- Browse by Subject
Browsing by Subject "Family history"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
Item Advanced natural language processing and temporal mining for clinical discovery(2015-08-17) Mehrabi, Saeed; Jones, Josette F.; Palakal, Mathew J.; Chien, Stanley Yung-Ping; Liu, Xiaowen; Schmidt, C. MaxThere has been vast and growing amount of healthcare data especially with the rapid adoption of electronic health records (EHRs) as a result of the HITECH act of 2009. It is estimated that around 80% of the clinical information resides in the unstructured narrative of an EHR. Recently, natural language processing (NLP) techniques have offered opportunities to extract information from unstructured clinical texts needed for various clinical applications. A popular method for enabling secondary uses of EHRs is information or concept extraction, a subtask of NLP that seeks to locate and classify elements within text based on the context. Extraction of clinical concepts without considering the context has many complications, including inaccurate diagnosis of patients and contamination of study cohorts. Identifying the negation status and whether a clinical concept belongs to patients or his family members are two of the challenges faced in context detection. A negation algorithm called Dependency Parser Negation (DEEPEN) has been developed in this research study by taking into account the dependency relationship between negation words and concepts within a sentence using the Stanford Dependency Parser. The study results demonstrate that DEEPEN, can reduce the number of incorrect negation assignment for patients with positive findings, and therefore improve the identification of patients with the target clinical findings in EHRs. Additionally, an NLP system consisting of section segmentation and relation discovery was developed to identify patients' family history. To assess the generalizability of the negation and family history algorithm, data from a different clinical institution was used in both algorithm evaluations.Item Delay Discounting in At-Risk Preadolescents: Brain Mechanisms and Behavior(2021-12) Butcher, Tarah J; Oberlin, Brandon; Lapish, Christopher; Hulvershorn, LeslieIt is well documented that adolescent substance use is associated with deficits in brain function and behavior. However, possible deficits that predate substance use initiation remain poorly characterized in preadolescents at-risk for developing substance use disorder (SUD). To characterize potential brain and behavioral differences that predate substance use, substance naïve preadolescents, ages 11–12, were recruited into three groups to complete functional magnetic resonance imaging delay discounting: (1) High-risk youth (n=35) with a family history of SUD and externalizing psychiatric disorders, (2) psychiatric controls (n=35) with no family history of SUD, but equivalent externalizing psychiatric disorders as high-risk youth, and (3) healthy controls (n=29) with no family history of SUD and minimal psychopathology. While no behavioral differences between groups were identified, there were group differences in posterior cingulate cortex (PCC) function during decision making. Specifically, the high-risk group showed stronger deactivation of the PCC than healthy controls. These results suggest that high-risk preadolescents may need to suppress activity of key nodes of the default mode network (a task negative network) to a greater extent to properly allocate attention to the task.Item Density and Dichotomous Family History Measures of Alcohol Use Disorder as Predictors of Behavioral and Neural Phenotypes: A Comparative Study Across Gender and Race/Ethnicity(Wiley, 2020-03) Pandey, Gayathri; Seay, Michael J.; Meyers, Jacquelyn L.; Chorlian, David B.; Pandey, Ashwini K.; Kamarajan, Chella; Ehrenberg, Morton; Pitti, Daniel; Kinreich, Sivan; de Viteri, Stacey Subbie-Saenz; Acion, Laura; Anokhin, Andrey; Bauer, Lance; Chan, Grace; Edenberg, Howard; Hesselbrock, Victor; Kuperman, Samuel; McCutcheon, Vivia V.; Bucholz, Kathleen K.; Schuckit, Marc; Porjesz, Bernice; Biochemistry and Molecular Biology, School of MedicineBackground: Family history (FH) is an important risk factor for the development of alcohol use disorder (AUD). A variety of dichotomous and density measures of FH have been used to predict alcohol outcomes; yet, a systematic comparison of these FH measures is lacking. We compared 4 density and 4 commonly used dichotomous FH measures and examined variations by gender and race/ethnicity in their associations with age of onset of regular drinking, parietal P3 amplitude to visual target, and likelihood of developing AUD. Methods: Data from the Collaborative Study on the Genetics of Alcoholism (COGA) were utilized to compute the density and dichotomous measures. Only subjects and their family members with DSM-5 AUD diagnostic information obtained through direct interviews using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) were included in the study. Area under receiver operating characteristic curves were used to compare the diagnostic accuracy of FH measures at classifying DSM-5 AUD diagnosis. Logistic and linear regression models were used to examine associations of FH measures with alcohol outcomes. Results: Density measures had greater diagnostic accuracy at classifying AUD diagnosis, whereas dichotomous measures presented diagnostic accuracy closer to random chance. Both dichotomous and density measures were significantly associated with likelihood of AUD, early onset of regular drinking, and low parietal P3 amplitude, but density measures presented consistently more robust associations. Further, variations in these associations were observed such that among males (vs. females) and Whites (vs. Blacks), associations of alcohol outcomes with density (vs. dichotomous) measures were greater in magnitude. Conclusions: Density (vs. dichotomous) measures seem to present more robust associations with alcohol outcomes. However, associations of dichotomous and density FH measures with different alcohol outcomes (behavioral vs. neural) varied across gender and race/ethnicity. These findings have great applicability for alcohol research examining FH of AUD.Item Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings(Elsevier, 2016) Bell, Richard L.; Hauser, Sheketha R.; McClintick, Jeanette; Rahman, Shafiqur; Edenberg, Howard J.; Szumlinski, Karen K.; McBride, William J.; Department of Psychiatry, IU School of MedicineHerein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression levels for a number of glutamate-associated genes and/or proteins are modulated by alcohol abuse and dependence. These changes in expression include metabotropic receptors and ionotropic receptor subunits as well as different glutamate transporters. Moreover, these changes in gene expression parallel the pharmacologic manipulation of these same receptors and transporters. Some of these gene expression changes may have predated alcohol abuse and dependence because a number of glutamate-associated polymorphisms are related to a genetic predisposition to develop alcohol dependence. Other glutamate-associated polymorphisms are linked to age at the onset of alcohol-dependence and initial level of response/sensitivity to alcohol. Finally, findings of innate and/or ethanol-induced glutamate-associated gene expression differences/changes observed in a genetic animal model of alcoholism, the P rat, are summarized. Overall, the existing literature indicates that changes in glutamate receptors, transporters, enzymes, and scaffolding proteins are crucial for the development of alcohol dependence and there is a substantial genetic component to these effects. This indicates that continued research into the genetic underpinnings of these glutamate-associated effects will provide important novel molecular targets for treating alcohol abuse and dependence.Item Functional connectivity in frontostriatal networks differentiate offspring of parents with substance use disorders from other high-risk youth(Elsevier, 2021) Kwon, Elizabeth; Hummer, Tom; Andrews, Katharine D.; Finn, Peter; Aalsma, Matthew; Bailey, Allen; Hanquier, Jocelyne; Wang, Ting; Hulvershorn, Leslie; Psychiatry, School of MedicineBackground: Family history (FH) of substance use disorders (SUDs) is known to elevate SUD risk in offspring. However, the influence of FH SUDs has been confounded by the effect of externalizing psychopathologies in the addiction risk neuroimaging literature. Thus, the current study aimed to assess the association between parental SUDs and offspring functional connectivity in samples matched for psychopathology and demographics. Methods: Ninety 11-12-year-old participants with externalizing disorders were included in the study (48 FH+, 42 FH-). We conducted independent component analyses (ICA) and seed-based analyses (orbitofrontal cortex; OFC, nucleus accumbens (NAcc), dorsolateral prefrontal cortex) with resting state data. Results: FH+ adolescents showed stronger functional connectivity between the right lateral OFC seed and anterior cingulate cortex compared to FH- adolescents (p < 0.05, corrected). Compared to FH-, FH+ adolescents showed stronger negative functional connectivity between the left lateral OFC seed and right postcentral gyrus and between the left NAcc seed and right middle occipital gyrus (p < 0.05, corrected). Poorer emotion regulation was associated with more negative connectivity between right occipital/left NAcc among FH+ adolescents based on the seed-based analysis. FH- adolescents had stronger negative functional connectivity between ventral attention/salience networks and dorsal attention/visuospatial networks in the ICA. Conclusions: Both analytic methods found group differences in functional connectivity between brain regions associated with executive functioning and regions associated with sensory input (e.g., postcentral gyrus, occipital regions). We speculate that families densely loaded for SUD may confer risk by altered neurocircuitry that is associated with emotion regulation and valuation of external stimuli beyond what would be explained by externalizing psychopathology alone.Item A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction(Elsevier, 2016) Bell, Richard L.; Hauser, S.; Rodd, Z. A.; Liang, T.; Sari, Y.; McClintick, J.; Rahman, S.; Engleman, E. A.; Department of Psychiatry, IU School of MedicineThe purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general.