68 results on '"Kowatch R"'
Search Results
2. Behavioral and emotional dysregulation trajectories marked by prefrontal–amygdala function in symptomatic youth
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Bertocci, M. A., Bebko, G., Olino, T., Fournier, J., Hinze, A. K., Bonar, L., Almeida, J. R. C., Perlman, S. B., Versace, A., Travis, M., Gill, M. K., Demeter, C., Diwadkar, V. A., White, R., Schirda, C., Sunshine, J. L., Arnold, L. E., Holland, S. K., Kowatch, R. A., Birmaher, B., Axelson, D., Youngstrom, E. A., Findling, R. L., Horwitz, S. M., Fristad, M. A., and Phillips, M. L.
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- 2014
3. Reward-related neural activity and structure predict future substance use in dysregulated youth.
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Bertocci, M. A., Bebko, G., Versace, A., Iyengar, S., Bonar, L., Forbes, E. E., Almeida, J. R. C., Perlman, S. B., Schirda, C., Travis, M. J., Gill, M. K., Diwadkar, V. A., Sunshine, J. L., Holland, S. K., Kowatch, R. A., Birmaher, B., Axelson, D. A., Frazier, T. W., Arnold, L. E., and Fristad, M. A.
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BRAIN physiology ,CEREBRAL cortex ,SUBSTANCE abuse & psychology ,ANALYSIS of variance ,BIOMARKERS ,EMOTIONS ,LIMBIC system ,MENTAL health ,NEURORADIOLOGY ,REGRESSION analysis ,REWARD (Psychology) - Abstract
Background. Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically unwell youth. Method. LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (S.D. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables. Results. Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%. Conclusions. These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]
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- 2017
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4. Interactive Cohort Identification of Sleep Disorder Patients Using Natural Language Processing and i2b2.
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Chen, W., Kowatch, R., Lin, S., Splaingard, M., and Huang, Y.
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- 2015
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5. Dosing strategies for lithium monotherapy in children and adolescents with bipolar I disorder.
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Findling RL, Kafantaris V, Pavuluri M, McNamara NK, McClellan J, Frazier JA, Sikich L, Kowatch R, Lingler J, Faber J, Rowles BM, Clemons TE, Taylor-Zapata P, Findling, Robert L, Kafantaris, Vivian, Pavuluri, Mani, McNamara, Nora K, McClellan, Jon, Frazier, Jean A, and Sikich, Linmarie
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- 2011
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6. Fluoxetine in child and adolescent depression: acute and maintenance treatment.
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Emslie, Graham J., Rush, A. John, Weinberg, Warren A., Kowatch, Robert A., Carmody, Tom, Mayes, Taryn L., Emslie, G J, Rush, A J, Weinberg, W A, Kowatch, R A, Carmody, T, and Mayes, T L
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FLUOXETINE ,MENTAL depression ,PSYCHIATRIC drugs ,CHILD psychology ,ADOLESCENT psychology - Abstract
The objective was to present naturalistic 1-year follow-up information of 96 child and adolescent outpatients with major depressive disorder who had been randomized in an 8-week double-blind, placebo-controlled trial of fluoxetine. Subjects were children and adolescents, ages 8-18 years, who were entered in a randomized clinical trial of fluoxetine. Following the acute treatment trial, treatment was not controlled. At 6 months and 1 year, the subjects and parents were interviewed using the Kiddie Longitudinal Interval Follow-up Evaluation (K-LIFE) for course of depression. Eighty-seven of the 96 subjects were followed for 1 year. Of these, 74 (85%) recovered from the depressive episode during that time (47 on fluoxetine, 22 on no medication, and 5 on other antidepressants or lithium). Twenty-nine of the subjects (39%) who recovered had a recurrence of depression during the 1-year follow-up, with 55% of these occurring within 6 months. Results of this study are similar to adult studies, with respect to response and recovery of depressive episodes. Most patients (85%) recover from the episode within 1 year, but approximately 40% have a recurrence within 12 months, which is a higher recurrence rate than in adults. Recovery was associated with younger age, lower severity of depressive symptoms, higher family functioning, and fewer comorbid diagnoses. Recurrence, which occurs both on and off medication, was difficult to predict, as there was little clinical data associated with recurrence in this population. [ABSTRACT FROM AUTHOR]
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- 1998
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7. 31 – Open-label treatment with olanzapine in adolescents with bipolar mania
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Tohen, M., Kryzhanovskaya, L., Carlson, G., Delbello, M., Wozniak, J., Kowatch, R., Wagner, K., Findling, R., Lin, D., Robertson-Plouch, C., Xu, W., Dittmann, R., and Biederman, J.
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- 2008
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8. Changes in metabolic parameters in olanzapine-treated adolescents with schizophrenia or bipolar I disorder: A pooled analysis of 4 studies
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Kryzhanovskaya, L., Carlson, G., DelBello, M., Findling, R., Kowatch, R., Schulz, S.C., Robertson-Plouch, C., Xu, W., Sethuraman, G., Carlson, J., and Tohen, M.
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- 2007
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9. Changes in prolactin in olanzapine-treated adolescents with schizophrenia or bipolar mania: A pooled analysis of 4 studies
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Robertson-Plouch, C., Carlson, G., DelBello, M., Findling, R., Kowatch, R., Schulz, S.C., Kryzhanovskaya, L., Xu, W., Carlson, J., and Tohen, M.
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- 2007
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10. The Collaborative Lithium Trials (CoLT): specific aims, methods, and implementation
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Hooper Stephen R, Hlastala Stefanie, Sikich Linmarie, Pavuluri Mani, McClellan Jon, Kowatch Robert, Kafantaris Vivian, Frazier Jean A, Findling Robert L, Demeter Christine A, Bedoya Denise, Brownstein Bernard, and Taylor-Zapata Perdita
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Pediatrics ,RJ1-570 ,Psychiatry ,RC435-571 - Abstract
Abstract Background Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity. Methods Under the auspices of the Best Pharmaceuticals for Children Act (BPCA), a Written Request (WR) pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA) to the National Institute of Child Health and Human Development (NICHD) in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP) soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies. Results The Collaborative Lithium Trials (CoLT) investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1) establish evidence-based dosing strategies for lithium; (2) characterize the pharmacokinetics and biodisposition of lithium; (3) examine the acute efficacy of lithium in pediatric bipolarity; (4) investigate the long-term effectiveness of lithium treatment; and (5) characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR), the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1) an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2) a 16-week Long-Term Effectiveness Phase; (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. The second study consists of: (1) an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2) an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase); (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. In December of 2006, enrollment into the first of these studies began across seven sites. Conclusion These innovative studies will not only provide data to inform the labeling of lithium in children and adolescents with bipolar disorder, but will also enhance clinical decision-making regarding the use of lithium treatment in pediatric bipolar illness. Trial Registration NCT00442039
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- 2008
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11. Oxcarbazepine is no more effective than placebo for reducing manic symptoms of bipolar I disorder in children and adolescents.
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Wagner, K. D., Kowatch, R. A., and Emslie, G. J.
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DRUG efficacy , *BIPOLAR disorder , *PHARMACODYNAMICS , *PLACEBOS , *MANIA - Abstract
The article presents information on a study that analyzed the effectiveness of oxcarbazepine in the treatment of children and adolescents with bipolar I disorder(BP-I). The manic symptoms between oxcarbazepine and placebo were found to be the same. It was concluded that oxcarbazepine increases adverse events and does not improve BP-I manic symptoms as compared with placebo.
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- 2007
12. Differential effect of morphine on central versus peripheral nociception : Brain Res., 88 (1975) 181–185
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Rosenfeld, J.P. and Kowatch, R.
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- 1976
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13. Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication.
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Bertocci MA, Hanford L, Manelis A, Iyengar S, Youngstrom EA, Gill MK, Monk K, Versace A, Bonar L, Bebko G, Ladouceur CD, Perlman SB, Diler R, Horwitz SM, Arnold LE, Hafeman D, Travis MJ, Kowatch R, Holland SK, Fristad MA, Findling RL, Birmaher B, and Phillips ML
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- Adolescent, Adult, Anxiety physiopathology, Anxiety Disorders physiopathology, Biomarkers, Bipolar Disorder physiopathology, Cerebral Cortex physiopathology, Depression physiopathology, Depressive Disorder, Major physiopathology, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Parietal Lobe physiopathology, Prognosis, Psychiatric Status Rating Scales, Risk Factors, Temporal Lobe physiopathology, Young Adult, Bipolar Disorder diagnosis, Bipolar Disorder metabolism, Neural Pathways physiopathology
- Abstract
We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.
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- 2019
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14. Diffusion imaging markers of bipolar versus general psychopathology risk in youth at-risk.
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Versace A, Ladouceur CD, Graur S, Acuff HE, Bonar LK, Monk K, McCaffrey A, Yendiki A, Leemans A, Travis MJ, Diwadkar VA, Holland SK, Sunshine JL, Kowatch RA, Horwitz SM, Frazier TW, Arnold LE, Fristad MA, Youngstrom EA, Findling RL, Goldstein BI, Goldstein T, Axelson D, Birmaher B, and Phillips ML
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- Adolescent, Bipolar Disorder genetics, Child, Diffusion Magnetic Resonance Imaging methods, Female, Humans, Male, Psychopathology, Risk Factors, Bipolar Disorder diagnostic imaging, Bipolar Disorder psychology, Child of Impaired Parents psychology, Diffusion Magnetic Resonance Imaging trends
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Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspring, however, it remains unclear whether such abnormalities reflect BD-specific or generic risk markers for future psychopathology. Using a tract-profile approach, we examined 18 major white matter tracts in 38 offspring of BD parents, 36 offspring of comparison parents with non-BD psychopathology (depression, attention-deficit/hyperactivity disorder), and 41 offspring of healthy parents. Both at-risk groups showed significantly lower fractional anisotropy (FA) in left-sided tracts (cingulum, inferior longitudinal fasciculus, forceps minor), and significantly greater FA in right-sided tracts (uncinate fasciculus and inferior longitudinal fasciculus), relative to offspring of healthy parents (P < 0.05). These abnormalities were present in both healthy and affected youth in at-risk groups. Only offspring (particularly healthy offspring) of BD parents showed lower FA in the right superior longitudinal fasciculus relative to healthy offspring of healthy parents (P < 0.05). We show, for the first time, important similarities, and some differences, in white matter structure between offspring of BD and offspring of non-BD parents. Findings suggest that lower left-sided and higher right-sided FA in tracts important for emotional regulation may represent markers of risk for general, rather than BD-specific, psychopathology. Lower FA in the right superior longitudinal fasciculus may protect against development of BD in offspring of BD parents.
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- 2018
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15. Double TEAM: Enhancing Response and Treating Depression in Patients With Bipolar Disorder During a Mixed or Manic Episode.
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Kowatch R
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- Depressive Disorder, Humans, Psychiatric Status Rating Scales, Bipolar Disorder, Depression
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- 2015
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16. Interactive Cohort Identification of Sleep Disorder Patients Using Natural Language Processing and i2b2.
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Chen W, Kowatch R, Lin S, Splaingard M, and Huang Y
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- Biological Ontologies, Cohort Studies, Data Mining, Humans, Terminology as Topic, User-Computer Interface, Medical Informatics methods, Natural Language Processing
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Unlabelled: Nationwide Children's Hospital established an i2b2 (Informatics for Integrating Biology & the Bedside) application for sleep disorder cohort identification. Discrete data were gleaned from semistructured sleep study reports. The system showed to work more efficiently than the traditional manual chart review method, and it also enabled searching capabilities that were previously not possible., Objective: We report on the development and implementation of the sleep disorder i2b2 cohort identification system using natural language processing of semi-structured documents., Methods: We developed a natural language processing approach to automatically parse concepts and their values from semi-structured sleep study documents. Two parsers were developed: a regular expression parser for extracting numeric concepts and a NLP based tree parser for extracting textual concepts. Concepts were further organized into i2b2 ontologies based on document structures and in-domain knowledge., Results: 26,550 concepts were extracted with 99% being textual concepts. 1.01 million facts were extracted from sleep study documents such as demographic information, sleep study lab results, medications, procedures, diagnoses, among others. The average accuracy of terminology parsing was over 83% when comparing against those by experts. The system is capable of capturing both standard and non-standard terminologies. The time for cohort identification has been reduced significantly from a few weeks to a few seconds., Conclusion: Natural language processing was shown to be powerful for quickly converting large amount of semi-structured or unstructured clinical data into discrete concepts, which in combination of intuitive domain specific ontologies, allows fast and effective interactive cohort identification through the i2b2 platform for research and clinical use.
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- 2015
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17. Decreased amygdala-insula resting state connectivity in behaviorally and emotionally dysregulated youth.
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Bebko G, Bertocci M, Chase H, Dwojak A, Bonar L, Almeida J, Perlman SB, Versace A, Schirda C, Travis M, Gill MK, Demeter C, Diwadkar V, Sunshine J, Holland S, Kowatch R, Birmaher B, Axelson D, Horwitz S, Frazier T, Arnold LE, Fristad M, Youngstrom E, Findling R, and Phillips ML
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- Adolescent, Anxiety physiopathology, Anxiety Disorders physiopathology, Attention Deficit and Disruptive Behavior Disorders physiopathology, Case-Control Studies, Depression physiopathology, Depressive Disorder physiopathology, Female, Functional Neuroimaging methods, Humans, Longitudinal Studies, Male, Personality Inventory, Young Adult, Amygdala physiopathology, Bipolar Disorder physiopathology, Emotions physiology, Magnetic Resonance Imaging methods
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The Research Domain Criteria (RDoC) adopts a dimensional approach for examining pathophysiological processes underlying categorically defined psychiatric diagnoses. We used this framework to examine relationships among symptom dimensions, diagnostic categories, and resting state connectivity in behaviorally and emotionally dysregulated youth selected from the Longitudinal Assessment of Manic Symptoms study (n=42) and healthy control youth (n=18). Region of interest analyses examined relationships among resting state connectivity, symptom dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory-10 Item Mania Scale [PGBI-10M]; dimensional severity measures of mania, depression, anxiety), and diagnostic categories (Bipolar Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Anxiety Disorders, and Disruptive Behavior Disorders). After adjusting for demographic variables, two dimensional measures showed significant inverse relationships with resting state connectivity, regardless of diagnosis: 1) PGBI-10M with amygdala-left posterior insula/bilateral putamen; and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with resting state connectivity. Resting state connectivity between amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression; this suggests an intrinsic functional uncoupling of key neural regions supporting emotion processing and regulation. These findings support the RDoC dimensional approach for characterizing pathophysiologic processes that cut across different psychiatric disorders., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
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- 2015
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18. Post-acute effectiveness of lithium in pediatric bipolar I disorder.
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Findling RL, Kafantaris V, Pavuluri M, McNamara NK, Frazier JA, Sikich L, Kowatch R, Rowles BM, Clemons TE, and Taylor-Zapata P
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- Adolescent, Antimanic Agents administration & dosage, Antimanic Agents adverse effects, Child, Female, Humans, Lithium Carbonate administration & dosage, Lithium Carbonate adverse effects, Male, Psychiatric Status Rating Scales, Remission Induction methods, Severity of Illness Index, Time Factors, Treatment Outcome, Antimanic Agents therapeutic use, Bipolar Disorder drug therapy, Lithium Carbonate therapeutic use
- Abstract
Objective: This study examined the long-term effectiveness of lithium for the treatment of pediatric bipolar disorder within the context of combination mood stabilizer therapy for refractory mania and pharmacological treatment of comorbid psychiatric conditions., Methods: Outpatients, ages 7-17 years, meeting American Psychiatric Association, diagnostic and statistical manual of mental disorders, 4th ed. (DSM-IV) diagnostic criteria for bipolar disorder I (BP-I) (manic or mixed) who demonstrated at least a partial response to 8 weeks of open-label treatment with lithium (phase I) were eligible to receive open-label lithium for an additional 16 weeks (phase II). Up to two adjunctive medications could be prescribed to patients experiencing residual symptoms of mania or comorbid psychiatric conditions, following a standardized algorithm., Results: Forty-one patients received continued open-label long-term treatment with lithium for a mean of 14.9 (3.0) weeks during phase II. The mean weight-adjusted total daily dose at end of phase II was 27.8 (6.7) mg/kg/day, with an average lithium concentration of 1.0 (0.3) mEq/L. Twenty-five of the 41 patients (60.9%) were prescribed adjunctive psychotropic medications for residual symptoms. The most frequent indications for adjunctive medications were refractory mania (n=13; 31.7%) and attention-deficit/hyperactivity disorder (ADHD) (n=15; 36.6%). At the end of this phase 28 (68.3%) patients met a priori criteria for response (≥50% reduction from phase I baseline in young mania rating scale [YMRS] summary score and a clinical global impressions-improvement [CGI-I] score of 1 or 2), with 22 (53.7%) considered to be in remission (YMRS summary score≤12 and CGI-severity score of 1 or 2). These data suggest that patients who initially responded to lithium maintained mood stabilization during continuation treatment, but partial responders did not experience further improvement during Phase II, despite the opportunity to receive adjunctive medications. The most commonly reported (≥20%) adverse events associated with lithium treatment were vomiting, headache, abdominal pain, and tremor., Conclusions: Lithium may be a safe and effective longer-term treatment for patients with pediatric bipolar disorder who respond to acute treatment with lithium. Partial responders to acute lithium did not appear to experience substantial symptom improvement during the continuation phase, despite the possibility that adjunctive medications could be prescribed.
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- 2013
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19. Pediatric bipolar disorder and ADHD: family history comparison in the LAMS clinical sample.
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Arnold LE, Mount K, Frazier T, Demeter C, Youngstrom EA, Fristad MA, Birmaher B, Horwitz S, Findling RL, Kowatch R, and Axelson D
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- Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity genetics, Bipolar Disorder diagnosis, Bipolar Disorder genetics, Child, Child of Impaired Parents psychology, Comorbidity, Family Health, Female, Humans, Male, Personality Inventory, Attention Deficit Disorder with Hyperactivity epidemiology, Bipolar Disorder epidemiology
- Abstract
Background: Transgenerational association of bipolar spectrum disorder (BPSD) and attention deficit/hyperactivity disorder (ADHD) has been reported, but inconclusively., Method: Children ages 6-12 were systematically recruited at first outpatient visit at 9 clinics at four universities and reliably diagnosed; 621 had elevated symptoms of mania (>12 on the Parent General Behavior Inventory 10-Item Mania Scale); 86 had scores below 12. We analyzed baseline data to test a familial association hypothesis: compared to children with neither BPSD nor ADHD, those with either BPSD or ADHD would have parents with higher rates of both bipolar and ADHD symptoms, and parents of comorbid children would have even higher rates of both., Results: Of 707 children, 421 had ADHD without BPSD, 45 BPSD without ADHD, 117 comorbid ADHD+BPSD, and 124 neither. The rate of parental manic symptoms was similar for the comorbid and BPSD-alone groups, significantly greater than for ADHD alone and "neither" groups, which had similar rates. ADHD symptoms in parents of children with BPSD alone were significantly less frequent than in parents of children with ADHD (alone or comorbid), and no greater than for children with neither diagnosis. Family history of manic symptoms, but not ADHD symptoms, was associated with parent-rated child manic-symptom severity over and above child diagnosis., Limitations: The sample was not epidemiologic, parent symptoms were based on family history questions, and alpha was 0.05 despite multiple tests., Conclusions: These results do not support familial linkage of BPSD and ADHD; they are compatible with heritability of each disorder separately with coincidental overlap., (Copyright © 2012 Elsevier B.V. All rights reserved.)
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- 2012
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20. Pediatric bipolar spectrum disorder and ADHD: comparison and comorbidity in the LAMS clinical sample.
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Arnold LE, Demeter C, Mount K, Frazier TW, Youngstrom EA, Fristad M, Birmaher B, Findling RL, Horwitz SM, Kowatch R, and Axelson DA
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- Age of Onset, Analysis of Variance, Child, Comorbidity, Developmental Disabilities epidemiology, Female, Humans, Longitudinal Studies, Male, Proportional Hazards Models, Psychiatric Status Rating Scales, Attention Deficit Disorder with Hyperactivity complications, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity epidemiology, Bipolar Disorder complications, Bipolar Disorder diagnosis, Bipolar Disorder epidemiology, Developmental Disabilities complications, Pediatrics
- Abstract
Objective: To compare attention-deficit hyperactivity disorder (ADHD), bipolar spectrum disorders (BPSDs), and comorbidity in the Longitudinal Assessment of Manic Symptoms (LAMS) study., Methods: Children ages 6-12 were recruited at first visit to clinics associated with four universities. A BPSD diagnosis required that the patient exhibit episodes. Four hypotheses were tested: (i) children with BPSD + ADHD would have a younger age of mood symptom onset than those with BPSD but no ADHD; (ii) children with BPSD + ADHD would have more severe ADHD and BPSD symptoms than those with only one disorder; (iii) global functioning would be more impaired in children with ADHD + BPSD than in children with either diagnosis alone; and (iv) the ADHD + BPSD group would have more additional diagnoses., Results: Of 707 children, 421 had ADHD alone, 45 had BPSD alone, 117 had both ADHD and BPSD, and 124 had neither. Comorbidity (16.5%) was slightly less than expected by chance (17.5%). Age of mood symptom onset was not different between the BPSD + ADHD group and the BPSD-alone group. Symptom severity increased and global functioning decreased with comorbidity. Comorbidity with other disorders was highest for the ADHD + BPSD group, but higher for the ADHD-alone than the BPSD-alone group. Children with BPSD were four times as likely to be hospitalized (22%) as children with ADHD alone., Conclusions: The high rate of BPSD in ADHD reported by some authors may be better explained as a high rate of both disorders in child outpatient settings rather than ADHD being a risk factor for BPSD. Co-occurrence of the two disorders is associated with poorer global functioning, greater symptom severity, and more additional comorbidity than for either single disorder., (© 2011 John Wiley and Sons A/S.)
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- 2011
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21. First-dose pharmacokinetics of lithium carbonate in children and adolescents.
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Findling RL, Landersdorfer CB, Kafantaris V, Pavuluri M, McNamara NK, McClellan J, Frazier JA, Sikich L, Kowatch R, Lingler J, Faber J, Taylor-Zapata P, and Jusko WJ
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- Administration, Oral, Adolescent, Age Factors, Antimanic Agents administration & dosage, Child, Dose-Response Relationship, Drug, Drug Monitoring methods, Female, Humans, Lithium Carbonate administration & dosage, Male, Nonlinear Dynamics, Randomized Controlled Trials as Topic, Time Factors, Tissue Distribution, Antimanic Agents pharmacokinetics, Bipolar Disorder drug therapy, Lithium Carbonate pharmacokinetics, Models, Biological
- Abstract
This study examines the pharmacokinetics of oral doses of lithium carbonate immediate-release capsules after administration of 600 or 900 mg in children and adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar I disorder. Lithium plasma concentrations were followed over 48 to 72 hours in 39 subjects (20 male and 19 female subjects; ages, 7-17 years) with mixed or manic episodes enrolled at 7 clinical sites participating in the Collaborative Lithium Trials. Population pharmacokinetic modeling was performed using NONMEM, and influences of patient covariates on pharmacokinetics parameters were examined. The pharmacokinetics of lithium was best described using a 2-compartment model with a lag time and first-order absorption. There was considerable variability in lithium exposures. Lithium clearance related best to fat-free mass. Inclusion of fat-free mass as a covariate reduced the between-subject variability from 52% to 42%. Lithium clearances did not vary systematically with age group, dose, sex, or creatinine clearances. Allometrically scaled clearance and volume of distribution from the population analysis were within the range reported in adults. Single-dose profiles of lithium in young patients with BP-1 show marked variability. Therefore, ongoing serum monitoring is needed during continued therapy. The developed population pharmacokinetic model may be used to predict other dosage regimens, support scaling from adult to pediatric pharmacokinetics, and support the design of future clinical trials.
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- 2010
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22. Disinhibition as a side effect of treatment with fluvoxamine in pediatric patients with obsessive-compulsive disorder.
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Harris E, Eng HY, Kowatch R, Delgado SV, and Saldaña SN
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- Aryl Hydrocarbon Hydroxylases metabolism, Child, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2D6 metabolism, Fluvoxamine therapeutic use, Humans, Inhibition, Psychological, Male, Obsessive-Compulsive Disorder drug therapy, Pharmacogenetics, Selective Serotonin Reuptake Inhibitors therapeutic use, Fluvoxamine adverse effects, Impulsive Behavior chemically induced, Selective Serotonin Reuptake Inhibitors adverse effects
- Abstract
Selective serotonin reuptake inhibitors (SSRIs) are usually well tolerated in the pediatric population, and widely used in the treatment of obsessive-compulsive disorder (OCD). Of the 51 pediatric patients with obsessive-compulsive disorder seen in our outpatient clinic between January 2009 and July 2009, 3 of them developed behavioral disinhibition after treatment with fluvoxamine. These cases are described and discussed in relation to the use of CYP2D6 and CYP2C19 pharmacogenetic testing in patients treated with serotonin-selective reuptake inhibitors.
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- 2010
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23. Pharmacologic treatment of pediatric bipolar disorder.
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Nandagopal JJ, DelBello MP, and Kowatch R
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- Adolescent, Anxiety Disorders diagnosis, Anxiety Disorders epidemiology, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity epidemiology, Attention Deficit and Disruptive Behavior Disorders diagnosis, Attention Deficit and Disruptive Behavior Disorders epidemiology, Bipolar Disorder diagnosis, Bipolar Disorder epidemiology, Child, Comorbidity, Conduct Disorder diagnosis, Conduct Disorder epidemiology, Depressive Disorder diagnosis, Depressive Disorder epidemiology, Diagnosis, Differential, Humans, Surveys and Questionnaires, Bipolar Disorder drug therapy, Drug Therapy methods
- Abstract
Bipolar disorder (BPD) is being diagnosed with increasing frequency in the pediatric population as the phenomenology of this disorder is becoming more clearly delineated. Early diagnosis and treatment of pediatric BPD is important to minimize psychosocial disability and improve prognosis. Traditional mood stabilizers and atypical antipsychotic agents are frequently used to treat BPD in youth, and there are emerging data to support their use in this population. This article provides a review of the literature on appropriate pharmacologic treatment strategies for BPD in children and adolescents. The complex treatment issues of comorbid BPD and attention deficit/hyperactivity disorder also are addressed.
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- 2009
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24. AACAP 2006 Research Forum--Advancing research in early-onset bipolar disorder: barriers and suggestions.
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Carlson GA, Findling RL, Post RM, Birmaher B, Blumberg HP, Correll C, DelBello MP, Fristad M, Frazier J, Hammen C, Hinshaw SP, Kowatch R, Leibenluft E, Meyer SE, Pavuluri MN, Wagner KD, and Tohen M
- Subjects
- Adolescent, Age of Onset, Bipolar Disorder diagnosis, Bipolar Disorder genetics, Child, Humans, Practice Guidelines as Topic, Review Literature as Topic, Risk Factors, Adolescent Psychiatry, Bipolar Disorder drug therapy, Bipolar Disorder epidemiology, Child Psychiatry, Research Design trends
- Abstract
Objective: The 2006 Research Forum addressed the goal of formulating a research agenda for early-onset bipolar disorder (EOBP) and improving outcome by understanding the risk and protective factors that contribute to its severity and chronicity., Method: Five work groups outlined barriers and research gaps in EOBP genetics, neuroimaging, prodromes, psychosocial factors, and pharmacotherapy., Results: There was agreement that the lack of consensus on the definition and diagnosis of EOBP is the primary barrier to advancing research in BP in children and adolescents. Related issues included: the difficulties in managing co-morbidity both statistically and clinically; acquiring adequate sample sizes to study the genetics, biology, and treatment; understanding the EOBP's developmental aspects; and identifying environmental mediators and moderators of risk and protection. Similarly, both psychosocial and medication treatment strategies for children with BP are hamstrung by diagnostic issues. To advance the research in EOBP, both training and funding mechanisms need to be developed with these issues in mind., Conclusions: EOBP constitutes a significant public health concern. Barriers are significant but identifiable and thus are not insurmountable. To advance the understanding of EOBP, the field must be committed to resolving diagnostic and assessment issues. Once achieved, with adequate personnel and funding resources, research into the field of EOBP will doubtless be advanced at a rapid pace.
- Published
- 2009
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25. Using natural language processing to classify suicide notes.
- Author
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Pestian JP, Matykiewicz P, Grupp-Phelan J, Lavanier SA, Combs J, and Kowatch R
- Subjects
- Data Mining, Information Storage and Retrieval methods, Terminology as Topic, United States, Artificial Intelligence, Correspondence as Topic, Natural Language Processing, Pattern Recognition, Automated methods, Semantics, Suicide classification, Writing
- Published
- 2008
- Full Text
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26. The Collaborative Lithium Trials (CoLT): specific aims, methods, and implementation.
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Findling RL, Frazier JA, Kafantaris V, Kowatch R, McClellan J, Pavuluri M, Sikich L, Hlastala S, Hooper SR, Demeter CA, Bedoya D, Brownstein B, and Taylor-Zapata P
- Abstract
Background: Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity., Methods: Under the auspices of the Best Pharmaceuticals for Children Act (BPCA), a Written Request (WR) pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA) to the National Institute of Child Health and Human Development (NICHD) in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP) soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies., Results: The Collaborative Lithium Trials (CoLT) investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1) establish evidence-based dosing strategies for lithium; (2) characterize the pharmacokinetics and biodisposition of lithium; (3) examine the acute efficacy of lithium in pediatric bipolarity; (4) investigate the long-term effectiveness of lithium treatment; and (5) characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR), the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1) an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2) a 16-week Long-Term Effectiveness Phase; (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. The second study consists of: (1) an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2) an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase); (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. In December of 2006, enrollment into the first of these studies began across seven sites., Conclusion: These innovative studies will not only provide data to inform the labeling of lithium in children and adolescents with bipolar disorder, but will also enhance clinical decision-making regarding the use of lithium treatment in pediatric bipolar illness., Trial Registration: NCT00442039.
- Published
- 2008
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27. Olanzapine versus placebo in the treatment of adolescents with bipolar mania.
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Tohen M, Kryzhanovskaya L, Carlson G, Delbello M, Wozniak J, Kowatch R, Wagner K, Findling R, Lin D, Robertson-Plouch C, Xu W, Dittmann RW, and Biederman J
- Subjects
- Adolescent, Age Factors, Alanine Transaminase blood, Antipsychotic Agents adverse effects, Aspartate Aminotransferases blood, Benzodiazepines adverse effects, Bipolar Disorder blood, Bipolar Disorder psychology, Blood Glucose analysis, Cholesterol blood, Double-Blind Method, Fasting, Female, Humans, Male, Obesity chemically induced, Olanzapine, Placebos, Prolactin blood, Psychiatric Status Rating Scales, Treatment Outcome, Uric Acid blood, Weight Gain drug effects, Antipsychotic Agents therapeutic use, Benzodiazepines therapeutic use, Bipolar Disorder drug therapy
- Abstract
Objective: The purpose of this study was to evaluate the efficacy and safety of olanzapine for the treatment of acute manic or mixed episodes associated with bipolar disorder in adolescents., Method: A 3-week multicenter, parallel, double-blind, randomized placebo-controlled trial was conducted at 24 sites in the United States and two sites in Puerto Rico. The participants were outpatient and inpatient male and female adolescents 13-17 years of age with an acute manic or mixed episode. Subjects received either olanzapine (2.5-20 mg/day [N=107]) or placebo (N=54). The mean change from baseline to endpoint in the Young Mania Rating Scale total score was the primary outcome measure., Results: The mean baseline-to-endpoint change in the Young Mania Rating Scale total score was significantly greater for patients receiving olanzapine relative to patients receiving placebo, and a greater proportion of olanzapine-treated patients met response and remission criteria (44.8% versus 18.5% and 35.2% versus 11.1%, respectively). The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo (3.7 kg versus 0.3 kg), and the incidence of treatment-emergent weight gain > or =7% of baseline was higher for olanzapine-treated patients (41.9% versus 1.9%). The mean baseline-to-endpoint changes in prolactin, fasting glucose, fasting total cholesterol, uric acid, and the hepatic enzymes aspartate transaminase and alanine transaminase were significantly greater in patients treated with olanzapine relative to patients receiving placebo., Conclusions: Olanzapine was effective in the treatment of bipolar mania in adolescent patients. Patients treated with olanzapine, however, had significantly greater weight gain and increases in the levels of hepatic enzymes, prolactin, fasting glucose, fasting total cholesterol, and uric acid.
- Published
- 2007
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28. Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder.
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McClellan J, Kowatch R, and Findling RL
- Subjects
- Adolescent, Child, Diagnostic and Statistical Manual of Mental Disorders, Humans, Adolescent Psychiatry, Bipolar Disorder diagnosis, Bipolar Disorder therapy, Child Psychiatry
- Abstract
This practice parameter reviews the literature on the assessment and treatment of children and adolescents with bipolar disorder. The parameter focuses primarily on bipolar 1 disorder because that is the type most often studied in juveniles. The presentation of bipolar disorder in youth, especially children, is often considered atypical compared with that of the classic adult disorder, which is characterized by distinct phases of mania and depression. Children who receive a diagnosis of bipolar disorder in community settings typically present with rapid fluctuations in mood and behavior, often associated with comorbid attention-deficit/hyperactivity disorder and disruptive behavior disorders. Thus, at this time it is not clear whether the atypical forms of juvenile mania and the classic adult form of the disorder represent the same illness. The question of diagnostic continuity has important treatment and prognostic implications. Although more controlled trials are needed, mood stabilizers and atypical antipsychotic agents are generally considered the first line of treatment. Although patients may respond to monotherapy, combination pharmacotherapy is necessary for some youth. Behavioral and psychosocial therapies are also generally indicated for juvenile mania to address disruptive behavior problems and the impact of the illness on family and community functioning.
- Published
- 2007
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29. Methodological issues and controversies in clinical trials with child and adolescent patients with bipolar disorder: report of a consensus conference.
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Carlson GA, Jensen PS, Findling RL, Meyer RE, Calabrese J, DelBello MP, Emslie G, Flynn L, Goodwin F, Hellander M, Kowatch R, Kusumakar V, Laughren T, Leibenluft E, McCracken J, Nottelmann E, Pine D, Sachs G, Shaffer D, Simar R, Strober M, Weller EB, Wozniak J, and Youngstrom EA
- Subjects
- Adolescent, Adolescent Psychiatry, Bipolar Disorder diagnosis, Bipolar Disorder drug therapy, Child, Child Psychiatry, Clinical Trials as Topic ethics, Humans, Treatment Outcome, Bipolar Disorder therapy, Clinical Trials as Topic methods, Research Design standards
- Abstract
Objective: To achieve consensus among researchers, pharmaceutical industry representatives, federal regulatory agency staff, and family advocates on a template for clinical trials of acute mania/bipolar disorder in children and adolescents., Method: The American Academy of Child and Adolescent Psychiatry, in collaboration with Best Practice, convened a group of experts from the key stakeholder communities (including adult psychiatrists with expertise in bipolar disorder) and assigned them to workgroups to examine core methodological issues surrounding the design of clinical trials and, ultimately, to generate a consensus statement encompassing: (1) inclusion/exclusion criteria, (2) investigator training needs and site selection, (3) assessment and outcome measures, (4) protocol design and ethical issues unique to trials involving children/adolescents, and (5) regulatory agency perspectives on these deliberations., Results: Conference participants reached agreement on 18 broad methodological questions. Key points of consensus were to assign priority to placebo-controlled studies of acute manic episodes in children and adolescents aged 10-17 years, who may or may not be hospitalized, and who may or may not suffer from common comorbid psychiatric disorders; to require that specialist diagnostic "gatekeepers" screen youths' eligibility to participate in trials; to monitor interviewer and rater competency over the course of the trial using agreed upon standards; and to develop new tools for assessment, including scales to measure aggression/rage and cognitive function, while using the best available instruments (e.g., Young Mania Rating Scale) in the interim., Conclusions: Methodologically rigorous, large-scale clinical trials of treatment of acute mania are urgently needed to provide information regarding the safety and efficacy, in youth, of diverse agents with potential mood-stabilizing properties.
- Published
- 2003
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30. Lifetime and novel psychiatric disorders after pediatric traumatic brain injury.
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Bloom DR, Levin HS, Ewing-Cobbs L, Saunders AE, Song J, Fletcher JM, and Kowatch RA
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- Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity epidemiology, Child, Depressive Disorder, Major diagnosis, Depressive Disorder, Major epidemiology, Female, Humans, Male, Prevalence, Psychiatric Status Rating Scales, Time Factors, Attention Deficit Disorder with Hyperactivity etiology, Brain Injuries psychology, Depressive Disorder, Major etiology
- Abstract
Objective: To assess lifetime and current psychiatric disorders at least 1 year after traumatic brain injury (TBI) in children and adolescents., Method: Forty-six youths who sustained a TBI between the ages of 6 through 15 years were evaluated at least 1 year post-TBI to identify the presence of lifetime and/or novel psychiatric disorders. Semistructured interviews of the parent and child and standardized parent self-report rating instruments were used., Results: Attention-deficit/hyperactivity disorder and depressive disorders were the most common lifetime and novel diagnoses. A wide variety and high rate of novel psychiatric disorders were identified; 74% of these disorders persisted in 48% of the injured children. Internalizing disorders were more likely to resolve than externalizing disorders. Both interviews and parent ratings were sensitive to current externalizing behaviors; interviews more often detected internalizing disorders, whereas parent ratings also identified cognitive difficulties., Conclusions: Findings were generally consistent with previous research demonstrating the high rate of novel psychiatric disorders following pediatric TBI. Psychiatric interviews were sensitive in identifying both lifetime and novel disorders.
- Published
- 2001
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31. Clinician, parent, and child prediction of medication or placebo in double-blind depression study.
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Hughes CW, Emslie G, Kowatch R, Weinberg W, Rintelmann J, and Rush AJ
- Subjects
- Adolescent, Child, Depressive Disorder psychology, Double-Blind Method, Female, Humans, Male, Psychiatric Status Rating Scales, Treatment Outcome, Antidepressive Agents, Second-Generation therapeutic use, Depressive Disorder drug therapy, Fluoxetine therapeutic use
- Abstract
To evaluate how well a blind is maintained in a double-blind study. Clinicians (n = 66), parents (n = 62), and depressed child/adolescent subjects (n = 62) predicted whether the patient had been on either placebo or active medication at the end of an eight-week double-blind placebo versus fluoxetine trial. Clinician, patient and parents' guesses as to which treatment they had received were at a chance level based on an overall analysis. However, when clinical response and condition assignment were controlled, all were correctly predicting placebo treatment but not medication treatment. The finding that subjects, parents and clinicians predict at a chance level is important for double-blind study design integrity. However, clinicians, parents and subjects were accurately predicting placebo treatment when clinical response and the assigned condition were taken into account but not medication. Since they do not know condition however, all remain essentially blinded, and this is an important finding for design and analysis integrity for double-blind studies.
- Published
- 2000
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32. Acute and continuation pharmacological treatment of children and adolescents with bipolar disorders; a summary of two previous studies.
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Kowatch RA, Carmody TJ, Suppes T, Hume JH, Kromelis M, Emslie GJ, and Weinberg WA
- Abstract
We report the results of an acute-phase and continuation-phase study of the pharmacological treatment of children and adolescents with bipolar disorders. The acute phase study, with a duration of 6-8 weeks, aimed at developing effect sizes (ES) for lithium, divalproex sodium, and carbamazepine, in the acute phase treatment of Bipolar I or II children and adolescents during a mixed or manic episode. During the acute-phase of treatment, 42 outpatients with a mean age of 11.4 yr. (20 with Bipolar I Disorder and 22 with Bipolar II Disorder) were randomly assigned to 6-8 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly CGI Improvement scores and the Young Mania Rating Scale. Using a ≥ 50% change from baseline to exit in the Y-MRS scores to define response, the effect size for divalproex sodium was 1.63,1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were: sodium divalproex 53%; lithium 38%; and carbamazepine 38% (x 2=0.85, 2 d.f., p=0.60). Thirty-five subjects continued in open, treatment for another 16-18 weeks, for a total of 24 weeks of prospective treatment. Overall, of the thirty-five continuation phase subjects, thirty (85%) were categorized as responders at the end of the continuation phase of treatment. Of these thirty-five subjects, 13 (37%) were only on a single mood stabilizer and no other psychotropic agents at the end of the continuation phase. Thirty-one percent of subjects in continuation were also treated with a stimulant medication in addition to mood stabilizers.
- Published
- 2000
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33. Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder.
- Author
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Kowatch RA, Suppes T, Carmody TJ, Bucci JP, Hume JH, Kromelis M, Emslie GJ, Weinberg WA, and Rush AJ
- Subjects
- Acute Disease, Adolescent, Age Factors, Antimanic Agents pharmacology, Carbamazepine pharmacology, Child, Dose-Response Relationship, Drug, Female, Humans, Lithium pharmacology, Male, Outpatients statistics & numerical data, Pilot Projects, Psychiatric Status Rating Scales, Valproic Acid pharmacology, Antimanic Agents therapeutic use, Bipolar Disorder drug therapy, Carbamazepine therapeutic use, Lithium therapeutic use, Valproic Acid therapeutic use
- Abstract
Objective: To develop effect sizes for 3 mood stabilizers--lithium, divalproex sodium, and carbamazepine--for the acute-phase treatment of bipolar I or II disorder, mixed or manic episode, in children and adolescents aged 8 to 18 years., Method: Forty-two outpatients with a mean age of 11.4 years (20 with bipolar I disorder and 22 with bipolar II disorder) were randomly assigned to 6 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale (Y-MRS)., Results: Using a > or = 50% change from baseline to exit in the Y-MRS scores to define response, the effect size was 1.63 for divalproex sodium, 1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were as follows: sodium divalproex, 53%; lithium, 38%; and carbamazepine, 38% (chi 2(2) = 0.85, p = .60). All 3 mood stabilizers were well tolerated, and no serious adverse effects were seen., Conclusions: Divalproex sodium, lithium, and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode.
- Published
- 2000
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34. Ultradian rhythms and temporal coherence in sleep EEG in depressed children and adolescents.
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Armitage R, Emslie GJ, Hoffmann RF, Weinberg WA, Kowatch RA, Rintelmann J, and Rush AJ
- Subjects
- Adolescent, Age Factors, Algorithms, Cheek physiology, Child, Electroencephalography, Electromyography methods, Electrooculography methods, Female, Functional Laterality physiology, Humans, Male, Mandible physiology, Psychiatric Status Rating Scales, Severity of Illness Index, Time Factors, Activity Cycles physiology, Depressive Disorder, Major diagnosis, Sleep, REM physiology
- Abstract
Background: It has been suggested that a primary ultradian (80-120 minute) rhythm disturbance in EEG underlies sleep abnormalities in adults with depression. The present study evaluated ultradian rhythm disturbances in childhood and adolescent depression., Methods: Sleep macroarchitecture and temporal coherence in quantitative EEG rhythms were investigated in 50 medication-free outpatients with major depression (25 children and 25 adolescents) and 15 healthy normal controls (5 children and 10 adolescents)., Results: Few of the macroarchitectural measures showed significant group effects. In fact, age and sex effects were stronger than disease-dependent components. Temporal coherence of EEG rhythms during sleep did differentiate those with MDD from controls. Both depressed children and adolescents had lower intrahemispheric coherence, whereas interhemispheric was only lower in depressed adolescents in comparison with controls. Gender differences were evident in adolescents, but not children, with MDD with lowest interhemispheric coherence in adolescent girls., Conclusions: These findings are in keeping with increased risk for depression in females beginning at adolescence and extending throughout adulthood. It was suggested that low temporal coherence in depression reflects a disruption in the fundamental basic rest-activity cycle of arousal and organization in the brain that is strongly influenced by gender.
- Published
- 2000
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35. Prediction of response to fluoxetine and placebo in children and adolescents with major depression: a hypothesis generating study.
- Author
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Kowatch RA, Carmody TJ, Emslie GJ, Rintelmann JW, Hughes CW, and Rush AJ
- Subjects
- Adolescent, Age Factors, Child, Double-Blind Method, Female, Humans, Male, Prognosis, Severity of Illness Index, Social Class, Antidepressive Agents, Second-Generation therapeutic use, Depressive Disorder drug therapy, Fluoxetine therapeutic use
- Abstract
Background: The results of multivariate analyses to identify potential predictors of response to fluoxetine or placebo separately in 96 child and adolescent outpatients with major depressive disorder from a recent controlled trial are presented., Methods: A variety of clinical, demographic and laboratory factors were examined as possible predictors of response to fluoxetine or placebo using logistic regression models., Results: No single variable or combination of variables strongly predicted response to fluoxetine. For the placebo group, a younger age, a shorter duration of depressive episode, and a lower socioeconomic status predicted response with an overall predictive power of 81%., Conclusions: This study is limited by the small sample size and should be considered hypothesis generating rather than confirming.
- Published
- 1999
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36. A SPECT HMPAO study of regional cerebral blood flow in depressed adolescents and normal controls.
- Author
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Kowatch RA, Devous MD Sr, Harvey DC, Mayes TL, Trivedi MH, Emslie GJ, and Weinberg WA
- Subjects
- Adolescent, Depressive Disorder diagnostic imaging, Female, Humans, Male, Reference Values, Regional Blood Flow, Brain blood supply, Brain diagnostic imaging, Depressive Disorder physiopathology, Radiopharmaceuticals, Technetium Tc 99m Exametazime, Tomography, Emission-Computed, Single-Photon methods
- Abstract
1. The objective of this study was to compare the relative regional cerebral blood flow (rCBF) patterns of a group of adolescents with major depressive disorder (MDD) to a group of normal controls. 2. Seven adolescent patients with symptomatic MDD and 7 age- and gender-matched normal controls, underwent SPECT imaging with 99mTc-HMPAO while unmedicated and in a resting state. These subject's data were normalized to whole brain counts, oriented in Talairach space, and analyzed using a voxel-based, t-image approach. 3. The authors found relative rCBF increases in the depressed group as compared to normals in the right mesial temporal cortex, the right superior-anterior temporal lobe, and the left infero-lateral temporal lobe. We found rCBF decreases in the depressed group as compared to normals in the left parietal lobe, the anterior thalamus and the right caudate. 4. Adolescents with MDD show rCBF abnormalities similar to those found in adult MDD rCBF studies. Further controlled studies with larger numbers of MDD subjects and normal age- and gender-matched controls are necessary before any definitive conclusions can be made from these findings.
- Published
- 1999
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37. Mood stabilizers and anticonvulsants.
- Author
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Kowatch RA and Bucci JP
- Subjects
- Adolescent, Age Factors, Anticonvulsants classification, Anticonvulsants pharmacology, Antidepressive Agents classification, Antidepressive Agents pharmacology, Child, Humans, Aggression drug effects, Anticonvulsants therapeutic use, Antidepressive Agents therapeutic use, Bipolar Disorder drug therapy, Conduct Disorder drug therapy, Intellectual Disability complications
- Abstract
This article provides pediatricians and other clinicians who treat children and adolescents with a working knowledge of mood stabilizers and their potential uses in children and adolescents with mood and behavior disorders. Mood stabilizers are ubiquitous agents that are often effective in the treatment of children and adolescents with bipolar disorders or conduct disorders and mentally retarded patients with aggressive behavior. The authors' also discuss mechanisms of action, pharmacokinetics, dosing, drug interactions, and potential uses. Following these medication details, specific information concerning the diagnosis and treatment of several child and adolescent mood and behavior disorders, and in which treatment with mood stabilizers may be helpful, is presented.
- Published
- 1998
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38. Mania in young children.
- Author
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Kowatch RA
- Subjects
- Attention Deficit Disorder with Hyperactivity psychology, Bipolar Disorder psychology, Child, Diagnosis, Differential, Humans, Psychiatric Status Rating Scales, Attention Deficit Disorder with Hyperactivity diagnosis, Bipolar Disorder diagnosis
- Published
- 1998
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39. Update on the management of bipolar illness.
- Author
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Shelton RC, Thase ME, Kowatch R, and Baldessarini RJ
- Subjects
- Adolescent, Adult, Age Factors, Antidepressive Agents, Tricyclic pharmacology, Bipolar Disorder diagnosis, Child, GTP-Binding Proteins drug effects, Humans, Irritable Mood drug effects, Lithium pharmacology, Psychotropic Drugs pharmacology, Psychotropic Drugs therapeutic use, Antidepressive Agents, Tricyclic therapeutic use, Bipolar Disorder drug therapy, Bipolar Disorder physiopathology, GTP-Binding Proteins physiology, Lithium therapeutic use, Monoamine Oxidase Inhibitors therapeutic use
- Published
- 1998
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40. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression.
- Author
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Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody T, and Rintelmann J
- Subjects
- Adolescent, Age Factors, Ambulatory Care, Child, Depressive Disorder psychology, Double-Blind Method, Female, Humans, Male, Placebos, Psychiatric Status Rating Scales, Severity of Illness Index, Single-Blind Method, Treatment Outcome, Depressive Disorder drug therapy, Fluoxetine therapeutic use
- Abstract
Background: Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression., Methods: Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale--Revised, a measure of the severity depressive symptoms., Results: Of the 96 patients, 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated "much" or "very much" improved on the Clinical Global Impressions scale at study exit (chi 2 = 5.1, df = 1, P = .02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale--Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n = 48) and those aged 13 years and older (n = 48). However, complete symptom remission (Children's Depression Rating Scale--Revised < or = 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients., Conclusion: Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare.
- Published
- 1997
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41. Plasma GABA in children and adolescents with mood, behavior, and comorbid mood and behavior disorders: a preliminary study.
- Author
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Prosser J, Hughes CW, Sheikha S, Kowatch RA, Kramer GL, Rosenbarger N, Trent J, and Petty F
- Subjects
- Adolescent, Child, Child Behavior Disorders complications, Child Behavior Disorders psychology, Female, Humans, Male, Mood Disorders complications, Mood Disorders psychology, Psychiatric Status Rating Scales, Regression Analysis, Child Behavior Disorders blood, Mood Disorders blood, gamma-Aminobutyric Acid blood
- Abstract
Plasma GABA concentrations (pGABA) were measured in 115 inpatients (aged 7-17) with child psychiatric disorders. Group mean pGABAs were compared for 38 patients with mood disorders only (MOOD), 29 with behavior disorders only (BEH), 48 with comorbid mood and behavior disorders (MOOD + BEH), and 14 normal controls (CON, aged 14-17). The BEH group was characterized by (a) high mean pGABAs (157 vs. 133 pmol/ml), (b) lower mean pGABAs in BEH subjects who had been receiving pharmacotherapy with SSRIs or other medications (p < 0.026), and (c) decreased pGABA with increasing age (p = 0.019). These features were not found in controls or in groups of patients with mood disorders (MOOD or MOOD + BEH). Elevated mean pGABA in the BEH group appeared specifically in patients with comorbid CD and ADHD, not in patients with ADHD or CD alone (p = 0.004). No patient in BEH (or CON) had pGABA below 100 pmol/ml, but low pGABAs were found in 15% of MOOD patients (who had no behavior disorder) and in 16% of MOOD + BEH patients. Pharmacotherapy did not change pGABAs in the MOOD or the MOOD + BEH groups. No pGABA differences were found among the anxiety disorders, either alone or with mood or behavior comorbidity. The finding that plasma GABA levels are elevated in nonmedicated behavior disorders that present in the absence of mood disorders, and appear to lower following medication treatments, merits increased attention to the pharmacological study of nonaffective behavior disorders.
- Published
- 1997
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42. The effects of extended evaluation on depressive symptoms in children and adolescents.
- Author
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Rintelmann JW, Emslie GJ, Rush AJ, Varghese T, Gullion CM, Kowatch RA, and Hughes CW
- Subjects
- Adolescent, Antidepressive Agents, Second-Generation therapeutic use, Child, Depression classification, Depression drug therapy, Depression psychology, Depressive Disorder classification, Depressive Disorder drug therapy, Depressive Disorder psychology, Double-Blind Method, Female, Fluoxetine therapeutic use, Follow-Up Studies, Humans, Male, Personality Assessment statistics & numerical data, Psychometrics, Recurrence, Depression diagnosis, Depressive Disorder diagnosis
- Abstract
A sample of 137 child and adolescent outpatients with major depressive disorder were examined to identify baseline clinical characteristics that predicted symptom severity at the end of a 3-week evaluation period and to determine whether change in symptom severity between week 1 and week 2 predicted symptom severity at week three. Subjects underwent three consecutive weekly evaluations prior to being considered for entry into a double-blind, placebo-controlled treatment trial of fluoxetine. Results indicated that the combination of age, social functioning, family history, Children's Depressive Rating Scale-Revised (CDRS-R) (Poznanski et al. (1985) Psychopharmacol. Bull. 21, 979-989) total score at visit one, and percent change in symptom severity between visit one and visit two were predictors of symptom severity at visit three. These findings suggest that (1) subjects should not be excluded from randomized controlled clinical treatment trials based solely on improvement of symptom severity between visits and (2) an extended evaluation period is warranted, especially for adolescents whose symptom severity tends to fluctuate from week to week.
- Published
- 1996
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43. Affective disorders in children: diagnosis and management.
- Author
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Emslie GJ, Kennard BD, and Kowatch RA
- Subjects
- Bipolar Disorder diagnosis, Bipolar Disorder psychology, Bipolar Disorder therapy, Child, Cognition, Depression diagnosis, Depression psychology, Depression therapy, Humans, Mood Disorders psychology, Mood Disorders therapy, Neuropsychological Tests, Psychological Tests, Social Support, Mood Disorders diagnosis
- Published
- 1995
- Full Text
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44. Cognitive-behavior therapy for late-life insomnia.
- Author
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Morin CM, Kowatch RA, Barry T, and Walton E
- Subjects
- Aged, Female, Follow-Up Studies, Humans, Male, Polysomnography, Sleep Initiation and Maintenance Disorders psychology, Cognitive Behavioral Therapy methods, Sleep Initiation and Maintenance Disorders therapy
- Abstract
Twenty-four older adults with persistent psychophysiological insomnia were randomly assigned to an immediate or a delayed cognitive-behavioral intervention in a waiting-list control group design. Cognitive-behavior therapy consisted of an 8-week group intervention aimed at changing maladaptive sleep habits and altering dysfunctional beliefs and attitudes about sleeplessness. Treatment was effective in reducing sleep latency, wake after sleep onset, and early morning awakening, and in increasing sleep efficiency. The magnitude of changes obtained on polysomnographic measures was smaller but in the same direction as that obtained on daily sleep diaries. Sleep improvements obtained by the immediate-treatment group were replicated with the delayed treatment condition. Therapeutic gains were well maintained at 3- and 12-month follow-ups. Clinical validation of outcome was obtained through collateral ratings from the patients and their significant others. The findings indicate that late-life insomnia can be effectively treated with nonpharmacological interventions.
- Published
- 1993
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45. Patients' acceptance of psychological and pharmacological therapies for insomnia.
- Author
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Morin CM, Gaulier B, Barry T, and Kowatch RA
- Subjects
- Aged, Analysis of Variance, Drug Therapy, Female, Humans, Male, Middle Aged, Psychotherapy, Patient Acceptance of Health Care, Sleep Initiation and Maintenance Disorders therapy
- Abstract
This study evaluated the acceptance of psychological and pharmacological therapies among chronic insomniacs and noncomplaining good sleepers. After reading a brief written description of two treatment methods commonly used for persistent insomnia (i.e. cognitive-behavior therapy and pharmacotherapy), the subjects rated in a counter-balanced order several dimensions of these two treatment modalities. The results showed that the psychological intervention was rated as more acceptable and more suitable than the pharmacological one among both insomniacs and their noncomplaining significant others. Behavior therapy was also expected to be more effective on a long-term basis and to produce fewer side effects as well as more benefits on daytime functioning. The clinical implications and relevance of treatment acceptance in the management of insomnia are discussed.
- Published
- 1992
- Full Text
- View/download PDF
46. Electroencephalographic sleep and mood during cocaine withdrawal.
- Author
-
Kowatch RA, Schnoll SS, Knisely JS, Green D, and Elswick RK
- Subjects
- Adult, Electroencephalography, Electrooculography, Female, Humans, Infant, Newborn, Male, Mental Disorders classification, Mental Disorders diagnosis, Mental Disorders etiology, Psychiatric Status Rating Scales, Serotonin analysis, Substance-Related Disorders complications, Affect drug effects, Cocaine adverse effects, Sleep drug effects, Substance Withdrawal Syndrome, Substance-Related Disorders diagnosis
- Abstract
We report on nine patients between the ages of 21 and 39 years who were admitted to an inpatient substance abuse treatment unit for cocaine treatment. The patients' sleep was studied in the laboratory for 4 nights during the first week, and 2 nights during the second and third weeks of their hospitalization. Daily mood ratings, cocaine craving scores and sleep logs were also recorded on each patient. During the first week of withdrawal, these patients had a markedly shortened REM latency, an increased REM sleep percentage, a very high REM density and a long total sleep period time. During the third week, REM latencies were very short and total percentage of REM sleep was increased. By week three of withdrawal the sleep continuity pattern was similar to that found in chronic insomnia, with a long sleep latency, an abnormally increased total time awake after sleep onset and a poor sleep efficiency. The subjects' ratings of cocaine craving, total POMS scores and depression fell precipitously after the first week of withdrawal and were at sub-clinical levels by week three of withdrawal.
- Published
- 1992
- Full Text
- View/download PDF
47. Sleep restriction for the inpatient treatment of insomnia.
- Author
-
Morin CM, Kowatch RA, and O'Shanick G
- Subjects
- Affect, Chronic Disease, Depressive Disorder therapy, Female, Hospitalization, Humans, Middle Aged, Pain complications, Pain Management, Sleep Initiation and Maintenance Disorders etiology, Time Factors, Transcutaneous Electric Nerve Stimulation, Depressive Disorder complications, Sleep Initiation and Maintenance Disorders therapy
- Abstract
This study evaluates the efficacy of sleep restriction therapy for treating insomnia on an inpatient psychiatric unit. A depressed patient with concomitant chronic pain and severe insomnia was treated with a sleep restriction procedure. This procedure consisted of curtailing the amount of time spent in bed and then gradually increasing it contingent upon improved sleep efficiency. The treatment was found to be effective for increasing total sleep time from an initial baseline of 2.5 h of sleep per night to 6 h of sleep per night at discharge time. Clinical gains were well maintained immediately after discharge and at a 4-month follow-up.
- Published
- 1990
48. Ten cases of head-injured, suicide-surviving adolescents: challenges for rehabilitation.
- Author
-
Parmelee DX, Kowatch RA, Sellman J, and Davidow D
- Subjects
- Adolescent, Adult, Craniocerebral Trauma therapy, Female, Humans, Male, Patient Care Team, Craniocerebral Trauma rehabilitation, Suicide, Attempted
- Abstract
This paper describes ten adolescents who made unequivocal suicide attempts which resulted in near-death and brain damage. As predicted from studies of successful suicide, this group was mostly male, in late adolescence, and with histories of psychiatric difficulties. The fact that each had tried to commit suicide was avoided by the medical care facilities and by the families. The term 'accident' was customary. This paper makes suggestions for mental health clinicians who consult to head-injury rehabilitation teams treating such adolescents. Two cases are presented to highlight the findings and recommendations of this study.
- Published
- 1989
- Full Text
- View/download PDF
49. Sleep and head injury.
- Author
-
Kowatch RA
- Subjects
- Humans, Sleep Wake Disorders therapy, Brain Injuries complications, Sleep Stages, Sleep Wake Disorders etiology
- Published
- 1989
50. Differential effect of morphine on central versus peripheral nociception.
- Author
-
Rosenfeld JP and Kowatch R
- Subjects
- Animals, Avoidance Learning drug effects, Electroshock, Male, Mesencephalon drug effects, Pons drug effects, Rats, Brain drug effects, Morphine pharmacology, Pain, Spinal Cord drug effects
- Published
- 1975
- Full Text
- View/download PDF
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