the menstrual cycle, intervention days were placed during the early follicular phase. Following intervention cognitive domains including affective memory, affective bias in emotion processing, moral emotions and social information preference were assessed. In a subgroup (n = 25), Positron Emission Tomography (PET) was used to image 5-HT4R brain binding at baseline with the [11C]SB207145 radiotracer. Results: No effect of oxytocin intervention relative to placebo was observed for any of the cognitive outcomes. Likewise, regional brain 5-HT4R binding at baseline was not associated with cognitive responses to oxytocin intervention. Conclusion: Our data suggest that intervention with intranasal oxytocin does not have an overall effect on hot cognition in healthy women and further that 5-HT4R brain architecture does not mediate cognitive effects of oxytocin in the healthy state.

Cognitive impairment and psychopathology in sudden out-of-hospital cardiac arrest survivors: Results from the REVIVAL cohort study.

AIM: To investigate cognitive impairment and psychopathology in out-of-hospital cardiac arrest (OHCA) survivors using a screening procedure during hospitalisation and examine the evolution of these parameters at three-month follow-up. METHODS: This multicentre cohort study screened for cognitive impairment using the Montreal Cognitive Assessment (MoCA), for symptoms of anxiety, depression and traumatic distress using the Hospital Anxiety and Depression Scale (HADS) and the Impact of Event Scale-revised (IES-R) during hospitalisation. At three-month follow-up, we evaluated cognitive impairment with a neuropsychological test battery and symptoms of psychopathology were re-assessed using HADS and IES-R. Logistic regression models were applied to examine associations between screening results and outcomes. RESULTS: This study included 297 OHCA survivors. During hospitalisation, 65% presented with cognitive impairment, 25% reported symptoms of anxiety, 20% symptoms of depression and 21% symptoms of traumatic distress. At follow-up, 53% reported cognitive impairment, 17% symptoms of anxiety, 15% symptoms of depression and 19% symptoms of traumatic distress. Cognitive impairment during hospitalisation was associated with higher odds (OR (95% CI) 2.55 (1.36-4.75), p = .02) of an unfavorable cognitive outcome at follow-up, and symptoms of psychopathology during hospitalisation were associated with higher odds of psychopathology at follow-up across all three symptom groups; anxiety (6.70 (2.40-18.72), p < .001), depression (4.69 (1.69-13.02), p < .001) and traumatic distress (7.07 (2.67-18.73), p < .001). CONCLUSION: OHCA survivors exhibited both cognitive impairment and symptoms of psychopathology during hospitalisation comparable to previous studies, which were associated with unfavorable mental health outcomes at three-month follow-up.

Sexual health and serotonin 4 receptor brain binding in unmedicated patients with depression-a NeuroPharm study.

Sexual dysfunction is prominent in Major Depressive Disorder (MDD) and affects women with depression more than men. Patients with MDD relative to healthy controls have lower brain levels of the serotonin 4 receptor (5-HT4R), which is expressed with high density in the striatum, i.e. a key hub of the reward system. Reduced sexual desire is putatively related to disturbed reward processing and may index anhedonia in MDD. Here, we aim to illuminate plausible underlying neurobiology of sexual dysfunction in unmedicated patients with MDD. We map associations between 5-HT4R binding, as imaged with [11C]SB207145 PET, in the striatum, and self-reported sexual function. We also evaluate if pre-treatment sexual desire score predicts 8-week treatment outcome in women. From the NeuroPharm study, we include 85 untreated MDD patients (71% women) who underwent eight weeks of antidepressant drug treatment. In the mixed sex group, we find no difference in 5-HT4R binding between patients with sexual dysfunction vs normal sexual function. However, in women we find lower 5-HT4R binding in the sexual dysfunctional group compared to women with normal sexual function (ß = -0.36, 95%CI[-0.62:-0.09], p = 0.009) as well as a positive association between sexual desire and 5-HT4R binding (ß = 0.07, 95%CI [0.02:0.13], p = 0.012). Sexual desire at baseline do not predict treatment outcome (ROC curve AUC = 52%[36%:67%]) in women. Taken together, we find evidence for a positive association between sexual desire and striatal 5-HT4R availability in women with depression. Interestingly, this raises the question if direct 5-HT4R agonism can target reduced sexual desire or anhedonia in MDD.

Sex Differences in Patient-Reported Outcomes in the Immediate Recovery Period After Resuscitation: Findings From the Cross-sectional DenHeart Survey.

BACKGROUND: A paucity of resuscitation studies have examined sex differences in patient-reported outcomes upon hospital discharge. It remains unclear whether male and female patients differ in health outcomes in their immediate responses to trauma and treatment after resuscitation. OBJECTIVES: The aim of this study was to examine sex differences in patient-reported outcomes in the immediate recovery period after resuscitation. METHODS: In a national cross-sectional survey, patient-reported outcomes were measured by 5 instruments: symptoms of anxiety and depression (Hospital Anxiety and Depression Scale), illness perception (Brief Illness Perception Questionnaire [B-IPQ]), symptom burden (Edmonton Symptom Assessment Scale [ESAS]), quality of life (Heart Quality of Life Questionnaire), and perceived health status (12-Item Short Form Survey). RESULTS: Of 491 eligible survivors of cardiac arrest, 176 (80% male) participated. Compared with male, resuscitated female reported worse symptoms of anxiety (Hospital Anxiety and Depression Scale-Anxiety score ≥8) (43% vs 23%; P = .04), emotional responses (B-IPQ) (mean [SD], 4.9 [3.12] vs 3.7 [2.99]; P = .05), identity (B-IPQ) (mean [SD], 4.3 [3.10] vs 4.0 [2.85]; P = .04), fatigue (ESAS) (mean [SD], 5.26 [2.48] vs 3.92 [2.93]; P = .01), and depressive symptoms (ESAS) (mean [SD], 2.60 [2.68] vs 1.67 [2.19]; P = .05). CONCLUSIONS: Between sexes, female survivors of cardiac arrest reported worse psychological distress and illness perception and higher symptom burden in the immediate recovery period after resuscitation. Attention should focus on early symptom screening at hospital discharge to identify those in need of targeted psychological support and rehabilitation.

Sexual function improves as depressive symptoms decrease during treatment with escitalopram: results of a naturalistic study of patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is closely associated with sexual dysfunction, which may worsen during treatment with selective serotonin reuptake inhibitors (SSRIs) due to the side effects of pharmacologic treatment. AIM: To examine the association between sexual function and severity of MDD in drug-naïve patients as compared with healthy controls and how treatment with SSRIs affects sexual function over time in individuals with MDD. Interaction with gender and treatment response was examined. METHODS: In 92 patients with MDD, we measured MDD severity with 6- and 17-item versions of the Hamilton Depression Rating Scale (HDRS6 and HDRS17) and the level of sexual function with the Changes in Sexual Functioning Questionnaire at baseline and 4, 8, and 12 weeks after initiating treatment with escitalopram. Baseline sexual function was compared with the sexual function of 73 healthy controls. Linear regression models were used to assess differences in sexual function between healthy controls and patients and change in sexual function from baseline to week 12. Linear mixed models were used to assess differences in change in sexual function between treatment response groups. OUTCOMES: Outcomes included total scores on the HDRS6, HDRS17, and Changes in Sexual Functioning Questionnaire and changes in total scores from baseline to week 12. RESULTS: Unmedicated patients with MDD reported impaired sexual function as compared with healthy controls. Level of sexual function was not associated with severity of MDD at baseline. Patients' sexual function improved significantly during treatment, which was coupled with amelioration of depressive symptoms. Treatment response groups (remitters, intermediate responders, nonresponders) did not predict change in sexual function. Gender had no effect on sexual dysfunction symptoms during treatment. CLINICAL IMPLICATIONS: Major depression is a risk factor for sexual problems, and improvement in sexual function was coupled with amelioration of depressive symptoms. STRENGTHS AND LIMITATIONS: Among its strengths, this was a naturalistic study reflecting real-world settings in clinical practice. It additionally included a baseline measurement of sexual function and MDD severity on drug-naïve patients prior to the initiation of treatment. Finally, the follow-up of 12 weeks extends beyond the acute phase of treatment in which previous research has observed a peak in sexual side effects. In terms of limitations, there was no placebo arm; thus, the study cannot attribute the effects on sexual function to treatment with antidepressants per se. Also, the patients were young, which may have served as a protective factor against sexual side effects. CONCLUSION: Sexual dysfunction was strongly associated with MDD and improved in parallel with overall symptoms of depression across a standard 12-week treatment with SSRI antidepressants. CLINICAL TRIAL REGISTRATION: NCT02869035 (https://clinicaltrials.gov/ct2/show/NCT02869035).

Subacute effects of a single dose of psilocybin on biomarkers of inflammation in healthy humans: An open-label preliminary investigation.

Rationale: Psilocybin is a serotonergic psychedelic that has gained prominent attention recently as a potential therapeutic for neuropsychiatric disorders including Major Depressive Disorder. Pre-clinical and initial studies in humans suggest that serotonin 2A receptor agonists, including serotonergic psychedelics, have anti-inflammatory effects. This may contribute to its therapeutic effects as previous studies indicate a link between neuropsychiatric disorders and inflammatory processes. However, the effect of psilocybin on biomarkers of inflammation has not been evaluated in humans. Objectives: Investigate the effect of a single dose of psilocybin on peripheral biomarkers of inflammation in healthy humans. Methods: Blood samples were collected from 16 healthy participants before and one day after the administration of a single oral dose of psilocybin (mean dose: 0.22 mg/kg) and subsequently analyzed for concentrations of high-sensitivity C-reactive protein (hsCRP), tumor-necrosis-factor (TNF) and soluble urokinase plasminogen activator receptor (suPAR). Change in inflammatory markers was evaluated using a paired t-test where p < 0.05 was considered statistically significant. Results: We did not observe statistically significant changes in any of the above biomarkers of inflammation (all Cohen's d ≤ 0.31; all p ≥ 0.23). Conclusions: Our data do not support that a single dose of psilocybin reduces biomarkers of inflammation in healthy individuals one day after administration. Nevertheless, we suggest that future studies consider additional markers of inflammation, including markers of neuroinflammation, and evaluate potential anti-inflammatory effects of psilocybin therapy in clinical cohorts where more prominent effects may be observable.

Music programming for psilocybin-assisted therapy: Guided Imagery and Music-informed perspectives.

The psychedelic drug psilocybin has been successfully explored as a novel treatment for a range of psychiatric disorders. Administration of psilocybin requires careful attention to psychological support and the setting in which the drug is administered. The use of music to support the acute psychoactive effects of psilocybin is recommended in current guidelines, but descriptions of how to compile music programs for the 4-6 h long sessions are still scarce. This article describes the procedural steps and considerations behind the curation of a new music program, the Copenhagen Music Program, tailored to the intensity profile of a medium/high dose psilocybin. The method of Guided Imagery and Music is presented as a music therapeutic framework for choosing and sequencing music in music programming and the Taxonomi of Therapeutic Music is presented as a rating tool to evaluate the music-psychological intensity of music pieces. Practical examples of how to organize the process of music programming are provided along with a full description of the Copenhagen Music Program and its structure. The aim of the article is to inspire others in their endeavours to create music programs for psychedelic interventions, while proposing that an informed music choice may support the therapeutic dynamics during acute effects of psilocybin.

Evaluating cognitive disturbances as treatment target and predictor of antidepressant action in major depressive disorder: A NeuroPharm study.

Cognitive disturbances in major depressive disorder (MDD) constitute a critical treatment target and hold promise as an early predictor of antidepressant treatment response; yet their clinical relevance is not fully established. Therefore, we here investigate if (1) cognitive performance improves over the course of antidepressant treatment and (2) cognitive performance at baseline is predictive of antidepressant treatment response. In the NeuroPharm study (clinical trial id: NCT02869035), 92 antidepressant-free patients with a moderate to severe depressive episode were assessed with a comprehensive cognitive test battery including both cold (emotion-independent) and hot (emotion-dependent) tasks. Patients were tested before and after 12 weeks of standard antidepressant treatment with escitalopram in flexible doses of 10-20 mg. Performance improved across most cognitive domains over the course of antidepressant treatment. Notably, these improvements were independent of improvement in mood symptoms, emphasizing that cognitive disturbances are a distinct symptom and therefore treatment target in MDD. Results did not suggest that performance on any single cognitive measure at baseline was associated with later clinical response to antidepressant treatment. However, a small cluster of patients (N = 28) with globally disturbed cognition at baseline exhibited poorer clinical response after 8 but not 12 weeks of antidepressant treatment, suggesting that severe cognitive disturbances may delay treatment response. Thus, while pretreatment cognitive performance on individual tests may not be useful as clinical markers of treatment response, profiles capturing performance across different cognitive domains may be useful for stratification of patients with MDD and could be helpful in future intervention trials.

Psilocybin-assisted therapy for reducing alcohol intake in patients with alcohol use disorder: protocol for a randomised, double-blinded, placebo-controlled 12-week clinical trial (The QUANTUM Trip Trial).

INTRODUCTION: Alcohol use disorder is a difficult-to-treat psychiatric disorder and a major burden on public health. Existing treatment efficacy is moderate, and relapse rates are high. Preliminary findings suggest that psilocybin, a psychedelic compound, can safely and reliably occasion highly meaningful experiences that may spur a positive change in drinking behaviour when administered in a therapeutic context. However, the efficacy of a single psilocybin administration and its potential neurobiological underpinnings still remain unknown. METHODS AND ANALYSIS: To establish efficacy, we will investigate the effects of psilocybin-assisted therapy versus placebo in a randomised, double-blinded, placebo-controlled 12-week clinical trial. Ninety treatment-seeking patients, aged 20-70 years, diagnosed with alcohol use disorder will be recruited from the community via advertisement and referrals from general practitioners or specialised treatment units. The psilocybin or placebo will be administered in accordance with a protocol for psychological support before, during and after the dosing. Outcome assessments will be carried out 1, 4, 8 and 12 weeks postdosing. The primary outcome is reduction in the percentage of heavy drinking days from baseline to follow-up at 12 weeks. Key secondary outcomes are as follows: (1) total alcohol consumption, (2) phosphatidyl-ethanol, an objective biomarker for alcohol, (3) plasma psilocin, the active metabolite, to establish a possible therapeutic range, (4) the acute subjective drug experience as a possible predictor of treatment outcome and (5) neuronal response to alcohol cues and cognitive flexibility within corticostriatal pathways by use of functional MR brain imaging 1-week postdosing. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Committee on Health Research Ethics of the Capital Region of Denmark (H-20043832). All patients will be provided oral and written information about the trial before screening. The study results will be disseminated by peer-review publications and conference presentations. TRIAL REGISTRATION NUMBER: EudraCT 2020-000829-55 and NCT05416229.

Lasting increases in trait mindfulness after psilocybin correlate positively with the mystical-type experience in healthy individuals.

Background: Psilocybin-induced mystical-type experiences are associated with lasting positive psychological outcomes. Recent studies indicate that trait mindfulness is increased 3 months after psilocybin intake, preceded by decreases in neocortical serotonin 2A receptor (5-HT2AR) binding. However, the association between psilocybin-induced mystical-type experiences and subsequent changes in trait mindfulness remains unexplored, as does the association between pre-drug trait mindfulness and 5-HT2AR binding in the healthy brain. Aim: We evaluated whether psilocybin induced lasting increases in trait mindfulness in healthy volunteers, and whether the mystical-type experience was associated with this increase. We further examined the association between pre-drug trait mindfulness and 5-HT2AR binding in neocortex and selected frontolimbic regions. Materials and methods: Forty-six medium-high dose psilocybin sessions were conducted in 39 healthy individuals. The mystical-type experience was measured with the Mystical Experience Questionnaire (MEQ) at the end of the session. Trait mindfulness was measured using the Mindful Attention and Awareness Scale (MAAS) at baseline and 3 months after the psilocybin session. Thirty-two of the participants completed pre-drug [11C]-Cimbi-36 positron emission tomography (PET) to assess 5-HT2AR binding in neocortex and, post-hoc, in the frontolimbic regions amygdala, frontal cortex, and anterior cingulate cortex. Results: The MAAS score was significantly increased at 3-month follow-up (p = 3.24 × 10-6), a change positively associated with the MEQ score (p = 0.035). Although the association between pre-drug MAAS score and neocortex 5-HT2AR binding was not significant (p = 0.24), post-hoc analyses revealed a significant negative association between MAAS and right amygdala 5-HT2AR binding (pFWER = 0.008). Conclusion: We here show that lasting changes in trait mindfulness following psilocybin administration are positively associated with intensity of the mystical-type experience, suggesting that the acute phenomenology of psilocybin facilitates a shift in awareness conducive for mindful living. We furthermore show that higher pre-drug trait mindfulness is associated with reduced 5-HT2AR binding in the right amygdala.

Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report.

Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. They also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. In this study (NCT03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). By the end of the dosing day, participants reported the intensity of their acute experience using the 30-item Mystical Experience Questionnaire (MEQ) and an open-form qualitative report from home. Persisting psychological effects attributed to the psilocybin experience were measured using the Persisting Effects Questionnaire (PEQ) 3-months after administration. Using a linear latent-variable model we show that the MEQ total score is positively associated with the later emergence of positive PEQ effects (p = 3 × 10-5). Moreover, the MEQ subscales "Positive Mood" (pcorr = 4.1 × 10-4) and "Mysticality" (pcorr = 2.0 × 10-4) are associated with positive PEQ whereas the subscales "Transcendence of Time and Space" (pcorr = 0.38) and "Ineffability" (pcorr = 0.45) are not. Using natural language pre-processing, we provide the first qualitative descriptions of the "Complete Mystical Experience" induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the Universe, familial love, and the experience of profound beauty. Combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects.

Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals.

BACKGROUND: Psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans. AIM: Evaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after one psilocybin dose in 10 healthy psychedelic-naïve volunteers and explore associations between change in RSFC and related measures. METHODS: Participants received 0.2-0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state functional magnetic resonance imaging (fMRI) scans at baseline, 1-week and 3-month post-administration and [11C]Cimbi-36 PET scans at baseline and 1 week. We examined changes in within-network, between-network and region-to-region RSFC. We explored associations between changes in RSFC and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2A receptor binding. RESULTS: Psilocybin was well tolerated and produced positive changes in well-being. At 1 week only, executive control network (ECN) RSFC was significantly decreased (Cohen's d = -1.73, pFWE = 0.010). We observed no other significant changes in RSFC at 1 week or 3 months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at 1 week predicted increased mindfulness at 3 months (r = -0.65). CONCLUSIONS: These findings in a small cohort indicate that psilocybin affects ECN function within the psychedelic 'afterglow' period. Our findings implicate ECN modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. Although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at 3 months, when personality changes are observed, remain to be identified.

Stress-Hormone Dynamics and Working Memory in Healthy Women Who Use Oral Contraceptives Versus Non-Users.

Background: Women who use oral contraceptives (OCs) may have a higher risk of developing a depression, which is associated with both vulnerability to stress and cognitive dysfunction. OCs disrupt the hypothalamic-pituitary-gonadal (HPG) axis by suppressing endogenous sex steroid production including estradiol. The HPG axis and the hypothalamic-pituitary-adrenal (HPA) axis are known to interact, possibly through modulations driven by estradiol. OCs may affect HPA regulation capacity, i.e., disturb cortisol dynamics such as the cortisol awakening response (CAR), and influence cognition such as working memory (WM). We hypothesize that OC use is associated with blunted cortisol dynamics and impaired WM performance relative to non-users. Methods: Data from 78 healthy women in the reproductive age were available from the CIMBI database. We evaluated if CAR and WM differed between OC users (n=25) and non-users (n=53) and if the level of estradiol modulated the OC use effect on CAR or WM in generalized least square models. Results: We found that OC users had a blunted CAR (p= 0.006) corresponding to a 61% reduction relative to non-users; however, no estradiol-BY-OC use interaction effect was observed on CAR. Also, OC users had higher cortisol levels at awakening compared to non-users (p = 0.03). We observed no effect of OC use or an estradiol-BY-OC use interaction effect on WM. Also, within the OC user group, neither CAR nor WM was associated with suppressed estradiol. CAR was not associated with WM. Conclusion: Healthy women who use OCs have blunted cortisol dynamics relative to non-users. However, we could not detect OC use effects on working memory in our sample size. We speculate that disrupted cortisol dynamics may be important for the emergence of depressive symptoms in OC users.

Trait aggression is associated with five-factor personality traits in males.

BACKGROUND: Although aggression is conceptualized as a dimensional construct with violent behavior representing the extreme end of a spectrum, studies on the involvement of personality traits in human aggression have typically only included data representing a restricted spectrum of aggressive behaviors. METHODS: In the current study, we therefore examine whether trait aggression is associated with five-factor model personality traits in an enriched sample of 259 men with a broad continuum of trait aggression, ranging from very low to very high including 39 incarcerated aggressive violent offenders. All participants completed the NEO Personality Inventory-Revised (NEO PI-R) and the Buss-Perry Aggression Questionnaire (BPAQ). The association between each of the five NEO PI-R personality traits and trait aggression (BPAQ) was investigated using five linear regression models, covarying for group status, age and educational level. RESULTS: Higher BPAQ scores were positively associated with Neuroticism and negatively associated with Agreeableness and Conscientiousness. CONCLUSION: Our results indicate that those high in Neuroticism and low in Agreeableness and Conscientiousness are at higher risk of exhibiting aggressive behavior, underlining the relevance of these higher order personality traits in understanding aggressive behavior. We argue that studying individual personality differences should be offered a greater attention within violent and criminal behaviors.

Feeling understood for the first time: experiences of participation in rehabilitation after out-of-hospital sudden cardiac arrest.

AIMS: Survivors of out-of-hospital sudden cardiac arrest (SCA) may suffer from long-term cognitive, psychological, or physical post-arrest consequences impacting and disrupting daily life. To adjust to and manage daily life is critical, and therefore a tailored rehabiliation programme was introduced to the participants. The study aimed to explore the lived experience among cardiac arrest survivors. METHODS AND RESULTS: Data were gathered through six focus group interviews during a cardiac arrest rehabilitation programme. Thirty-three out-of-hospital SCA survivors (8 women and 25 men) participated. Time since cardiac arrest was on average 12-57 months. An exploratory qualitative design inspired by Ricoeur's phenomenological hermeneutics was applied. Two main themes emerged from the analysis and interpretation: (i) a lack of support from the health system in the transition from hospital to daily life; and (ii) feeling understood for the first time. The findings revealed that out-of-hospital SCA survivors experience a knowledge gap struggling for support. Attending the programme, gaining knowledge and experiencing peer support was described as a revelation for them. CONCLUSION: The findings suggest that out-of-hospital SCA survivors felt understood for the first time when attending a cardiac arrest rehabilitation programme. A post-arrest pathway is needed led by a coordinating cardiac arrest specialist nursing service together with allied healthcare professionals. Focus on hypoxic brain injuries, emotional burdens, and supportive strategies are essential in the transition to daily life. Facilitated peer support is warranted.

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans.

BACKGROUND: Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal consciousness. AIMS: We evaluated whether pre-drug brain 5-HT2AR binding predicted the three phases of psilocybin subjective drug intensity (SDI) and retrospective self-report of mystical type experiences in healthy individuals. METHOD: Sixteen participants completed a pre-drug [11C]Cimbi-36 positron emission tomography scan to assess 5-HT2AR binding. On a separate day, participants completed a single psilocybin session (oral dose range 0.2-0.3 mg/kg), during which SDI was assessed every 20 min. The Mystical Experience Questionnaire (MEQ) was completed at the end of the session. The three SDI phases were modelled using segmented linear regressions. We evaluated the associations between neocortex 5-HT2AR binding and SDI/MEQ outcomes using linear regression models. RESULTS: Neocortex 5-HT2AR was statistically significantly negatively associated with peak plateau duration and positively with time to return to normal waking consciousness. It was also statistically significantly negatively associated with MEQ total score. CONCLUSION: This is the first study to investigate how individual brain 5-HT2AR binding predicts subjective effects of a single dose of psilocybin. Our findings reinforce the role of cerebral 5-HT2AR in shaping the temporal and mystical features of the psychedelic experience. Future studies should examine whether individual brain levels of 5-HT2AR have an impact on therapeutic outcomes in clinical studies.

Short-term oestrogen as a strategy to prevent postpartum depression in high-risk women: protocol for the double-blind, randomised, placebo-controlled MAMA clinical trial.

INTRODUCTION: Postpartum depression affects 10%-15% of women and has a recurrence rate of 40% in subsequent pregnancies. Women who develop postpartum depression are suspected to be more sensitive to the rapid and large fluctuations in sex steroid hormones, particularly estradiol, during pregnancy and postpartum. This trial aims to evaluate the preventive effect of 3 weeks transdermal estradiol treatment immediately postpartum on depressive episodes in women at high risk for developing postpartum depression. METHODS AND ANALYSIS: The Maternal Mental Health Trial is a double-blind, randomised and placebo-controlled clinical trial. The trial involves three departments of obstetrics organised under Copenhagen University Hospital in Denmark. Women who are singleton pregnant with a history of perinatal depression are eligible to participate. Participants will be randomised to receive either transdermal estradiol patches (200 µg/day) or placebo patches for 3 weeks immediately postpartum. The primary outcome is clinical depression, according to the Diagnostic and Statistical Manual of Mental Disorders-V criteria of Major Depressive Disorder with onset at any time between 0 and 6 months postpartum. Secondary outcomes include, but are not limited to, symptoms of depression postpartum, exclusive breastfeeding, cortisol dynamics, maternal distress sensitivity and cognitive function. The primary statistical analysis will be performed based on the intention-to-treat principle. With the inclusion of 220 participants and a 20% expected dropout rate, we anticipate 80% power to detect a 50% reduction in postpartum depressive episodes while controlling the type 1 error at 5%. ETHICS AND DISSEMINATION: The study protocol is approved by the Regional Committees on Health Research Ethics in the Capital Region of Denmark, the Danish Medicines Agency and the Centre for Data Protection Compliance in the Capital Region of Denmark. We will present results at scientific meetings and in peer-reviewed journals and in other formats to engage policymakers and the public. TRIAL REGISTRATION NUMBER: NCT04685148.

Prevalence of cognitive impairment and its relation to mental health in Danish lymphoma survivors.

PURPOSE: This study sought to investigate the prevalence of self-reported cognitive impairment and its relation to illness and treatment characteristics and mental health in Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) survivors as cancer-related cognitive impairment has not been extensively studied in lymphoma survivors. METHODS: One hundred fifteen HL and DLBCL survivors (mean age = 40.3 years, mean months since completed treatment = 29.6) completed questionnaires on executive function and mental health. We examined the prevalence of executive impairment and compared illness and treatment characteristics and mental health across survivors reporting impaired and non-impaired executive functioning using chi-square, Cochran-Armitage, and Mann-Whitney U tests. RESULTS: We found that 39% reported executive impairment. Survivors reporting impaired executive functioning reported worse mental health (ps < .001) than survivors reporting non-impaired executive functioning. A larger proportion of the impaired group had received a high chemo dose compared to the non-impaired group although this result fell short of significance after adjustment for multiple comparisons (p = .017). CONCLUSIONS: Self-reported cognitive impairment is prevalent in HL and DLBCL survivors and is associated with worse mental health and possibly high chemo dose. Future studies should investigate objective impairment and the possible dose-response relationship between chemo dose and cognitive impairment in lymphoma survivors.