[Show abstract][Hide abstract] ABSTRACT: The factor structure of several self-report questionnaires assessing depression-relevant cognitions frequently employed in clinical research was examined in a sample of 390 adolescents (M age = 14.54; 216 girls; 74% Caucasian) with current major depressive disorder enrolled in the Treatment of Adolescents with Depression Study. A four-factor solution resulted, accounting for 65% of the total variance. The factors were labeled (a) Cognitive Distortions and Maladaptive Beliefs, (b) Cognitive Avoidance, (c) Positive Outlook, and (d) Solution-Focused Thinking. Internal consistencies for the factor-based composite scores were .83, .85, .84, and .82, respectively. Girls endorsed more negative cognitions than boys on three of the four factors. Maladaptive cognitions were positively related to severity of depression and predicted treatment response. Taken together, findings indicated that there are four distinct domains of cognitions that are present among adolescents with depression that are tapped by several widely used self-report measures of cognitions.
[Show abstract][Hide abstract] ABSTRACT: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).
The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission.
At week 36, the estimated remission rates for intention-to-treat cases were as follows: combination, 60%; fluoxetine, 55%; cognitive-behavioral therapy, 64%; and overall, 60%. Paired comparisons reveal that, at week 24, all active treatments converge on remission outcomes. The recovery rate at week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36.
Most depressed adolescents in all three treatment modalities achieved remission at the end of 9 months of treatment.
Journal of the American Academy of Child and Adolescent Psychiatry 02/2009; 48(2):186-95. DOI:10.1097/CHI.0b013e31819176f9 · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obese patients are at increased risk of acute coronary syndromes (ACS). We evaluated the prevalence of obesity in a large ACS population, as well as the relationship between body mass index (BMI) and the use of cardiac medications and procedures, clinical outcomes, and treatment effects between enoxaparin and unfractionated heparin (UFH).
Using the database of the SYNERGY trial, we identified 9978 patients in 12 countries who were randomly assigned to receive enoxaparin or UFH. Patient weight at baseline and 30-day follow-up was recorded. BMI information was available on 9837 patients. BMI was analyzed in clinically meaningful categories (<20, 20-25, 30-35, > or =35 kg/m(2)) and as a continuous variable.
Thirty-two percent of patients were obese (BMI> or =30), with a greater proportion of patients with obesity from North America (36%) compared with other regions. Enoxaparin was dosed as 1 mg/kg regardless of body weight without maximum. The first dose of enoxaparin was underdosed in 15% of patients assigned enoxaparin, and obese patients were more likely to be underdosed than non-obese patients. Obese patients were younger, less often white, had more diabetes, hypertension, hyperlipidemia, family history of coronary artery disease, and congestive heart failure but fewer strokes, less peripheral vascular disease, and less often smoked. After adjustment, increased BMI was not an independent predictor of bleeding outcomes or 30-day death/myocardial infarction (MI), but increased BMI was predictive of lower 1-year mortality in the subgroup of patients with BMI at baseline below approximately 30 kg/m(2). No statistical interaction term was observed between obesity and randomized therapy for the outcomes of death/MI at 30 days and 6 months; death at 30 days, 6 months, and 1 year; and GUSTO or TIMI bleeding.
Nearly one third of patients in SYNERGY were obese. Despite multiple comorbidities, obese patients had better unadjusted short- and long-term outcomes. After adjustment, higher BMI was not an independent predictor of in-hospital bleeding events or 30-day death/MI, but increased BMI was an independent predictor of 1-year mortality in patients with lower BMI but not in heavier patients. No interaction between the randomized treatment and obesity for efficacy and safety outcomes was observed across the range of BMI in this dataset. Standard dosing of enoxaparin should be used in patients without extreme obesity due to limited outcome data in these patients.
International journal of cardiology 11/2008; 139(2):123-33. DOI:10.1016/j.ijcard.2008.10.008 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several neuroanatomic abnormalities have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, findings are not always consistent, perhaps because of heterogeneous subject samples. Studying youths with documented familial ADHD provides an opportunity to examine a more homogeneous population.
Twenty-four youths with a confirmed history of familial ADHD and 10 control youths underwent high-resolution structural magnetic resonance imaging examinations. Archived magnetic resonance imaging scan data from 12 control youths were included in the analysis to increase statistical power. Individually drawn region-of-interest methods were used to examine the frontal lobe gyri and caudate.
Cerebral total tissue was similar between groups. The volumes of the right caudate and right inferior frontal lobe were larger in the ADHD youths compared with the control youths. Data from a subgroup of the ADHD youths suggest that increasing left caudate volume is associated with decreasing functional activation of this region.
Because previous studies have focused primarily on younger subjects or used an extended age range, the present results may reflect neurodevelopmental changes specific to late adolescence in familial ADHD.
Journal of the American Academy of Child and Adolescent Psychiatry 10/2008; 47(11):1321-8. DOI:10.1097/CHI.0b013e318185d285 · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies suggest that ethnicity and socioeconomic factors may relate to differences in treatment expectancies and the attributions made for emotional or behavioral problems. We examined ethnic differences in (1) parents' attributions about the causes of adolescent behavioral and emotional problems and (2) treatment expectancies among 236 adolescent participants who enrolled in a 36-week randomized controlled trial for depression. Controlling for education and income, European American parents were more likely to endorse beliefs reflecting physical causes of depression than African American parents. There were no ethnic differences for beliefs reflecting external, familial, or community factors. Ethnic differences were observed in the treatment expectancies reported by parents, but not adolescents, with African American parents more likely than European Americans and Other minorities to endorse positive expectations for CBT. These findings may have implications for understanding discrepancies in mental health service use.
International Journal of Cognitive Therapy 07/2008; 1(2):163-178. DOI:10.1680/ijct.2008.1.2.163 · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Treatment for Adolescents With Depression Study evaluated fluoxetine (FLX), cognitive behavioral therapy (CBT), and FLX/CBT combination (COMB) vs pill placebo in 439 adolescents with major depressive disorder. Treatment consisted of 3 stages: (1) acute (12 weeks), (2) continuation (6 weeks), and (3) maintenance (18 weeks).
To examine rates of achieving and maintaining sustained response during continuation and maintenance treatments.
Randomized controlled trial. Response was determined by blinded independent evaluators.
Thirteen US sites.
Two hundred forty-two FLX, CBT, and COMB patients in their assigned treatment at the end of stage 1.
Stage 2 treatment varied based on stage 1 response. Stage 3 consisted of 3 CBT and/or pharmacotherapy sessions and, if applicable, continued medication.
Sustained response was defined as 2 consecutive Clinical Global Impression-Improvement ratings of 1 or 2 ("full response"). Patients achieving sustained response were classified on subsequent nonresponse status.
Among 95 patients (39.3%) who had not achieved sustained response by week 12 (29.1% COMB, 32.5% FLX, and 57.9% CBT), sustained response rates during stages 2 and 3 were 80.0% COMB, 61.5% FLX, and 77.3% CBT (difference not significant). Among the remaining 147 patients (60.7%) who achieved sustained response by week 12, CBT patients were more likely than FLX patients to maintain sustained response through week 36 (96.9% vs 74.1%; P = .007; 88.5% of COMB patients maintained sustained response through week 36). Total rates of sustained response by week 36 were 88.4% COMB, 82.5% FLX, and 75.0% CBT.
Most adolescents with depression who had not achieved sustained response during acute treatment did achieve that level of improvement during continuation and maintenance therapies. The possibility that CBT may help the subset of adolescents with depression who achieve early sustained response maintain their response warrants further investigation.
clinicaltrials.gov Identifier: NCT00006286.
Archives of general psychiatry 05/2008; 65(4):447-55. DOI:10.1001/archpsyc.65.4.447 · 14.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many studies have linked the structure and function of frontostriatal circuitry to cognitive control deficits in attention deficit hyperactivity disorder (ADHD). Few studies have examined the role of white matter tracts between these structures or the extent to which white matter tract myelination and regularity correlate in family members with the disorder.
Functional imaging maps from a go/nogo task were used to identify portions of the ventral prefrontal cortex and striatum involved in suppressing an inappropriate action (i.e., cognitive control) in 30 parent-child dyads (N=60), including 20 dyads (N=40) with ADHD and 10 dyads (N=20) without ADHD. An automated fiber-tracking algorithm was used to delineate white matter fibers adjacent to these functionally defined regions based on diffusion tensor images. Fractional anisotropy, an index of white matter tract myelination and regularity derived from diffusion tensor images, was calculated to characterize the associations between white matter tracts and function.
Fractional anisotropy in right prefrontal fiber tracts correlated with both functional activity in the inferior frontal gyrus and caudate nucleus and performance of a go/nogo task in parent-child dyads with ADHD, even after controlling for age. Prefrontal fiber tract measures were tightly associated between ADHD parents and their children.
Collectively, these findings support previous studies suggesting heritability of frontostriatal structures among individuals with ADHD and suggest disruption in frontostriatal white matter tracts as one possible pathway to the disorder.
American Journal of Psychiatry 12/2007; 164(11):1729-36. DOI:10.1176/appi.ajp.2007.06101754 · 12.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological abnormalities and response to stimulant medication.
A group of concordantly diagnosed ADHD parent-child dyads was compared to a matched sample of normal parent-child dyads. In addition, ADHD dyads were administered double-blind methylphenidate and placebo in a counterbalanced fashion over two consecutive days of testing. Frontostriatal function was measured using functional magnetic resonance imaging (fMRI) during performance of a go/no-go task.
Youths and adults with ADHD showed attenuated activity in fronto-striatal regions. In addition, adults with ADHD appeared to activate non-fronto-striatal regions more than normals. A stimulant medication trial showed that among youths, stimulant medication increased activation in fronto-striatal and cerebellar regions. In adults with ADHD, increases in activation were observed in the striatum and cerebellum, but not in prefrontal regions.
This study extends findings of fronto-striatal dysfunction to adults with ADHD and highlights the importance of frontostriatal and frontocerebellar circuitry in this disorder, providing evidence of an endophenotype for examining the genetics of ADHD.
Journal of Child Psychology and Psychiatry 10/2007; 48(9):899-913. DOI:10.1111/j.1469-7610.2007.01761.x · 6.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study serves to detail the specific procedures for a mock scanner protocol, report on its use in the context of a multi-site study, and make suggestions for improving such protocols based on data acquired during study scanning. Specifically, a mock scanner compliance training protocol was used in a functional imaging study with a group of adolescents and adults with Attention Deficit Hyperactivity Disorder (ADHD) and a matched sample of healthy children and adults. Head motion was measured during mock and actual scanning. Participants across groups exhibited excess motion (>2 mm) on 43% of runs during the mock scanner. During actual scanning, excessive motion was limited to 10% of runs. There was a clear task-correlated head motion during a go/no-go task that occurred even after the compliance training: participants had a tendency to respond with increased head motion immediately after committing an error. This study illustrates the need to (1) report data attrition due to head motion, (2) assess task-related motion, and (3) consider mock scanner training in functional imaging protocols.
Psychiatry Research 05/2007; 155(1):75-82. DOI:10.1016/j.pscychresns.2006.12.009 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Processing speed is often described as a fundamental resource determining individual (e.g., I.Q.) and group (e.g., developmental) differences in cognition. However, most tests that measure speed present many items on a single page. Because many groups with slowed responding are also distractible, we compared younger and older adults on high-distraction (i.e., standard) versus low-distraction versions of two classic speed tasks. Reducing distraction improved the performance of older adults but had little or no effect on younger adults, suggesting that the ability to limit attentional access to task-relevant information can affect performance on tests designed to measure processing speed.
[Show abstract][Hide abstract] ABSTRACT: While studies have increasingly investigated deficits in reaction time (RT) and RT variability in children with attention deficit/hyperactivity disorder (ADHD), few studies have examined the effects of stimulant medication on these important neuropsychological outcome measures.
316 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA) completed the Conners' Continuous Performance Test (CPT) at the 24-month assessment point. Outcome measures included standard CPT outcomes (e.g., errors of commission, mean hit reaction time (RT)) and RT indicators derived from an Ex-Gaussian distributional model (i.e., mu, sigma, and tau).
Analyses revealed significant effects of medication across all neuropsychological outcome measures. Results on the Ex-Gaussian outcome measures revealed that stimulant medication slows RT and reduces RT variability.
This demonstrates the importance of including analytic strategies that can accurately model the actual distributional pattern, including the positive skew. Further, the results of the study relate to several theoretical models of ADHD.
Journal of Child Psychology and Psychiatry 06/2006; 47(5):446-56. DOI:10.1111/j.1469-7610.2005.01469.x · 6.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Differences in reaction time (RT) variability have been documented between children with and without Attention Deficit Hyperactivity Disorder (ADHD). Most previous research has utilized estimates of normal distributions to examine variability. Using a nontraditional approach, the present study evaluated RT distributions on the Conners' Continuous Performance Test in children and adolescents from the Multimodal Treatment Study of ADHD sample compared to a matched sample of normal controls (n = 65 pairs). The ex-Gaussian curve was used to model RT and RT variability. Children with ADHD demonstrated faster RT associated with the normal portion of the curve and a greater proportion of abnormally slow responses associated with the exponential portion of the curve. These results contradict previous interpretation that children with ADHD have slower than normal responding and demonstrate why slower RT is found when estimates of variability assume normal Gaussian distributions. Further, results of this study suggest that the greater number of abnormally long RTs of children with ADHD reflect attentional lapses on some but not all trials.
[Show abstract][Hide abstract] ABSTRACT: Significant ethnic differences have been consistently documented on attention-deficit/hyperactivity disorder (ADHD) teacher rating scales. Whether these ethnic differences result from a teacher rating bias or reflect actual classroom behavior patterns is unknown. Ethnic differences between Caucasian and African American (AA) elementary schoolchildren on teacher ratings and codings of observed classroom behavior were examined with latent variables. In structural equation models, correlations between teacher ratings and observed classroom behavior suggested nonbiased teacher ratings of AA schoolchildren with diagnosed ADHD. Ethnic differences were documented for both teacher ratings of ADHD and classroom behavior. Differences in classroom behavior were attenuated when the behavior of an average child in the classroom was taken into account. Multiple explanations for this pattern of results are discussed.
Journal of Consulting and Clinical Psychology 07/2005; 73(3):424-34. DOI:10.1037/0022-006X.73.3.424 · 4.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: From the perspective of the Hasher, Zacks, and May (1999) inhibitory framework, optimal performance occurs only when there is control over nonrelevant information. Relative to a current, goal-directed task, there are at least two potential sources of nonrelevant information that need to be controlled. The first is no longer relevant information. Such information would include, for example, a previous topic of conversation, or, in our work, a previous list of materials presented for study and recall. The second source of nonrelevant information is currently present (in thought or in the world) stimuli that are not relevant to the task at hand. Inhibitory processes are critical to the effective control of both sources of information—the no longer relevant past and the irrelevant present. If inhibitory processes are inefficient, irrelevant information from both the past and the present will disrupt performance on the current task. We illustrate this with studies showing the role of irrelevant information in reducing the working memory capacity of older adults and in slowing them down as they do even reasonably simple tasks.
European Journal of Cognitive Psychology 03/2001; 13(1-1-2):107-122. DOI:10.1080/09541440126215 · 1.09 Impact Factor