7 results on '"King, Robert"'
Search Results
2. Multimodal Neuroimaging of Frontolimbic Structure and Function Associated With Suicide Attempts in Adolescents and Young Adults With Bipolar Disorder.
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Johnston, Jennifer A.y., Wang, Fei, Liu, Jie, Blond, Benjamin N., Wallace, Amanda, Liu, Jiacheng, Spencer, Linda, Cox Lippard, Elizabeth T., Purves, Kirstin L., Landeros-Weisenberger, Angeli, Hermes, Eric, Pittman, Brian, Zhang, Sheng, King, Robert, Martin, Andrés, Oquendo, Maria A., and Blumberg, Hilary P.
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BIPOLAR disorder , *SUICIDAL behavior , *BRAIN imaging , *GRAY matter (Nerve tissue) , *SUICIDAL ideation , *PHYSIOLOGY , *PROGNOSIS , *DIAGNOSIS , *PATIENTS , *BASAL ganglia , *BRAIN , *CEREBELLUM , *CEREBRAL dominance , *FRONTAL lobe , *HIPPOCAMPUS (Brain) , *LIMBIC system , *MAGNETIC resonance imaging , *NERVOUS system , *RESEARCH funding , *RISK assessment , *STATISTICS , *PSYCHOLOGY - Abstract
Objective: Bipolar disorder is associated with high risk for suicidal behavior that often develops in adolescence and young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents and young adults with bipolar disorder with and without a history of suicide attempts combines structural, diffusion tensor, and functional MR imaging methods to investigate implicated abnormalities in the morphology and structural and functional connectivity within frontolimbic systems.Method: The study had 26 participants with bipolar disorder who had a prior suicide attempt (the attempter group) and 42 participants with bipolar disorder without a suicide attempt (the nonattempter group). Regional gray matter volume, white matter integrity, and functional connectivity during processing of emotional stimuli were compared between groups, and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors.Results: Compared with the nonattempter group, the attempter group showed significant reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum; white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala functional connectivity to the left ventral and right rostral prefrontal cortex. In exploratory analyses, among attempters, there was a significant negative correlation between right rostral prefrontal connectivity and suicidal ideation and between left ventral prefrontal connectivity and attempt lethality.Conclusions: Adolescent and young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral frontolimbic neural system subserving emotion regulation. Among attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicidal ideation and attempt lethality. [ABSTRACT FROM AUTHOR]- Published
- 2017
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3. Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.
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Darrow, Sabrina M., Hirschtritt, Matthew E., Davis, Lea K., Illmann, Cornelia, Osiecki, Lisa, Grados, Marco, Sandor, Paul, Dion, Yves, King, Robert, Pauls, David, Budman, Cathy L., Cath, Danielle C., Greenberg, Erica, Lyon, Gholson J., Yu, Dongmei, McGrath, Lauren M., McMahon, William M., Lee, Paul C., Delucchi, Kevin L., and Scharf, Jeremiah M.
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TOURETTE syndrome , *HUMAN phenotype , *SYMPTOMS , *MEDICAL genetics , *EXPLORATORY factor analysis , *GENETICS , *DIAGNOSIS of obsessive-compulsive disorder , *CHILDREN of people with mental illness , *ATTENTION-deficit hyperactivity disorder , *DISEASE susceptibility , *PSYCHOLOGY of mothers , *OBSESSIVE-compulsive disorder , *RESEARCH funding , *RISK assessment , *PHENOTYPES , *COMORBIDITY , *SEQUENCE analysis , *PSYCHOLOGICAL factors , *PSYCHOLOGY , *DIAGNOSIS - Abstract
Objective: Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts.Method: Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated.Results: The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not.Conclusions: The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses. [ABSTRACT FROM AUTHOR]- Published
- 2017
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4. Neuropsychiatric Disorders Associated With Streptococcal Infection: A Case-Control Study Among Privately Insured Children.
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Leslie, Douglas L., Kozma, Laura, Martin, Andrés, Landeros, Angeli, Katsovich, Liliya, King, Robert A., and Leckman, James F.
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STREPTOCOCCAL diseases , *OBSESSIVE-compulsive disorder , *ATTENTION-deficit hyperactivity disorder , *BEHAVIOR disorders in children , *COMPULSIVE behavior , *INFECTION , *JUVENILE diseases , *DIAGNOSIS , *MEDICAL research - Abstract
The article presents a study that aims to determine the role of antecedent streptococcal infection in increasing the risk of diagnosis of disported in children including obsessive-compulsive disorder and attention-deficit/hyperactivity disorder. It examines the number of streptococcal infections recorded after the incident diagnosis of the disorders. It explores the specificity of new-onset of the disorders as sequelae of streptococcal infection with the use of a comparable association analysis. Information on the results of the study is also presented.
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- 2008
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5. Development of the Yale Children's Global Stress Index (YCGSI) and its application in children and adolescents ith Tourette's syndrome and obsessive-compulsive disorder.
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Findley, Diane B., Leckman, James E., Katsovich, Liliya, Lin, Haiquin, Zhang, Heping, Grantz, Heidi, Otka, Jessica, Lombroso, Paul J., King, Robert A., Leckman, James F, and Lin, Haiqun
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STRESS in children , *PSYCHOMETRICS , *DIAGNOSIS of obsessive-compulsive disorder , *TOURETTE syndrome , *PSYCHOLOGICAL adjustment testing , *CHRONIC diseases , *COMPARATIVE studies , *DISEASES , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *RESEARCH funding , *EVALUATION research , *SEVERITY of illness index , *DIAGNOSIS ,RESEARCH evaluation - Abstract
Objective: The Yale Children's Global Stress Index (YCGSI) is a new clinical rating instrument designed to provide objective global clinician ratings of psychosocial stress in studies of children and adolescents. This study was designed to evaluate the psychometric properties of the YCGSI.Method: Independent ratings of clinical severity and psychosocial stress were obtained at two time points separated by 4 months from 33 subjects with Tourette's syndrome (TS) and/or early-onset obsessive-compulsive disorder (OCD), aged 7 to 17 years, and 25 age-matched control subjects. Parents and children were interviewed separately. Multiple measures of stress were obtained including the YCGSI and the Daily Life Stressors Scale (DLSS).Results: Data support the interrater reliability and convergent and divergent validity of the YCGSI. At both time points, children and adolescents with TS and OCD had, on average, experienced significantly more psychosocial stress than did the controls. Cross-sectional ratings of tic and obsessive-compulsive symptom severity did not correlate with the YCGSI, but did correlate with self-report ratings of stress on the DLSS. In contrast, ratings on the YCGSI were associated with clinician ratings of depression.Conclusions: The YCGSI has acceptable psychometric properties. Children and adolescents with TS and OCD appear to be at increased risk of experiencing higher levels of psychosocial stress and adversities compared with their peers in the community. Future studies need to examine the possible differential contributions of distinctive forms of stress on the intramorbid course of these disorders. [ABSTRACT FROM AUTHOR]- Published
- 2003
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6. Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.
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Huang, Alden Y., Yu, Dongmei, Davis, Lea K., Sul, Jae Hoon, Tsetsos, Fotis, Ramensky, Vasily, Zelaya, Ivette, Ramos, Eliana Marisa, Osiecki, Lisa, Chen, Jason A., McGrath, Lauren M., Illmann, Cornelia, Sandor, Paul, Barr, Cathy L., Grados, Marco, Singer, Harvey S., Nöthen, Markus M., Hebebrand, Johannes, King, Robert A., and Dion, Yves
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NEURAL circuitry , *TOURETTE syndrome , *MICROARRAY technology , *DELETION mutation , *DIAGNOSIS , *DISEASE risk factors - Abstract
Summary Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI [1.39–3.79], p = 1.2 × 10 −3 ) and known, pathogenic CNVs (OR = 3.03 [1.85–5.07], p = 1.5 × 10 −5 ). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk ( NRXN1 deletions, OR = 20.3, 95% CI [2.6–156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3–45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS. [ABSTRACT FROM AUTHOR]
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- 2017
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7. Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.
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Williams, Kyle A., Swedo, Susan E., Farmer, Cristan A., Grantz, Heidi, Grant, Paul J., D’Souza, Precilla, Hommer, Rebecca, Katsovich, Liliya, King, Robert A., Leckman, James F., and D'Souza, Precilla
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NEUROBEHAVIORAL disorders , *STREPTOCOCCAL diseases , *CHILDREN'S health , *JUVENILE diseases , *PATIENTS , *DIAGNOSIS , *THERAPEUTICS , *THERAPEUTIC use of immunoglobulins , *OBSESSIVE-compulsive disorder , *AUTOIMMUNE diseases , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *STREPTOCOCCUS , *EVALUATION research , *RANDOMIZED controlled trials , *TREATMENT effectiveness , *BLIND experiment - Abstract
Objective: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are hypothesized to occur as a result of cross-reactive antibodies produced in response to group A streptococcal infections. Previous research suggests that immunomodulatory therapies, such as intravenous immunoglobulin (IVIG), may lead to rapid and sustained symptom improvement in patients with PANDAS.Method: A total of 35 children meeting criteria for PANDAS and moderate to severe obsessive-compulsive disorder (OCD) were enrolled in a randomized-entry, double-blind, placebo-controlled, 6-week trial of IVIG (1 g/kg/day on 2 consecutive days), followed by optional open-label treatment for nonresponders, with follow-up at 12 and 24 weeks. Primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions-Improvement (CGI-I) rating. "Responders" were defined, a priori, by a ≥ 30% decrease in CY-BOCS total score, and a "much" or "very much" improved rating on CGI-I.Results: During the double-blind phase, the mean decrease in CY-BOCS score was 24% ± 31% in the IVIG group (n = 17) and 12% ± 27% in the placebo group (n = 18), with six responders in the IVIG group (35%) versus four (22%) in the placebo group; these differences were not statistically significant. Twenty-four participants met criteria for nonresponse to double-blind infusion and received open-label IVIG at week 6. Among all participants, the mean CY-BOCS improvement from baseline was 55% ± 33% at week 12 and 62% ± 33% at week 24.Conclusion: IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted. Clinical trial registration information-Intravenous Immunoglobulin for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections); http://clinicaltrials.gov/; NCT01281969ZIAMH002666. [ABSTRACT FROM AUTHOR]- Published
- 2016
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