Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the ...two compounds have largely been studied separately.
To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers.
A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor.
Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p < 0.01), an increase in heart rate (p < 0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable.
In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.
Structure and function in the human brain are closely related. At the onset of psychosis, brain imaging studies have identified robust changes in brain function and structure, but no data are ...available relating these two domains. After systematic literature searches, we included all available studies reporting whole-brain structural or cognitive functional imaging findings in first-episode (FEP) subjects in multimodal Signed Differential Mapping (SDM). Forty-three studies met the inclusion criteria. The structural database comprised 965 FEP subjects matched with 1040 controls whilst the functional cohort included 362 FEP subjects matched with 403 controls. The analysis identified conjoint structural and functional differences in the insula/superior temporal gyrus and the medial frontal/anterior cingulate cortex bilaterally. In these regions, large and robust decreases in grey matter volume were found with either reduced or enhanced activation. Meta-regression analyses indicated that grey matter volume in the anterior cingulate and left insular clusters was influenced by exposure to antipsychotics: patients receiving medication were more likely to show structural abnormalities in these regions.
Prevention of psychosis has become a major objective of modern clinical psychiatry. An increasing number of new services have been established in Europe and in the world. The OASIS team has become an ...established model where clinical practice and research are fully integrated in the field of preventative interventions in psychosis.
Comprehensive analysis of different clinical and service measures describing the 2001–2011 implementation of the OASIS team.
Over the last decade, the OASIS team has received a total of 1102 referrals, mostly young males from ethnic minorities. After the assessment, 35% were diagnosed with an At Risk Mental State (ARMS) while 32% were already psychotic. Within the ARMS, 70% met the inclusion criteria for the attenuated psychotic symptoms subgroup, 1% met the inclusion criteria for the genetic deterioration syndrome, 9% met inclusion criteria for a brief and self-limited intermittent psychotic episode and the others met inclusion criteria for more than one subgroup. Most of them had at least one comorbid diagnosis, mainly relating to anxiety and depressive domains. The majority of the OASIS clients received cognitive behavioural therapy alone or in combination with antidepressants/antipsychotics. Over the 2-year follow-up time, 44 subjects (15.2%) developed a frank psychotic episode.
The OASIS service represents one of the largest and most established prodromal services in the world. The burden of research evidence and the translational impact produced on the clinical practice support the OASIS as a model for the development of similar services.
In summer 2018, central and northern Europe were stricken by extreme drought and heat (DH2018). The DH2018 differed from previous events in being preceded by extreme spring warming and brightening, ...but moderate rainfall deficits, yet registering the fastest transition between wet winter conditions and extreme summer drought. Using 11 vegetation models, we show that spring conditions promoted increased vegetation growth, which, in turn, contributed to fast soil moisture depletion, amplifying the summer drought. We find regional asymmetries in summer ecosystem carbon fluxes: increased (reduced) sink in the northern (southern) areas affected by drought. These asymmetries can be explained by distinct legacy effects of spring growth and of water-use efficiency dynamics mediated by vegetation composition, rather than by distinct ecosystem responses to summer heat/drought. The asymmetries in carbon and water exchanges during spring and summer 2018 suggest that future land-management strategies could influence patterns of summer heat waves and droughts under long-term warming.
In Europe, three widespread extreme summer drought and heat (DH) events have occurred in 2003, 2010 and 2018. These events were comparable in magnitude but varied in their geographical distribution ...and biomes affected. In this study, we perform a comparative analysis of the impact of the DH events on ecosystem CO
fluxes over Europe based on an ensemble of 11 dynamic global vegetation models (DGVMs), and the observation-based FLUXCOM product. We find that all DH events were associated with decreases in net ecosystem productivity (NEP), but the gross summer flux anomalies differ between DGVMs and FLUXCOM. At the annual scale, FLUXCOM and DGVMs indicate close to neutral or above-average land CO
uptake in DH2003 and DH2018, due to increased productivity in spring and reduced respiration in autumn and winter compensating for less photosynthetic uptake in summer. Most DGVMs estimate lower gross primary production (GPP) sensitivity to soil moisture during extreme summers than FLUXCOM. Finally, we show that the different impacts of the DH events at continental-scale GPP are in part related to differences in vegetation composition of the regions affected and to regional compensating or offsetting effects from climate anomalies beyond the DH centres. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
Subjects at ultra high-risk (UHR) for psychosis have an enhanced vulnerability to develop the disorder but the risk factors accounting for this accrued risk are undetermined.
Systematic review of ...associations between genetic or environmental risk factors for psychosis that are widely established in the literature and UHR state, based on comparisons to controls.
Forty-four studies encompassing 170 independent datasets and 54 risk factors were included. There were no studies on association between genetic or epigenetic risk factors and the UHR state that met the inclusion criteria. UHR subjects were more likely to show obstetric complications, tobacco use, physical inactivity, childhood trauma/emotional abuse/physical neglect, high perceived stress, childhood and adolescent low functioning, affective comorbidities, male gender, single status, unemployment and low educational level as compared to controls.
The increased vulnerability of UHR subjects can be related to environmental risk factors like childhood trauma, adverse life events and affective dysfunction. The role of genetic and epigenetic risk factors awaits clarification.
Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available ...structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment.
Fourteen voxel-based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk HR) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and "signed differential mapping" voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables.
Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta-analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results.
Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms.
In early stage psychosis research the identification of neurobiological correlates of vulnerability to schizophrenia is an important hurdle.
We systematically reviewed the neuroimaging publications ...on high-risk subjects with subsequent transition to psychosis (HR-T) and conducted a meta-analysis calculating the effect size Cohen's d.
Out of 30 identified studies 25 met the inclusion criteria. Structural (s)MRI studies showed small to medium effect sizes of decreased prefrontal, cingulate, insular and cerebellar gray matter volume in HR-T compared to high-risk subjects without transition (HR-NT). Meta-analysis revealed relatively larger whole brain volumes in HR-T compared to HR-NT subjects (mean Cohen's d 0.36, 95% CI 0.27–0. 46). Compared to HR-NT, HR-T subjects showed in functional imaging studies reduced brain activation in prefrontal cortex, reduced neuronal density, and increased membrane turnover in frontal and cingulate cortex with medium to large effect sizes.
Despite methodological differences between studies, structural and neurochemical abnormalities in prefrontal, anterior cingulate, medial temporal and cerebellar cortex might be predictive for development of psychosis within HR subjects.
Many research groups have attempted to predict which individuals with an at-risk mental state (ARMS) for psychosis will later develop a psychotic disorder. However, it is difficult to predict the ...course and outcome based on individual symptoms scores.
Data from 318 ARMS individuals from two specialized services for ARMS subjects were analysed using latent class cluster analysis (LCCA). The score on the Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to explore the number, size and symptom profiles of latent classes.
LCCA produced four high-risk classes, censored after 2 years of follow-up: class 1 (mild) had the lowest transition risk (4.9%). Subjects in this group had the lowest scores on all the CAARMS items, they were younger, more likely to be students and had the highest Global Assessment of Functioning (GAF) score. Subjects in class 2 (moderate) had a transition risk of 10.9%, scored moderately on all CAARMS items and were more likely to be in employment. Those in class 3 (moderate-severe) had a transition risk of 11.4% and scored moderately severe on the CAARMS. Subjects in class 4 (severe) had the highest transition risk (41.2%), they scored highest on the CAARMS, had the lowest GAF score and were more likely to be unemployed. Overall, class 4 was best distinguished from the other classes on the alogia, avolition/apathy, anhedonia, social isolation and impaired role functioning.
The different classes of symptoms were associated with significant differences in the risk of transition at 2 years of follow-up. Symptomatic clustering predicts prognosis better than individual symptoms.
Social isolation is a relevant problem for veterans who are at risk for disengaging from others as a function of transition stress from military life to civilian life, and given high rates of ...exposure to trauma and psychological distress. Few researchers have examined social isolation in veterans over time, particularly during COVID-19 that led to significant barriers and restrictions on social interactions. The purpose of this longitudinal study was to assess veterans' experience of social isolation and its mental health and social functioning correlates during a 6-month period of the COVID-19 pandemic. Participants were 188 United States veterans of the Iraq and Afghanistan wars. A total of four assessments were administered: one every two months for a total duration of six months. The average number of completed assessments across all participants was 3.70 (SD = 0.75) with 159 participants (84.13%) completing all four timepoints. Surveys included measures of global mental health and social functioning as indicated by perceived emotional support, quality of marriage, and couple satisfaction. Multilevel modeling was used to assess 1) growth models to determine whether social isolation changed over time and the trajectory of that change (i.e., linear or quadratic); and 2) whether social isolation was related to both concurrent and prospective indicators of mental health and social functioning. All analyses included person mean centered and grand mean centered isolation to assess for within-and between-person effects. Veterans reported a quadratic trajectory in social isolation that decreased slightly and stabilized over time. Findings indicate that higher social isolation, at both the within- and between-person level, was negatively associated with concurrent emotional support, mental health, quality of marriage, and couple satisfaction. However, all prospective effects were nonsignificant at the within-person level. Results suggest although isolation may decrease over time, veterans report worse mental health and social functioning during times when they report higher levels of social isolation compared to themselves and others. Future work is needed to determine if interventions can be applied during those times to prevent or target those negative associations.
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