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PW01-157 - Mesolimbic Dysfunction During Novelty Detection In Schizophrenia
- K. Zierhut, A. Schulte-Kemna, B. Bogerts, K. Schiltz
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- Journal:
- European Psychiatry / Volume 25 / Issue S1 / 2010
- Published online by Cambridge University Press:
- 17 April 2020, 25-E1556
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Introduction
Schizophrenia is characterized by marked disturbances of cognitive functions. One core finding is a memory dysfunction. Recently, this has been attributed to impaired hippocampus function that is crucial in comparing new to known information. Hippocampal novelty detection triggers activity of neurons in the ventral tegmental areal (VTA) to which it is reciprocally connected.
AimsHere, we examined whether neuronal activation during the detection of novel information is impaired in these structures.
MethodsWe investigated novelty detection using an fMRI oddball face paradigm with repeated novel oddballs (1-4 repetitions) in 25 patients (12 female, mean age 26 years) suffering from paranoid-hallucinatory schizophrenia and 25 healthy controls (12 female, mean age 25 years).
ResultsSchizophrenia patients, relative to control subjects, showed impaired patterns of activation in mediotemporal areas, including the hippocampus, as well as in VTA/ Substantia Nigra during novelty detection. Furthermore, the activity related to detection of previously novel but repeatedly presented stimuli shows an altered adaptation in the patients.
ConclusionsIn schizophrenia, the Hippocampus-VTA-loop displays a dysregulated activity pattern during novelty detection that is crucial for encoding into long-term memory. As this loop is mainly governed by dopaminergic neurotransmission these results underline the pivotal pathophysiological role of mesolimbic dopaminergic dysregulation in the pathophysiology of memory dysfunction in schizophrenia.
P03-125 - Memory Dysfunction and Defective Novelty Detection in Schizophrenia
- K. Schiltz, K.C. Zierhut, B. Bogerts
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- Journal:
- European Psychiatry / Volume 25 / Issue S1 / 2010
- Published online by Cambridge University Press:
- 17 April 2020, 25-E1094
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Objectives
Patients suffering from schizophrenia display an impairment of memory performance among other cognitive deficits. Long term memory impairment can arise from disturbed encoding and/or retrieval processes subserved by mediotemporal, mesencephalic as well as prefrontal brain regions. We assessed functional and structural integrity of these regions in schizophrenia, specifically during cognitive processes of memory encoding and retrieval.
MethodsWe assessed in a set of 3 fMRI studies in a total of 50 schizophrenia patients and an equal number of matched controls whether
1) hippocampal/parahippocampal activity during encoding into long term memory is impaired,
2) this impairment is related to the memory deficit,
3) impaired memory retrieval is associated to mediotemporal/prefrontal dysfunction,
4) hippocampal dysfunction is related to symptoms in schizophrenia,
5) mesolimbic novelty detection is defective.
Functional alterations were related to structural brain changes as detected by voxel-based morphometry.
ResultsPatients with schizophrenia displayed a markedly impaired memory performance in our studies. It was related to dysfunction of hippocampal areas during memory encoding as well as novelty detection. During novelty detection, patients had a significantly impaired activity in the mesolimbic loop (hippocampus-ventral tegmental area). Prefrontral and mediotemporal hypofunction was evident during memory retrieval. Positive symptoms were related to a more dysregulated hippocampus activity during memory encoding.
ConclusionEvident memory dysfunction in schizophrenia is related to severely altered neuronal processes subserving memory encoding and retrieval which importantly include defective mesolimbic novelty detection. Dysregulated hippocampal activity is related to positive symptoms in schizophrenia and importantly provides a neurobiological link to cognitive deficits.
3354 Biomedical Informatics/Health Informatics A Preliminary Study of Glaucoma: The Intersection of Genetics and Survey Data from the Health and Retirement Study
- Jessica Cooke Bailey, Tyler G. Kinzy, Nicholas K. Schiltz
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, pp. 26-27
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OBJECTIVES/SPECIFIC AIMS: Glaucoma is a leading cause of irreversible blindness worldwide; in the United States alone, over 2.7 million individuals are affected. Various risk factors for glaucoma are known and include age, race/ethnicity, genetics, and ocular measures. Despite numerous studies, molecular and environmental factors that contribute to glaucoma remain elusive. Our objective was to conduct a genome-wide association for glaucoma among black and white HRS respondents, and to determine the feasibility for future analyses examining shared genetic markers between glaucoma and other comorbidities, behaviors, and environmental risk factors. METHODS/STUDY POPULATION: The University of Michigan Health and Retirement Study (HRS) is a longitudinal survey of a representative sample of Americans over the age of 50. Supported by the National Institute on Aging and the Social Security Administration, the HRS is designed to provide reliable data on the decisions, choices, and behaviors of people as they age and respond to changes in public policy, the economy, and health. The study obtains information every two years about income and wealth, health and use of health services, work and retirement, and family connections. Through its unique and in-depth interviews, the HRS provides an invaluable and growing body of multidisciplinary data that researchers can use to address important questions about the challenges and opportunities of aging. Because of its innovation and importance, the HRS has become the model and hub for a growing network of harmonized longitudinal aging studies around the world. Saliva was collected on half of the HRS sample each wave starting in 2006 and respondents were genotyped on the Illumina Human Omni2.5-Quad (Omni2.5) BeadChip at the NIH Center for Inherited Disease Research. We accessed survey results to evaluate prevalence of glaucoma in this dataset and performed a genome-wide association study (GWAS) adjusting for age, sex, and significant Principal Components and stratifying by self-reported race (White / Black). RESULTS/ANTICIPATED RESULTS: Of 8179 respondents passing quality filters, 6409 (78.40%) were white and 985 (12.05%) were black. Self-reported glaucoma prevalence was 7.85% and 16.34% in white and black respondents, respectively. White respondents had a mean age of 76.97 (SD 7.53) and were 57.25% female. Black respondents had a similar mean age of 74.96 (SD 7.27) and were 62.54% female. More than 87% of both groups were assessed in 2012. Preliminary GWAS analyses did not replicate known glaucoma loci and no variants attained genome-wide significance. A suggestive variant (p<1e-05) in the black population was within 10kb of a known locus, rs1196998. Future analyses will evaluate genetic association with combinations of glaucoma and comorbidities. DISCUSSION/SIGNIFICANCE OF IMPACT: Glaucoma risk is higher in minority groups than in whites, and the majority of reported genetic studies of glaucoma have been performed in individuals of European descent. It is imperative to better understand the role of genetics, environment, and health behavior in glaucoma risk. Further, understanding common mechanisms underlying diseases that co-occur with glaucoma could illuminate novel disease mechanisms that can be targeted for early intervention and/or treatment.