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JAMA Sep 2023Psilocybin shows promise as a treatment for major depressive disorder (MDD).
IMPORTANCE
Psilocybin shows promise as a treatment for major depressive disorder (MDD).
OBJECTIVE
To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD.
DESIGN, SETTING, AND PARTICIPANTS
In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing.
INTERVENTIONS
Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support.
MAIN OUTCOMES AND MEASURES
The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment.
RESULTS
A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs.
CONCLUSIONS AND RELEVANCE
Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03866174.
Topics: Adult; Humans; Female; Male; Depressive Disorder, Major; Hallucinogens; Psilocybin; Mental Health; Niacin
PubMed: 37651119
DOI: 10.1001/jama.2023.14530 -
International Journal of Environmental... Jun 2023The double vulnerability of women with disabilities places them at the center of this research paper. Intersectionality is key in research on gender-based violence. This...
The double vulnerability of women with disabilities places them at the center of this research paper. Intersectionality is key in research on gender-based violence. This study analyzes the perspective of the victims and non-victims themselves on this issue, through a comparative analysis between women with and without disabilities, at two levels of analysis: quantitative, through the adaptation of various scales (Assessment Screen-Disability/AAS-D, and the Woman Abuse Screening Tool/WAST), and qualitative, with semi-structured interviews (open scripts and different themes), and focus groups with experts from the associative network. The results obtained indicate that the most frequent type of violence is physical, followed by psychological and sexual, mainly perpetrated by partners. The higher their level of education, the more they defend themselves; receiving public aid can be a risk factor for domestic and sexual violence, and belonging to the associative movement and having paid work outside the home act as preventive measures. In conclusion, it is necessary to establish strategic protection measures and effective detection and intervention systems to make victims visible and care for them.
Topics: Humans; Female; Spouse Abuse; Violence; Socioeconomic Factors; Sex Offenses; Disabled Persons; Domestic Violence
PubMed: 37372777
DOI: 10.3390/ijerph20126191 -
The Lancet. Global Health Apr 2024Neurological conditions are the leading cause of death and disability combined. This public health crisis has become a global priority with the introduction of WHO's... (Review)
Review
Neurological conditions are the leading cause of death and disability combined. This public health crisis has become a global priority with the introduction of WHO's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP). 18 months after this plan was adopted, global neurology stakeholders, including representatives of the OneNeurology Partnership (a consortium uniting global neurology organisations), take stock and advocate for urgent acceleration of IGAP implementation. Drawing on lessons from relevant global health contexts, this Health Policy identifies two priority IGAP targets to expedite national delivery of the entire 10-year plan: namely, to update national policies and plans, and to create awareness campaigns and advocacy programmes for neurological conditions and brain health. To ensure rapid attainment of the identified priority targets, six strategic drivers are proposed: universal community awareness, integrated neurology approaches, intersectoral governance, regionally coordinated IGAP domestication, lived experience-informed policy making, and neurological mainstreaming (advocating to embed brain health into broader policy agendas). Contextualised with globally emerging IGAP-directed efforts and key considerations for intersectoral policy design, this novel framework provides actionable recommendations for policy makers and IGAP implementation partners. Timely, synergistic pursuit of the six drivers might aid WHO member states in cultivating public awareness and policy structures required for successful intersectoral roll-out of IGAP by 2031, paving the way towards brain health for all.
Topics: Humans; Global Health; Health Policy; Policy Making; Public Health; Brain
PubMed: 38485433
DOI: 10.1016/S2214-109X(23)00598-3 -
European Journal of Obstetrics &... Mar 2024The quality of marital relationships is positively impacted by women's sexual self-esteem. This study aims to determine the factors that affect sexual self-esteem among...
INTRODUCTION
The quality of marital relationships is positively impacted by women's sexual self-esteem. This study aims to determine the factors that affect sexual self-esteem among Iranian women.
METHODS
A total of 1176 eligible women who have been referred to comprehensive healthcare centers of Rasht, participated in this analytical cross-sectional study. A stratified two-stage cluster sampling methodology was applied to achieve samples. Data were collected using a validated Persian version of the Sexual Self-Esteem Inventory in Women-Short Form and related factors checklist.
RESULTS
The mean sexual self-esteem score of the respondents was 103.97(SD =5.29) in this study. Education level of the woman (B = 2.622, P < 0.032), employment status of the woman (B= 9.24, P < 0.01), duration of the marriage (B = 11.47, P < 0.01), body image (B = 3.446, P < 0.01), childhood sexual abuse experiences (B = -0.363, P < 0.01), was related with sexual self-esteem. The sexual self-esteem score increased with an increase in higher levels of education, employment of women, an increase in the duration of the marriage, and a positive body image. However, there was an inverse relationship between the experience of childhood sexual abuse and sexual self-esteem.
CONCLUSIONS
The findings revealed that sexual self-esteem in women is influenced by background, intrapersonal, and interpersonal factors that should be approached in education, counseling, and therapy.
PubMed: 38323102
DOI: 10.1016/j.eurox.2024.100284 -
Substance Abuse : Research and Treatment 2023The parent-infant relationship is critical for socioemotional development and is adversely impacted by perinatal substance use. This systematic review posits that the... (Review)
Review
The parent-infant relationship is critical for socioemotional development and is adversely impacted by perinatal substance use. This systematic review posits that the mechanisms underlying these risks to mother-infant relationships center on 3 primary processes: (1) mothers' childhood maltreatment experiences; (2) attachment styles and consequent internal working models of interpersonal relationships; and (3) perinatal substance use. Further, the review considers the role of hyperkatifeia, or hypersensitivity to negative affect which occurs when people with substance use disorders are not using substances, and which drives the negative reinforcement in addiction. The authors performed a systematic review of articles (published 2000-2022) related to these constructs and their impact on mother-infant relationships and offspring outcomes, including original clinical research articles addressing relationships between these constructs, and excluding case studies, reviews, non-human animal studies, intervention studies, studies with fewer than 30% female-sex participants, clinical guidelines, studies limited to obstetric outcomes, mechanistic/biological studies, and studies with methodological issues precluding interpretation. Overall 1844 articles were screened, 377 were selected for full text review, and data were extracted from 157 articles. Results revealed strong relationships between mothers' childhood maltreatment experiences, less optimal internal working models, and increased risk for perinatal substance use, and importantly, all of these predictors interacted with hyperkatifeia and exerted a marked impact on mother-infant relationships with less data available on offspring outcomes. These data strongly support the need for future studies addressing the additive impact of maternal childhood maltreatment experiences, suboptimal internal working models, and perinatal substance use, with hyperkatifeia as a potential moderator, and their interacting effects on mother-infant socioemotional outcomes.
PubMed: 37476500
DOI: 10.1177/11782218231186371 -
Child Abuse & Neglect Oct 2023Marital status is a well-known social determinant of health. Adverse childhood experiences (ACEs) affect attachment, critical to establishing and maintaining intimate...
BACKGROUND
Marital status is a well-known social determinant of health. Adverse childhood experiences (ACEs) affect attachment, critical to establishing and maintaining intimate relationships, such as marital status.
OBJECTIVE
This study examined the association between ACEs and marital status among older Japanese adults.
PARTICIPANTS AND SETTING
This research used data from a nationwide population-based study among functionally independent people aged 65 and above in Japan.
METHODS
ACEs were assessed by self-reported questionnaires on the following experiences before 18 years old: parental death, parental divorce, parental mental disease, exposure to intimate partner violence, physical abuse, psychological neglect, psychological abuse, and poverty. Marital status was asked as currently having a spouse (including common-law marriage), widowed, divorced, or unmarried. Associations between the total number of ACEs and marital status were analyzed by multinomial logistic regression.
RESULTS
Three or more ACEs showed higher risks of being widowed, divorced, or unmarried. Psychological neglect led to higher divorce risks among males (RRR, 95%CI = 1.41, 1.13-1.76) and females (RRR, 95%CI = 1.56, 1.28-1.89). Childhood poverty showed higher risks of unmarried among males (RRR, 95%CI = 1.25, 1.02-1.53) and females (RRR, 95%CI = 1.41, 1.18-1.69). Association between ACEs and divorce risks showed gender differences (RRR, 95%CI of having three or more ACEs in males: 2.19, 1.66-2.90; in females: 3.45, 2.71-4.38; p for interaction = 0.034).
CONCLUSIONS
ACEs showed higher risks of being widowed, divorced, and unmarried among older Japanese people. Policy to tackle ACEs and research investigating how ACEs, attachment, and relationship quality influence marital status are required to promote well-being in later life.
Topics: Male; Female; Humans; Aged; Adolescent; Adverse Childhood Experiences; East Asian People; Marital Status; Divorce; Mental Disorders
PubMed: 37467673
DOI: 10.1016/j.chiabu.2023.106340 -
Molecular Psychiatry Dec 2023Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma...
Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.
Topics: Humans; Stress Disorders, Post-Traumatic; Male; Female; Adult; Diffusion Tensor Imaging; White Matter; Internal Capsule; Child Abuse; Adult Survivors of Child Abuse; Middle Aged; Anisotropy; Brain; Depression; Anxiety; Self Report; Young Adult
PubMed: 36932158
DOI: 10.1038/s41380-023-02012-3