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Search Results for all work with filters:

  • 2019
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Work 1-8 of 8

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Article

Maladaptive Aggression: With a Focus on Impulsive Aggression in Children and Adolescents

by Daniel F. Connor; Jeffrey H. Newcorn; Keith E. Saylor; Birgit H. Amann; Lawrence Scahill; Adelaide S. Robb; Peter S. Jensen; Benedetto Vitiello; Robert L. Findling; Jan K. Buitelaar

2019

Subjects
  • Psychology, Developmental
  • Psychology, Behavioral
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Abstract:Close

Objective: Aggressive behavior is among the most common reasons for referral to psychiatric clinics and confers significant burden on individuals. Aggression remains poorly defined; there is currently no consensus on the best ways to recognize, diagnose, and treat aggression in clinical settings. In this review, we synthesize the available literature on aggression in children and adolescents and propose the concept of impulsive aggression (IA) as an important construct associated with diverse and enduring psychopathology. Methods: Articles were identified and screened from online repositories, including PubMed, PsychInfo, the Cochrane Database, EMBase, and relevant book chapters, using combinations of search terms such as "aggression," "aggressive behavio(u)r," "maladaptive aggression," "juvenile," and "developmental trajectory." These were evaluated for quality of research before being incorporated into the article. The final report references 142 sources, published from 1987 to 2019. Results: Aggression can be either adaptive or maladaptive in nature, and the latter may require psychosocial and biomedical interventions when it occurs in the context of central nervous system psychopathology. Aggression can be categorized into various subtypes, including reactive/proactive, overt/covert, relational, and IA. IA in psychiatric or neurological disorders is reviewed along with current treatments, and an algorithm for systematic evaluation of aggression in the clinical setting is proposed. Conclusions: IA is a treatable form of maladaptive aggression that is distinct from other aggression subtypes. It occurs across diverse psychiatric and neurological diagnoses and affects a substantial subpopulation. IA can serve as an important construct in clinical practice and has considerable potential to advance research.

Article

Genomic updates in understanding PTSD

by Sumeet Sharma; Kerry Ressler

2019

Subjects
  • Biology, Neuroscience
  • Psychology, Social
  • Biology, Genetics
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Abstract:Close

Twin studies as well as more recent genetics-based heritability analyses demonstrate that up to 40 to 50% of the variance in predicting PTSD following trauma is heritable. However, most of the specific gene pathways and mechanism that mediate risk vs. resilience for PTSD following trauma exposure have yet to be elucidated. This review will examine the latest results from large scale Genome-wide association studies as well as other approaches aimed at understanding mechanisms of development of and recovery from PTSD.

Article

Behavioral predictors of autism recurrence are genetically independent and influence social reciprocity: evidence that polygenic ASD risk is mediated by separable elements of developmental liability

by Alexa Pohl; Warren Jones; Natasha Marrus; Yi Zhang; Ami Klin; John N. Constantino

2019

Subjects
  • Health Sciences, Mental Health
  • Psychology, Developmental
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Abstract:Close

The preponderance of causal influence on total population attributable risk for autism is polygenic in nature, but it is not known how such liability engenders the development of the syndrome. In 348 epidemiologically ascertained toddler twins, we explored associations between autistic traits and three robust, highly heritable predictors of familial autism recurrence: variation in attention, motor coordination, and parental autistic trait burden. We observed that these predictors—despite collectively accounting for over one third of variance in clinical recurrence—are genetically independent in early childhood, and jointly account for a comparable share of inherited influence on early reciprocal social behavior in the general population. Thus, combinations of what are otherwise discrete, inherited behavioral liabilities—some not specific to autism—appear to jointly mediate common genetic risk for autism. Linking genetic variants and neural signatures to these independent traits prior to the onset of the development of autism will enhance understanding of mechanisms of causation in familial autistic syndromes. Moreover, ongoing biomarker discovery efforts will benefit from controlling for the effects of these common liabilities, which aggregate in individuals with autism but are also continuously distributed in “controls”. Finally, early inherited liabilities that participate in the early ontogeny of autistic syndromes represent parsimonious intervention targets for polygenic forms of the condition, and represent candidate trans-diagnostic endophenotypes of potential relevance to a diversity of neuropsychiatric syndromes.

Article

Overlapping genetic effects between suicidal ideation and neurocognitive functioning

by Leslie Brick; Maria E. Marraccini; Lauren Micalizzi; Chelsie E. Benca-Bachman; Valerie S. Knopik; Rohan Palmer

2019

Subjects
  • Biology, Genetics
  • Biology, Neuroscience
  • Psychology, Cognitive
  • Sociology, Public and Social Welfare
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Abstract:Close

Background: Suicide is the second leading cause of death among adolescents and young adults. Several studies have indicated significant genetic influences on suicide-related phenotypes and mounting evidence from neurobiological research has linked deficits in neurocognitive abilities to suicide phenotypes. The goal of the present study was to estimate the heritability of suicidal ideation (SI) in a large sample of adolescents and determine if SI is genetically correlated with neurocognitive functioning. Methods: Genome-wide data (N = 3564 unrelated individuals of European Ancestry) were drawn from the Philadelphia Neurodevelopment Cohort. Adolescents completed a psychiatric assessment, as well as a computerized neurocognitive battery to assess performance across four domains: memory, executive function, social cognition, and complex cognition. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimation was used to determine SNP-heritability (h 2SNP ) of SI and the genetic correlation (r G ) between SI and neurocognitive domains. Results: Nearly 17% of adolescents reported SI. The SNP-heritability estimate for SI was marginally significant (h 2SNP = 11%, SE = 8%, p = 0.086). Bivariate analyses indicated a significant r G between SI and emotion identification (r G = 0.79, SE = 0.45, p = 0.006; phenotypic correlation r = 0.04, p = 0.017). Limitations: It is possible that SI may represent a related, but differentially heritable construct from suicide attempts/completion and other comorbid psychopathology. Additionally, though genetic correlations point to shared genetic factors across traits, direct causal mechanisms cannot be deduced. Conclusions: Common heritable factors contribute to variation in SI and neurocognitive functioning. Genetic factors influencing emotion identification have significant genetic overlap with SI.

Article

Association of sickle cell trait with atrial fibrillation: The REGARDS cohort

by Daniel R. Douce; Elsayed Z. Soliman; Rakhi Naik; Hyacinth Hyacinth; Mary Cushman; Cheryl A. Winkler; George Howard; Ethan M. Lange; Leslie A. Lange; Marguerite R. Irvin; Neil A. Zakai

2019

Subjects
  • Health Sciences, Epidemiology
  • Biology, Cell
  • Health Sciences, Oncology
  • Biology, Biostatistics
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Abstract:Close

Background: Sickle cell trait (SCT), sickle cell disease’s (SCD) carrier status, has been recently associated with worse cardiovascular and renal outcomes. An increased prevalence of atrial fibrillation (AF) is documented in SCD patients; however, studies in individuals with SCT are lacking. Objectives: To determine the association of SCT with AF Methods: Among African-American participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study we assessed the association of SCT (by ECG or medical history) with prevalent AF using logistic regression adjusting for age, sex, income, education, history of stroke, myocardial infarction, diabetes, hypertension, and chronic kidney disease. A second evaluation was performed a mean of 9.2 years later among available participants, and the same model was used to test the association of SCT with incident AF. Results: In 10,409 participants with baseline ECG data and genotyping, 778 (7.5%) had SCT and 811 (7.8%) had prevalent AF. After adjusting for age, sex, education and income, SCT was associated with AF, OR 1.32 (95% CI 1.03–1.70). The association with incident AF assessed at the second in-home visit with the same adjustments was similar; OR 1.25 (95% CI 0.77–2.03). Conclusions: SCT was associated with a higher prevalence of AF and a non-significantly higher incident AF over a 9.2 year period independent of AF risk factors. SCT remained associated with prevalent AF after adjusting for potential factors on the causal pathway such as hypertension and chronic kidney disease suggesting alternate mechanisms for the increased risk.

Article

Sickle cell trait and risk of cognitive impairment in African-Americans: The REGARDS cohort

by Christina R. Cahill; Justin M. Leach; Leslie A. McClure; Marguerite Ryan Irvin; Neil A. Zakai; Rakhi Naik; Frederick Unverzagt; Virginia G. Wadley; Hyacinth Hyacinth; Jennifer Manly; Suzanne E. Judd; Cheryl Winkler; Mary Cushman

2019

Subjects
  • Biology, Biostatistics
  • Health Sciences, Pathology
  • Psychology, Cognitive
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Abstract:Close

Background: Sickle cell anemia may be associated with cognitive dysfunction, and some complications of sickle cell anemia might affect those with sickle cell trait (SCT), so we hypothesized that SCT is a risk factor for cognitive impairment. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a national cohort of 30,239 white and black Americans from 2003 to 7, who are followed every 6 months. Baseline and annual global cognitive function testing used the Six-Item Screener (SIS), a validated instrument (scores range 0–6; ≤ 4 indicates cognitive impairment). Participants with baseline cognitive impairment and whites were excluded. Logistic regression was used to calculate the association of SCT with incident cognitive impairment, adjusted for risk factors. Linear mixed models assessed multivariable-adjusted change in test scores on a biennially administered 3-test battery measuring learning, memory, and semantic and phonemic fluency. Findings: Among 7743 participants followed for a median of 7·1 years, 85 of 583 participants with SCT (14·6%) developed incident cognitive impairment compared to 902 of 7160 (12·6%) without SCT. In univariate analysis, the odds ratio (OR) of incident cognitive impairment was 1·18 (95% CI: 0·93, 1·51) for those with SCT vs. those without. Adjustment did not impact the OR. There was no difference in change on 3-test battery scores by SCT status (all p > 0·11). Interpretation: In this prospective cohort study of black Americans, SCT was not associated with incident cognitive impairment or decline in test scores of learning, memory and executive function. Funding: National Institutes of Health, American Society of Hematology.

Article

Association of sickle cell trait with measures of cognitive function and dementia in African Americans

by Nemin Chen; Christina Caruso; Alvaro Alonso; Vimal K. Derebail; Abhijit V. Kshirsagar; A. Richey Sharrett; Nigel S. Key; Rebecca F. Gottesman; Megan L. Grove; Jan Bressler; Eric Boerwinkle; B. Gwen Windham; Thomas H. Mosley, Jr.; Hyacinth Idu Hyacinth

2019

Subjects
  • Biology, Neuroscience
  • Biology, Genetics
  • Health Sciences, Epidemiology
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Abstract:Close

Objective: The incidence and prevalence of cognitive decline and dementia are significantly higher among African Americans compared with non-Hispanic Whites. The aim of this study was to determine whether inheritance of the sickle cell trait (SCT) i.e. heterozygosity for the sickle cell mutation increases the risk of cognitive decline or dementia Among African Americans. Methods: We studied African American participants enrolled in the Atherosclerosis Risk in Communities study. SCT genotype at baseline and outcome data from cognitive assessments at visits 2, 4 and 5, and an MRI performed at visit 5 were analyzed for the association between SCT and risk of cognitive impairment and/or dementia. Results: There was no significant difference in risk factors profile between participants with SCT (N = 176) and those without SCT (N = 2532). SCT was not independently associated with a higher prevalence of global or domain-specific cognitive impairment at baseline or with more rapid cognitive decline. Participants with SCT had slightly lower incidence of dementia (HR = 0.63 [0.38, 1.05]). On the other hand, SCT seems to interact with the apolipoprotein E ε4 risk allele resulting in poor performance on digit symbol substitution test at baseline (z-score = −0.08, Pinteraction = 0.05) and over time (z-score = −0.12, Pinteraction = 0.04); and with diabetes mellitus leading to a moderately increased risk of dementia (HR = 2.06 [0.89, 4.78], Pinteraction = 0.01). Conclusions: SCT was not an independent risk factor for prevalence or incidence of cognitive decline or dementia, although it may interact with and modify other putative risk factors for cognitive decline and dementia.

Article

Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program

by Jacklyn N. Hellwege; Digna R. Velez Edwards; Ayush Giri; Chengxiang Qiu; Jihwan Park; Eric S. Torstenson; Jacob M. Keaton; O.D. Wilson; Cassianne Robinson-Cohen; Cecilia P. Chung; Christianne Roumie; Derek Klarin; Scott M. Damrauer; Scott L. DuVall; Edward Siew; Elvis A. Akwo; Matthias Wuttke; Mathias Gorski; Man Li; Yong Li; J. Michael Gaziano; Peter Wilson; Philip S. Tsao; Christopher J. O'Donnell; Csaba P. Kovesdy; Cristian Pattaro; Anna Koettgen; Katalin Susztak; Todd L. Edwards; Adriana M. Hung

2019

Subjects
  • Biology, Genetics
  • File Download
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Abstract:Close

Chronic kidney disease (CKD), defined by low estimated glomerular filtration rate (eGFR), contributes to global morbidity and mortality. Here we conduct a transethnic Genome-Wide Association Study of eGFR in 280,722 participants of the Million Veteran Program (MVP), with replication in 765,289 participants from the Chronic Kidney Disease Genetics (CKDGen) Consortium. We identify 82 previously unreported variants, confirm 54 loci, and report interesting findings including association of the sickle cell allele of betaglobin among non-Hispanic blacks. Our transcriptome-wide association study of kidney function in healthy kidney tissue identifies 36 previously unreported and nine known genes, and maps gene expression to renal cell types. In a Phenome-Wide Association Study in 192,868 MVP participants using a weighted genetic score we detect associations with CKD stages and complications and kidney stones. This investigation reinterprets the genetic architecture of kidney function to identify the gene, tissue, and anatomical context of renal homeostasis and the clinical consequences of dysregulation.
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