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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., HIGHLIGHTS We anticipate that up to 30% of survivors of severe COVID will develop PTSD, yet PTSD is frequently undetected in primary and secondary care settings.There is, therefore, a clear case for establishing systematic screening and ensuring timely access to treatment.

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.

Background: Mindfulness-meditation has a variety of benefits on well-being. However, individuals with primary attentional impairments (e.g. attention deficit disorder) or attentional symptoms secondary to anxiety, depression or addiction, may be less likely to benefit, and require additional mindfulness-augmenting strategies. Aims: To determine whether a single dose of the cognitive enhancer, modafinil, acutely increases subjective and behavioural indices of mindfulness, and augments brief mindfulness training. Methods: A randomised, double-blind, placebo-controlled, 2 (drug: placebo, modafinil) × 2 (strategy: mindfulness, relaxation control) experiment was conducted. Seventy-nine meditation-naïve participants were assigned to: placebo–relaxation, placebo–mindfulness, modafinil–relaxation or modafinil–mindfulness. Pre-drug, post-drug and post-strategy state mindfulness, affect and autonomic activity, along with post-strategy sustained attention and mind-wandering were assessed within a single lab session. After the session, participants were instructed to practice their assigned behavioural strategy daily for one week, with no further drug administration, after which, follow-up measures were taken. Results: As predicted, modafinil acutely increased state mindfulness and improved sustained attention. Differential acute strategy effects were found following mindfulness on autonomic activity but not state mindfulness. There were no strategy or drug effects on mind-wandering. However, exploratory analyses indicated that participants receiving modafinil engaged in more strategy practice across strategy conditions during follow-up. Conclusions: Modafinil acutely mimicked the effects of brief mindfulness training on state mindfulness but did not enhance the effects of this training. Limitations of the current study, and recommendations for future research examining modafinil as an adjunct to mindfulness- (or relaxation-) based treatments are discussed.

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.

Background: Cannabidiol has potential therapeutic benefits for people with psychiatric disorders characterised by reward function impairment. There is existing evidence that cannabidiol may influence some aspects of reward processing. However, it is unknown whether cannabidiol acutely affects brain function underpinning reward anticipation and feedback. Hypotheses: We predicted that cannabidiol would augment brain activity associated with reward anticipation and feedback. Methods: We administered a single 600 mg oral dose of cannabidiol and matched placebo to 23 healthy participants in a double-blind, placebo-controlled, repeated-measures design. We employed the monetary incentive delay task during functional magnetic resonance imaging to assay the neural correlates of reward anticipation and feedback. We conducted whole brain analyses and region-of-interest analyses in pre-specified reward-related brain regions. Results: The monetary incentive delay task elicited expected brain activity during reward anticipation and feedback, including in the insula, caudate, nucleus accumbens, anterior cingulate and orbitofrontal cortex. However, across the whole brain, we did not find any evidence that cannabidiol altered reward-related brain activity. Moreover, our Bayesian analyses showed that activity in our regions-of-interest was similar following cannabidiol and placebo. Additionally, our behavioural measures of motivation for reward did not show a significant difference between cannabidiol and placebo. Discussion: Cannabidiol did not acutely affect the neural correlates of reward anticipation and feedback in healthy participants. Future research should explore the effects of cannabidiol on different components of reward processing, employ different doses and administration regimens, and test its reward-related effects in people with psychiatric disorders.

Developmental trauma is associated with an increased risk of psychosis and predicts poor prognosis. Despite this association, little is known about which treatments work best for survivors of developmental trauma with psychosis. We sought to do the first review, to our knowledge, to investigate treatments for people with psychotic and dissociative symptoms who have a history of developmental trauma. We searched MEDLINE, PsychINFO, and Google Scholar for studies reporting psychological and pharmacological treatments of psychotic or dissociative symptoms in adult survivors of developmental trauma. We identified 24 studies, most of which investigated various modalities of psychotherapy with two case reports of pharmacological treatments. There is preliminary evidence in favour of third wave cognitive therapies. However, because of low methodological quality and reporting in most of the studies found, it remains unknown which treatments are most effective in this clinical group. Nonetheless, our findings of potential treatment targets, including emotion regulation, acceptance, interpersonal skills, trauma re-processing, and the integration of dissociated ego states, could guide future work in this area. Methodologically rigorous studies are needed to enable clinicians and patients to collaboratively form evidence-based treatment plans. Our Review is registered with PROSPERO, number CRD42018104533.

Objectives: Posttraumatic stress disorder (PTSD) is a potentially debilitating mental health problem. There has been a recent surge of interest regarding the use of cannabinoids in the treatment of PTSD. We therefore sought to systematically review and assess the quality of the clinical evidence of the effectiveness of cannabinoids for the treatment of PTSD. Method: We included all studies published until December 2018 where a patient has had PTSD diagnosed and had been prescribed or were using a cannabinoid for the purpose of reducing PTSD symptoms. Our primary outcome measure was the reduction in PTSD symptoms using a validated instrument. In the absence of randomized controlled trials, we included the next best available levels of evidence including observational and retrospective studies and case reports. We assessed risk of bias and quality using validated tools appropriate for the study design. Results: We included 10 studies in this review, of which only one study was a pilot randomized, double-blind, placebo-controlled, crossover clinical trial. Every identified study had medium to high risk of bias and was of low quality. We found that cannabinoids may decrease PTSD symptomology, in particular sleep disturbances and nightmares. Conclusions: Most studies to date are small and of low quality, with significant limitations to the study designs precluding any clinical recommendations about its use in routine clinical practice. Evidence that cannabinoids may help reduce global PTSD symptoms, sleep disturbances, and nightmares indicates that future well-controlled, randomized, double-blind clinical trials are highly warranted. PROSPERO registration number: 121646.

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.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).Developmental trauma exposure was associated with psychotic experiences (OR: 7.89, p.001), which remained significant after controlling for demographic and clinical confounds (adjusted RToM 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.

BackgroundAcute 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).MethodsTwo 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.ResultsIn 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.ConclusionsInhalation 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.

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., HIGHLIGHTS A phased-based approach to treating CPTSD has been recommended by experts; however Phase 3 ‘Reintegration’ interventions have been subject to little research. This review showed such interventions may reduce CPTSD symptoms and enhance integration, but research evidence is currently weak.

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. \ud \ud 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. \ud \ud 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. \ud \ud 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.

Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between dexamphetamine-induced dopamine release, dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, dexamphetamine-induced dopamine release as the mediator variable, and dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.

Background: Two major constituents of cannabis are Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component; CBD may buffer the user against the harmful effects of THC. Aims: We examined the effects of two strains of cannabis and placebo on the human brain’s resting-state networks using fMRI. Methods: Seventeen healthy volunteers (experienced with cannabis, but not regular users) underwent three drug treatments and scanning sessions. Treatments were cannabis containing THC (Cann−CBD; 8 mg THC), cannabis containing THC with CBD (Cann+CBD; 8 mg THC + 10 mg CBD), and matched placebo cannabis. Seed-based resting-state functional connectivity analyses were performed on three brain networks: the default mode (DMN; defined by positive connectivity with the posterior cingulate cortex: PCC+), executive control (ECN; defined by negative connectivity with the posterior cingulate cortex: PCC−) and salience (SAL; defined by positive connectivity with the anterior insula: AI+) network. Results: Reductions in functional connectivity (relative to placebo) were seen in the DMN (PCC+) and SAL (AI+) networks for both strains of cannabis, with spatially dissociable effects. Across the entire salience network (AI+), Cann−CBD reduced connectivity relative to Cann+CBD. The PCC in the DMN was specifically disrupted by Cann−CBD, and this effect correlated with subjective drug effects, including feeling ‘stoned’ and ‘high’. Conclusions: THC disrupts the DMN, and the PCC is a key brain region involved in the subjective experience of THC intoxication. CBD restores disruption of the salience network by THC, which may explain its potential to treat disorders of salience such as psychosis and addiction.

Heavy cannabis use is associated with an increased risk of psychosis. However, the psychological mechanisms involved, and interactions with established risk factors for cannabis-related psychosis, remain unclear. This study examined the role of cognitive fusion, a candidate vulnerability factor for psychosis, during acute THC intoxication, and the interaction with key risk factors–developmental trauma and schizotypy. Twenty general population cannabis-using participants were administered THC or placebo in a within-participants, double-blinded randomised study. Developmental trauma, schizotypy and cognitive fusion were all associated with psychotic experiences during intoxication. Cognitive fusion accounted for increased psychotic experiences in those with developmental trauma and high schizotypy. Cognitive fusion may be a key mechanism by which developmental trauma and schizotypy increase risk of psychosis from cannabis use. This initial study is limited by a small sample and correlational design; a larger scale mediation study is now needed to support a causal argument. The findings have implications for psychological treatments and identifying those at risk of cannabis-related psychosis. Psychological interventions that target cognitive fusion may be more effective than generic approaches. People prone to cognitive fusion, particularly those with a history of developmental trauma and high in schizotypy, may be at higher risk for cannabis-related psychosis.

Background The coronavirus disease 2019 (COVID-19) pandemic is having a well-documented impact on the mental health of front-line health and social care workers (HSCWs). However, little attention has been paid to the experiences of, and impact on, the mental health professionals who were rapidly tasked with supporting them. Aims We set out to redress this gap by qualitatively exploring UK mental health professionals’ experiences, views and needs while working to support the well-being of front-line HSCWs during the COVID-19 pandemic. Method Mental health professionals working in roles supporting front-line HSCWs were recruited purposively and interviewed remotely. Transcripts of the interviews were analysed by the research team following the principles of reflexive thematic analysis. Results We completed interviews with 28 mental health professionals from varied professional backgrounds, career stages and settings across the UK. Mental health professionals were motivated and driven to develop new clinical pathways to support HSCWs they perceived as colleagues and many experienced professional growth. However, this also came at some costs, as they took on additional responsibilities and increased workloads, were anxious and uncertain about how best to support this workforce and tended to neglect their own health and well-being. Many were professionally isolated and were affected vicariously by the traumas and moral injuries that healthcare workers talked about in sessions. Conclusions This research highlights the urgent need to consider the mental well-being, training and support of mental health professionals who are supporting front-line workers.

Background: Healthcare workers across the world have risen to the demands of treating COVID-19 patients, potentially at significant cost to their own health and wellbeing. There has been increasing recognition of the potential mental health impact of COVID-19 on frontline workers and calls to provide psychosocial support for them. However, little attention has so far been paid to understanding the impact of working on a pandemic from healthcare workers’ own perspectives or what their views are about support. Methods: We searched key healthcare databases (Medline, PsychINFO and PubMed), reviewed relevant grey literature, screened pre-print servers and hand searched reference lists of key texts for all published accounts of healthcare workers’ experiences of working on the frontline and views about support during COVID-19 and previous pandemics/epidemics. Final searches took place on September 28, 2020. We conducted a meta-synthesis of all qualitative results to synthesise findings and develop an overarching set of themes and sub-themes which captured the experiences and views of frontline healthcare workers across the studies. Results: This review identified 46 qualitative studies which explored healthcare workers’ experiences and views from pandemics or epidemics including and prior to COVID-19. Meta-synthesis derived eight key themes which largely transcended temporal and geographical boundaries. Participants across all the studies were deeply concerned about their own and/or others’ physical safety. This was greatest in the early phases of pandemics and exacerbated by inadequate PPE, insufficient resources, and inconsistent information. Workers struggled with high workloads and long shifts and desired adequate rest and recovery. Many experienced stigma. Healthcare workers’ relationships with families, colleagues, organisations, media and the wider public were complicated and nuanced and could be experienced concomitantly as sources of support but also sources of stress. Conclusions: The experiences of healthcare workers during the COVID-19 pandemic are not unprecedented; the themes that arose from previous pandemics and epidemics were remarkably resonant with what we are hearing about the impact of COVID-19 globally today. We have an opportunity to learn from the lessons of these previous crises, mitigate the negative mental health impact of COVID-19 and support the longer-term wellbeing of the healthcare workforce worldwide.

Background: Studies have shown that working in frontline healthcare roles during epidemics and pandemics was associated with PTSD, depression, anxiety, and other mental health disorders. Objectives: The objectives of this study were to identify demographic, work-related and other predictors for clinically significant PTSD, depression, and anxiety during the COVID-19 pandemic in UK frontline health and social care workers (HSCWs), and to compare rates of distress across different groups of HCSWs working in different roles and settings. Methods: A convenience sample (n = 1194) of frontline UK HCSWs completed an online survey during the first wave of the pandemic (27 May – 23 July 2020). Participants worked in UK hospitals, nursing or care homes and other community settings. PTSD was assessed using the International Trauma Questionnaire (ITQ); Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9); Anxiety was assessed using the Generalized Anxiety Disorder Scale (GAD-7). Results: Nearly 58% of respondents met the threshold for a clinically significant disorder (PTSD = 22%; anxiety = 47%; depression = 47%), and symptom levels were high across occupational groups and settings. Logistic regression analyses found that participants who were concerned about infecting others, who could not talk with their managers if there were not coping, who reported feeling stigmatized and who had not had reliable access to personal protective equipment (PPE) were more likely to meet criteria for a clinically significant mental disorder. Being redeployed during the pandemic, and having had COVID were associated with higher odds for PTSD. Higher household income was associated with reduced odds for a mental disorder. Conclusions: This study identified predictors of clinically significant distress during COVID-19 and highlights the need for reliable access to PPE and further investigation of barriers to communication between managers and staff., HIGHLIGHTS During the first UK COVID-19 wave, 22% met criteria for PTSD, 47% met criteria for anxiety, and 47% met criteria for depression. Being concerned about infecting others, not being able to tell managers about not coping, feeling stigmatized, and not having reliable access to personal protective equipment raised odds for distress.

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.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.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.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.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.

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.

Background The COVID-19 pandemic has placed a significant burden on the mental health and wellbeing of frontline health and social care workers. The need to support frontline staff has been recognised. However, there is to date little research specifically on how best to support the mental health needs of frontline workers, and none on their own experiences and views about what might be most helpful. Aims We set out to redress this research gap by qualitatively exploring UK frontline health and social care workers’ own experiences and views of psychosocial support during the pandemic. Method Frontline health and social care workers were recruited purposively through social media and by snowball sampling via healthcare colleagues. Workers who volunteered to take part in the study were interviewed remotely following a semi-structured interview guide. Transcripts of the interviews were analysed by the research team following the principles of Reflexive Thematic Analysis. Results We conducted 25 interviews with frontline workers from a variety of professional groups working in health and social care settings across the UK. Themes derived from our analysis showed that workers’ experiences and views about psychosocial support were complex. Peer support was many workers’ first line of support but could also be experienced as a burden. Workers were ambivalent about support shown by organisations, media and the public. Whilst workers valued psychological support services, there were many disparities in provision and barriers to access. Conclusions The results of this study show that frontline health and social care workers are likely to need a flexible system of support including peer, organisational and professional support. More research is needed to fully unpack the structural, systemic and individual barriers to accessing psychosocial support. Greater collaboration, consultation and co-production of support services and their evaluation is warranted.

Background: Healthcare workers (HCWs) are considered at elevated risk of experiencing mental health disorders in working with patients with COVID-19. Objective: To estimate the prevalence of common mental health disorders in HCWs based in hospitals where pandemic-affected patients were treated. Method: Databases were searched for studies published before 30 March 2020. Quantitative synthesis was used to obtain estimates of the prevalence of mental health disorders in four time windows, determined a priori (the acute phase, i.e. during and up to 1.5 months post-pandemic; 1.5–5.9 months; 6–11.9 months; 12 months and later). Results: Nineteen studies met the review criteria. They predominantly addressed the acute phase of the SARS outbreak in Asia. The most studied outcomes were clinically significant post-traumatic stress symptoms (PTSS) and general psychiatric caseness. For clinically significant PTSS in the acute phase, the prevalence estimate was 23.4% (95% CI 16.3, 31.2; N = 4147; I2 = 96.2%); in the 12 months plus window, the estimate was 11.9% (8.4, 15.8; N = 1136; I2 = 74.3%). For general psychiatric caseness, prevalence estimates were acute phase, 34.1% (18.7, 51.4; N = 3971; I2 = 99.1%); 6–12 months, 17.9% (13.1, 23.2; N = 223; I2 = 0.0%); 12 months plus, 29.3% (6.0, 61.0; N = 710; I2 = 97.8%). No differences between doctors and nurses with respective to PTSS and general psychiatric caseness were apparent in the acute phase. Conclusions: Mental health disorders are particularly common in HCWs working with pandemic-afflicted patients immediately following a pandemic, but the course of disorders following this period is poorly understood. There was considerable heterogeneity between studies, likely linked to methodological differences. More extended follow up of HCWs is needed., HIGHLIGHTS: • Mental health difficulties, in particular post-traumatic stress, are common in healthcare workers working with patients infected during a pandemic. The long-term impact of working in such environments is poorly understood, however.

Background Healthcare workers across the world have risen to the demands of treating COVID-19 patients, potentially at significant cost to their own health and wellbeing. There has been increasing recognition of the potential mental health impact of COVID-19 on frontline workers and calls to provide psychosocial support for them. However, little attention has so far been paid to understanding the impact of working on a pandemic from healthcare workers’ own perspectives or what their views are about support. Methods We searched key healthcare databases (Medline, PsychINFO and PubMed) from inception to September 28, 2020. We also reviewed relevant grey literature, screened pre-print servers and hand searched reference lists of key texts for all published accounts of healthcare workers’ experiences of working on the frontline and views about support during COVID-19 and previous pandemics/epidemics. We conducted a meta-synthesis of all qualitative results to synthesise findings and develop an overarching set of themes and sub-themes which captured the experiences and views of frontline healthcare workers across the studies. Results This review identified 46 qualitative studies which explored healthcare workers’ experiences and views from pandemics or epidemics including and prior to COVID-19. Meta-synthesis derived eight key themes which largely transcended temporal and geographical boundaries. Participants across all the studies were deeply concerned about their own and/or others’ physical safety. This was greatest in the early phases of pandemics and exacerbated by inadequate Personal Protective Equipment (PPE), insufficient resources, and inconsistent information. Workers struggled with high workloads and long shifts and desired adequate rest and recovery. Many experienced stigma. Healthcare workers’ relationships with families, colleagues, organisations, media and the wider public were complicated and could be experienced concomitantly as sources of support but also sources of stress. Conclusions The experiences of healthcare workers during the COVID-19 pandemic are not unprecedented; the themes that arose from previous pandemics and epidemics were remarkably resonant with what we are hearing about the impact of COVID-19 globally today. We have an opportunity to learn from the lessons of previous crises, mitigate the negative mental health impact of COVID-19 and support the longer-term wellbeing of the healthcare workforce worldwide.

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have somewhat opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In particular the striatum is implicated in the pathophysiology of several psychiatric disorders, but it is unclear how THC and CBD influence striato-cortical connectivity. Across two placebo-controlled, double-blind studies, we examine the effects of THC, CBD, and THC+CBD on the functional connectivity of striatal sub-divisions (associative, limbic, and sensorimotor) using resting-state functional Magnetic Resonance Imaging (fMRI) and seed-based functional connectivity analyses. Study 1 (N=17; inhaled 8mg THC, 8mg THC+10mg CBD, placebo) showed strong disruptive effects of both THC and THC+CBD conditions on connectivity in the associative and sensorimotor networks, but a specific effect of THC in the limbic striatum, which was alleviated in the THC+CBD condition such that it did not differ from placebo. In Study 2 (N=23, oral 600mg CBD, placebo) CBD increased connectivity in the associative network, but relatively minor decreases/disruptions were found in the limbic and sensorimotor. In conclusion, THC strongly disrupts striato-cortical networks, and this effect is selectively mitigated in the limbic striatum when co-administered with CBD. When administered alone, 600mg oral CBD has a more complex effect profile of relative increases and decreases in connectivity. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis related disorders, and the development of cannabinoid therapeutics.

BackgroundDevelopmental psychological trauma can impact several key neurocognitive domains, including reward processing, and is associated with increased risk of psychosis in adulthood. Aberrant reinforcement learning (RL), an important component of reward processing, has been implicated in the pathophysiology of psychosis by altering information processing through changes in hierarchical predictive coding. We therefore sought to investigate RL in survivors of developmental trauma and its relationship to psychotic experiences.MethodsWe recruited two groups of adults, one with self-reported exposure to multiple forms of developmental trauma (n=115), and a control group without any known history of maltreatment (n=85). Participants completed measures of psychotic experiences (Community Assessment of Psychic Experiences) and undertook a probabilistic selection task designed to assess RL from positive versus negative outcomes. We analysed group differences for main effects and investigated relationships between developmental trauma, RL and psychotic experiences using regression modelling and mediation analysis.ResultsDevelopmental trauma was associated with psychotic experiences (adjusted R2=0.41,p=0.004) and impaired RL (Fdf=6.291,89,p=0.014). Impaired RL mediated the association between developmental trauma and psychotic experiences (indirect effectβ= 0.60, 95% CI, 0.01–1.36).ConclusionsOur findings implicate aberrant RL as a possible mechanism through which developmental trauma may increase risk of psychosis. Further research is therefore warranted to understand the specific processes that characterise these putative trauma-induced vulnerability mechanisms and how they may contribute to the development of psychopathology.

BackgroundStudies have shown that working in frontline healthcare roles during epidemics and pandemics was associated with PTSD, depression, anxiety, and other mental health disorders.ObjectivesThe objectives of this study were to identify demographic, work-related and other predictors for clinically significant PTSD, depression, and anxiety during the COVID-19 pandemic in UK frontline health and social care workers (HSCWs), and to compare rates of distress across different groups of HCSWs working in different roles and settings.MethodsA convenience sample (n=1194) of frontline UK HCSWs completed an online survey during the first wave of the pandemic (27 May – 23 July 2020). Participants worked in UK hospitals, nursing or care homes and other community settings. PTSD was assessed using the International Trauma Questionnaire (ITQ); Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9); Anxiety was assessed using the Generalized Anxiety Disorder Scale (GAD-7).ResultsNearly 58% of respondents met the threshold for clinically significant PTSD, anxiety or depression, and symptom levels were high across occupational groups and settings. Logistic regression analyses found that participants who were concerned about infecting others, who felt they could not talk with their managers, who reported feeling stigmatised and who had not had reliable access to personal protective equipment (PPE) were more likely to meet criteria for a clinically significant mental disorder. Being redeployed during the pandemic, and having had COVID were associated with higher odds for PTSD. Higher household income was associated with reduced odds for a mental disorder.ConclusionsThis study identified predictors of clinically significant distress during COVID-19 and highlights the need for reliable access to PPE and further investigation of barriers to communication between managers and staff.

The theory that dopaminergic mechanisms play a role in psychosis has evolved since the mid-twentieth century. This followed research which found that the clinical potency of antipsychotics was directly related to their affinity for dopamine receptors and drugs that cause dopamine release caused psychotic symptoms. Molecular imaging studies have found consistent evidence that elevated striatal dopamine synthesis capacity is associated with psychotic symptoms including in people with schizophrenia, people at risk of psychosis and first-degree relatives of people with schizophrenia. Importantly, dopamine elevation has been positively correlated with severity of psychotic symptoms. There is also evidence that dopamine dysfunction may be a transdiagnostic feature of psychosis. The dopamine system plays a key role in cognition, including reward prediction error signaling and salience processing. Dopaminergic dysfunction has been hypothesized to give rise to psychosis through aberrant salience processing. Since stressful experiences are highly salient for an organism’s survival, the dopamine system plays a key role in the brain’s response to stressors. Chronic stressors occurring during development can induce long-term changes in dopamine function and may thus provide a pathway through which environmental risk factors for psychosis alter neurobiology to give rise to psychosis. At least some genetic risk factors for psychosis also converge on the dopamine system. These findings have given rise to a “dual hit” model of dopaminergic dysfunction involving genetic vulnerability and responses to environmental stressors.

Cannabis and its main psychoactive component, ΔWe 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.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.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.

Acute and chronic exposure to cannabis and its main psychoactive component, Δ 9-tetrahydrocannabinol (THC), is associated with changes in brain function and cerebral blood flow (CBF). We therefore sought to systematically review the literature on the effects of THC on CBF following PRISMA guidelines. Studies assessing the acute and chronic effects of THC on CBF, perfusion and volume were searched in the PubMed database between January 1972 and June 2019. We included thirty-four studies, which altogether investigated 1259 humans and 28 animals. Acute and chronic THC exposure have contrasting and regionally specific effects on CBF. While acute THC causes an overall increase in CBF in the anterior cingulate cortex, frontal cortex and insula, in a dose-dependent manner, chronic cannabis use results in an overall reduction in CBF, especially in the prefrontal cortex, which may be reversed upon prolonged abstinence from the drug. Future studies should focus on standardised methodology and longitudinal assessment to strengthen our understanding of the region-specific effects of THC on CBF and its clinical and functional significance.

Religious leaders are at risk of psychological trauma and moral injury during the COVID-19 pandemic. This article highlights potentially traumatic or morally injurious experiences for religious leaders and provides evidence-based recommendations for mitigating their impact. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Summary 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.

ObjectivesCOVID-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.DesignData 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.SettingThe majority of participants worked in hospitals (53%), in nursing or care homes (15%), or in other community settings (30%).ParticipantsOf 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 measuresThreshold for severe anxiety according to the Generalised Anxiety Disorder Scale-7 or moderately severe depression according to the Patient Health Questionnaire-9.ResultsAnswering 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.ConclusionsAnswering two simple yes/no questions can provide simple and immediate guidance to assist with decisions about whether to seek further assessment or treatment.

Chronic psychosocial adversity induces vulnerability to mental illnesses. Animal studies demonstrate that this may be mediated by dopaminergic dysfunction. We therefore investigated whether long-term exposure to psychosocial adversity was associated with dopamine dysfunction and its relationship to psychological and physiological responses to acute stress. Using 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F]-DOPA) positron emission tomography (PET), we compared dopamine synthesis capacity in n = 17 human participants with high cumulative exposure to psychosocial adversity with n = 17 age- and sex-matched participants with low cumulative exposure. The PET scan took place 2 hr after the induction of acute psychosocial stress using the Montréal Imaging Stress Task to induce acute psychosocial stress. We found that dopamine synthesis correlated with subjective threat and physiological response to acute psychosocial stress in the low exposure group. Long-term exposure to psychosocial adversity was associated with dampened striatal dopaminergic function (p=0.03, d = 0.80) and that psychosocial adversity blunted physiological yet potentiated subjective responses to acute psychosocial stress. Future studies should investigate the roles of these changes in vulnerability to mental illnesses.

Acute and chronic exposure to cannabis and its main psychoactive component, Δ

N-methyl-d-aspartate receptor (NMDA-R) autoantibodies have been reported in people with acute psychosis. We hypothesised that their presence may be implicated in the aetiology of treatment-refractory psychosis. We sought to ascertain the point prevalence of NMDA-R antibody positivity in patients referred to services for treatment-refractory psychosis. We found that 3 (7.0%) of 43 individuals had low positive NMDA-R antibody titres. This suggests that NMDA-R autoantibodies are unlikely to account for a large proportion of treatment-refractory psychosis.

There is growing evidence that developmental trauma (including emotional, sexual, or physical abuse in childhood and/or adolescence) increases the risk of psychotic symptoms in adulthood. At least one type of developmental trauma is reported in half of individuals with psychosis, and individuals with psychosis report significantly more developmental trauma when compared with those without psychosis, including psychiatric comparison groups. There is evidence that the association between developmental trauma and psychosis fulfills Bradford Hill criteria for medical causation including strong and consistent associations between developmental trauma and psychosis, temporal relationships, and dose-effects. Crucially, developmental trauma has been estimated to cause approximately a third of cases of psychosis. Psychosis in adult survivors of developmental trauma is under-researched and there is a pressing need to improve treatments for this patient group. This is because adult survivors of developmental trauma who experience psychosis are at a higher risk of poor prognostic outcomes including more severe illness, higher risk of re-hospitalization, and worse response to treatment. Despite this, we have a striking lack of precision in our understanding of how developmental psychological trauma disrupts brain and cognitive function to induce vulnerability to psychosis. In this context, there is recent evidence that there may be brain imaging and cognitive differences between patients with psychosis who have and have not survived developmental trauma suggestive of a possible traumatogenic psychosis ecophenotype. This symposium will provide a state-of-the-art review with new data on developmental trauma and psychosis. Professor Mary Cannon from the Royal College of Surgeons in Ireland will first provide an update on the epidemiology of childhood trauma and psychosis. Advances in epidemiological research have resulted in new conceptualizations of psychosis and it is now being considered as a continuous phenotype rather than a binary and dichotomous pathological construct (Van Os et al., 2009, Kelleher et al., 2010). She will argue that there is a need for a more integrated and nuanced understanding of how and why psychotic symptoms emerge and, for a small minority, become entrenched and result in significant social and functional impairment. Professor Robin Emsley from Stellenbosch will then look to brain imaging and cognitive studies and examine how these help inform the mechanisms and specificity of the links between trauma and psychotic symptoms. Our attention will then turn to neurobiology. Dr Michael Bloomfield from University College London will present the current state of knowledge of the complex effects of developmental stress and trauma exposure on dopaminergic function in adulthood. Stress exposure potentiates aspects of dopaminergic processing including amplifying threat-related signaling in the ventral (limbic) striatum. This may occur alongside dopaminergic blunting in the amygdala resulting in deficits in fear extinction, impairing the ability to distinguish safe from unsafe environments. Finally, Professor Anthony Grace will present data from rodent models of prepubertal stress and the importance of this critical period in development will shed light into how early life stressors lead to increased susceptibility to schizophrenia even in individuals without a genetic predisposition. Professor Lynn DeLisi from Harvard Medical School will then discuss the symposium in light of her extensive clinical and research experience in both psychosis and trauma.

One of the most statistically significant loci to result from large-scale GWAS of schizophrenia is 10q24.32. However, it is still unclear how this locus is involved in the pathoaetiology of schizophrenia. The hypothesis that presynaptic dopamine dysfunction underlies schizophrenia is one of the leading theories of the pathophysiology of the disorder. Supporting this, molecular imaging studies show evidence for elevated dopamine synthesis and release capacity. Thus, altered dopamine function could be a potential mechanism by which this genetic variant acts to increase the risk of schizophrenia. We therefore tested the hypothesis that the 10q24.32 region confers genetic risk for schizophrenia through an effect on striatal dopamine function. To this aim we investigated the in vivo relationship between a GWAS schizophrenia-associated SNP within this locus and dopamine synthesis capacity measured using [18F]-DOPA PET in healthy controls. 92 healthy volunteers underwent [18F]-DOPA PET scans to measure striatal dopamine synthesis capacity (indexed as Ki cer) and were genotyped for the SNP rs7085104. We found a significant association between rs7085104 genotype and striatal Ki cer. Our findings indicate that the mechanism mediating the 10q24.32 risk locus for schizophrenia could involve altered dopaminergic function. Future studies are needed to clarify the neurobiological pathway implicated in this association.

Background Developmental trauma (DT) induces vulnerability to psychosis in adulthood. Adult survivors of DT with psychosis (ASDTP) have worse prognosis across a range of outcomes compared to individuals with psychosis without DT exposure. It has been suggested that this may reflect a developmental ‘traumatogenic’ psychosis phenotype, distinct from idiopathic schizophrenia. Given the implications for precision medicine, we therefore sought to test this hypothesis by conducting systematic reviews and meta-analyses of the literature comparing psychotic symptoms and neuroimaging findings between adults with psychosis diagnoses with and without developmental trauma. Methods We registered our search protocols in PROSPERO (CRD42018105021 and CRD42019131245). We systematically searched literature databases for relevant studies published up to July 2019. “Embase”, “MEDLINE”, and “PsychINFO” were systematically searched. Reference lists, OpenGrey, and Google scholar were hand-searched. Phenomenological outcomes of interests were quantitative and/or qualitative differences in psychotic symptom expression (primary outcome) and other domains of psychopathology (secondary outcome) between ASDTP and people with psychosis who did not report developmental trauma. Neuroimaging outcomes of interest including markers of brain volume and function (e.g. task-induced blood-oxygen dependent signal). Results Seventeen studies of symptomatology were included. Of these, four were meta-analysed. There was a relationship between DT and greater positive (Hedges g=0.53; p Discussion Adult survivors of developmental trauma have more severe psychotic symptoms than those without developmental trauma histories. Alongside findings of differences in symptom expression and neuroimaging, the evidence suggests that there may be developmental traumatogenic psychosis phenotype. However, a key mechanistic gap remains how clinical and neuroimaging findings relate to each other. Nonetheless, alternative interpretations, such as an underdiagnosis of post-traumatic stress disorder, could also be plausible. These findings warrant further research to elucidate vulnerability and resilience mechanisms for psychosis in adult survivors of developmental trauma.

Understanding genetic factors that contribute to cannabis use disorder (CUD) is important, but to date, findings have been equivocal. Single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 gene (CNR1; rs1049353 and rs806378) and fatty acid amide hydrolase (FAAH) gene (rs324420) have been implicated in CUD. Their relationship to addiction endophenotypes such as cannabis-related state satiety, the salience of appetitive cues, and craving after acute cannabinoid administration has not been investigated. Forty-eight cannabis users participated in a double-blind, placebo-controlled, four-way crossover experiment where they were administered treatments in a randomized order via vaporization: placebo, Δ 9 -tetrahydrocannabinol (THC) (8 mg), THC + cannabidiol (THC + CBD) (8 + 16 mg), and CBD (16 mg). Cannabis-related state satiety, appetitive cue salience (cannabis and food), and cannabis craving were assessed each day. Participants were genotyped for rs1049353, rs806378, and rs324420. Results indicated that CNR1 rs1049353 GG carriers showed increased state satiety after THC/THC + CBD administration in comparison with placebo and reduced the salience of appetitive cues after THC in comparison with CBD administration; A carriers did not vary on either of these measures indicative of a vulnerability to CUD. CNR1 rs806378 CC carriers showed greater salience to appetitive cues in comparison with T carriers, but there was no evidence for changes in state satiety. FAAH rs324420 A carriers showed greater bias to appetitive cues after THC, in comparison with CC carriers. FAAH CC carriers showed reduced bias after THC in comparison with CBD. No SNPs modulated craving. These findings identify candidate neurocognitive mechanisms through which endocannabinoid system genetics may influence vulnerability to CUD.

The laws governing cannabis are evolving worldwide and associated with changing patterns of use. The main psychoactive drug in cannabis is Δ9-tetrahydrocannabinol (THC), a partial agonist at the endocannabinoid CB1 receptor. Acutely, cannabis and THC produce a range of effects on several neurocognitive and pharmacological systems. These include effects on executive, emotional, reward and memory processing via direct interactions with the endocannabinoid system and indirect effects on the glutamatergic, GABAergic and dopaminergic systems. Cannabidiol, a non-intoxicating cannabinoid found in some forms of cannabis, may offset some of these acute effects. Heavy repeated cannabis use, particularly during adolescence, has been associated with adverse effects on these systems, which increase the risk of mental illnesses including addiction and psychosis. Here, we provide a comprehensive state of the art review on the acute and chronic neuropsychopharmacology of cannabis by synthesizing the available neuroimaging research in humans. We describe the effects of drug exposure during development, implications for understanding psychosis and cannabis use disorder, and methodological considerations. Greater understanding of the precise mechanisms underlying the effects of cannabis may also give rise to new treatment targets.

Whilst the role of the Disrupted-in-Schizophrenia 1 (DISC1) gene in the aetiology of major mental illnesses is debated, the characterization of its function lends it credibility as a candidate. A key aspect of this functional characterization is the determination of the role of common non-synonymous polymorphisms on normal variation within these functions. The common allele (A) of the DISCI single-nucleotide polymorphism (SNP) rs821616 encodes a serine (ser) at the Ser704Cys polymorphism, and has been shown to increase the phosphorylation of extracellular signal-regulated protein Kinases 1 and 2 (ERK1/2) that stimulate the phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme for dopamine biosynthesis. We therefore set out to test the hypothesis that human ser (A) homozygotes would show elevated dopamine synthesis capacity compared with cysteine (cys) homozygotes and heterozygotes (TT and AT) for rs821616. [F-18]-DOPA positron emission tomography (PET) was used to index striatal dopamine synthesis capacity as the influx rate constant K-i(cer) in healthy volunteers DISC1 rs821616 ser homozygotes (N = 46) and healthy volunteers DISC1. rs821616 cys homozygotes and heterozygotes (N = 56), matched for age, gender, ethnicity and using three scanners. We found DISC1 rs821616 ser homozygotes exhibited a significantly higher striatal K-i(cer) compared with cys homozygotes and heterozygotes (P = 0.012) explaining 6.4% of the variance (partial eta(2) = 0.064). Our finding is consistent with its previous association with heightened activation of ERK1/2, which stimulates tyrosine hydroxylase activity for dopamine synthesis. This could be a potential mechanism mediating risk for psychosis, lending further credibility to the fact that DISC1. is of functional interest in the aetiology of major mental illness. info:eu-repo/semantics/acceptedVersion

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Ethnic minority individuals have an increased risk of developing a psychotic disorder, particularly if they live in areas of ethnic segregation, or low own group ethnic density. The neurobiological mechanisms underlying this ethnic minority associated risk are unknown. We used functional MRI to investigate neural responses to faces of different ethnicity, in individuals of black ethnicity, and a control group of white British ethnicity individuals.In total 20 individuals of black ethnicity, and 22 individuals of white British ethnicity underwent a 3T MRI scan while viewing faces of black and white ethnicity. Own group ethnic density was calculated from the 2011 census. Neighbourhood segregation was quantified using the Index of Dissimilarity method.At the within-group level, both groups showed greater right amygdala activation to outgroup faces. Between groups, the black ethnicity group showed greater right amygdala activation to white faces, compared to the white ethnicity group. Within the black ethnicity group, individuals living in areas of lower own group ethnic density showed greater right amygdala reactivity to white faces (r = -0.61, p = 0.01).This is the first time an increased amygdala response to white faces has been demonstrated in individuals of black ethnicity. In the black ethnicity group, correlations were observed between amygdala response and neighbourhood variables associated with increased psychosis risk. These results may have relevance for our understanding of the increased rates of paranoia and psychotic disorders in ethnic minority individuals.