A systematic review and meta-analysis of the traumatogenic phenotype hypothesis of psychosis.

BACKGROUND: Developmental trauma increases psychosis risk and is associated with poor prognosis. It has been proposed that psychosis in survivors of developmental trauma gives rise to a distinct 'traumatogenic' phenotype. AIMS: Given the implications for personalised treatment, we sought to explore the traumatogenic psychosis phenotype hypothesis in a systematic review and meta-analysis of studies comparing psychotic presentations between adults with and without developmental trauma histories. METHOD: We registered the systematic review on PROSPERO (CRD42019131245) and systematically searched EMBASE, Medline and PsycINFO. The outcomes of interests were quantitative and qualitative comparisons in psychotic symptom expression (positive, negative, cognitive) and other domains of psychopathology, including affect regulation, sleep, depression and anxiety, between adults with and without experience of developmental trauma. RESULTS: Of 34 studies included (N = 13 150), 11 were meta-analysed (n = 2842). A significant relationship was found between developmental trauma and increased symptom severity for positive (Hedge's g = 0.27; 95% CI 0.10-0.44; P = 0.002), but not negative symptoms (Hedge's g = 0.13; 95% CI -0.04 to 0.30; P = 0.14). Developmental trauma was associated with greater neurocognitive, specifically executive, deficits, as well as poorer affect, dissociation and social cognition. Furthermore, psychotic symptom content thematically related to traumatic memories in survivors of developmental trauma. CONCLUSIONS: Our findings that developmental trauma is associated with more severe positive and affective symptoms, and qualitative differences in symptom expression, support the notion that there may be a traumatogenic psychosis phenotype. However, underdiagnosis of post-traumatic stress disorder may also explain some of these findings. More research is needed to explore this further.

Unveiling temporal dynamics of PTSD and its functional impairments: A longitudinal study in UK healthcare workers.

PTSD has been associated with negative long-term consequences, including social and occupational impairments. Yet, a nuanced understanding of the interplay between PTSD symptoms and distinct domains of impairments on a short-term basis (weeks/ months) at the within-person level remains underexplored. In a large sample (nwave 1 = 1096, nwave 7 = 304) of UK healthcare workers assessed across seven assessment waves during the COVID-19 pandemic (spaced 6 weeks apart), we employed exploratory graphical vector autoregression models (GVAR) models to discern within-person temporal (across time) and contemporaneous (within same time window) dynamics between PTSD symptoms and functional impairment domains. The contemporaneous network highlighted strong co-occurrences between different symptoms and impairments. The temporal network revealed a mutually reinforcing cycle between intrusion and avoidance symptoms. Intrusion symptoms showed the highest out-strength (i.e., most predictive symptom), predicting avoidance symptoms, elevated sense of current threat, and various functional impairments. Avoidance symptoms, elevated after increased levels of intrusions, predicted work impairments that in turn were associated with difficulties in fulfilling other obligations. Our findings underscore the dynamics between perceived threat and intrusions, and the role intrusions may play in predicting a cascade of adverse effects. Targeted interventions aimed at mitigating intrusions may disrupt this negative cycle.

The acute effects of cannabis, with and without cannabidiol, on attentional bias to cannabis related cues: a randomised, double-blind, placebo-controlled, cross-over study.

RATIONALE: Attentional bias to drug-related stimuli is hypothesised to contribute towards addiction. However, the acute effects of Δ9-tetrahydrocannabinol (THC) on attentional bias to cannabis cues, the differential response in adults and adolescents, and the moderating effect of cannabidiol (CBD) are unknown. OBJECTIVES: Our study investigated (1) the acute effects of vaporised cannabis on attentional bias to cannabis-related images in adults and adolescents and (2) the moderating influences of age and CBD. METHODS: We conducted a randomised, double-blind, placebo-controlled, cross-over study where three weight-adjusted vaporised cannabis preparations: 'THC' (8 mg THC for a 75-kg person), 'THC + CBD' (8 mg THC and 24 mg CBD for a 75-kg person) and PLA (matched placebo). Cannabis was administered on 3 separate days to 48 participants, who used cannabis 0.5-3 days/week: 24 adolescents (12 females, aged 16-17) and 24 adults (12 females, aged 26-29). Participants completed a visual probe task with cannabis cues. Our primary outcome was attentional bias to cannabis stimuli, measured using the differential reaction time to a cannabis vs. neutral probe, on 200-ms trials. RESULTS: In contrast to hypotheses, attention was directed away from cannabis cues on placebo, and there was a main effect of the drug (F(2,92) = 3.865, p = 0.024, η2p = 0.077), indicating THC administration eliminated this bias. There was no significant impact of CBD nor an age-by-drug interaction. CONCLUSIONS: Acute THC intoxication eliminated attentional bias away from cannabis cues. There was no evidence of differential response in adolescents compared to adults and no evidence that a moderate vaporised dose of CBD altered the impact of cannabis on attentional bias. TRIAL REGISTRATION: This study was listed with the US National Library of Medicine and registered on ClinicalTrials.gov, URL: Do Adolescents and Adults Differ in Their Acute Response to Cannabis?-Full Text View-ClinicalTrials.gov, registration number: NCT04851392.

Post-incident psychosocial interventions after a traumatic incident in the workplace: a systematic review of current research evidence and clinical guidance.

Background: After a traumatic incident in the workplace organisations want to provide support for their employees to prevent PTSD. However, what is safe and effective to offer has not yet been established, despite many organisations offering some form of intervention after a traumatic event.Objective: To systematically review the evidence for post-incident psychosocial interventions offered within one month of a workplace trauma, and to compare the content, effectiveness and acceptability of these interventions. Given the lack of a yet clearly established evidence-base in this field, we sought to examine both published empirical research as well as guidelines published by expert groups working with staff in high-risk roles.Methods: We conducted systematic searches for empirical research across bibliographic databases and searched online for clinical practice guidelines to April 2023. We were also referred to potentially relevant literature by experts in workplace trauma. Both empirical research and clinical guidelines were appraised for their quality.Results: A total of 80 research studies and 11 clinical practice guidelines were included in the review. Interventions included Critical Incident Stress Debriefing (CISD), Critical Incident Stress Management (CISM), unspecified Debriefing, Trauma Risk Management (TRiM), Psychological First Aid (PFA), EMDR, CBT and group counselling. Most research and guidance were of poor quality. The findings of this review do not demonstrate any harm caused by CISD, CISM, PFA, TRiM, EMDR, group counselling or CBT interventions when delivered in a workplace setting. However, they do not conclusively demonstrate benefits of these interventions nor do they establish superiority of any specific intervention. Generic debriefing was associated with some negative outcomes. Current clinical guidelines were inconsistent with the current research evidence base. Nevertheless, interventions were generally valued by workers.Conclusions: Better quality research and guidance is urgently needed, including more detailed exploration of the specific aspects of delivery of post-incident interventions.

Organisations often seek to provide some form of psychosocial intervention after a traumatic event in the workplace.Previous reviews have contraindicated particular forms of 'debriefing', however, the evidence for post-incident psychosocial interventions in the workplace has not previously been systematically reviewed.Research evidence was generally of poor quality with limited evidence of effectiveness and clinical guidelines were inconsistent with the evidence. Nevertheless, research did not demonstrate harm from most established interventions and support was valued by workers.

Exposure to potentially morally injurious events in U.K. health and social care workers during COVID-19: Associations with PTSD and complex PTSD.

OBJECTIVE: Health and social care workers (HSCWs) have been shown to be at risk of exposure to potentially morally injurious events (PMIEs) and mental health problems during the COVID-19 pandemic. This study aimed to examine associations between exposure to PMIEs and meeting threshold criteria for probable posttraumatic stress disorder (PTSD) and probable complex PTSD (CPTSD) in U.K. HSCWs immediately after the peak of the first COVID-19 wave. METHOD: Frontline HSCWs from across the United Kingdom working in diverse roles in hospitals, nursing or care homes, and other community settings were recruited to the Frontline-COVID study via social media. Participants (n = 1,056) completed a cross-sectional online survey (May 27, 2020-July 23, 2020) which assessed exposure to PMIEs (nine-item Moral Injury Events Scale), and meeting symptom thresholds for probable PTSD and probable CPTSD (International Trauma Questionnaire). RESULTS: PMIEs related to witnessing others' wrongful actions and betrayal events were more commonly endorsed than perceived self-transgressions. The rate of probable International Classification of Diseases, 11th Revision (ICD-11) PTSD was 8.3%, and of probable ICD-11 CPTSD was 14.2%. Betrayal-related PMIEs were a significant predictor of probable PTSD or probable CPTSD, together with having been redeployed during the pandemic. The only variable that differentially predicted probable CPTSD as compared with probable PTSD was not having had reliable access to personal protective equipment; none of the PMIE types were differential predictors for screening positive for probable PTSD versus probable CPTSD. CONCLUSIONS: Exposure to PIMEs could be important for PTSD and CPTSD development. Interventions for moral injury in HSCWs should be investigated. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Expert international trauma clinicians' views on the definition, composition and delivery of reintegration interventions for complex PTSD.

Background: Research has previously distinguished between complex post-traumatic stress disorder (CPTSD) and PTSD, with the former including a range of disturbances in self-regulatory capacities in addition to difficulties associated with PTSD. Clinical guidelines have previously recommended a phase-based approach for the treatment of CPTSD, yet the final 'reintegration' phase of treatment has been overlooked in research, with limited evidence into its value and effectiveness, and inconsistencies in its definitions and understanding.Objective: We set out to define and determine the key principles of 'reintegration' and to specify the components and method of delivery of treatment.Method: Leading national and international clinical and academic experts in CPTSD were interviewed and asked about their views of how 'reintegration' should be defined, its role in the treatment of CPTSD, what it should be composed of, the key principles of its delivery, and how it should be evaluated. We analysed transcripts of the interviews following the principles of Codebook Thematic Analysis.Results: We conducted 16 interviews with leading national and international experts with at least 10 years' experience of treating people with CPTSD. Themes derived from our analysis demonstrated that while the definition and composition of reintegration varied greatly between experts, the key principles in its delivery were consistent across all experts.Conclusions: The results of this study lay the foundation for a framework of what reintegration is and how it can be used in, but also highlight the need for more research to be conducted on the role of reintegration in the treatment of CPTSD. Consensus for the definition and composition of reintegration is still yet to be reached. Possible measures for evaluating reintegration should also be explored in the future.

Reintegration is one of the recommended phases of treatment for CPTSD, however recent research has found that there are inconsistencies in its definition, role and value.The current study shows the opinions of experts, highlighting areas of consensus as well as differences in views with regards to the definition, composition and key principles in the delivery of reintegration.

Shared sources and mechanisms of healthcare worker distress in COVID-19: a comparative qualitative study in Canada and the UK.

Background: COVID-19 has had a significant impact on the wellbeing of healthcare workers, with quantitative studies identifying increased stress, anxiety, depression, insomnia, and PTSD in a wide range of settings. Limited qualitative data so far has offered in-depth details concerning what underlies these challenges, but none provide comprehensive comparison across different healthcare systems. Objective: To explore qualitative findings relating to healthcare worker distress from two different countries to understand the nuanced similarities and differences with respect to the sources and impact of distress relating to COVID-19. Method: A comparative interpretive thematic analysis was carried out between two qualitative data sets examining healthcare workers' experiences of distress during the COVID-19 pandemic. Data from Canada and the UK were collected in parallel and analyzed in an iterative, collaborative process. Results: A number of sources of distress cut across both study settings including concerns about safety and patient care, challenges at home or in one's personal life, communication issues, work environment, media and public perception, and government responses to the pandemic. These sit on a spectrum from individual to institutional sources and were mutually reinforcing. Our analysis also suggested that common mechanisms such as exacerbations in uncertainty, hypervigilance, and moral injury underpinned these sources, which contributed to how they were experienced as distressing. Conclusion: This is the first international collaboration utilising qualitative data to examine this pressing issue. Despite differences in the political, social, health service, and pandemic-related context, the sources and mechanisms of distress experienced by healthcare workers in Canada and the UK were remarkably similar. HIGHLIGHTS This international comparative qualitative study explores how mechanisms that lead to distress are shared across different geographies and cultures, even as the local context shapes the sources of distress themselves.

Antecedentes: La COVID-19 ha tenido un impacto significativo en el bienestar de los trabajadores de la salud, con estudios cuantitativos que identifican un aumento del estrés, la ansiedad, la depresión, el insomnio, y el TEPT en una amplia variedad de entornos. Hasta ahora, los datos cualitativos son limitados y han ofrecido un profundo detalle sobre lo que subyace a estos desafíos, pero ninguno proporciona una comparación exhaustiva entre los diferentes sistemas de atención de salud.Objetivo: Explorar los hallazgos cualitativos relacionados con la angustia de los trabajadores de la salud de dos países diferentes para comprender las sutiles similitudes y diferencias con respecto a las fuentes y el impacto de la angustia relacionada con la COVID-19.Método: Se llevó a cabo un análisis temático interpretativo comparativo entre dos conjuntos de datos cualitativos que examinaron las experiencias de angustia de los trabajadores de la salud durante la pandemia de la COVID-19. Los datos de Canadá y el Reino Unido se recopilaron en paralelo y se analizaron en un proceso colaborativo iterativo.Resultados: Una serie de fuentes de angustia atraviesan ambos entornos de estudio, incluidas las preocupaciones sobre la seguridad y el cuidado del paciente, los desafíos en el hogar o en la vida personal, los problemas de comunicación, el entorno laboral, la percepción pública y de los medios de comunicación, y las respuestas gubernamentales a la pandemia. Estos se ubican en un espectro desde fuentes individuales hasta institucionales y se reforzaron mutuamente. Nuestro análisis también sugirió que mecanismos comunes como las exacerbaciones de la incertidumbre, la hipervigilancia, y el daño moral sustentaban estas fuentes, lo que contribuyó a que se experimentaran como angustiosas.Conclusión: Esta es la primera colaboración internacional que utiliza datos cualitativos para examinar este apremiante problema. A pesar de las diferencias en el contexto político, social, de servicios de salud y relacionado con la pandemia, las fuentes y los mecanismos de angustia experimentados por los trabajadores de la salud en Canadá y el Reino Unido fueron notablemente similares.

A polygenic score indexing a DRD2-related co-expression network is associated with striatal dopamine function.

The D2 dopamine receptor (D2R) is the primary site of the therapeutic action of antipsychotics and is involved in essential brain functions relevant to schizophrenia, such as attention, memory, motivation, and emotion processing. Moreover, the gene coding for D2R (DRD2) has been associated with schizophrenia at a genome-wide level. Recent studies have shown that a polygenic co-expression index (PCI) predicting the brain-specific expression of a network of genes co-expressed with DRD2 was associated with response to antipsychotics, brain function during working memory in patients with schizophrenia, and with the modulation of prefrontal cortex activity after pharmacological stimulation of D2 receptors. We aimed to investigate the relationship between the DRD2 gene network and in vivo striatal dopaminergic function, which is a phenotype robustly associated with psychosis and schizophrenia. To this aim, a sample of 92 healthy subjects underwent 18F-DOPA PET and was genotyped for genetic variations indexing the co-expression of the DRD2-related genetic network in order to calculate the PCI for each subject. The PCI was significantly associated with whole striatal dopamine synthesis capacity (p = 0.038). Exploratory analyses on the striatal subdivisions revealed a numerically larger effect size of the PCI on dopamine function for the associative striatum, although this was not significantly different than effects in other sub-divisions. These results are in line with a possible relationship between the DRD2-related co-expression network and schizophrenia and extend it by identifying a potential mechanism involving the regulation of dopamine synthesis. Future studies are needed to clarify the molecular mechanisms implicated in this relationship.

The acute effects of cannabidiol on emotional processing and anxiety: a neurocognitive imaging study.

RATIONALE: There is growing interest in the therapeutic potential of cannabidiol (CBD) across a range of psychiatric disorders. CBD has been found to reduce anxiety during experimentally induced stress in anxious individuals and healthy controls. However, the mechanisms underlying the putative anxiolytic effects of CBD are unknown. OBJECTIVES: We sought to investigate the behavioural and neural effects of a single dose of CBD vs. placebo on a range of emotion-related measures to test cognitive-mechanistic models of its effects on anxiety. METHODS: We conducted a randomised, double-blind, placebo-controlled, crossover, acute oral challenge of 600 mg of CBD in 24 healthy participants on emotional processing, with neuroimaging (viewing emotional faces during functional magnetic resonance imaging) and cognitive (emotional appraisal) measures as well as subjective response to experimentally induced anxiety. RESULTS: CBD did not produce effects on brain responses to emotional faces and cognitive measures of emotional processing, or modulate experimentally induced anxiety, relative to placebo. CONCLUSIONS: Given the rising popularity of CBD for its putative medical benefits, these findings question whether further research is warranted to investigate the clinical potential of CBD for the treatment of anxiety disorders.

The effects of developmental trauma on theory of mind and its relationship to psychotic experiences: A behavioural study.

BACKGROUND: Developmental psychological trauma induces vulnerability to psychosis. However, the mechanisms underlying this association are poorly understood. Impairments in Theory of Mind (ToM) have been observed in adult survivors of developmental trauma and individuals with psychosis. ToM is therefore a candidate mechanism underlying the association between developmental trauma and psychosis. METHODS: We used a computerised version of the Director task - where a participant is instructed by a confederate to move an object around a 4 × 4 grid, whilst taking account of whether these objects are visible to a confederate who instructs the participant - to investigate impairments in ToM in 209 participants (age: M = 37.8, SD=13.6; 56% female). Participants were divided into a) developmental trauma-positive (DT+) and control groups (DT-) based on their history of developmental trauma and b) then further into subclinical (S) and healthy groups (H) as based on psychotic experiences indexed by the CAPE-P15. After exclusion, the numbers in each group were: DT+H (47), DT+S (84), DT-H (54), DT-S (12). (Total: 197). RESULTS: Developmental trauma exposure was associated with psychotic experiences (OR: 7.89, p < .001), which remained significant after controlling for demographic and clinical confounds (adjusted R2 = 0.452, R2 change = 0.0184, p = .009). Participants with developmental trauma (F1, 194) = 5.46, p = .020, ηp2 = 0.027) and participants more prone to psychotic experiences (F1, 194) = 4.71, p = .031, ηp2 = 0.024) demonstrated significantly lower accuracy on the Director task relative to their respective control, after controlling for the effects of age. CONCLUSIONS: ToM deficits are associated with self-reported developmental trauma and psychotic experiences. Further work is needed to explore these relationships further and whether they represent generalised or specific effect effects on developmental trauma and psychopathological domains.

Effectiveness of psychosocial interventions in mitigating adverse mental health outcomes among disaster-exposed health care workers: A systematic review.

Health care workers worldwide are at an increased risk of a range of adverse mental health outcomes, including posttraumatic stress disorder (PTSD), following the unprecedented demand placed upon them during the COVID-19 pandemic. Psychosocial interventions offered to mitigate these risks should be based on the best available evidence; however, limited information regarding the comparative effectiveness of interventions is available. We undertook a systematic review of psychosocial interventions delivered to health care workers before, during, and after disasters. Eight databases were searched, including the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE, EMBASE, and PsycINFO. Our primary outcomes were changes in symptoms of PTSD, anxiety, depression, and sleep. We calculated effect sizes, where unreported, and reliable change indices to appraise intervention effectiveness. The study was registered with PROSPERO (CRD42020182774). In total, 12,198 papers were screened, 14 of which were included in the present review. Interventions based on evidence-based protocols, including individual and group-based cognitive behavioral therapy (CBT) for PTSD, anxiety, and depression were found to lead to reliable changes in PTSD and anxiety symptoms. Single-session debriefing and psychological first aid workshops showed limited efficacy. There is limited evidence on psychosocial interventions for health care workers faced with disasters, with the strongest evidence base for CBT-based approaches. Future research should include controlled evaluations of interventions and aim to target identified risk factors.

Anticipating PTSD in severe COVID survivors: the case for screen-and-treat.

Based on research from previous pandemics, studies of critical care survivors, and emerging COVID-19 data, we estimate that up to 30% of survivors of severe COVID will develop PTSD. PTSD is frequently undetected across primary and secondary care settings and the psychological needs of survivors may be overshadowed by a focus on physical recovery. Delayed PTSD diagnosis is associated with poor outcomes. There is a clear case for survivors of severe COVID to be systematically screened for PTSD, and those that develop PTSD should receive timely access to evidence-based treatment for PTSD and other mental health problems by multidisciplinary teams.

Basados en la investigación de pandemias previas, los estudios de los sobrevivientes a cuidados críticos, y los datos emergentes de COVID-19, estimamos que hasta un 30% de los sobrevivientes del COVID grave desarrollarán TEPT. El TEPT es frecuentemente subdetectado en los servicios de salud primarios y secundarios y las necesidades psicológicas de los sobrevivientes puede verse eclipsadas por un enfoque en la recuperación física. El diagnóstico tardío de TEPT se asocia con pobres resultados. Existe un caso claro para que los sobrevivientes del COVID grave sean evaluados sistemáticamente para detectar el TEPT, y aquellos que desarrollan un TEPT deben tener acceso oportuno a tratamientos basados en la evidencia para el TEPT y para otros problemas de salud mental por equipos multidisciplinarios.

What symptoms best predict severe distress in an online survey of UK health and social care staff facing COVID-19: development of the two-item Tipping Point Index.

OBJECTIVES: COVID-19 has altered standard thresholds for identifying anxiety and depression. A brief questionnaire to determine when individuals are at a tipping point for severe anxiety or depression would greatly help decisions about when to seek assessment or treatment. DESIGN: Data were collected as part of the Frontline-COVID Study, a cross-sectional national online survey with good coverage of health and social care settings. New questionnaire items reflecting when coping was actually breaking down were compared with standard measures of severe anxiety and depression. Data were collected between 27 May and 23 July 2020. SETTING: The majority of participants worked in hospitals (53%), in nursing or care homes (15%), or in other community settings (30%). PARTICIPANTS: Of 1194 qualifying respondents, 1038 completed the six tipping point items. Respondents included nurses, midwives, doctors, care workers, healthcare assistants, allied healthcare professionals and other non-medical staff. Over 90% were white and female. MAIN OUTCOME MEASURES: Threshold for severe anxiety according to the Generalised Anxiety Disorder Scale-7 or moderately severe depression according to the Patient Health Questionnaire-9. RESULTS: Answering yes to one of two simple questions ('Over the last week have you been often feeling panicky or on the point of losing control of your emotions?', 'Over the last week have you felt complete hopelessness about the future?') demonstrated very high sensitivity (0.95, 95% CI 0.92 to 0.97) and negative predictive value (0.97, 95% CI 0.95 to 0.98). Answering yes to both questions yielded high specificity (0.90, 95% CI 0.87 to 0.92) and positive predictive value (0.72, 95% CI 0.67 to 0.77). Results were replicated in two random subsamples and were consistent across different genders, ethnic backgrounds, and health or social care settings. CONCLUSIONS: Answering two simple yes/no questions can provide simple and immediate guidance to assist with decisions about whether to seek further assessment or treatment.

Reintegration interventions for CPTSD: a systematic review.

Background: Clinical guidelines recommend a phase-based approach to treatment for complex post-traumatic stress disorder (CPTSD), yet little is known about what interventions are being offered and which may be effective in the final 'reintegration' phase. Objective: To systematically review literature on reintegration interventions for CPTSD, describing the nature and effectiveness of interventions. Method: We searched four electronic databases (Medline, PsycINFO, Embase, and PTSDpubs) for interventions aiming to facilitate reintegration for participants with probable CPTSD. We had two aims: firstly, to describe the interventions and secondly, to describe their effectiveness as measured through measures of reintegration, PTSD and/or disturbances in self-organization (DSO), or qualitative data describing changes experienced. Results are presented using narrative synthesis. Results: Fifteen studies met our inclusion criteria. Interventions included yoga, exercise, use of service dogs, residential treatment, education, self-defence and patient research involvement. Overall study quality was low, as assessed by critical appraisal tools. Of the six studies including a control group, two reported a statistically significant improvement in the measure of reintegration between the intervention and control group, four studies reported a statistically significant difference in the measure of PTSD symptoms, but none reported any significant differences between intervention and control groups in DSO. Of all eight quantitative studies, three reported a statistically significant difference in the reintegration measure pre- to post-intervention for the intervention group, five a statistically significant improvement in the measure of PTSD symptoms, and three a significant difference in the DSO measure. From eight studies reporting qualitative date we synthesized themes into eight categories, within which facilitation of connection with others was the most commonly reported benefit. Conclusions: The interventions outlined may facilitate reintegration, however, research in this area is still in its infancy and quality research is lacking. Further research is needed to establish whether reintegration interventions enhance treatment for CPTSD.

Antecedentes: Las guías clínicas recomiendan un enfoque basado en fases para el tratamiento del trastorno de estrés postraumático complejo (TEPTC), aunque se sabe poco acerca de las intervenciones que se ofrecen y cuáles pueden ser efectivas en la fase final de 'reintegración'.Objetivo: Revisar la literatura en forma sistemática acerca de intervenciones de reintegración para el TEPTC, describiendo la naturaleza y efectividad de las intervenciones.Método: Para las intervenciones cuyo objetivo era facilitar la reintegración de los participantes con probable TEPTC, buscamos en cuatro bases de datos electrónicas (Medline, PsycINFO, Embase, y PTSDpubs). Teníamos dos objetivos: en primer lugar, describir las intervenciones y, en segundo lugar, describir su efectividad medida a través de mediciones de reintegración, TEPT y/o alteraciones en la auto-organización (DSO en sus siglas en ingles), o datos cualitativos que describieran los cambios experimentados. Los resultados se presentan mediante síntesis narrativa.Resultados: Quince estudios reunieron nuestros criterios de inclusión, La intervenciones incluían yoga, ejercicio, uso de perros de servicio, tratamiento residencial, educación, autodefensa y la implicación del paciente en la investigación. La calidad del estudio en general fue baja, según la evaluación de las herramientas de evaluación críticas. De los seis estudios que incluyeron un grupo control, dos reportaron una mejoría estadísticamente significativa en la medición de la reintegración entre la intervención y el grupo control, cuatro estudios reportaron una diferencia estadísticamente significativa en la medición de los síntomas de TEPT, pero ninguno reportó alguna diferencia significativa en los síntomas DSO entre los grupos de intervención y control. De los ocho estudios cuantitativos, tres reportaron una diferencia estadísticamente significativa en la medición de la reintegración pre y post intervención para el grupo con intervención, cinco una mejoría estadísticamente significativa en la medición de los síntomas de TEPT, y tres una diferencia significativa en la medición de los síntomas DSO. De los ocho estudios que reportaron datos cualitativos los sintetizamos por temas en ocho categorías, dentro de las cuales la facilitación de la conexión con otros fue el beneficio más comúnmente reportado.Conclusiones: Las intervenciones descritas pueden facilitar la reintegración, sin embargo, la investigación en esta área aún está dando sus primeros pasos y se carece investigación de calidad. Se necesita más investigación para establecer si las intervenciones de reintegración mejoran el tratamiento para el TEPTC.

The Effects of Acute Δ9-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study.

BACKGROUND: Cannabis and its main psychoactive component, Δ9-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. METHODS: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. RESULTS: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p = .58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. CONCLUSIONS: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate.

Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta-analysis.

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta-analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty-two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post-traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross-sectional research. Our findings suggest that there may be distinct psy-chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.

Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence.

BACKGROUND: Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2). METHODS: Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis. RESULTS: In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3-7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI. CONCLUSIONS: Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.

Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial.

Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design. METHODS: We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000361-36). FINDINGS: Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose. Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11). At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg. For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by -94·21 ng/mL (95% interval estimate -161·83 to -35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82). Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by -72·02 ng/mL (-135·47 to -19·52) and increased abstinence from cannabis by 0·27 days per week (-0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment. INTERPRETATION: In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use. FUNDING: Medical Research Council.

The effects of acute cannabidiol on cerebral blood flow and its relationship to memory: An arterial spin labelling magnetic resonance imaging study.

BACKGROUND: Cannabidiol (CBD) is being investigated as a potential treatment for several medical indications, many of which are characterised by altered memory processing. However, the mechanisms underlying these effects are unclear. AIMS: Our primary aim was to investigate how CBD influences cerebral blood flow (CBF) in regions involved in memory processing. Our secondary aim was to determine if the effects of CBD on CBF were associated with differences in working and episodic memory task performance. METHODS: We used a randomised, crossover, double-blind design in which 15 healthy participants were administered 600 mg oral CBD or placebo on separate days. We measured regional CBF at rest using arterial spin labelling 3 h after drug ingestion. We assessed working memory with the digit span (forward, backward) and n-back (0-back, 1-back, 2-back) tasks, and we used a prose recall task (immediate and delayed) to assess episodic memory. RESULTS: CBD increased CBF in the hippocampus (mean (95% confidence intervals) = 15.00 (5.78-24.21) mL/100 g/min, t14 = 3.489, Cohen's d = 0.75, p = 0.004). There were no differences in memory task performance, but there was a significant correlation whereby greater CBD-induced increases in orbitofrontal CBF were associated with reduced reaction time on the 2-back working memory task ( r= -0.73, p = 0.005). CONCLUSIONS: These findings suggest that CBD increases CBF to key regions involved in memory processing, particularly the hippocampus. These results identify potential mechanisms of CBD for a range of conditions associated with altered memory processing, including Alzheimer's disease, schizophrenia, post-traumatic stress disorder and cannabis-use disorders.