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Opposite Effects of Δ-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology
Δ-9-tetrahydrocannabinol (Δ-9-THC) and Cannabidiol (CBD), the two main ingredients of the
Cannabis sativa
plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Δ-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Δ-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Δ-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Δ-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Δ-9-THC. Δ-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Δ-9-tetrahydrocannabinol. Δ-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Δ-9-THC.
Journal Article
Supporting successful interventions in schools : tools to plan, evaluate, and sustain effective implementation
\"Evidence-based interventions only benefit learners when they are implemented fully. Yet many educators struggle with successful implementation. This unique book gives practitioners a research-based framework for working with PreK-12 educators to support the effective delivery of academic, behavioral, and social-emotional interventions. Step-by-step procedures are presented for assessing existing implementation efforts and using a menu of support strategies to promote intervention fidelity. In a large-size format with lay-flat binding for easy photocopying, the book includes 24 reproducible worksheets, strategy guides, and fidelity assessment tools. Purchasers get access to a Web page where they can download and print the reproducible materials. This book is in The Guilford Practical Intervention in the Schools Series, edited by T. Chris Riley-Tillman\"-- Provided by publisher.
Book
Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD
Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically induced effects. Previously, using pharmacological neuroimaging, we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to agonism of the serotonin-2A receptor (Preller et al., 2018). Here, we integrate brain-wide transcriptomics with biophysically based circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical large-scale spatiotemporal dynamics. Our model captures the inter-areal topography of LSD-induced changes in cortical blood oxygen level-dependent (BOLD) functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal-neuronal gain is a circuit mechanism through which LSD alters cortical functional topography. Individual-subject model fitting captures patterns of individual neural differences in pharmacological response related to altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to systems-level functional alterations, with implications for precision medicine.
Journal Article
The effect of brief case management on emergency department use of frequent users in mental health: Findings of a randomized controlled trial
Frequent users of hospital emergency departments (EDs) are a medically and socially vulnerable population. The Coordinated Access to Care from Hospital EDs (CATCH-ED) study examined the effectiveness of a brief case management intervention in reducing ED use and improving health outcomes among frequent ED users with mental health or addiction challenges in a large urban centre. Adults (≥18 years of age) who had five or more ED visits in the past 12-months, with at least one visit for mental health or addictions problems were randomized to either brief case management (N = 83) or usual care (N = 83) and followed for 12 months. The primary outcome of effectiveness was the frequency of ED visits during 12 months after study enrolment. Secondary outcomes included days in hospital, mental health and addiction symptom severity and health-related quality of life, measured by the SF-12. Compared to usual care, CATCH-ED participants saw a 14% reduction in frequency of ED visits during the 12-month post-randomization period [rate ratio (RR) = 0.86, 95% CI 0.64-1.15)], however, this finding did not reach statistical significance. There were also no statistically significant differences between the groups at 12 months in the number of days spent in hospital (RR = 1.16, 95% CI 0.59-2.29), physical (1.50, 95% CI -2.15-5.15) or mental (-3.97, 95% CI -8.13-0.19) component scores of the SF-12, severity of psychiatric symptoms (-0.41, 95% CI -2.30-1.49), alcohol (0.053 95% -0.017-0.12) or drug (-0.0027, 95% CI -0.0028-0.023) use. Compared to usual care, a brief case management intervention did not result in significantly reduced ED use or improved health outcomes among frequent ED users with mental health or addictions challenges in a large urban centre in Canada. Future studies need to evaluate the availability and accessibility of community-based resources for individuals with frequent ED use.
Journal Article
Personality, Attentional Biases towards Emotional Faces and Symptoms of Mental Disorders in an Adolescent Sample
To investigate the role of personality factors and attentional biases towards emotional faces, in establishing concurrent and prospective risk for mental disorder diagnosis in adolescence.
Data were obtained as part of the IMAGEN study, conducted across 8 European sites, with a community sample of 2257 adolescents. At 14 years, participants completed an emotional variant of the dot-probe task, as well two personality measures, namely the Substance Use Risk Profile Scale and the revised NEO Personality Inventory. At 14 and 16 years, participants and their parents were interviewed to determine symptoms of mental disorders.
Personality traits were general and specific risk indicators for mental disorders at 14 years. Increased specificity was obtained when investigating the likelihood of mental disorders over a 2-year period, with the Substance Use Risk Profile Scale showing incremental validity over the NEO Personality Inventory. Attentional biases to emotional faces did not characterise or predict mental disorders examined in the current sample.
Personality traits can indicate concurrent and prospective risk for mental disorders in a community youth sample, and identify at-risk youth beyond the impact of baseline symptoms. This study does not support the hypothesis that attentional biases mediate the relationship between personality and psychopathology in a community sample. Task and sample characteristics that contribute to differing results among studies are discussed.
Journal Article
Impact of a Participatory Intervention with Women’s Groups on Psychological Distress among Mothers in Rural Bangladesh: Secondary Analysis of a Cluster-Randomised Controlled Trial
Perinatal common mental disorders (PCMDs) are a major cause of disability among women and disproportionately affect lower income countries. Interventions to address PCMDs are urgently needed in these settings, and group-based and peer-led approaches are potential strategies to increase access to mental health interventions. Participatory women's health groups led by local women previously reduced postpartum psychological distress in eastern India. We assessed the effect of a similar intervention on postpartum psychological distress in rural Bangladesh.
We conducted a secondary analysis of data from a cluster-randomised controlled trial with 18 clusters and an estimated population of 532,996. Nine clusters received an intervention comprising monthly meetings during which women's groups worked through a participatory learning and action cycle to develop strategies for improving women's and children's health. There was one group for every 309 individuals in the population, 810 groups in total. Mothers in nine control clusters had access to usual perinatal care. Postpartum psychological distress was measured with the 20-item Self Reporting Questionnaire (SRQ-20) between six and 52 weeks after delivery, during the months of January to April, in 2010 and 2011.
We analysed outcomes for 6275 mothers. Although the cluster mean SRQ-20 score was lower in the intervention arm (mean 5.2, standard deviation 1.8) compared to control (5.3, 1.2), the difference was not significant (β 1.44, 95% CI 0.28, 3.08).
Despite promising results in India, participatory women's groups focused on women's and children's health had no significant effect on postpartum psychological distress in rural Bangladesh.
Journal Article
White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals
Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders.
Journal Article
Effects of ketamine-induced psychopathological symptoms on continuous overt rhyme fluency
The
N
-methyl-
d
-aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. Administered to healthy individuals, a subanesthetic dose of the noncompetitive NMDAR antagonist ketamine reproduces several psychopathological symptoms commonly observed in patients with schizophrenia. In a counterbalanced,
placebo
-controlled, double-blind, within-participants study, fifteen healthy subjects were administered a continuous subanesthetic
S
-ketamine infusion while cortical activation was measured using functional magnetic resonance imaging. While being scanned, subjects performed an overt word generation task. Ketamine-induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Ketamine administration elicited effects on psychopathology, including difficulties in abstract thinking, lack of spontaneity and flow of conversation as well as formal thought disorder. On a behavioral level, verbal fluency performance was unaffected. The PANSS score for formal thought disorder positively correlated with activation measures encompassing the left superior temporal gyrus, the right middle and inferior frontal gyrus and the precuneus. Difficulty in abstract thinking was correlated with pronounced activations in prefrontal as well as in anterior cingulate regions, whereas hyperactivations in the left superior temporal gyrus were found in association with a lack of spontaneity and flow of conversation. In the absence of behavioral impairments during verbal fluency, NMDAR blocking evoked psychopathological symptoms and cortical activations in regions previously reported in schizophrenia patients. The results provide further support for the hypothesis of an NMDAR dysfunction in the pathophysiology of schizophrenia.
Journal Article
5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology
L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed.
Journal Article