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RATIONALE: Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been surprisingly little empirical investigation of the "psychotherapy" in PAP, leaving critical questions about the necessary and sufficient components of PAP unanswered. OBJECTIVES: As clinical trials for psychedelic compounds continue the transition from safety- and feasibility-testing to evaluating efficacy, the role of the accompanying psychotherapy must be better understood to enhance scientific understanding of the mechanisms underlying therapeutic change, optimize clinical outcomes, and inform cost-effectiveness. RESULTS: The present paper first reviews the current status of psychotherapy in the PAP literature, starting with recent debates regarding "psychotherapy" versus "psychological support" and then overviewing published clinical trial psychotherapy models and putative models informed by theory. We then delineate lessons that PAP researchers can leverage from traditional psychotherapy research regarding standardizing treatments (e.g., publish treatment manuals, establish eligibility criteria for providers), identifying mechanisms of change (e.g., measure established mechanisms in psychotherapy), and optimizing clinical trial designs (e.g., consider dismantling studies, comparative efficacy trials, and cross-lagged panel designs). Throughout this review, the need for increased research into the psychotherapeutic components of treatment in PAP is underscored. CONCLUSIONS: PAP is a distinct, integrative, and transdisciplinary intervention. Future research designs should consider transdisciplinary research methodologies to identify best practices and inform federal guidelines for PAP administration.
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Hallucinogènes , Troubles mentaux , Psychothérapie , Humains , Hallucinogènes/administration et posologie , Hallucinogènes/pharmacologie , Hallucinogènes/usage thérapeutique , Psychothérapie/méthodes , Troubles mentaux/traitement médicamenteux , Troubles mentaux/thérapie , Troubles liés à une substance/thérapieRÉSUMÉ
RATIONALE: Treatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about these interactions is limited, as most clinical psilocybin research has prohibited concomittant SSRI use. OBJECTIVES: We aimed to explore potential interactions between psilocybin and SSRIs by characterizing peoples' real-world experiences using psilocybin mushrooms and SSRIs together. METHODS: We conducted a systematic search of Reddit for posts describing psilocybin mushroom and SSRI coadministration. We identified 443 eligible posts and applied qualitative content analysis to each. RESULTS: 8% of posts reported negative physical or psychological effects resulting from coadministration. These included 13 reports that may reflect serotonin toxicity, and 1 concerning for a psychotic/manic episode. 54% of posts described reduced intensity of the acute psilocybin experience, but 39% reported unchanged intensity with SSRI coadministration. CONCLUSIONS: Psilocybin's interactions with SSRIs are likely complex and may depend on multiple factors. Prospective studies are needed to evaluate whether psilocybin treatments are reliably safe and effective in the setting of SSRI use.
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Agaricales , Interactions médicamenteuses , Hallucinogènes , Psilocybine , Inbiteurs sélectifs de la recapture de la sérotonine , Psilocybine/administration et posologie , Psilocybine/pharmacologie , Humains , Inbiteurs sélectifs de la recapture de la sérotonine/administration et posologie , Inbiteurs sélectifs de la recapture de la sérotonine/pharmacologie , Hallucinogènes/administration et posologie , Hallucinogènes/pharmacologieRÉSUMÉ
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.
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This Viewpoint examines the benefits and challenges of psychedelic therapy using 4 fundamental questions.
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Hallucinogènes , Humains , Hallucinogènes/usage thérapeutiqueRÉSUMÉ
Understanding correlates of COVID-19 vaccine intentions is critical for increasing vaccine uptake. Given associations of trauma exposure and posttraumatic stress disorder (PTSD) with alterations in threat sensitivity and health behaviors, we hypothesized they could influence COVID-19 vaccine acceptance and hesitancy and be important variables to consider in the design of vaccination campaigns. Data came from a longitudinal online study of 544 US adults with high levels of pre-pandemic trauma and PTSD, assessed in August/September 2020 and March/April 2021. Individuals reported socio-demographic factors, pandemic factors, lifetime trauma history and PTSD symptoms, and COVID-19 vaccinations or intentions. We estimated bivariate associations between socio-demographics, pandemic factors, and trauma and PTSD symptoms at baseline and follow-up with COVID-19 vaccine acceptance versus hesitancy (i.e., vaccinated against COVID-19 or willing to get vaccinated versus unsure or unwilling to get vaccinated) six months later. Multiple socio-demographics (e.g., race/ethnicity, income, education, political preference) and pandemic factors (e.g., perceived likelihood of infection, household COVID-19 infection) were associated with COVID-19 vaccine hesitancy (27.2% were hesitant). However, trauma history, PTSD symptoms, and other mental health factors were not associated with COVID-19 vaccine acceptance versus hesitancy. Socio-demographic and pandemic-related factors appear more important than trauma or mental health for understanding COVID-19 vaccine intentions.
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COVID-19 , Troubles de stress post-traumatique , Adulte , COVID-19/épidémiologie , COVID-19/prévention et contrôle , Vaccins contre la COVID-19 , Humains , Pandémies , Troubles de stress post-traumatique/psychologie , Réticence à l'égard de la vaccinationRÉSUMÉ
RATIONALE: Psychedelic research continues to garner significant public and scientific interest with a growing number of clinical studies examining a wide range of conditions and disorders. However, expectancy effects and effective condition masking have been raised as critical limitations to the interpretability of the research. OBJECTIVE: In this article, we review the many methodological challenges of conducting psychedelic clinical trials and provide recommendations for improving the rigor of future research. RESULTS: Although some challenges are shared with psychotherapy and pharmacology trials more broadly, psychedelic clinical trials have to contend with several unique sources of potential bias. The subjective effects of a high-dose psychedelic are often so pronounced that it is difficult to mask participants to their treatment condition; the significant hype from positive media coverage on the clinical potential of psychedelics influences participants' expectations for treatment benefit; and participant unmasking and treatment expectations can interact in such a way that makes psychedelic therapy highly susceptible to large placebo and nocebo effects. Specific recommendations to increase the success of masking procedures and reduce the influence of participant expectancies are discussed in the context of study development, participant recruitment and selection, incomplete disclosure of the study design, choice of active placebo condition, as well as the measurement of participant expectations and masking efficacy. CONCLUSION: Incorporating the recommended design elements is intended to reduce the risk of bias in psychedelic clinical trials and thereby increases the ability to discern treatment-specific effects of psychedelic therapy.
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Hallucinogènes , Hallucinogènes/pharmacologie , Hallucinogènes/usage thérapeutique , Humains , Motivation , Psychothérapie , Plan de rechercheRÉSUMÉ
OBJECTIVE: Psychiatric disorders increase risk for contracting coronavirus disease 2019 (COVID-19), but we know little about relationships between psychiatric symptoms and COVID-19 risky and protective behaviors. Posttraumatic stress disorder (PTSD) has been associated with increased propensity to engage in risky behaviors, but may also be associated with increased COVID-19 protective behaviors due to increased threat sensitivity and social isolation. METHOD: We examined associations of PTSD symptoms with COVID-19-related protective and risky behaviors using data from a cross-sectional online United States study among 845 US adults in August through September 2020. PTSD symptoms (PTSD Checklist-5), sociodemographics, COVID-19-related experiences and vulnerabilities, and past 30-day engagement in 10 protective and eight risky behaviors for COVID-19 were assessed via self-report. We examined associations between PTSD symptoms and COVID-19 protective and risky behaviors with linear regressions, adjusting for covariates. RESULTS: Probable PTSD and higher PTSD symptom severity were associated with greater engagement in protective behaviors, but also greater engagement in risky behaviors. Associations were only slightly attenuated by adjustment for COVID-19 exposures and perceived likelihood and severity of COVID-19. Associations varied by PTSD clusters: intrusions and arousal were associated with both more protective and more risky behaviors, whereas negative cognitions or mood was associated only with more risky, and avoidance only with more protective, behaviors. CONCLUSION: Higher PTSD symptoms were associated with engagement in more protective but also more risky behaviors for COVID-19. Mental health should be considered in the design of public health campaigns dedicated to limiting infectious disease spread. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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COVID-19 , Troubles de stress post-traumatique , Adulte , COVID-19/prévention et contrôle , Études transversales , Humains , Prise de risque , SARS-CoV-2 , Troubles de stress post-traumatique/psychologie , États-Unis/épidémiologieRÉSUMÉ
Co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common and particularly associated with elevation of hyperarousal compared to PTSD alone. Treatment options are limited. Oxytocin regulates physiological stress response. Intranasal oxytocin administration has demonstrated potential in reducing symptoms of both PTSD and AUD. This study addresses a gap in the literature by investigating effects of intranasal oxytocin on startle reactivity, an important potential marker of both PTSD and AUD symptomatology. This is a randomized, double-blind, placebo-controlled, within- and between-participant, crossover, dose-ranging study examining the effects of a single administration of oxytocin 20 IU versus 40 IU versus placebo on psychophysiological responses to a common laboratory fear-potentiated acoustic startle paradigm in participants with PTSD-AUD (nâ¯=â¯47) and controls (nâ¯=â¯37) under three different levels of threat. Contrary to our hypothesis, for the PTSD-AUD group, oxytocin 20 IU had no effect on startle reactivity, while oxytocin 40 IU increased measures of startle reactivity. Additionally, for PTSD-AUD only, ambiguous versus low threat was associated with an elevated skin conductance response. For controls only, oxytocin 20 IU versus placebo was associated with reduced startle reactivity.
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Alcoolisme , Troubles de stress post-traumatique , Acoustique , Alcoolisme/complications , Alcoolisme/diagnostic , Alcoolisme/traitement médicamenteux , Peur , Humains , Ocytocine/pharmacologie , Ocytocine/usage thérapeutique , Réflexe de sursaut , Troubles de stress post-traumatique/complications , Troubles de stress post-traumatique/diagnostic , Troubles de stress post-traumatique/traitement médicamenteuxRÉSUMÉ
Individual behaviors are critical for preventing the spread of coronavirus disease 2019 (COVID-19) infection. Given that both protective and risky behaviors influence risk of infection, it is critical that we understand how such behaviors cluster together and in whom. Using a data-driven approach, we identified clusters of COVID-19-related protective and risky behaviors and examined associations with socio-demographic, pandemic, and mental health factors. Data came from a cross-sectional online U.S. nationwide study of 832 adults with high levels of pre-pandemic trauma. Latent class analysis was performed with ten protective (e.g., washing hands, wearing masks) and eight risky (e.g., attending indoor restaurants, taking a flight) behaviors for COVID-19. Then, we examined distributions of socio-demographic and pandemic factors across behavior classes using ANOVA or Chi-square tests, and associations between mental health factors (depressive, anxiety, posttraumatic stress symptoms) and behavior classes using multinomial logistic regression. We identified four classes, including three classes with relatively low risky but high (28.8%), moderate (33.5%) and minimal (25.5%) protective behaviors and one high risky behaviors class with associated moderate protective behaviors (12.1%). Age, sexual orientation, political preference, and most pandemic factors differed significantly across behavior classes. Anxiety and posttraumatic stress symptoms, but not depression, were higher in the High Risk, but also Highly and Moderately Protective classes, relative to Minimally Protective. Prevention and intervention efforts should examine constellations of protective and risky behaviors to comprehensively understand risk, and consider current anxiety and posttraumatic stress symptoms as potential risk indicators.
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Patients and psychotherapists often exhibit behavioral, psychological, and physiological similarity. Here, we test whether oxytocin-a neuropeptide that can enhance expressivity and social perception-influences time-lagged "linkage" of autonomic nervous system responses among participants and facilitators during group therapy. Physiological linkage estimates (n = 949) were created from ten cohorts, each with two facilitators (n = 5) and four to six participants (n = 48), over six weekly sessions of group therapy for methamphetamine use disorder. All participants of a cohort received oxytocin or placebo intranasally in a randomized double-blind procedure before each session. Cardiac interbeat intervals (IBI) were measured continuously during sessions to estimate physiological linkage, operationalized as one cohort-mate's IBI reactivity during one minute predicting another cohort-mate's IBI reactivity during the following minute. In oxytocin cohorts, participants and facilitators experienced significant physiological linkage to their cohort-mates (i.e., their physiological responses were predicted by the prior responses of their cohort-mates) and significantly more linkage than people in placebo cohorts. Both effects occurred during the first and second sessions but not later sessions. Results suggest that oxytocin may enhance psychosocial processes often associated with linkage-such as social engagement-in groups and highlight oxytocin's potential to improve group cohesion during group therapy.Clinical Trials Registration: NCT02881177, First published on 26/08/2016.
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Troubles liés aux amphétamines/thérapie , Stimulants du système nerveux central/effets indésirables , Métamfétamine/effets indésirables , Ocytocine/administration et posologie , Psychothérapie de groupe , Adolescent , Adulte , Sujet âgé , Troubles liés aux amphétamines/diagnostic , Troubles liés aux amphétamines/étiologie , Association thérapeutique , Prise en charge de la maladie , Humains , Mâle , Adulte d'âge moyen , Psychothérapie de groupe/méthodes , Minorités sexuelles , Résultat thérapeutique , Jeune adulteRÉSUMÉ
Analysis of client and therapist behavior in counseling sessions can provide helpful insights for assessing the quality of the session and consequently, the client's behavioral outcome. In this paper, we study the automatic classification of standardized behavior codes (i.e. annotations) used for assessment of psychotherapy sessions in Motivational Interviewing (MI). We develop models and examine the classification of client behaviors throughout MI sessions, comparing the performance by models trained on large pretrained embeddings (RoBERTa) versus interpretable and expert-selected features (LIWC). Our best performing model using the pretrained RoBERTa embeddings beats the baseline model, achieving an F1 score of 0.66 in the subject-independent 3-class classification. Through statistical analysis on the classification results, we identify prominent LIWC features that may not have been captured by the model using pretrained embeddings. Although classification using LIWC features underperforms RoBERTa, our findings motivate the future direction of incorporating auxiliary tasks in the classification of MI codes.
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Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.
Sujet(s)
Effets secondaires indésirables des médicaments/épidémiologie , N-Méthyl-3,4-méthylènedioxy-amphétamine/administration et posologie , Troubles de stress post-traumatique/traitement médicamenteux , Adulte , Association thérapeutique , Méthode en double aveugle , Effets secondaires indésirables des médicaments/anatomopathologie , Femelle , Humains , Mâle , Adulte d'âge moyen , N-Méthyl-3,4-méthylènedioxy-amphétamine/effets indésirables , Troubles de stress post-traumatique/épidémiologie , Troubles de stress post-traumatique/anatomopathologie , Résultat thérapeutiqueRÉSUMÉ
INTRODUCTION: Mentalizing, the ability to infer other people's intentions and emotions, is commonly impaired in schizophrenia and may represent an endophenotype. The hypothalamic neuropeptide oxytocin has been shown to improve mentalizing in men with schizophrenia, but its effects in women remain unclear. Given sex differences in the clinical manifestations of schizophrenia and oxytocin system function, this is an important gap to address. METHODS: We tested the effects of a single-dose oxytocin challenge (40 IU) on mentalizing task performance among 26 women with schizophrenia and 38 healthy control women using a randomized, placebo-controlled, double-blind, crossover design. We aimed to replicate our prior study of oxytocin effects on mentalizing in men with schizophrenia, using the same oxytocin administration procedures and performance-based assessments. We used mixed-effects models and equivalence testing as well as Bayesian hierarchical models to examine oxytocin effects. RESULTS: In contrast to our previous finding in a male sample, oxytocin did not improve mentalizing in this sample of women with schizophrenia. Exploratory analyses showed that higher anti-dopaminergic medication dosage was associated with a decreased response to oxytocin, consistent with previous findings in men. CONCLUSION: These findings provide preliminary evidence that exogenous oxytocin administration may have sex-specific effects on mentalizing in schizophrenia. Inclusion of women in future clinical studies with larger samples is critical, as oxytocin effects observed in men may not extend to women with the disorder.
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Mentalisation , Schizophrénie , Administration par voie nasale , Théorème de Bayes , Études croisées , Méthode en double aveugle , Femelle , Humains , Mâle , Ocytocine/pharmacologie , Ocytocine/usage thérapeutique , Schizophrénie/traitement médicamenteux , Perception socialeRÉSUMÉ
BACKGROUND: Methamphetamine (METH) use is a public health crisis that disproportionately affects men who have sex with men (MSM). There are currently no FDA-approved pharmacological interventions to treat methamphetamine use disorder (MUD). MUD is associated with social impairments and extremely high treatment attrition rates. Administration of oxytocin, a neuropeptide involved in social attachment, may be a novel approach to addressing these issues. Moreover, oxytocin administration has shown promise for reducing METH-related addictive behavior in animal models, but has not yet been investigated in clinical trials for MUD. Last, oxytocin is known to modulate stress responsivity via regulation of the autonomic nervous system, which is dysregulated in METH users. We hypothesize that oxytocin, in combination with group psychotherapy, will increase treatment engagement, reduce addiction behavior, and mitigate stress hyperreactivity. METHODS: This is a randomized, double blind trial of oxytocin 40-IU (n = 24) or placebo (n = 24) administered intranasally prior to each of six weekly motivational interviewing group therapy (MIGT) sessions for MUD in MSM. PRIMARY OUTCOME: (a) session attendance. SECONDARY OUTCOMES: (b) group cohesion, (c) anxiety, (d) METH craving, (e) METH use, and (f) in-session cardiac physiology. RESULTS: Participants receiving oxytocin had significantly higher group therapy attendance than those receiving placebo, OR 3.26, 95% CI [1.27-8.41], p = .014. There was a small effect of oxytocin on group cohension, but not anxiety or craving. METH use did not change over the six-week MIGT course in either treatment arm. Participants receiving oxytocin had lower average heart rates during MIGT sessions and higher heart rate variability. There were positive main effects of MIGT over Time regardless of study drug. CONCLUSIONS: This evidence, and the lack of any serious adverse events, suggests that oxytocin may safely increase treatment attendance. One possible mechanism by which it may do so is its modulation of the autonomic nervous system. Further investigation is warranted.
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Stimulants du système nerveux central , Métamfétamine , Psychothérapie de groupe , Minorités sexuelles , Comportement de recherche de substances , Homosexualité masculine , Humains , Mâle , Ocytocine , AutoadministrationRÉSUMÉ
BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with increased risk for morbidity and mortality, which may be mediated through elevated inflammation. In contrast, social support appears to protect against morbidity and mortality, reduce levels of inflammation, and improve PTSD outcomes. METHODS: We examined relationships among social isolation, perceived social support, and inflammation in Veterans Affairs (VA) patients with and without PTSD. Our sample included 735 (35% PTSD+) participants from the Mind Your Heart Study (mean age = 58 ± 11; 94% male). Social isolation was assessed with the Berkman Syme Social Network Index; perceived social support with the Multidimensional Scale of Perceived Social Support; and PTSD with the Clinician Administered PTSD Scale. Inflammation was indexed by high sensitivity C-reactive protein, white blood cell count, and fibrinogen. Hierarchical linear regression was used to examine associations between social measures and inflammation. PROCESS was used to examine the interactive effects of social relationships and PTSD on inflammation. RESULTS: Social isolation, but not low perceived social support, trended towards an association with elevated inflammation in the full sample. However, considering groups with and without PTSD separately, social isolation was significantly associated with all inflammatory markers among individuals without PTSD, but not among those with PTSD. CONCLUSIONS: Social integration is associated with reduced inflammation in individuals without, but not with, PTSD. Socially integrated individuals with PTSD did not have lower levels of inflammatory markers than socially isolated individuals with PTSD.
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Troubles de stress post-traumatique , Anciens combattants , Sujet âgé , Femelle , Humains , Inflammation , Mâle , Adulte d'âge moyen , Insertion sociale , Soutien socialRÉSUMÉ
BACKGROUND: Aberrant sensitivity to social reward may be an important contributor to abnormal social behavior that is a core feature of schizophrenia. The neuropeptide oxytocin impacts the salience of social information across species, but its effect on social reward in schizophrenia is unknown. METHODS: We used a competitive economic game and computational modeling to examine behavioral dynamics and oxytocin effects on sensitivity to social reward among 39 men with schizophrenia and 54 matched healthy controls. In a randomized, double-blind study, participants received one dose of oxytocin (40 IU) or placebo and completed a 35-trial Auction Game that quantifies preferences for monetary v. social reward. We analyzed bidding behavior using multilevel linear mixed models and reinforcement learning models. RESULTS: Bidding was motivated by preferences for both monetary and social reward in both groups, but bidding dynamics differed: patients initially overbid less compared to controls, and across trials, controls decreased their bids while patients did not. Oxytocin administration was associated with sustained overbidding across trials, particularly in patients. This drug effect was driven by a stronger preference for winning the auction, regardless of monetary consequences. Learning rate and response variability did not differ between groups or drug condition, suggesting that differences in bidding derive primarily from differences in the subjective value of social rewards. CONCLUSIONS: Our findings suggest that schizophrenia is associated with diminished motivation for social reward that may be increased by oxytocin administration.
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Comportement compétitif/physiologie , Prise de décision/physiologie , Motivation/physiologie , Ocytocine/pharmacologie , Renforcement social , Récompense , Schizophrénie/physiopathologie , Comportement compétitif/effets des médicaments et des substances chimiques , Prise de décision/effets des médicaments et des substances chimiques , Méthode en double aveugle , Humains , Mâle , Adulte d'âge moyen , Motivation/effets des médicaments et des substances chimiques , Ocytocine/administration et posologieRÉSUMÉ
Negative symptoms are core contributors to vocational and social deficits in schizophrenia (SZ). Available antipsychotic medications typically fail to reduce these symptoms. The neurohormone oxytocin (OT) is a promising treatment for negative symptoms, given its role in complex social behaviors mediated by the amygdala. In sample 1, we used a double-blind, placebo-controlled, crossover design to test the effects of a single dose of intranasal OT on amygdala resting-state functional connectivity (rsFC) in SZ (n = 22) and healthy controls (HC, n = 24) using a whole-brain corrected approach: we identified regions for which OT modulated SZ amygdala rsFC, assessed whether OT-modulated circuits were abnormal in SZ relative to HC on placebo, and evaluated whether connectivity on placebo and OT-induced connectivity changes correlated with baseline negative symptoms in SZ. Given our modest sample size, we used a second SZ (n = 183) and HC (n = 178) sample to replicate any symptom correlations. In sample 1, OT increased rsFC between the amygdala and left middle temporal gyrus, superior temporal sulcus, and angular gyrus (MTG/STS/AngG) in SZ compared to HC. Further, SZ had hypo-connectivity in this circuit compared to HC on placebo. More severe negative symptoms correlated with less amygdala-to-left-MTG/STS/AngG connectivity on placebo and with greater OT-induced connectivity increases. In sample 2, we replicated the correlation between amygdala-left-MTG/STS/AngG hypo-connectivity and negative symptoms, finding a specific association with expressive negative symptoms. These data suggest intranasal OT can normalize functional connectivity in an amygdala-to-left-MTG/STS/AngG circuit that contributes to negative symptoms in SZ.
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Amygdale (système limbique)/effets des médicaments et des substances chimiques , Cortex cérébral/effets des médicaments et des substances chimiques , Connectome , Réseau nerveux/effets des médicaments et des substances chimiques , Ocytocine/pharmacologie , Troubles psychotiques/traitement médicamenteux , Schizophrénie/traitement médicamenteux , Adulte , Amygdale (système limbique)/imagerie diagnostique , Amygdale (système limbique)/physiopathologie , Cortex cérébral/imagerie diagnostique , Cortex cérébral/physiopathologie , Études croisées , Méthode en double aveugle , Femelle , Humains , Imagerie par résonance magnétique , Mâle , Réseau nerveux/imagerie diagnostique , Réseau nerveux/physiopathologie , Ocytocine/administration et posologie , Troubles psychotiques/imagerie diagnostique , Troubles psychotiques/physiopathologie , Schizophrénie/imagerie diagnostique , Schizophrénie/physiopathologie , Résultat thérapeutiqueRÉSUMÉ
Although behavioral therapies are effective for posttraumatic stress disorder (PTSD), access for patients is limited. Attention-bias modification (ABM), a cognitive-training intervention designed to reduce attention bias for threat, can be broadly disseminated using technology. We remotely tested an ABM mobile app for PTSD. Participants (N = 689) were randomly assigned to personalized ABM, nonpersonalized ABM, or placebo training. ABM was a modified dot-probe paradigm delivered daily for 12 sessions. Personalized ABM included words selected using a recommender algorithm. Placebo included only neutral words. Primary outcomes (PTSD and anxiety) and secondary outcomes (depression and PTSD clusters) were collected at baseline, after training, and at 5-week-follow-up. Mechanisms assessed during treatment were attention bias and self-reported threat sensitivity. No group differences emerged on outcomes or attention bias. Nonpersonalized ABM showed greater declines in self-reported threat sensitivity than placebo (p = .044). This study constitutes the largest mobile-based trial of ABM to date. Findings do not support the effectiveness of mobile ABM for PTSD.
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Schizophrenia-spectrum disorders (SSD) are associated with deficits in emotional prosody recognition. Whether administration of oxytocin can improve emotional prosody recognition accuracy in SSD is unknown. Sixty individuals with SSD and ninety-seven controls completed a placebo-controlled, double-blind, cross-over trial examining the effects of oxytocin on emotional prosody recognition accuracy. Compared to controls, SSD was associated with poorer emotional prosody recognition accuracy, regardless of stimulus valence or intensity, suggesting a generalized deficit. Oxytocin had no effect on emotional prosody recognition in either group, which is consistent with previous work suggesting that oxytocin only improves high-level social cognition in SSD.