Publications by authors named "Scott A Schobel"

Background: Remote monitoring of Huntington disease (HD) signs and symptoms using digital technologies may enhance early clinical diagnosis and tracking of disease progression, guide treatment decisions, and monitor response to disease-modifying agents. Several recent studies in neurodegenerative diseases have demonstrated the feasibility of digital symptom monitoring.

Objective: The aim of this study was to evaluate a novel smartwatch- and smartphone-based digital monitoring platform to remotely monitor signs and symptoms of HD.

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Huntington's disease (HD) is characterised by a triad of cognitive, behavioural, and motor symptoms which lead to functional decline and loss of independence. With potential disease-modifying therapies in development, there is interest in accurately measuring HD progression and characterising prognostic variables to improve efficiency of clinical trials. Using the large, prospective Enroll-HD cohort, we investigated the relative contribution and ranking of potential prognostic variables in patients with manifest HD.

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Huntington disease (HD) is caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene, HTT, that results in expression of variant (mutant) huntingtin protein (HTT). Therapeutic strategies that reduce HTT levels are currently being pursued to slow or stop disease progression in people with HD. These approaches are supported by robust preclinical data indicating that reducing variant huntingtin protein is associated with decreased HD pathology.

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Background: Huntington's disease is an autosomal-dominant neurodegenerative disease caused by CAG trinucleotide repeat expansion in , resulting in a mutant huntingtin protein. IONIS-HTT (hereafter, HTT) is an antisense oligonucleotide designed to inhibit messenger RNA and thereby reduce concentrations of mutant huntingtin.

Methods: We conducted a randomized, double-blind, multiple-ascending-dose, phase 1-2a trial involving adults with early Huntington's disease.

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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 of blood oxygen level dependence (tb-fMRI and rs-fMRI) and cerebral blood flow (CBF) using arterial spin labeling. This information is critical to designing properly powered longitudinal studies. Here we comprehensively quantified and compared the test-retest reliability and reproducibility performance of 8 commonly applied fMRI tasks, 6 rs-fMRI metrics and CBF in 30 healthy volunteers.

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Background: The authors developed a practical and clinically useful model to predict the risk of psychosis that utilizes clinical characteristics empirically demonstrated to be strong predictors of conversion to psychosis in clinical high-risk (CHR) individuals. The model is based upon the Structured Interview for Psychosis Risk Syndromes (SIPS) and accompanying clinical interview, and yields scores indicating one's risk of conversion.

Methods: Baseline data, including demographic and clinical characteristics measured by the SIPS, were obtained on 199 CHR individuals seeking evaluation in the early detection and intervention for mental disorders program at the New York State Psychiatric Institute at Columbia University Medical Center.

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Article Synopsis
  • * Analyzed data from 1,668 early HD patients over 30-36 months, using the Unified Huntington Disease Rating Scale (UHDRS) and other brain atrophy measures.
  • * This new composite measure aligns more closely with brain atrophy and may improve efficiency in clinical trials compared to traditional individual measures.
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Background/objectives: Anhedonia is associated with poor social function in schizophrenia. Here, we examined this association in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders, taking into account social anxiety. We then explored correlations between anhedonia and basal metabolic activity in selected forebrain regions implicated in reward processing.

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Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring.

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GABAergic interneuron hypofunction is hypothesized to underlie hippocampal dysfunction in schizophrenia. Here, we use the cyclin D2 knockout (Ccnd2(-/-)) mouse model to test potential links between hippocampal interneuron deficits and psychosis-relevant neurobehavioral phenotypes. Ccnd2(-/-) mice show cortical PV(+) interneuron reductions, prominently in hippocampus, associated with deficits in synaptic inhibition, increased in vivo spike activity of projection neurons, and increased in vivo basal metabolic activity (assessed with fMRI) in hippocampus.

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The hippocampus in schizophrenia is characterized by both hypermetabolism and reduced size. It remains unknown whether these abnormalities are mechanistically linked. Here we addressed this question by using MRI tools that can map hippocampal metabolism and structure in patients and mouse models.

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The hippocampal formation has been implicated in a growing number of disorders, from Alzheimer's disease and cognitive ageing to schizophrenia and depression. How can the hippocampal formation, a complex circuit that spans the temporal lobes, be involved in a range of such phenotypically diverse and mechanistically distinct disorders? Recent neuroimaging findings indicate that these disorders differentially target distinct subregions of the hippocampal circuit. In addition, some disorders are associated with hippocampal hypometabolism, whereas others show evidence of hypermetabolism.

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We describe here a coordinated brain imaging and animal models approach in which we have shown that the hippocampal CA1 region is a principal node in schizophrenia pathogenesis and have identified a novel treatment approach to the disorder based on inhibition of glutamate release. To identify biomarkers, we have focused on the putative prodromal period, typically lasting a few years, preceding the first onset of psychosis. About one-third of a high-risk cohort followed prospectively for 2.

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Context: Because schizophrenia and related disorders have a chronic time course and subtle histopathology, it is difficult to identify which brain regions are differentially targeted.

Objective: To identify brain sites differentially targeted by schizophrenia, we applied a high-resolution variant of functional magnetic resonance imaging to clinically characterized patients and matched healthy controls and to a cohort of prodromal subjects who were prospectively followed up. Additionally, to explore the potential confound of medication use, the fMRI variant was applied to rodents receiving an antipsychotic agent.

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Objective: Numerous studies have implicated the hippocampus and prefrontal cortex in schizophrenia. However, precisely which subregions of the hippocampus and prefrontal cortex are abnormal remain unknown. Our study goal was to investigate the structure of the anterior hippocampus, posterior hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex (OFC) simultaneously in thirty-eight patients with schizophrenia and twenty-nine controls to determine which of these subregions are abnormal in schizophrenia.

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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 of schizophrenic illness and treatment effects with hippocampal volumes.

Method: Quantitative 1.

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