A5086367626- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Treatment of Major Depression
- Bioinformatics and Genomic Networks
- Neurological Disease Mechanisms and Treatments
- Mental Health Research Topics
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Inflammation biomarkers and pathways
- Sleep and related disorders
- Sleep and Wakefulness Research
- Private Equity and Venture Capital
- Mathematics Education and Teaching Techniques
- Bipolar Disorder and Treatment
- Identity, Memory, and Therapy
- Corporate Finance and Governance
- Mining and Resource Management
- Reading and Literacy Development
- Entrepreneurship Studies and Influences
- Neuroendocrine regulation and behavior
- Circadian rhythm and melatonin
- Cognitive and developmental aspects of mathematical skills
- Neuroscience and Neuropharmacology Research
UCB Pharma (United Kingdom)
2019-2025
Eli Lilly (United Kingdom)
2016-2021
King's College London
2010-2019
Eli Lilly (United States)
2018
National Research Tomsk State University
2015
Al Akhawayn University
2011-2012
PharmacoGenetics (China)
2012
GTx (United States)
2012
The outcome of treatment with antidepressants varies markedly across people the same diagnosis. A clinically significant prediction outcomes could spare frustration trial and error approach improve major depressive disorder through individualized selection. It is likely that a combination multiple predictors needed to achieve such prediction. We used elastic net regularized regression optimize symptom improvement remission during escitalopram or nortriptyline identify contributing from range...
Epidemiological studies have recognized a genetic diathesis for suicidal behavior, which is independent of other psychiatric disorders. Genome-wide association (GWAS) on suicide attempt (SA) and ideation failed to identify specific variants. Here, we conduct further GWAS the first time, use polygenic score analysis in cohorts patients with mood disorders, test common variants disorders phenotypes. SA were conducted RADIANT GSK-Munich recurrent depression samples London Bipolar Affective...
Abstract Human genome-wide association studies (GWAS), transcriptome analyses of animal models, and candidate gene have advanced our understanding the genetic architecture aggressive behaviors. However, each these methods presents unique limitations. To generate a more confident comprehensive view complex genetics underlying aggression, we undertook an integrated, cross-species approach. We focused on human rodent models to derive eight lists from three main categories evidence: two sets...
One of sleep’s putative functions is mediation adaptation to waking experiences. Chronic stress a common experience; however, which specific aspect sleep most responsive, and how changes relate behavioral disturbances molecular correlates remain unknown. We quantified sleep, physical, endocrine, variables, as well the brain blood transcriptome in mice exposed 9 weeks unpredictable chronic mild (UCMS). Comparing 46 phenotypic variables revealed that rapid–eye-movement (REMS), corticosterone...
The datasets generated by DNA methylation analyses are getting bigger. With the release of HumanMethylationEPIC micro-array and containing thousands samples, these large using R becoming impractical due to memory requirements. As a result there is an increasing need for computationally efficient methodologies perform meaningful analysis on high dimensional data.Here we introduce bigmelon package, which provides workflow that enables users complex, scale required in epigenome wide association...
Individuals with depression differ substantially in their response to treatment antidepressants. Specific predictors explain only a small proportion of these differences. To meaningfully predict who will respond which antidepressant, it may be necessary combine multiple biomarkers and clinical variables. Using statistical learning on common genetic variants information training sample 280 individuals randomly allocated 12-week antidepressants escitalopram or nortriptyline, we derived models...
Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence stress prior to onset results in either 'reactive' 'endogenous' subtypes disorder, respectively. Several lines research suggest biological underpinnings may also differ, resulting differential response treatment. We investigated this hypothesis by comparing gene-expression profiles three animal models and depression. then translated these findings clinical samples using a human post-mortem mRNA...
Abstract Despite moderate heritability estimates, progress in uncovering the molecular substrate underpinning major depressive disorder (MDD) has been slow. In this study, we used prefrontal cortex (PFC) gene expression from a genetic rat model of MDD to inform probe set prioritization PFC human post-mortem study uncover genes and pathways associated with MDD. Gene differences between Flinders sensitive (FSL) resistant (FRL) lines were statistically evaluated using RankProd, non-parametric...
To develop a predictive model for the classification of seizure freedom under first-line monotherapy with levetiracetam in patients newly diagnosed epilepsy. Clinical data and routine EEG recordings epilepsy who were started on analyzed retrospectively. had been acquired prior to initiation treatment all patients. Patients experienced no further seizures until last follow-up labeled as seizure-free. Spectral features (band power, peak frequency) functional connectivity computed each patient...
Aim: This study aims to identify novel genes associated with major depressive disorder and pharmacological treatment response using animal human mRNA studies. Materials & methods: Weighted gene coexpression network analysis was used uncover stress factors in mice inform probe set selection a post-mortem of depression. Results: A total 171 were found be differentially regulated both early late protocols mouse study. Ten genes, orthologous expressed by stress, also dysregulated depressed cases...
Despite moderate heritability estimates, the molecular architecture of aggressive behavior remains poorly characterized. This study compared gene expression profiles from a genetic mouse model aggression with zebrafish, an animal traditionally used to aggression. A meta‐analytic, cross‐species approach was identify genomic variants associated behavior. The Rankprod algorithm evaluated mRNA differences prefrontal cortex tissues three sets lines (N = 18) selectively bred for low and high...
Individual differences in number sense correlate with mathematical ability and performance, although the presence strength of this relationship differs across studies. Inconsistencies literature may stem from heterogeneity constructs. Sample characteristics also play a role as changes between mathematics differ development cultural contexts. In study, 4,984 16-year-old students were assessed on estimation ability, one aspect sense. Estimation was measured using 2 different tasks: line...
Abstract Although monozygotic (MZ) twins share the majority of their genetic makeup, they can be phenotypically discordant on several traits and diseases. DNA methylation is an epigenetic mechanism that influenced by genetic, environmental stochastic events may have important impact individual variability. In this study we explored differences in peripheral blood samples three MZ twin studies major depressive disorder (MDD). Epigenetic data for pairs were collected as part a previous using...
To extend to biomarker studies the consensus clinical significance criterion of a three-point difference in Hamilton Rating Scale for Depression.We simulated datasets modeled on large trials.In typical trial comparing active treatment and placebo, three Depression (HRSD) points at end corresponds 6.3% variance outcome explained. achieve similar explanatory power, genotypes with minor allele frequencies 5, 10, 20, 30 50% need attain per 4.7, 3.6, 2.8, 2.4 2.2 HRSD points, respectively. A...
BALB/cJ is a strain susceptible to stress and extremely defective hedonic impact in response chronic stressors. The offers much promise as an animal model for the study of related disorders. We present comparative hippocampal gene expression on effects unpredictable mild C57BL/6J mice. Affymetrix MOE 430 was used measure from 16 animals two different strains (BALB/cJ C57BL/6J) both sexes subjected either (UCMS) or no stress. Differences were statistically evaluated through supervised...
Rare heterozygous coding variants in the triggering receptor expressed myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer's disease, have been identified. We examined transcriptional consequences loss Trem2 mouse brain to better understand its role disease using differential expression and coexpression network analysis knockout wild-type mice. generated RNA-Seq data from cortex hippocampus sampled at 4 8 months. Using cell-type markers ontology...
Rationale Monoaminergic imbalances play a role in the pathogenesis of depression and most common antidepressant drugs act on monoamine neurotransmitters. However, lag time between restoring neurochemical balance symptom improvement suggests that response to involves complex biological events downstream primary targets have not yet been fully characterized. Here, we report mouse mRNA expression study evaluate effect escitalopram (a serotonergic antidepressant) nortriptyline noradrenergic...
Rationale Selecting an effective treatment for patients with major depressive disorder is a perpetual problem psychiatrists. It of particular interest to explore the interaction between genetic predisposition and environmental factors. Objectives Mouse inbred strains vary in baseline performance depression-related behaviour tests, which were originally validated as tests antidepressant response. Therefore, we investigated interactions stress, genotype, drug response multifactorial study....
Background Peripheral nerve injury causes changes in expression of multiple receptors and mediators that participate pain processing. We investigated the microRNAs (miRNAs) – a class post-transcriptional regulators involved many physiological pathophysiological processes their potential role development or maintenance chronic neuropathic following lingual human rat. Methods profiled miRNA Sprague-Dawley rat neuromas using TaqMan® low-density array cards. Expression miRNAs interest was...