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Find video protocols related to scientific articles indexed in Pubmed.
Hoarding in Children and Adolescents with Obsessive-Compulsive Disorder.
J Obsessive Compuls Relat Disord
PUBLISHED: 10-14-2014
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Compared to studies in adults, there have been few studies of hoarding in children and adolescents with obsessive-compulsive disorder (OCD). In the current study, we evaluated OCD clinical features, Axis I disorders, and social reciprocity scores in 641 children and adolescents with OCD, of whom 163 (25%) had hoarding compulsions and 478 did not. We found that, as a group, youth with hoarding had an earlier age at onset and more severe lifetime OCD symptoms, poorer insight, more difficulty making decisions and completing tasks, and more overall impairment. The hoarding group also had a greater lifetime prevalence of panic disorder, specific phobia, Tourette disorder, and tics. As measured with the Social Reciprocity Scale, the hoarding group had more severe deficits in parent-rated domains of social communication, social motivation, and restricted interests and repetitive behavior. In a multivariable model, the overall social reciprocity score, age at onset of OCD symptoms, symmetry obsessions, and indecision were independently related to hoarding in these children and adolescents with OCD. These features should be considered as candidate risk factors for the development of hoarding behavior in pediatric OCD.
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Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD.
Dongmei Yu, Carol A Mathews, Jeremiah M Scharf, Benjamin M Neale, Lea K Davis, Eric R Gamazon, Eske M Derks, Patrick Evans, Christopher K Edlund, Jacquelyn Crane, Jesen A Fagerness, Lisa Osiecki, Patience Gallagher, Gloria Gerber, Stephen Haddad, Cornelia Illmann, Lauren M McGrath, Catherine Mayerfeld, Sampath Arepalli, Cristina Barlassina, Cathy L Barr, Laura Bellodi, Fortu Benarroch, Gabriel Bedoya Berrió, O Joseph Bienvenu, Donald W Black, Michael H Bloch, Helena Brentani, Ruth D Bruun, Cathy L Budman, Beatriz Camarena, Desmond D Campbell, Carolina Cappi, Julio C Cardona Silgado, Maria C Cavallini, Denise A Chavira, Sylvain Chouinard, Edwin H Cook, M R Cookson, Vladimir Coric, Bernadette Cullen, Daniele Cusi, Richard Delorme, Damiaan Denys, Yves Dion, Valsama Eapen, Karin Egberts, Peter Falkai, Thomas Fernandez, Eduardo Fournier, Helena Garrido, Daniel Geller, Donald Gilbert, Simon L Girard, Hans J Grabe, Marco A Grados, Benjamin D Greenberg, Varda Gross-Tsur, Edna Grünblatt, John Hardy, Gary A Heiman, Sian M J Hemmings, Luis D Herrera, Dianne M Hezel, Pieter J Hoekstra, Joseph Jankovic, James L Kennedy, Robert A King, Anuar I Konkashbaev, Barbara Kremeyer, Roger Kurlan, Nuria Lanzagorta, Marion Leboyer, James F Leckman, Leonhard Lennertz, Chunyu Liu, Christine Lochner, Thomas L Lowe, Sara Lupoli, Fabio Macciardi, Wolfgang Maier, Paolo Manunta, Maurizio Marconi, James T McCracken, Sandra C Mesa Restrepo, Rainald Moessner, Priya Moorjani, Jubel Morgan, Heike Muller, Dennis L Murphy, Allan L Naarden, Erika Nurmi, William Cornejo Ochoa, Roel A Ophoff, Andrew J Pakstis, Michele T Pato, Carlos N Pato, John Piacentini, Christopher Pittenger, Yehuda Pollak, Scott L Rauch, Tobias Renner, Victor I Reus, Margaret A Richter, Mark A Riddle, Mary M Robertson, Roxana Romero, Maria C Rosário, David Rosenberg, Stephan Ruhrmann, Chiara Sabatti, Erika Salvi, Aline S Sampaio, Jack Samuels, Paul Sandor, Susan K Service, Brooke Sheppard, Harvey S Singer, Jan H Smit, Dan J Stein, Eric Strengman, Jay A Tischfield, Maurizio Turiel, Ana V Valencia Duarte, Homero Vallada, Jeremy Veenstra-VanderWeele, Susanne Walitza, Ying Wang, Mike Weale, Robert Weiss, Jens R Wendland, Herman G M Westenberg, Yin Yao Shugart, Ana G Hounie, Euripedes C Miguel, Humberto Nicolini, Michael Wagner, Andrés Ruiz-Linares, Danielle C Cath, William McMahon, Danielle Posthuma, Ben A Oostra, Gerald Nestadt, Guy A Rouleau, Shaun Purcell, Michael A Jenike, Peter Heutink, Gregory L Hanna, David V Conti, Paul D Arnold, Nelson B Freimer, S Evelyn Stewart, James A Knowles, Nancy J Cox, David L Pauls.
Am J Psychiatry
PUBLISHED: 08-26-2014
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Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.
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Endoplasmic reticulum stress-dependent activation of ATF3 mediates the late phase of ischemic preconditioning.
J. Mol. Cell. Cardiol.
PUBLISHED: 08-23-2014
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Ischemic preconditioning (PC) is an adaptive response to transient myocardial ischemia that protects the heart from subsequent ischemia/reperfusion (I/R) injury. However, the mechanisms underlying its cardioprotective effects remain unclear. Myocardium of adult male C57/BL6 mice, preconditioned by 6cycles of 4minute coronary occlusion and reperfusion, showed nuclear translocation of ATF3 and ATF6 and PERK phosphorylation 30min after PC. The abundance of ER proteins, ATF3 and ATF4 was increased 24h after PC; however, there was no evidence of IRE-1 activation in WT or ER-stress activated indicator (ERAI) mice expressing XBP-1-Venus fusion protein. PC-induced nuclear translocation of ATF3 was attenuated in transgenic mice with cardiac-restricted overexpression of inducible ATF6. Ischemic PC increased the abundance of inducible nitric oxide synthase, cyclooxygenase-2, heme oxygenase-1 and aldose reductase to levels similar between WT and ATF3-null hearts; however, the increase in IL-6 and ICAM-1 was exaggerated in ATF3-null hearts. Genetic deletion of ATF3 did not increase infarct size in non-preconditioned hearts but abolished the cardioprotective effects of PC. Larger infarct size in preconditioned ATF3-null hearts was associated with greater neutrophil infiltration in the myocardium, but no ATF3-dependent changes in the total or relative abundance of inflammatory monocytes were observed. Ischemic PC activates the unfolded protein response (UPR) and the activation of ATF3 by ER stress is essential for the cardioprotective effects of late PC.
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Acrolein exposure is associated with increased cardiovascular disease risk.
J Am Heart Assoc
PUBLISHED: 08-08-2014
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Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. It is also generated endogenously by lipid peroxidation and the oxidation of amino acids by myeloperoxidase. In animals, acrolein exposure is associated with the suppression of circulating progenitor cells and increases in thrombosis and atherogenesis. The purpose of this study was to determine whether acrolein exposure in humans is also associated with increased cardiovascular disease (CVD) risk.
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Innovative and community-driven communication practices of the South Carolina cancer prevention and control research network.
Prev Chronic Dis
PUBLISHED: 07-25-2014
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The South Carolina Cancer Prevention and Control Research Network (SC-CPCRN) is 1 of 10 networks funded by the Centers for Disease Control and Prevention and the National Cancer Institute (NCI) that works to reduce cancer-related health disparities. In partnership with federally qualified health centers and community stakeholders, the SC-CPCRN uses evidence-based approaches (eg, NCI Research-tested Intervention Programs) to disseminate and implement cancer prevention and control messages, programs, and interventions. We describe the innovative stakeholder- and community-driven communication efforts conducted by the SC-CPCRN to improve overall health and reduce cancer-related health disparities among high-risk and disparate populations in South Carolina. We describe how our communication efforts are aligned with 5 core values recommended for dissemination and implementation science: 1) rigor and relevance, 2) efficiency and speed, 3) collaboration, 4) improved capacity, and 5) cumulative knowledge.
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Examination of aggression and self-injury in children with autism spectrum disorders and serious behavioral problems.
Child Adolesc Psychiatr Clin N Am
PUBLISHED: 06-24-2014
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This study identified subtypes of aggression in a sample of 206 children with autism spectrum disorder (ASD) who participated in 2 risperidone trials. The narratives were derived from a parent interview about each child's 2 most pressing problems. Five subtypes of aggression emerged: hot aggression only, cold aggression only, self-injurious behavior (SIB) only, aggression and SIB, and nonaggressive. All groups showed a high rate of positive response to risperidone with no differences across subtypes. These study findings extend understanding of aggression in ASD and may be useful to guide further study on biological mechanisms and individualized treatment in ASD.
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Clinical correlates and genetic linkage of social and communication difficulties in families with obsessive-compulsive disorder: Results from the OCD Collaborative Genetics Study.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 04-11-2014
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Some individuals with obsessive-compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical examinations on, and collected DNA samples from, 706 individuals with OCD in 221 multiply affected OCD families. Using the Pragmatic Rating Scale (PRS), we compared the prevalence of pragmatic impairment in OCD-affected relatives of probands with and without pragmatic impairment. We also compared clinical features of OCD-affected individuals in families having at least one, versus no, individual with pragmatic impairment, and assessed for linkage to OCD in the two groups of families. The odds of pragmatic impairment were substantially greater in OCD-affected relatives of probands with pragmatic impairment. Individuals in high-PRS families had greater odds of separation anxiety disorder and social phobia, and a greater number of schizotypal personality traits. In high-PRS families, there was suggestive linkage to OCD on chromosome 12 at marker D12S1064 and on chromosome X at marker DXS7132 whereas, in low-PRS families, there was suggestive linkage to chromosome 3 at marker D3S2398. Pragmatic impairment aggregates in OCD families. Separation anxiety disorder, social phobia, and schizotypal personality traits are part of a clinical spectrum associated with pragmatic impairment in these families. Specific regions of chromosomes 12 and X are linked to OCD in high-PRS families. Thus, pragmatic impairment may distinguish a clinically and genetically homogeneous subtype of OCD.
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Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.
Lauren M McGrath, Dongmei Yu, Christian Marshall, Lea K Davis, Bhooma Thiruvahindrapuram, Bingbin Li, Carolina Cappi, Gloria Gerber, Aaron Wolf, Frederick A Schroeder, Lisa Osiecki, Colm O'Dushlaine, Andrew Kirby, Cornelia Illmann, Stephen Haddad, Patience Gallagher, Jesen A Fagerness, Cathy L Barr, Laura Bellodi, Fortu Benarroch, O Joseph Bienvenu, Donald W Black, Michael H Bloch, Ruth D Bruun, Cathy L Budman, Beatriz Camarena, Danielle C Cath, Maria C Cavallini, Sylvain Chouinard, Vladimir Coric, Bernadette Cullen, Richard Delorme, Damiaan Denys, Eske M Derks, Yves Dion, Maria C Rosário, Valsama Eapen, Patrick Evans, Peter Falkai, Thomas V Fernandez, Helena Garrido, Daniel Geller, Hans J Grabe, Marco A Grados, Benjamin D Greenberg, Varda Gross-Tsur, Edna Grünblatt, Gary A Heiman, Sian M J Hemmings, Luis D Herrera, Ana G Hounie, Joseph Jankovic, James L Kennedy, Robert A King, Roger Kurlan, Nuria Lanzagorta, Marion Leboyer, James F Leckman, Leonhard Lennertz, Christine Lochner, Thomas L Lowe, Gholson J Lyon, Fabio Macciardi, Wolfgang Maier, James T McCracken, William McMahon, Dennis L Murphy, Allan L Naarden, Benjamin M Neale, Erika Nurmi, Andrew J Pakstis, Michele T Pato, Carlos N Pato, John Piacentini, Christopher Pittenger, Yehuda Pollak, Victor I Reus, Margaret A Richter, Mark Riddle, Mary M Robertson, David Rosenberg, Guy A Rouleau, Stephan Ruhrmann, Aline S Sampaio, Jack Samuels, Paul Sandor, Brooke Sheppard, Harvey S Singer, Jan H Smit, Dan J Stein, Jay A Tischfield, Homero Vallada, Jeremy Veenstra-VanderWeele, Susanne Walitza, Ying Wang, Jens R Wendland, Yin Yao Shugart, Euripedes C Miguel, Humberto Nicolini, Ben A Oostra, Rainald Moessner, Michael Wagner, Andrés Ruiz-Linares, Peter Heutink, Gerald Nestadt, Nelson Freimer, Tracey Petryshen, Danielle Posthuma, Michael A Jenike, Nancy J Cox, Gregory L Hanna, Helena Brentani, Stephen W Scherer, Paul D Arnold, S Evelyn Stewart, Carol A Mathews, James A Knowles, Edwin H Cook, David L Pauls, Kai Wang, Jeremiah M Scharf.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 03-16-2014
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Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date.
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Parental Anxiety as a Predictor of Medication and CBT Response for Anxious Youth.
Child Psychiatry Hum Dev
PUBLISHED: 03-11-2014
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The aim of this investigation was to evaluate how parental anxiety predicted change in pediatric anxiety symptoms across four different interventions: cognitive-behavioral therapy, medication (sertraline; SRT), their combination (COMB), and pill placebo. Participants were 488 youths (ages 7-17) with separation anxiety disorder, generalized anxiety disorder, and/or social phobia and their primary caregivers. Latent growth curve modeling assessed how pre-treatment parental trait anxiety symptoms predicted trajectories of youth anxiety symptom change across 12 weeks of treatment at four time points. Interactions between parental anxiety and treatment condition were tested. Parental anxiety was not associated with youth's pre-treatment anxiety symptom severity. Controlling for parental trait anxiety, youth depressive symptoms, and youth age, youths who received COMB benefitted most. Counter to expectations, parental anxiety influenced youth anxiety symptom trajectory only within the SRT condition, whereas parental anxiety was not significantly associated with youth anxiety trajectories in the other treatment conditions. Specifically, within the SRT condition, higher levels of parental anxiety predicted a faster and greater reduction in youth anxiety over the acute treatment period compared to youths in the SRT condition whose parents had lower anxiety levels. While all active treatments produced favorable outcomes, results provide insight regarding the treatment-specific influence of parental anxiety on the time course of symptom change.
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24- and 36-week outcomes for the Child/Adolescent Anxiety Multimodal Study (CAMS).
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 02-26-2014
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We report active treatment group differences on response and remission rates and changes in anxiety severity at weeks 24 and 36 for the Child/Adolescent Anxiety Multimodal Study (CAMS).
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Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 01-30-2014
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Autism spectrum disorder is characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills that arise in the first years of life. Although frequently associated with intellectual disability, this condition is distinctive in its course, impact, and treatment. Autism spectrum disorder has a wide range of syndrome expression and its management presents particular challenges for clinicians. Individuals with an autism spectrum disorder can present for clinical care at any point in development. The multiple developmental and behavioral problems associated with this condition necessitate multidisciplinary care, coordination of services, and advocacy for individuals and their families. Early, sustained intervention and the use of multiple treatment modalities are indicated.
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Electroencephalography correlates of spatial working memory deficits in attention-deficit/hyperactivity disorder: vigilance, encoding, and maintenance.
J. Neurosci.
PUBLISHED: 01-24-2014
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In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7-14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8-12 Hz) to evaluate encoding processes and frontal midline theta (4-7 Hz) to evaluate maintenance processes. We tested for effects of task difficulty and cue processing to evaluate vigilance. Children with ADHD showed attenuated alpha band event-related desynchronization (ERD) during encoding. This effect was more pronounced when task difficulty was low (consistent with impaired vigilance) and was predictive of memory task performance and symptom severity. Correlated with alpha ERD during encoding were alpha power increases during the maintenance period (relative to baseline), suggesting a compensatory effort. Consistent with this interpretation, midfrontal theta power increases during maintenance were stronger in ADHD and in high-load memory conditions. Furthermore, children with ADHD exhibited a maturational lag in development of posterior alpha power whereas age-related changes in frontal theta power deviated from the TD pattern. Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group.
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A probabilistic and individualized approach for predicting treatment gains: an extension and application to anxiety disordered youth.
Behav Ther
PUBLISHED: 01-14-2014
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The objective of this study was to extend the probability of treatment benefit method by adding treatment condition as a stratifying variable, and illustrate this extension of the methodology using the Child and Adolescent Anxiety Multimodal Study data. The probability of treatment benefit method produces a simple and practical way to predict individualized treatment benefit based on pretreatment patient characteristics. Two pretreatment patient characteristics were selected in the production of the probability of treatment benefit charts: baseline anxiety severity, measured by the Pediatric Anxiety Rating Scale, and treatment condition (cognitive-behavioral therapy, sertraline, their combination, and placebo). We produced two charts as exemplars which provide individualized and probabilistic information for treatment response and outcome to treatments for child anxiety. We discuss the implications of the use of the probability of treatment benefit method, particularly with regard to patient-centered outcomes and individualized decision-making in psychology and psychiatry.
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Predictors and moderators of treatment response in childhood anxiety disorders: results from the CAMS trial.
J Consult Clin Psychol
PUBLISHED: 01-13-2014
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We sought to examine predictors and moderators of treatment outcomes among 488 youths ages 7-17 years (50% female; 74% ? 12 years) meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) criteria for diagnoses of separation anxiety disorder, social phobia, or generalized anxiety disorder who were randomly assigned to receive either cognitive behavioral therapy (CBT), sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) in the Child/Adolescent Anxiety Multimodal Study (CAMS).
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Measuring repetitive behaviors as a treatment endpoint in youth with autism spectrum disorder.
Autism
PUBLISHED: 11-22-2013
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Restricted interests and repetitive behaviors vary widely in type, frequency, and intensity among children and adolescents with autism spectrum disorder. They can be stigmatizing and interfere with more constructive activities. Accordingly, restricted interests and repetitive behaviors may be a target of intervention. Several standardized instruments have been developed to assess restricted interests and repetitive behaviors in the autism spectrum disorder population, but the rigor of psychometric assessment is variable. This article evaluated the readiness of available measures for use as outcome measures in clinical trials. The Autism Speaks Foundation assembled a panel of experts to examine available instruments used to measure restricted interests and repetitive behaviors in youth with autism spectrum disorder. The panel held monthly conference calls and two face-to-face meetings over 14 months to develop and apply evaluative criteria for available instruments. Twenty-four instruments were evaluated and five were considered "appropriate with conditions" for use as outcome measures in clinical trials. Ideally, primary outcome measures should be relevant to the clinical target, be reliable and valid, and cover the symptom domain without being burdensome to subjects. The goal of the report was to promote consensus across funding agencies, pharmaceutical companies, and clinical investigators about advantages and disadvantages of existing outcome measures.
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Autism spectrum disorders: an overview on diagnosis and treatment.
Rev Bras Psiquiatr
PUBLISHED: 10-22-2013
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Pervasive developmental disorders are now commonly referred to as autism spectrum disorders (ASDs). ASDs present with a range of severity and impairments, and often are a cause of severe disability, representing a major public health concern. The diagnostic criteria require delays or abnormal functioning in social interaction, language, and/or imaginative play within the first 3 years of life, resulting in a deviation from the developmental pattern expected for the age. Because establishing a diagnosis of ASD is possible as early as 18-24 months of age, clinicians should strive to identify and begin intervention in children with ASD as soon as signs are manifest. Increasing efforts are underway to make ASD screening universal in pediatric healthcare. Given the crucial importance of early identification and multiple modalities of treatment for ASD, this review will summarize the diagnostic criteria, key areas for assessment by clinicians, specific scales and instruments for assessment, and discussion of evidence-based treatment programs and the role of specific drug therapies for symptom management.
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Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.
Lea K Davis, Dongmei Yu, Clare L Keenan, Eric R Gamazon, Anuar I Konkashbaev, Eske M Derks, Benjamin M Neale, Jian Yang, S Hong Lee, Patrick Evans, Cathy L Barr, Laura Bellodi, Fortu Benarroch, Gabriel Bedoya Berrió, Oscar J Bienvenu, Michael H Bloch, Rianne M Blom, Ruth D Bruun, Cathy L Budman, Beatriz Camarena, Desmond Campbell, Carolina Cappi, Julio C Cardona Silgado, Danielle C Cath, Maria C Cavallini, Denise A Chavira, Sylvain Chouinard, David V Conti, Edwin H Cook, Vladimir Coric, Bernadette A Cullen, Dieter Deforce, Richard Delorme, Yves Dion, Christopher K Edlund, Karin Egberts, Peter Falkai, Thomas V Fernandez, Patience J Gallagher, Helena Garrido, Daniel Geller, Simon L Girard, Hans J Grabe, Marco A Grados, Benjamin D Greenberg, Varda Gross-Tsur, Stephen Haddad, Gary A Heiman, Sian M J Hemmings, Ana G Hounie, Cornelia Illmann, Joseph Jankovic, Michael A Jenike, James L Kennedy, Robert A King, Barbara Kremeyer, Roger Kurlan, Nuria Lanzagorta, Marion Leboyer, James F Leckman, Leonhard Lennertz, Chunyu Liu, Christine Lochner, Thomas L Lowe, Fabio Macciardi, James T McCracken, Lauren M McGrath, Sandra C Mesa Restrepo, Rainald Moessner, Jubel Morgan, Heike Muller, Dennis L Murphy, Allan L Naarden, William Cornejo Ochoa, Roel A Ophoff, Lisa Osiecki, Andrew J Pakstis, Michele T Pato, Carlos N Pato, John Piacentini, Christopher Pittenger, Yehuda Pollak, Scott L Rauch, Tobias J Renner, Victor I Reus, Margaret A Richter, Mark A Riddle, Mary M Robertson, Roxana Romero, Maria C Rosário, David Rosenberg, Guy A Rouleau, Stephan Ruhrmann, Andrés Ruiz-Linares, Aline S Sampaio, Jack Samuels, Paul Sandor, Brooke Sheppard, Harvey S Singer, Jan H Smit, Dan J Stein, E Strengman, Jay A Tischfield, Ana V Valencia Duarte, Homero Vallada, Filip Van Nieuwerburgh, Jeremy Veenstra-VanderWeele, Susanne Walitza, Ying Wang, Jens R Wendland, Herman G M Westenberg, Yin Yao Shugart, Euripedes C Miguel, William McMahon, Michael Wagner, Humberto Nicolini, Danielle Posthuma, Gregory L Hanna, Peter Heutink, Damiaan Denys, Paul D Arnold, Ben A Oostra, Gerald Nestadt, Nelson B Freimer, David L Pauls, Naomi R Wray, S Evelyn Stewart, Carol A Mathews, James A Knowles, Nancy J Cox, Jeremiah M Scharf.
PLoS Genet.
PUBLISHED: 10-01-2013
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The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
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Baseline factors predicting placebo response to treatment in children and adolescents with autism spectrum disorders: a multisite randomized clinical trial.
JAMA Pediatr
PUBLISHED: 09-25-2013
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The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population.
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Brief Report: social disability in autism spectrum disorder: results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network trials.
J Autism Dev Disord
PUBLISHED: 08-16-2013
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There is growing interest in measuring social disability as a core element of autism spectrum disorders in medication trials. We conducted a secondary analysis on the Aberrant Behavior Checklist Social Withdrawal subscale using data from two federally-funded, multi-site, randomized trials with risperidone. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. Study 2 included 49 subjects assigned to risperidone only and 75 subjects assigned to risperidone plus parent training. After 8 weeks of treatment, all active treatments were superior to placebo (effect sizes ranging from 0.42 to 0.65). The findings suggest that the Social Withdrawal subscale may be a useful measure of social disability in acute treatment trials.
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Assessing Anxiety in Youth with the Multidimensional Anxiety Scale for Children.
J Clin Child Adolesc Psychol
PUBLISHED: 07-11-2013
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The present study examined the psychometric properties, including discriminant validity and clinical utility, of the youth self-report and parent-report forms of the Multidimensional Anxiety Scale for Children (MASC) among youth with anxiety disorders. The sample included parents and youth (N = 488, 49.6% male) ages 7 to 17 who participated in the Child/Adolescent Anxiety Multimodal Study. Although the typical low agreement between parent and youth self-reports was found, the MASC evidenced good internal reliability across MASC subscales and informants. The main MASC subscales (i.e., Physical Symptoms, Harm Avoidance, Social Anxiety, and Separation/Panic) were examined. The Social Anxiety and Separation/Panic subscales were found to be significantly predictive of the presence and severity of social phobia and separation anxiety disorder, respectively. Using multiple informants improved the accuracy of prediction. The MASC subscales demonstrated good psychometric properties and clinical utilities in identifying youth with anxiety disorders.
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Palliative care and hematological malignancies: increased referrals at a comprehensive cancer centre.
J Palliat Med
PUBLISHED: 07-05-2013
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Current evidence indicates that patients with hematological malignancies are less likely to receive input from specialist palliative care services compared to those with solid tumors.
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Up in smoke? A preliminary open-label trial of nicotine replacement therapy and cognitive behavioral motivational enhancement for smoking cessation among youth in Los Angeles.
Subst Use Misuse
PUBLISHED: 07-03-2013
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In 2008-2009, we conducted a 6-week, open-label trial of transdermal nicotine replacement therapy and practical counseling for 34 adolescents seeking smoking cessation in Los Angeles. Dependent outcomes were study retention, use of the patch, and 7-day quit status at the end-of-study and at follow-up visits. Predictors of outcomes included cigarette dependence, withdrawal symptoms, demographic and psychiatric measures, and other substance use. Variables significant in bivariate analysis (p < .10) were retained in a multivariate model. Subjects had significant pre-to-post reductions in quit rates, dependence, and withdrawal symptoms. Subjects also reported a high number of comorbidities. Implications for clinicians are discussed.
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Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development.
J. Neurosci.
PUBLISHED: 06-28-2013
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Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.
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The therapeutic relationship in cognitive-behavioral therapy and pharmacotherapy for anxious youth.
J Consult Clin Psychol
PUBLISHED: 06-10-2013
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We examined the therapeutic relationship with cognitive-behavioral therapists and with pharmacotherapists for youth from the Child/Adolescent Anxiety Multimodal Study (Walkup et al., 2008). The therapeutic relationship was examined in relation to treatment outcomes.
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How acceptable are primary health care nurse practitioners to Australian consumers?
Collegian
PUBLISHED: 05-18-2013
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International evidence indicates that nurses working in primary care can provide effective care and achieve positive health outcomes for patients similar to that provided by doctors. Nurse practitioners employed in primary health care perform some tasks previously exclusive to the GP role due to their advanced skills, knowledge and training. In November 2010 Medicare provider rights and Pharmaceutical Benefits Scheme rights were provided for nurse practitioners working in private practice, and in collaboration with a medical practitioner. However, there is limited evidence about how acceptable nurse practitioners are to Australian consumers and what knowledge consumers have of the nurse practitioner role in the delivery of primary health care. The aim of this study was to examine Australian health care consumers perceptions of nurse practitioners working in primary health care. This paper reports on the results of seven focus groups (n = 77 participants) conducted around Australia. Focus groups participants were asked how acceptable nurse practitioners are as provides of primary health care. Although there was some confusion about the role of nurse practitioners and how this role differed from other primary health care nurses, participants in the focus groups were very positive about nurse practitioners and would find them acceptable in providing primary health care.
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Findings from the Community Health Intervention Program in South Carolina: implications for reducing cancer-related health disparities.
J Cancer Educ
PUBLISHED: 05-07-2013
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The South Carolina Cancer Prevention and Control Research Network (SC-CPCRN) implemented the Community Health Intervention Program (CHIP) mini-grants initiative to address cancer-related health disparities and reduce the cancer burden among high-risk populations across the state. The mini-grants project implemented evidence-based health interventions tailored to the specific needs of each community. This study aims to support the SC-CPCRNs goals of moving toward greater dissemination and implementation of evidence-based programs in the community to improve public health, prevent disease, and reduce the cancer burden. Three community-based organizations were awarded $10,000 each to implement one of the National Cancer Institutes evidence-based interventions. Each group had 12 months to complete their project. SC-CPCRN investigators and staff provided guidance, oversight, and technical assistance for each project. Grantees provided regular updates and reports to their SC-CPCRN liaisons to capture vital evaluation information. The intended CHIP mini-grant target population reach was projected to be up to 880 participants combined. Actual combined reach of the three projects reported upon completion totaled 1,072 individuals. The majority of CHIP participants were African-American females. Participants ranged in age from 19 to 81 years. Evaluation results showed an increase in physical activity, dietary improvements, and screening participation. The success of the initiative was the result of a strong community-university partnership built on trust. Active two-way communication and an honest open dialogue created an atmosphere for collaboration. Communities were highly motivated. All team members shared a common goal of reducing cancer-related health disparities and building greater public health capacity across the state.
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A potential electroencephalography and cognitive biosignature for the child behavior checklist-dysregulation profile.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 04-26-2013
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The Child Behavior Checklist-Dysregulation Profile (CBCL/DP) identifies youth at increased risk for significant psychopathology. Although the genetic architecture and several biological correlates of the CBCL/DP have been described, little work has elucidated its underlying neurobiology. We examined the potential utility of electroencephalography (EEG), along with behavioral and cognitive assessments, in differentiating individuals based on the CBCL/DP.
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Childrens Yale-Brown Obsessive Compulsive Scale in Autism Spectrum Disorder: Component Structure and Correlates of Symptom Checklist.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 04-18-2013
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Repetitive behaviors in autism spectrum disorders (ASD) range from motor stereotypy to immersion in restricted interests. The modified Childrens Yale-Brown Obsessive Compulsive Scale for children with autism spectrum disorder (CYBOCS-ASD) includes a Symptom Checklist (behavior present or absent) and 5 severity scales (Time Spent, Interference, Distress, Resistance and Control).
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Exploring the manifestations of anxiety in children with autism spectrum disorders.
J Autism Dev Disord
PUBLISHED: 02-13-2013
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This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.
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The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-year follow-up.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 02-08-2013
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To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS).
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Protein O-GlcNAcylation is a novel cytoprotective signal in cardiac stem cells.
Stem Cells
PUBLISHED: 01-22-2013
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Clinical trials demonstrate the regenerative potential of cardiac stem cell (CSC) therapy in the postinfarcted heart. Despite these encouraging preliminary clinical findings, the basic biology of these cells remains largely unexplored. The principal requirement for cell transplantation is to effectively prime them for survival within the unfavorable environment of the infarcted myocardium. In the adult mammalian heart, the ?-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to proteins is a unique post-translational modification that confers cardioprotection from various otherwise lethal stressors. It is not known whether this signaling system exists in CSCs. In this study, we demonstrate that protein O-GlcNAcylation is an inducible stress response in adult murine Sca-1(+) /lin(-) CSCs and exerts an essential prosurvival role. Posthypoxic CSCs responded by time-dependently increasing protein O-GlcNAcylation upon reoxygenation. We used pharmacological interventions for loss- and gain-of-function, that is, enzymatic inhibition of O-GlcNAc transferase (OGT) (adds the O-GlcNAc modification to proteins) by TT04, or inhibition of OGA (removes O-GlcNAc) by thiamet-G (ThG). Reduction in the O-GlcNAc signal (via TT04, or OGT gene deletion using Cre-mediated recombination) significantly sensitized CSCs to posthypoxic injury, whereas augmenting O-GlcNAc levels (via ThG) enhanced cell survival. Diminished O-GlcNAc levels render CSCs more susceptible to the onset of posthypoxic apoptotic processes via elevated poly(ADP-ribose) polymerase cleavage due to enhanced caspase-3/7 activation, whereas promoting O-GlcNAcylation can serve as a pre-emptive antiapoptotic signal regulating the survival of CSCs. Thus, we report the primary demonstration of protein O-GlcNAcylation as an important prosurvival signal in CSCs, which could enhance CSC survival prior to in vivo autologous transfer.
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Pilot randomized trial of bupropion for adolescent methamphetamine abuse/dependence.
J Adolesc Health
PUBLISHED: 01-17-2013
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To perform a pilot clinical trial of bupropion for methamphetamine abuse/dependence among adolescents.
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Spaceflight Enhances Cell Aggregation and Random Budding in Candida albicans.
PLoS ONE
PUBLISHED: 01-01-2013
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This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans-induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.
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Remission after acute treatment in children and adolescents with anxiety disorders: findings from the CAMS.
J Consult Clin Psychol
PUBLISHED: 11-30-2011
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To report on remission rates in anxious youth who participated in the Child/Adolescent Anxiety Multimodal Study (CAMS). The CAMS, a multisite clinical trial, randomized 488 children and adolescents (ages 7-17 years; 79% Caucasian; 50% female) with separation, social, and/or generalized anxiety disorder to a 12-week treatment of sertraline (SRT), cognitive behavioral therapy (CBT), their combination (COMB), or clinical management with pill placebo (PBO).
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Risperidone-related improvement of irritability in children with autism is not associated with changes in serum of epidermal growth factor and interleukin-13.
J Child Adolesc Psychopharmacol
PUBLISHED: 11-09-2011
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Risperidone has been shown to improve serious behavioral problems in children with autism. Here we asked whether risperidone-associated improvement was related to changes in concentrations of inflammatory molecules in the serum of these subjects. Seven molecules were identified as worthy of further assessment by performing a pilot analysis of 31 inflammatory markers in 21 medication-free subjects with autism versus 15 healthy controls: epidermal growth factor (EGF), interferon-? (IFN-?), interleukin (IL)-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), IL-1 and IL-1-receptor antagonist. Serum concentrations of these markers were then established in a different set of subjects that participated in a double-blind, clinical trial and an expanded group of healthy subjects. In the first analysis, samples obtained from subjects with autism at baseline visits were compared to visits after 8-week treatment with placebo (n=37) or risperidone (n=40). The cytokine concentrations remained stable over the 8-week period for both risperidone and placebo groups. In the second analysis, we explored further the differences between medication-free subjects with autism (n=77) and healthy controls (recruited independently; n=19). Serum levels of EGF were elevated in subjects with autism (median=103 pg/mL, n=75) in comparison to healthy controls (75 pg/mL, n=19; p<0.05), and levels of IL-13 were decreased in autism (median=0.8 pg/mL, n=77) in comparison to controls (9.8 pg/mL, n=19; p=0.0003). These changes did not correlate with standardized measures used for a diagnosis of autism. In summary, risperidone-induced clinical improvement in subjects with autism was not associated with changes in the serum inflammatory markers measured. Whether altered levels of EGF and IL-13 play a role in the pathogenesis or phenotype of autism requires further investigation.
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Antidepressant exposure as a predictor of clinical outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) study.
J Clin Psychopharmacol
PUBLISHED: 10-14-2011
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This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents. Adolescents (n = 334) with major depression who had not responded to a selective serotonin reuptake inhibitor (SSRI) were randomized to 1 of 4 treatments: switch to another SSRI (fluoxetine, citalopram, or paroxetine), switch to venlafaxine, switch to SSRI plus cognitive behavior therapy, or switch to venlafaxine plus cognitive behavior therapy. Adolescents who did not improve by 6 weeks had their dose increased. Plasma concentrations of medication and metabolites were measured at 6 weeks in 244 participants and at 12 weeks in 204 participants. Adolescents treated with citalopram whose plasma concentration was equal to or greater than the geometric mean (GM) showed a higher response rate compared to those with less than the GM, with parallel but nonsignificant findings for fluoxetine. A dose increase of citalopram or fluoxetine at week 6 was most likely to result in response when it led to a change in concentration from less than the GM at 6 weeks to the GM or greater at week 12. Plasma levels of paroxetine, venlafaxine, or O-desmethylvenlafaxine were not related to clinical response. Exposure was associated with more cardiovascular and dermatologic side effects in those receiving venlafaxine. Antidepressant concentration may be useful in optimizing treatment for depressed adolescents receiving fluoxetine or citalopram.
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Differential effects of pandemic (H1N1) 2009 on remote and indigenous groups, Northern Territory, Australia, 2009.
Emerging Infect. Dis.
PUBLISHED: 09-06-2011
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Pandemic (H1N1) 2009 influenza spread through the Northern Territory, Australia, during June-August 2009. We performed 2 cross-sectional serologic surveys on specimens from Northern Territory residents, with 445 specimens obtained prepandemic and 1,689 specimens postpandemic. Antibody titers were determined by hemagglutination inhibition against reference virus A/California/7/2009 on serum samples collected opportunistically from outpatients. All specimens had data for patients gender, age, and address, with patients indigenous status determined for 94.1%. Protective immunity (titer >40) was present in 7.6% (95% confidence interval [CI] 5.2%-10.1%) of prepandemic specimens and 19.5% (95% CI 17.6%-21.4%) of postpandemic specimens, giving a population-standardized attack rate of 14.9% (95% CI 11.0%-18.9%). Prepandemic proportion of immune persons was greater with increasing age but did not differ by other demographic characteristics. Postpandemic proportion of immune persons was greater in younger groups and around double in indigenous persons. Postpandemic proportion immune was geographically heterogeneous, particularly among remote-living and indigenous groups.
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Controlled comparison of family cognitive behavioral therapy and psychoeducation/relaxation training for child obsessive-compulsive disorder.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 07-29-2011
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To examine the efficacy of exposure-based cognitive-behavioral therapy (CBT) plus a structured family intervention (FCBT) versus psychoeducation plus relaxation training (PRT) for reducing symptom severity, functional impairment, and family accommodation in youths with obsessive-compulsive disorder (OCD).
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MRSI correlates of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 07-25-2011
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The brain mechanisms of cognitive-behavioral therapy (CBT), a highly effective treatment for pediatric obsessive-compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging (1H MRSI).
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Acrolein inhalation prevents vascular endothelial growth factor-induced mobilization of Flk-1+/Sca-1+ cells in mice.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 04-28-2011
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Acrolein is a toxic chemical present in tobacco, wood, and coal smoke, as well as automobile exhaust. Because exposure to these pollutants is associated with an increase in cardiovascular disease risk, we studied the effects of acrolein on Flk-1(+)/Sca-1(+) cells that are involved in vascular repair.
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Genome-wide association study of the child behavior checklist dysregulation profile.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 04-27-2011
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A potentially useful tool for understanding the distribution and determinants of emotional dysregulation in children is a Child Behavior Checklist profile, comprising the Attention Problems, Anxious/Depressed, and Aggressive Behavior clinical subscales (CBCL-DP). The CBCL-DP indexes a heritable trait that increases susceptibility for later psychopathology, including severe mood problems and aggressive behavior. We have conducted a genome-wide association study of the CBCL-DP in children with attention-deficit/hyperactivity disorder (ADHD).
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Suicide attempts and nonsuicidal self-injury in the treatment of resistant depression in adolescents: findings from the TORDIA study.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 03-18-2011
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To evaluate the clinical and prognostic significance of suicide attempts (SAs) and nonsuicidal self-injury (NSSI) in adolescents with treatment-resistant depression.
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Comprehensive family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 03-02-2011
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SLC1A1 encodes a neuronal glutamate transporter and is a promising candidate gene for obsessive-compulsive disorder (OCD). Several independent research groups have reported significant associations between OCD and single nucleotide polymorphisms (SNPs) in this gene. Previously, we evaluated 13 SNPs in, or near, SLC1A1 and reported a strong association signal with rs301443, a SNP 7.5 kb downstream of the gene [Shugart et al. (2009); Am J Med Genet Part B 150B:886–892]. The aims of the current study were first, to further investigate this finding by saturating the region around rs301443; and second, to explore the entire gene more thoroughly with a dense panel of SNP markers. We genotyped an additional 111 SNPs in or near SLC1A1, covering from 9 kb upstream to 84 kb downstream of the gene at average spacing of 1.7 kb per SNP, and conducted family-based association analyses in 1,576 participants in 377 families.We found that none of the surrounding markers were in linkage disequilibrium with rs301443, nor were any associated with OCD. We also found that SNP rs4740788, located about 8.8 kb upstream of the gene, was associated with OCD in all families (P = 0.003) and in families with male affecteds (P = 0.002). A three-SNP haplotype (rs4740788–rs10491734–rs10491733) was associated with OCD in the total sample (P = 0.00015) and in families with male affecteds (P = 0.0007). Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD.
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Diminished gray matter within the hypothalamus in autism disorder: a potential link to hormonal effects?
Biol. Psychiatry
PUBLISHED: 02-22-2011
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Subjects with autism suffer from impairments of social interaction, deviations in language usage, as well as restricted and stereotyped patterns of behavior. These characteristics are found irrespective of age, IQ, and gender of affected subjects. However, brain changes due to age, IQ, and gender might pose potential confounds in autism neuroimaging analyses.
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The role of treatment expectancy in youth receiving exposure-based CBT for obsessive compulsive disorder.
Behav Res Ther
PUBLISHED: 02-10-2011
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The purpose of this investigation was to examine correlates of parent, child, and therapist treatment expectations and their role in the exposure-based treatment of childhood obsessive compulsive disorder (OCD). Treatment expectations were assessed among 49 youth with primary OCD, their parents, and therapists as part of the baseline evaluation and post-treatment clinical outcomes were determined by blind evaluators. Baseline depressive symptoms, child/parent-rated functional impairment, externalizing behavior problems, number of comorbid psychiatric disorders, and a lower perception of control were associated with lower pre-treatment expectations. Parent expectation was associated with parental OCD symptoms, child depressive symptoms and child-reported impairment. Therapist expectations inversely correlated with child depressive symptoms, externalizing problems, and child-rated impairment. Pre-treatment OCD severity and prior treatment history were not linked to expectancy. Finally, higher treatment expectations were linked to better treatment response, lower attrition, better homework compliance, and reduced impairment.
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Separation anxiety disorder in OCD.
Depress Anxiety
PUBLISHED: 02-09-2011
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A history of separation anxiety disorder (SAD) is frequently reported by patients with obsessive-compulsive disorder (OCD). The purpose of this study was to determine if there are clinical differences between OCD-affected individuals with, versus without, a history of SAD.
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Development of tumor-infiltrating CD8+ T cell memory precursor effector cells and antimelanoma memory responses are the result of vaccination and TGF-? blockade during the perioperative period of tumor resection.
J. Immunol.
PUBLISHED: 02-02-2011
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A main goal of cancer immunology research is the formation of Ag-specific memory T cell immunity capable of activation upon tumor re-encounter. The requirements necessary to overcome the inhibitory signals present in the tumor microenvironment and form such memory T cell responses are unknown. In contrast to previous studies targeting tumors expressing highly immunogenic model Ags, we demonstrate that alleviating tumor-induced suppression along with vaccination against authentic Ags during the perioperative period provides long-lasting protection against a highly suppressive and poorly immunogenic melanoma. In this study, we employed DNA vaccination with an immunologically optimized mouse melanoma-shared Ag, Trp1ee/ng, combined with systemic TGF-? blockade during the perioperative period of primary tumor resection, to confer protection against B16 melanoma, and against JBRH, an independently derived melanoma unrelated to B16. Importantly, we demonstrate that correlative to memory responses, perioperative immunotherapy increases the formation of tumor-infiltrating and tumor-reactive CD8(+) T cells expressing low levels of the transcription factor T-bet, defined as memory precursor effector cells. We show that conditions for an immunologically fertile environment are met when TGF-? blockade and vaccination are applied during the perioperative period of primary tumor resection. These findings address limitations of current CD8(+) T cell immunotherapies against cancer by generating effective CD8(+) T cell memory recall responses.
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Impact of physical and sexual abuse on treatment response in the Treatment of Resistant Depression in Adolescent Study (TORDIA).
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 01-14-2011
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We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings.
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Long-term outcome of adolescent depression initially resistant to selective serotonin reuptake inhibitor treatment: a follow-up study of the TORDIA sample.
J Clin Psychiatry
PUBLISHED: 01-07-2011
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We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive-behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while nonresponders were given open treatment.
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Clinical and cognitive correlates of depressive symptoms among youth with obsessive compulsive disorder.
J Clin Child Adolesc Psychol
PUBLISHED: 08-14-2010
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Depression is the most common comorbidity among adults with obsessive compulsive disorder (OCD), yet little is known about depressive symptoms in childhood OCD. This study examined clinical and cognitive variables associated with depressive symptomatology in 71 youths (62% male, M age = 12.7 years) with primary OCD. Youths presented with a range of depressive symptoms, with 21% scoring at or above the clinical cutoff on the self-report measure of depression. Higher levels of depressive symptoms were associated with higher levels of cognitive distortions assessed on measures of insight, perceived control, competence, and contingencies. Depressive symptoms were also linked to older age and more severe OCD. Low perceived control and self-competence and high OCD severity independently predicted depression scores.
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Co-Occurrence of ADHD and high IQ: a case series empirical study.
J Atten Disord
PUBLISHED: 06-24-2010
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The validity of a diagnosis of ADHD in children with a high intelligence quotient (IQ) remains controversial. Using a multidisciplinary approach, rigorous diagnostic criteria, and worldwide-validated psychometric instruments, we identified a group of children attending public schools in southern Brazil for co-occurrence of high IQ and ADHD.
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Atypical EEG beta asymmetry in adults with ADHD.
Neuropsychologia
PUBLISHED: 06-22-2010
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Abnormal brain laterality (ABL) is well established in ADHD. However, its clinical specificity and association to cognitive and clinical symptoms is not yet understood. Previous studies indicate increased right hemisphere (RH) contribution in both ADHD and reading impaired samples. The current study investigates whether this ABL characteristic occurs in adults with ADHD absent comorbid language impairment.
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Comparison of clinical features among youth with tic disorders, obsessive-compulsive disorder (OCD), and both conditions.
Psychiatry Res
PUBLISHED: 05-21-2010
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The comorbidity of tic disorders (TD) and obsessive-compulsive disorder (OCD) has long been recognized in the clinical literature and appears to be bidirectional, affecting 20-60% of individuals with each disorder. Coffey et al. (1998) found that adults with TD+OCD had a more severe comorbidity profile than adults with OCD or TD alone. This exploratory study in children attempts to evaluate whether heightened diagnostic severity, increased comorbidity load, and lower functioning is more commonplace in youth with TD+OCD in comparison to either syndrome alone. Participants were 306 children (seeking clinical evaluation) with TD, OCD, or TD+OCD. Assessment consisted of a diagnostic battery (including structured diagnostic interviews and standardized parent-report inventories) to evaluate diagnostic severity, comorbid psychopathology, behavioral and emotional correlates, and general psychosocial functioning. Data from this study sample were not supportive of the premise that youth with both a tic disorder and OCD present with elevated diagnostic severity, higher risk-for or intensity-of comorbidity, increased likelihood of externalizing/internalizing symptomatology, or lower broad-based adaptive functioning. The OCD group had elevated rates of comorbid anxiety disorders and attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) were more prevalent among youth in the TD group. The three groups also differed on key demographic variables. Our findings suggest that, in contrast to adults, TD+OCD in children and adolescents does not represent a more severe condition than either disorder alone on the basis of diagnostic comorbidity, symptom severity, or functional impairment.
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Treatment of Resistant Depression in Adolescents (TORDIA): week 24 outcomes.
Am J Psychiatry
PUBLISHED: 05-17-2010
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The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome.
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Manganese in children with attention-deficit/hyperactivity disorder: relationship with methylphenidate exposure.
J Child Adolesc Psychopharmacol
PUBLISHED: 04-27-2010
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Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder that affects children worldwide. The etiology of ADHD is complex and not fully understood. Earlier studies associated elevated levels of manganese (Mn) with learning problems, attention deficits, and ADHD. Furthermore, it has also been shown that the dopamine (DA) system, the primary site of action of pharmacological ADHD treatments, is influenced by high levels of Mn. Recent studies have suggested that Mn accumulates in dopaminergic neurons via the presynaptic dopamine transporter (DAT). A role for altered functioning of the dopaminergic system in the etiology of ADHD has been well established through neurochemical, neurophysiological, imaging, and genetics studies. Methylphenidate (MPH) is a psychostimulant commonly used to manage ADHD symptoms. The pharmacotherapeutic effect of MPH occurs primarily through its action of inhibiting DAT, and thus increasing dopamine, as well as other catecholamines, at the synapse. We assessed a group of children with ADHD and matched control children without psychopathology attending public schools in a southern Brazilian city and reported elevated serum concentrations of Mn in treatment-naïve children with ADHD compared to normal controls. Interestingly, children with ADHD receiving concurrent MPH showed no difference in Mn serum levels versus controls. We then prospectively assessed the impact of naturalistic treatment with MPH and determined that Mn concentrations were significantly reduced from baseline values following MPH exposure.
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Moderators, mediators, and other predictors of risperidone response in children with autistic disorder and irritability.
J Child Adolesc Psychopharmacol
PUBLISHED: 04-27-2010
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The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology (RUPP) Autism Network found an effect size of d = 1.2 in favor of risperidone on the main outcome measure in an 8-week double-blind, placebo-controlled trial for irritability in autistic disorder. This paper explores moderators and mediators of this effect.
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Familial clustering and DRD4 effects on electroencephalogram measures in multiplex families with attention deficit/hyperactivity disorder.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 04-23-2010
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The current study tests electroencephalogram (EEG) measures as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD) by examining sibling and parent-offspring similarity, familial clustering with the disorder, and association with the dopamine receptor D4 (DRD4) candidate gene.
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Possible influence of variant of the P-glycoprotein gene (MDR1/ABCB1) on clinical response to guanfacine in children with pervasive developmental disorders and hyperactivity.
J Child Adolesc Psychopharmacol
PUBLISHED: 02-20-2010
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Guanfacine has been shown to reduce hyperactive behaviors in children with attention-deficit/hyperactivity disorder (ADHD) and possibly in children with pervasive developmental disorder (PDD) and hyperactivity. The aim of this exploratory study was to examine whether gene variants encoding the multidrug resistance protein (MDR1 or ABCB1) , a drug transporter at the blood-brain barrier, are associated with variability in the efficacy of guanfacine in children with PDD and hyperactivity.
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Family-based genome-wide association scan of attention-deficit/hyperactivity disorder.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 02-02-2010
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Genes likely play a substantial role in the etiology of attention-deficit/hyperactivity disorder (ADHD). However, the genetic architecture of the disorder is unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of DSM-IV-TR ADHD.
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Clinical characteristics of anxiety disordered youth.
J Anxiety Disord
PUBLISHED: 01-26-2010
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Reports the characteristics of a large, representative sample of treatment-seeking anxious youth (N=488). Participants, aged 7-17 years (mean 10.7 years), had a principal DSM-IV diagnosis of separation anxiety disorder (SAD), generalized anxiety disorder (GAD), or social phobia (SP). Although youth with a co-primary diagnosis for which a different disorder-specific treatment would be indicated (e.g., major depressive disorder, substance abuse) were not included, there were few other exclusion criteria. Participants and their parent/guardian underwent an extensive baseline assessment using a broad array of measures capturing diagnostic status, anxiety symptoms and severity, and areas of functional impairment. Means and standard deviations of the measures of psychopathology and data on diagnostic status are provided. The sample had moderate to severe anxiety disorder and was highly comorbid, with 55.3% of participants meeting criteria for at least one non-targeted DSM-IV disorder. Anxiety disorders in youth often do not present as a single/focused disorder: such disorders in youth overlap in symptoms and are highly comorbid among themselves.
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CD34-based enrichment of genetically engineered human T cells for clinical use results in dramatically enhanced tumor targeting.
Cancer Immunol. Immunother.
PUBLISHED: 01-06-2010
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Objective clinical responses can be achieved in melanoma patients by infusion of T cell receptor (TCR) gene transduced T cells. Although promising, the therapy is still largely ineffective, as most patients did not benefit from treatment. That only a minority of the infused T cells were genetically modified and that these were extensively expanded ex vivo may have prevented their efficacy. We developed novel and generally applicable retroviral vectors that allow rapid and efficient selection of T cells transduced with human TCRs. These vectors encode two TCR chains and a truncated CD34 molecule (CD34t) in a single mRNA transcript. Transduced T cells were characterized and the effects of CD34-based enrichment of redirected T cells were evaluated. Both CD8(+) and CD4(+) T cells could be transduced and efficiently co-expressed all introduced transgenes on their surface. Importantly, more than fivefold enrichment of both the frequency of transduced cells and the specific anti-tumor reactivity of the effector population could be achieved by magnetic beads-based enrichment procedures readily available for clinical grade hematopoietic stem cell isolation. This CD34-based enrichment technology will improve the feasibility of adoptive transfer of clinically relevant effectors. In addition to their enhanced tumor recognition, the enriched redirected T cells may also show superior reactivity and persistence in vivo due to the high purity of transduced cells and the shortened ex vivo culture.
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Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods.
Child Adolesc Psychiatry Ment Health
PUBLISHED: 01-05-2010
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To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents.
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Correlates of insight among youth with obsessive-compulsive disorder.
J Child Psychol Psychiatry
PUBLISHED: 12-17-2009
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Individuals with Obsessive-Compulsive Disorder (OCD) may lack insight into the irrational nature of their symptoms. Among adults with OCD, poor insight has been linked to greater symptom severity, increased likelihood of comorbid symptoms, lower adaptive functioning, and worse treatment outcomes. Parallel work regarding insight among children and adolescents, with OCD, is lacking. The aim of this research was to examine links between insight and demographic, cognitive, and clinical factors among youth with OCD.
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A candidate gene analysis of methylphenidate response in attention-deficit/hyperactivity disorder.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 10-28-2009
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This study examines the potential role of candidate genes in moderating treatment effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD).
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Widespread cortical thinning is a robust anatomical marker for attention-deficit/hyperactivity disorder.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 09-05-2009
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This cross-sectional study sought to confirm the presence and regional profile of previously reported changes in laminar cortical thickness in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) compared with typically developing control subjects.
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Trial design challenges when combining medication and parent training in children with pervasive developmental disorders.
J Autism Dev Disord
PUBLISHED: 08-12-2009
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This paper presents the rationale for a 24-week, randomized trial designed to test whether risperidone plus structured parent training would be superior to risperidone only on measures of noncompliance, irritability and adaptive functioning. In this model, medication reduces tantrums, aggression and self-injury; parent training promotes improvement in noncompliance and adaptive functioning. Thus, medication and parent training target related, but separate, outcomes. At week 24, the medication was gradually withdrawn to determine whether subjects in the combined treatment group could be managed on a lower dose or off medication without relapse. Both symptom reduction and functional improvement are important clinical treatment targets. Thus, experimental evidence on the beneficial effects of combining pharmacotherapy and exportable behavioral interventions is needed to guide clinical practice.
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ADHD familial loading and abnormal EEG alpha asymmetry in children with ADHD.
J Psychiatr Res
PUBLISHED: 07-28-2009
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Abnormal brain laterality (ABL) is indicated in ADHD. ADHD and brain laterality are heritable. Genetic factors contributing to lateralization of brain function may contribute to ADHD. If so, increased ADHD family loading should be associated with greater ABL. Previous studies have shown increased rightward alpha asymmetry in ADHD. We tested whether this was more pronounced in ADHD children with increased ADHD family loading.
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Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder.
J Clin Psychopharmacol
PUBLISHED: 07-14-2009
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The placebo response shows pronounced interindividual variability. Placebos are postulated to act through central reward pathways that are modulated by monoamines. Because monoaminergic signaling is under strong genetic control, we hypothesized that common functional polymorphisms modulating monoaminergic tone would be related to degree of improvement during placebo treatment of subjects with major depressive disorder. We examined polymorphisms in genes encoding the catabolic enzymes catechol-O-methyltransferase and monoamine oxidase A. Subjects with monoamine oxidase A G/T polymorphisms (rs6323) coding for the highest activity form of the enzyme (G or G/G) had a significantly lower magnitude of placebo response than those with other genotypes. Subjects with ValMet catechol-O-methyltransferase polymorphisms coding for a lower-activity form of the enzyme (2 Met alleles) showed a statistical trend toward a lower magnitude of placebo response. These findings support the hypothesis that genetic polymorphisms modulating monoaminergic tone are related to degree of placebo responsiveness in major depressive disorder.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.