A5008618034- Genetic Neurodegenerative Diseases
- Schizophrenia research and treatment
- Neurological disorders and treatments
- Neuroscience and Neuropharmacology Research
- Functional Brain Connectivity Studies
- Mitochondrial Function and Pathology
- Tryptophan and brain disorders
- Advanced MRI Techniques and Applications
- Receptor Mechanisms and Signaling
- Advanced Neuroimaging Techniques and Applications
- Psychosomatic Disorders and Their Treatments
- Mental Health and Psychiatry
- Computational Drug Discovery Methods
- Memory and Neural Mechanisms
- Bipolar Disorder and Treatment
- Stress Responses and Cortisol
- Neurogenesis and neuroplasticity mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Alzheimer's disease research and treatments
- Atomic and Subatomic Physics Research
- Mental Health Research Topics
- Muscle Physiology and Disorders
- Neuroendocrine regulation and behavior
- Neurotransmitter Receptor Influence on Behavior
Uniformed Services University of the Health Sciences
2024
Walter Reed National Military Medical Center
2024
Roche (Switzerland)
2014-2023
Columbia University
2005-2018
University of Iowa
2017
University College London
2017
Massachusetts General Hospital
2017
Harvard University
2017
CHDI Foundation
2017
University of British Columbia
2017
Huntington's disease is an autosomal-dominant neurodegenerative caused by CAG trinucleotide repeat expansion in HTT, resulting a mutant huntingtin protein. IONIS-HTTRx (hereafter, HTTRx) antisense oligonucleotide designed to inhibit HTT messenger RNA and thereby reduce concentrations of huntingtin. We conducted randomized, double-blind, multiple-ascending-dose, phase 1-2a trial involving adults with early disease. Patients were randomly assigned 3:1 ratio receive HTTRx or placebo as bolus...
<h3>Context</h3> Because schizophrenia and related disorders have a chronic time course subtle histopathology, it is difficult to identify which brain regions are differentially targeted. <h3>Objective</h3> To sites targeted by schizophrenia, we applied high-resolution variant of functional magnetic resonance imaging clinically characterized patients matched healthy controls cohort prodromal subjects who were prospectively followed up. Additionally, explore the potential confound medication...
Huntington's disease (HD) is a genetic progressive neurodegenerative disorder, caused by mutation in the HTT gene, for which there currently no cure. The identification of sensitive indicators progression and therapeutic outcome could help development effective strategies treating HD. We assessed mutant huntingtin (mHTT) neurofilament light (NfL) protein concentrations cerebrospinal fluid (CSF) blood parallel with clinical evaluation magnetic resonance imaging premanifest manifest HD...
Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The Nrg1 gene is a schizophrenia susceptibility gene. To understand the contribution of to adult brain structure behaviors, we studied regulation type III expression evaluated effect decreased isoforms. Type transcribed by promoter distinct from those for other isoforms and, in brain, expressed medial prefrontal cortex, ventral hippocampus, subiculum, regions involved...
Background Social dysfunction is a hallmark symptom of schizophrenia which commonly precedes the onset psychosis. It unclear if social symptoms in clinical high-risk patients reflect depressive or are manifestation negative symptoms. Method We compared function scores on Adjustment Scale-Self Report between 56 young people (aged 13–27 years) at high risk for psychosis and 22 healthy controls. The cases were also assessed ‘prodromal’ (subthreshold positive, negative, disorganized general...
Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link observed alterations to specific neurophysiological processes. In particular, sensitivity activity changes neurotransmitter systems remains unclear. We address this question probing healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms action. use a novel framework aimed at...
<h3>Objective:</h3> To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group randomized double-blind trials. <h3>Methods:</h3> We studied Unified Disease Rating Scale (UHDRS) non-UHDRS measures brain progressive atrophy 1,668 individuals with HD followed up prospectively for to 30 36 months longitudinal follow-up. <h3>Results:</h3> The results demonstrated that a composite motor,...
Longitudinal analysis in 80 patients shows that mutant huntingtin and neurofilament light could predict Huntington’s disease progression.
Background Reduced hippocampal volume is a consistently described structural abnormality in schizophrenia but its cause and timing are not known. Aims To examine the relationship of duration schizophrenic illness treatment effects with volumes. Method Quantitative 1.5 T magnetic resonance imaging brain scans young male patients early stage were compared those chronically ill older patients. Scans also acquired for controls matched to both patient groups age handedness. Duration was recorded...
Background Increased sensitivity and exposure to stress are associated with psychotic symptoms in schizophrenia its risk states, but little is known about the co-evolution of positive other a clinical high-risk (CHR) cohort. Method A combined cross-sectional longitudinal design was used examine associations over time (i.e. life events) ‘prodromal’ cohort 65 CHR patients assessed quarterly for up 4 years, at baseline 24 healthy controls similar age gender. Results Impaired tolerance greater...
Significance Hippocampal hyperactivity predicts psychosis and may disrupt aspects of cognition in schizophrenia. Here, we use interneuron precursor transplants mice lacking cyclin D2 ( Ccnd2 ) to test links between hippocampal GABAergic interneurons psychosis-relevant phenotypes. -null show parvalbumin deficits increased vivo excitatory neuron spiking metabolic activity. This disinhibition is associated with cognitive excess dopamine Transplanting progenitors derived from the embryonic...
Despite their wide-spread use, only limited information is available on the comparative test-retest reliability of task-based functional and resting state magnetic resonance imaging measures blood oxygen level dependence (tb-fMRI rs-fMRI) cerebral flow (CBF) using arterial spin labeling. This critical to designing properly powered longitudinal studies. Here we comprehensively quantified compared reproducibility performance 8 commonly applied fMRI tasks, 6 rs-fMRI metrics CBF in 30 healthy...
Background DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Positive Symptom (APSS) in Structured Interview Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis a 2015 NAPLS-2 Consortium report. We sought independently replicate this large single-site high-risk cohort, identify baseline demographic clinical predictors beyond current APS/APSS...
Abstract Background The authors developed a practical and clinically useful model to predict the risk of psychosis that utilizes clinical characteristics empirically demonstrated be strong predictors conversion in high-risk (CHR) individuals. is based upon Structured Interview for Psychosis Risk Syndromes (SIPS) accompanying interview, yields scores indicating one's conversion. Methods Baseline data, including demographic measured by SIPS, were obtained on 199 CHR individuals seeking...