scholarly journals Epigenetic mediation of AKT1 rs1130233 s effect on delta-9-tetrahydrocannabinol-induced medial temporal function during fear processing

2021 ◽  
Author(s):  
Grace Blest-Hopley ◽  
Marco Colizzi ◽  
Diana Prata ◽  
Vincent Giampietro ◽  
Michael Brammer ◽  
...  
Keyword(s):  
Brain Function ◽  
Brain Regions ◽  
Parahippocampal Gyrus ◽  
Double Blind ◽  
Single Nucleotide ◽  
Epigenetic Methylation ◽  
Temporal Function ◽  
Dopamine Signaling ◽  
High Doses ◽  
Epigenetic Modulation

High doses of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, have been shown to have anxiogenic effects. Also, THC effects have been shown to be modulated by genotype, including the single nucleotide polymorphism (SNP) rs1130233 at the protein kinase AKT1 gene, a key component of the dopamine signaling cascade. As such, it is likely that epigenetic methylation around this SNP may affect AKT gene expression, which may in turn impact on the acute effects of THC on brain function. We investigated the genetic (AKT1 rs1130233) and epigenetic modulation of brain function during fear processing in a 2-session, double-blind, cross-over, randomized placebo-controlled THC administration, in 36 healthy males. Fear processing was assessed using an emotion (fear processing) paradigm, under functional magnetic resonance imaging (fMRI). Complete genetic and fMRI data was available for 34 participants. THC caused an increase in anxiety and transient psychotomimetic symptoms and para-hippocampal gyrus/ amygdala activation. Number of A alleles at the AKT1 rs1130233 SNP, and percentage methylation at the CpG11-12 site, were independently associated with a greater effect of THC on activation in a network of brain regions including left and right parahippocampal gyri, respectively. AKT1 rs1130233 moderation of the THC effect on left parahippocampal activation persisted after covarying for methylation percentage, and was partially mediated in sections of the left parahippocampal gyrus/ hippocampus by methylation percentage. These results may offer an example of how genetic and epigenetic variations influence the psychotomimetic and neurofunctional effects of THC.

scholarly journals Epigenetic Mediation of AKT1 rs1130233′s Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing

2021 ◽  
Vol 11 (9) ◽  
pp. 1240
Author(s):  
Grace Blest-Hopley ◽  
Marco Colizzi ◽  
Diana Prata ◽  
Vincent Giampietro ◽  
Michael Brammer ◽  
...  
Keyword(s):  
Brain Function ◽  
Brain Regions ◽  
Parahippocampal Gyrus ◽  
Double Blind ◽  
Single Nucleotide ◽  
Epigenetic Methylation ◽  
Temporal Function ◽  
Left And Right ◽  
High Doses ◽  
Epigenetic Modulation

High doses of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, have been shown to have anxiogenic effects. Additionally, THC effects have been shown to be modulated by genotype, including the single nucleotide polymorphism (SNP) rs1130233 at the protein kinase AKT1 gene, a key component of the dopamine signalling cascade. As such, it is likely that epigenetic methylation around this SNP may affect AKT gene expression, which may in turn impact on the acute effects of THC on brain function. We investigated the genetic (AKT1 rs1130233) and epigenetic modulation of brain function during fear processing in a 2-session, double-blind, cross-over, randomized placebo-controlled THC administration, in 36 healthy males. Fear processing was assessed using an emotion (fear processing) paradigm, under functional magnetic resonance imaging (fMRI). Complete genetic and fMRI data were available for 34 participants. THC caused an increase in anxiety and transient psychotomimetic symptoms and para-hippocampal gyrus/ amygdala activation. Number of A alleles at the AKT1 rs1130233 SNP, and percentage methylation at the CpG11–12 site, were independently associated with a greater effect of THC on activation in a network of brain regions including left and right parahippocampal gyri, respectively. AKT1 rs1130233 moderation of the THC effect on left parahippocampal activation persisted after covarying for methylation percentage, and was partially mediated in sections of the left parahippocampal gyrus/ hippocampus by methylation percentage. These results may offer an example of how genetic and epigenetic variations influence the psychotomimetic and neurofunctional effects of THC.

scholarly journals Genetic Determinants of Neurobehavioral Responses to Caffeine Administration during Sleep Deprivation: A Randomized, Cross Over Study (NCT03859882)

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 555
Author(s):  
Mégane Erblang ◽  
Fabien Sauvet ◽  
Catherine Drogou ◽  
Michaël Quiquempoix ◽  
Pascal Van Beers ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Placebo Condition ◽  
Double Blind ◽  
Single Nucleotide ◽  
Psychomotor Vigilance Test ◽  
Tnf Α ◽  
And Performance ◽  
Psychomotor Vigilance

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).

Methylphenidate reduces orienting bias in healthy individuals

2021 ◽  
pp. 026988112199688
Author(s):  
Leehe Peled-Avron ◽  
Hagar Gelbard Goren ◽  
Noa Brande-Eilat ◽  
Shirel Dorman-Ilan ◽  
Aviv Segev ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Asymmetric Effect ◽  
Healthy Individuals ◽  
Double Blind ◽  
Spatial Orienting ◽  
Individual Trait ◽  
Neurological Patients ◽  
Dopamine Signaling ◽  
First Time ◽  
Neural Effect

Background: Healthy individuals show subtle orienting bias, a phenomenon known as pseudoneglect, reflected in a tendency to direct greater attention toward one hemispace. Accumulating evidence indicates that this bias is an individual trait, and attention is preferentially directed contralaterally to the hemisphere with higher dopamine signaling. Administration of methylphenidate (MPH), a dopamine transporter inhibitor, was shown to normalize aberrant spatial attention bias in psychiatric and neurological patients, suggesting that the reduced orienting bias following administration of MPH reflects an asymmetric effect of the drug, increasing extracellular dopamine in the hemisphere with lower dopamine signaling. Aim: We predicted that, similarly to its effect on patients with brain pathology, MPH will reduce the orienting bias in healthy subjects. Methods: To test this hypothesis, we examined the behavioral effects of a single dose (20 mg) of MPH on orienting bias in 36 healthy subjects (18 females) in a randomized, double-blind placebo-controlled, within-subject design, using the greyscales task, which has been shown to detect subtle attentional biases in both patients and healthy individuals. Results/outcomes: Results demonstrate that healthy individuals vary in both direction and magnitude of spatial orienting bias and show reduced magnitude of orienting bias following MPH administration, regardless of the initial direction of asymmetry. Conclusions/interpretations: Our findings reveal, for the first time in healthy subjects, that MPH decreases spatial orienting bias in an asymmetric manner. Given the well-documented association between orienting bias and asymmetric dopamine signaling, these findings also suggest that MPH might exert a possible asymmetric neural effect in the healthy brain.

scholarly journals Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110024
Author(s):  
Xin Chen ◽  
Yuanchun Ma ◽  
Xiongjun Mou ◽  
Hao Liu ◽  
Hao Ming ◽  
...  
Keyword(s):  
Animal Behavior ◽  
Neural Circuit ◽  
Concentration Level ◽  
Brain Regions ◽  
Mild Stress ◽  
Depression Effect ◽  
Monoamine Neurotransmitters ◽  
Reward Circuitry ◽  
High Doses ◽  
The Brain

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.

A rigorous approach for testing the constructionist hypotheses of brain function

2012 ◽  
Vol 35 (3) ◽  
pp. 148-149 ◽  
Author(s):  
Gopikrishna Deshpande ◽  
K. Sathian ◽  
Xiaoping Hu ◽  
Joseph A. Buckhalt
Keyword(s):  
Granger Causality ◽  
Strong Evidence ◽  
Bayesian Modeling ◽  
Brain Function ◽  
Brain Regions ◽  
Causal Modeling ◽  
Dynamic Causal Modeling ◽  
Rigorous Approach ◽  
Target Article ◽  
Co Activation

AbstractAlthough the target article provides strong evidence against the locationist view, evidence for the constructionist view is inconclusive, because co-activation of brain regions does not necessarily imply connectivity between them. We propose a rigorous approach wherein connectivity between co-activated regions is first modeled using exploratory Granger causality, and then confirmed using dynamic causal modeling or Bayesian modeling.

Structural and Functional MRI Brain Changes in Patients with Schizophrenia Following Electroconvulsive Therapy: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Yuchao Jiang ◽  
Mingjun Duan ◽  
Hui He ◽  
Dezhong Yao ◽  
Cheng Luo
Keyword(s):  
Systematic Review ◽  
Functional Mri ◽  
Electroconvulsive Therapy ◽  
Brain Regions ◽  
Parahippocampal Gyrus ◽  
Medical Subject Headings ◽  
Therapeutic Mechanisms ◽  
Brain Changes ◽  
Meta Analyses ◽  
Induced Changes

Background: Schizophrenia (SZ) is a severe psychiatric disorder typically characterized by multidimensional psychotic syndromes. Electroconvulsive therapy (ECT) is a treatment option for medication-resistant patients with SZ or to resolve acute symptoms. Although the efficacy of ECT has been demonstrated in clinical use, its therapeutic mechanisms in the brain remain elusive. Objective: This study aimed to summarize brain changes on structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) after ECT. Methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was carried out. The PubMed and Medline databases were systematically searched using the following medical subject headings (MeSH): (electroconvulsive therapy OR ECT) AND (schizophrenia) AND (MRI OR fMRI OR DTI OR DWI). Results: This review yielded 12 MRI studies, including 4 with sMRI, 5 with fMRI and 3 with multimodal MRI. Increases in volumes of the hippocampus and its adjacent regions (parahippocampal gyrus and amygdala) as well as insula and frontotemporal regions were noted after ECT. fMRI studies found ECT-induced changes in different brain regions/networks, including the hippocampus, amygdala, default model network, salience network and other regions/networks that are thought to highly correlate with the pathophysiologic characteristics of SZ. The results of the correlation between brain changes and symptom remissions are inconsistent Conclusion: Our review provides evidence supporting ECT-induced brain changes on sMRI and fMRI in SZ and explores the relationship between these changes and symptom remission.

Effects of Contralateral Electroacupuncture on Brain Function: A Double-Blind, Randomized, Pilot Clinical Trial

2006 ◽  
Vol 12 (8) ◽  
pp. 813-815 ◽  
Author(s):  
Young-Min Woo ◽  
Myeong Soo Lee ◽  
Young Nam ◽  
Hye-Jin Cho ◽  
Byung-Cheul Shin
Keyword(s):  
Clinical Trial ◽  
Brain Function ◽  
Double Blind

Diffusion tensor imaging (DTI) findings in schizophrenia: A review

2011 ◽  
Vol 26 (S2) ◽  
pp. 960-960
Author(s):  
J.L. Villegas Martínez ◽  
J.A. Blanco Garrote ◽  
F. Uribe Ladrón de Cegama ◽  
B. Arribas Simón ◽  
G. Cabús Piñol
Keyword(s):  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Cochrane Review ◽  
Brain Structures ◽  
Brain Regions ◽  
Parahippocampal Gyrus ◽  
First Episode ◽  
Chronic Patients ◽  
Brain White Matter ◽  
Diffusion Tensor Imaging Dti

IntroductionDiffusion tensor imaging (DTI) is a magnetic resonance imaging technique that have increasingly being used for the non-invasive evaluation of brain white matter (WM) abnormalities. Several studies suggest that the normal integration of cerebral function may be compromised in schizophrenia. Abnormalities in WM tracts may be directly relevant for the neuropathology of schizophrenia.ObjetivesThe purpose of this review was to discuss recent DTI findings in schizophrenia and a methodologic analysis.MethodsThe literature search was performed with the search engine PubMed of the U.S. National Library of Medicine. Search strategy used was based on the Cochrane review technique, limited to the period between 1998 (first report on DTI and schizophrenia) and May 2010. And limited to ‘Title/Abstract’. The reference lists of these studies were used to identify additional studies.ResultsThere is a striking amount of heterogeneity in findings, probably by methodologic problems. Brain regions such as the cingulate bundle, corpus callosum, and regions within frontal and temporal WM have a proportionally larger number of positive findings across the studies. In addition, WM tracts as The superior longitudinal fasciculus, fronto-occipital longitudinal fasciculi, uncinate fasciculi, frontal longitudinal fasciculus and the arcuate fasciculus have also positive findings in patients with schizophrenia. Other brain structures as the cerebellar peduncles, the fornix, the hippocampus and parahippocampal gyrus, the thalamic and optic radiations have been evaluated and shown positive findings. However, these findings are not present in all studies. DTI abnormalities in first-episode patients are less robust than in chronic patients.ConclusionsRecent DTI findings further support the hypothesis of structural dysconnectivity in schizophrenia.

Distinct Effects of D9-tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
P. Fusar-Poli
Keyword(s):  
Emotional Processing ◽  
Electrodermal Activity ◽  
Brain Regions ◽  
Posterior Cingulate Cortex ◽  
Psychotic Symptoms ◽  
Neural Activation ◽  
Double Blind ◽  
Posterior Cingulate ◽  
Fearful Faces ◽  
Scanning Session

Aims:Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.Method:Fifteen healthy English-native right-handed men were studied on three separate occasions using an event-related fMRI paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10mg of D-9-THC, 600mg of CBD, or a placebo, in a double-blind, randomised, placebo controlled design. Electrodermal activity (Skin Conductance Response, SCR) and objective and subjective ratings of anxiety were recorded durign the scanning.Results:D-9THC increased anxiety, as well as levels of intoxication, sedation and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of D-9THC but decreased following administration of CBD. CBD attenuated the BOLD signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and posterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. D-9-THC mainly modulated activation in frontal and parietal areas.Conclusions:D-9-THC and CBD had clearly distinct effects on the neural, eclectrodermal and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of D-9-THC may be related to effects in other brain regions.

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