A5081369396- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Telomeres, Telomerase, and Senescence
- Genetics and Neurodevelopmental Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- Birth, Development, and Health
- HIV Research and Treatment
- Health, Environment, Cognitive Aging
- COVID-19 Clinical Research Studies
- Bipolar Disorder and Treatment
- Neuroendocrine regulation and behavior
- Neurogenesis and neuroplasticity mechanisms
- Bioinformatics and Genomic Networks
- Maternal Mental Health During Pregnancy and Postpartum
- Vitamin D Research Studies
- MicroRNA in disease regulation
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- Neuroscience and Neuropharmacology Research
- Nutritional Studies and Diet
- Chromosomal and Genetic Variations
- Genetic Associations and Epidemiology
- Computational Drug Discovery Methods
- COVID-19 diagnosis using AI
King's College London
2014-2024
Cornell University
2019-2024
Weill Cornell Medicine
2020-2021
Medical Research Council
2019
National Institute for Health Research
2017-2018
Centre for Mental Health
2017-2018
Maudsley Hospital
2017-2018
NIHR Biomedical Research Centre at The Royal Marsden and the ICR
2017-2018
University of Colorado Health
2005
Interferon-γ induces cellular and transcriptomic changes in human neural cells associated with neurodevelopmental disorders.
Abstract Human endogenous retroviruses (HERVs) are repetitive elements previously implicated in major psychiatric conditions, but their role aetiology remains unclear. Here, we perform specialised transcriptome-wide association studies that consider HERV expression quantified to precise genomic locations, using RNA sequencing and genetic data from 792 post-mortem brain samples. In Europeans, identify 1238 HERVs with regulated cis , of which 26 represent signals associated disorders, ten...
Overlapping characteristics between human depressive phenotypes and mouse behaviors has led to the creation of models that aim investigate pathophysiology treatment unipolar depression. Behavioral tests in mice are used assess quantify extent which a model displays depression-like phenotype. The forced swim test tail suspension test, sucrose preference novelty suppressed feeding all measure different components However, each one these strengths weaknesses terms predictive, face construct...
Abstract Transcriptional differences in interleukin-11 ( IL11 ) after antidepressant treatment have been found to correspond clinical response major depressive disorder (MDD) patients. Expression were partly mediated by a single-nucleotide polymorphism (rs1126757), identified as predictor of part genome-wide association study. Here we attempt identify whether DNA methylation, another baseline factor known affect transcription binding, might also predict response, using samples collected from...
Abstract Variation in telomere length is heritable and currently considered a promising biomarker of susceptibility for neuropsychiatric disorders, particularly because its association with memory function hippocampal morphology. Here, we investigate connection to familial risk disease expression bipolar disorder (BD). We used quantitative PCRs telomere-sequence single-copy-gene-sequence ratio method determine genomic DNA extracted from buccal smears 63 patients BD, 74 first-degree relatives...
Telomere length is a promising biomarker for age-related disease and potential anti-ageing drug target. Here, we study the genetic architecture of telomere repositioning lithium as an medication. LD score regression applied to largest genome-wide association to-date, revealed SNP-chip heritability estimates 7.29%, with polygenic risk scoring capturing 4.4% variance in independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated length, most significant being...
Studies have provided evidence that both childhood maltreatment and depressive disorders are associated with shortened telomere lengths. However, as is a risk factor for depression, it remains unclear whether this may be driving lengths observed amongst depressed patients. Furthermore, it's if the effects of on length shortening more pervasive patients relative to controls, consequently biological ageing contribute depression's pathophysiology. The current study assesses maltreatment,...
Mood disorders consist of two etiologically related, but distinctly treated illnesses, major depressive disorder (MDD) and bipolar (BPD). These share similarities in their clinical presentation, thus show high rates misdiagnosis. Recent research has revealed significant transcriptional differences within the inflammatory cytokine pathway between MDD patients controls, BPD suggesting this may possess important biomarker properties. This exploratory study attempts to identify disorder-specific...
Abstract Short telomere length is a risk factor for age-related disease, but it also associated with reduced hippocampal volumes, cognitive decline and psychiatric disorder risk. The current study explored whether shortening might have an influence on function pathophysiology, via its hypothesised effects adult neurogenesis. We modelled in human progenitor cells vitro using serial passaging protocol that mimics the end-replication problem. Serially passaged progenitors demonstrated shorter...
Abstract Background Vaccination programs have been launched worldwide to halt the spread of COVID-19. However, identification existing, safe compounds with combined treatment and prophylactic properties would be beneficial individuals who are waiting vaccinated, particularly in less economically developed countries, where vaccine availability may initially limited. Methods We used a data-driven approach, combining results from screening large transcriptomic database (L1000) molecular docking...
Abstract Lithium is a first-line treatment for bipolar disorder, where it acts as mood-stabilizing agent. Although its precise mechanism remains unclear, neuroimaging studies have shown that lithium accumulates in the hippocampus and chronic use amongst disorder patients associated with larger hippocampal volumes. Here, we tested effects of low (0.75 mM) high (2.25 doses on human progenitor cells used immunocytochemistry to investigate cell parameters implicated neurogenesis. Corresponding...
COVID-19 is the disease caused by SARS-CoV-2 which has led to 2,643,000 deaths worldwide, a number rapidly increasing. Urgent studies identify new antiviral drugs, repurpose existing or drugs that can target overactive immune response are ongoing. Antiretroviral (ARVs) have been tested in past human coronavirus infections, and also against SARS-CoV-2, but trial of lopinavir ritonavir failed show any clinical benefit COVID-19. However, there limited data as course people living with HIV, some...
Background: Since the neurotrophic hypothesis of depression was formulated, conflicting results have been reported regarding role growth factor proteins in depressed patients, including whether there are state or trait alterations found patients compared to controls and they represent predictors treatment response. Recently it has hypothesised that heterogeneity findings within this literature might be partly explained by participants' history treatment-resistant depression. This study aimed...
Previous studies have indicated that sex hormones such as prolactin, estradiol and testosterone may play a role in the modulation of adult hippocampal neurogenesis (AHN) rodents non-human primates, but so far there has been no investigation their impact on human neurogenesis. Here, we quantify expression levels relevant receptors post-mortem tissue progenitor cell (HPC) line. Secondly, investigate how these modulate using vitro cellular model. Human female HPCs were cultured with...
Background: Previous studies have revealed associations between psychiatric disorder diagnosis and shorter telomere length. Here, we attempt to discern whether genetic risk for disease, or use of pharmacological treatments (i.e. antidepressants), predict length ageing-related disease in a UK population sample. Methods: DNA samples from blood were available 351 participants who recruited as part the South East London Community Health (SELCoH) Study, which whole-genome genotype data was...
Abstract The zinc finger protein 804A ( ZNF804A ) and the 5′‐nucleotidase cytosolic II NT5C2 genes are amongst first schizophrenia susceptibility to have been identified in large‐scale genome‐wide association studies. has implicated regulation of neuronal morphology is required for activity‐dependent changes dendritic spines. Conversely, shown regulate 5′ adenosine monophosphate‐activated kinase activity synthesis human neural progenitor cells. Schizophrenia risk genotype associated with...
Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between duration of use, biological ageing and mortality. The UK Biobank observational middle-aged older adults. We tested associations use (number prescriptions, total first prescription period) telomere length, frailty, metabolomic age (MileAge) delta, pulse rate all-cause Five...
Previous studies have revealed increased biological ageing amongst major depressive disorder (MDD) patients, as assayed by shorter leukocyte telomere lengths (TL). Stressors such childhood maltreatment are more common MDD and it has been suggested that this might contribute to TL present patients. However, our knowledge, no study yet tested for reverse causality, i.e. whether a genetic predisposition predispose or an earlier onset of MDD. This used Mendelian randomisation design investigate...
Background Childhood maltreatment is one of the strongest predictors adulthood depression and alterations to circulating levels inflammatory markers putative mechanism mediating risk or resilience. Aims To determine effects childhood on 41 in healthy individuals those with a major depressive disorder (MDD) diagnosis. Method We investigated association two groups, 164 patients MDD 301 controls, using multiplex electrochemiluminescence methods applied blood serum. Results was not associated...