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Mark A Riddle,
Kseniya Yershova,
Deborah Lazzaretto,
Natalya Paykina,
Gayane Yenokyan,
Laurence Greenhill,
Howard Abikoff,
Benedetto Vitiello,
Tim Wigal,
James T McCracken,
Scott H Kollins,
Desiree W Murray,
Sharon Wigal, Elizabeth Kastelic,
James J McGough,
Susan Dosreis,
Audrey Bauzó-Rosario,
Annamarie Stehli,
Kelly Posner
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ABSTRACT: To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS).
A total of 207 participants (75% male) from the original PATS, assessed at baseline (mean age, 4.4 years, when all met criteria for ADHD) and 3 months later (before medication treatment), were re-evaluated in three follow-up assessment visits (year 3, mean age 7.4 years; year 4, 8.3 years; and year 6, 10.4 years). Parents and teachers rated symptom severity, and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis.
Parent- and teacher-rated symptom severity decreased from baseline to year 3 but remained relatively stable and in the moderate-to-severe clinical range through year 6. Girls showed generally steeper decreases in symptom T-scores. At year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at year 6 in the multiple logistic model. Medication status during follow-up, on versus off, did not predict symptom severity change from year 3 to year 6 after adjustment for other variables.
ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group.
Journal of the American Academy of Child and Adolescent Psychiatry 03/2013; 52(3):264-278.e2. · 4.98 Impact Factor
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Kelly Posner,
Glenn A Melvin,
Desiree W Murray,
S Sonia Gugga,
Prudence Fisher,
Anne Skrobala,
Charles Cunningham,
Benedetto Vitiello,
Howard B Abikoff,
Jaswinder K Ghuman, [......],
Tim Wigal,
James T McCracken,
James J McGough, Elizabeth Kastelic,
Roy Boorady,
Mark Davies,
Shirley Z Chuang,
James M Swanson,
Mark A Riddle,
Laurence L Greenhill
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John Curry,
Susan Silva,
Paul Rohde,
Golda Ginsburg,
Betsy Kennard,
Christopher Kratochvil,
Anne Simons,
Jerry Kirchner,
Diane May,
Taryn Mayes, [......],
Mark Reinecke,
Rachel Jacobs,
Emily Becker-Weidman,
Elizabeth Weller,
Graham Emslie,
John Walkup, Elizabeth Kastelic,
Barbara Burns,
Karen Wells,
John March
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ABSTRACT: This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD).
For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in the Treatment for Adolescents with Depression Study (TADS; TADS Team, 2004) and who had no prior diagnoses of AUD or SUD. TADS initial treatments were cognitive behavior therapy (CBT), fluoxetine alone (FLX), the combination of CBT and FLX (COMB), or clinical management with pill placebo (PBO). We used both the original TADS treatment response rating and a more restrictive symptom count rating. During follow-up, diagnostic interviews were completed at 6- or 12-month intervals to assess onset of AUD or SUD as well as MDD recovery and recurrence.
Achieving a positive response to MDD treatment was unrelated to subsequent AUD but predicted a lower rate of subsequent SUD, regardless of the measure of positive response (11.65% vs. 24.72%, or 10.0% vs. 24.5%, respectively). Type of initial MDD treatment was not related to either outcome. Prior to depression treatment, greater involvement with alcohol or drugs predicted later AUD or SUD, as did older age (for AUD) and more comorbid disorders (for SUD). Among those with recurrent MDD and AUD, AUD preceded MDD recurrence in 24 of 25 cases.
Effective short-term adolescent depression treatment significantly reduces the rate of subsequent SUD but not AUD. Alcohol or drug use should be assessed prior to adolescent MDD treatment and monitored even after MDD recovery.
Journal of Consulting and Clinical Psychology 01/2012; 80(2):299-312. · 4.85 Impact Factor
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John I Nurnberger,
Melvin McInnis,
Wendy Reich, Elizabeth Kastelic,
Holly C Wilcox,
Anne Glowinski,
Philip Mitchell,
Carrie Fisher,
Mariano Erpe,
Elliot S Gershon, [......],
Gina Laite,
Robert Schweitzer,
Kelly Rhoadarmer,
Vegas V Coleman,
Xueya Cai,
Faouzi Azzouz,
Hai Liu,
Masoud Kamali,
Christine Brucksch,
Patrick O Monahan
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ABSTRACT: The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy.
To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects.
A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical characteristics following best-estimate procedures.
Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009.
Offspring aged 12 to 21 years in families with a proband with BP (n = 141, designated as cases) and similarly aged offspring of control parents (n = 91).
Lifetime DSM-IV diagnosis of a major affective disorder (BP type I; schizoaffective disorder, bipolar type; BP type II; or major depression).
At a mean age of 17 years, cases showed a 23.4% lifetime prevalence of major affective disorders compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in controls (adjusted P = .007). No significant difference was seen in the prevalence of other affective, anxiety, disruptive behavior, or substance use disorders. Among case subjects manifesting major affective disorders (n = 33), there was an increased risk of anxiety and externalizing disorders compared with cases without mood disorder. In cases but not controls, a childhood diagnosis of an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of major affective disorders.
Childhood anxiety and externalizing diagnoses predict major affective illness in adolescent offspring in families with probands with BP.
Archives of general psychiatry 10/2011; 68(10):1012-20. · 12.26 Impact Factor
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John Curry,
Susan Silva,
Paul Rohde,
Golda Ginsburg,
Christopher Kratochvil,
Anne Simons,
Jerry Kirchner,
Diane May,
Betsy Kennard,
Taryn Mayes, [......],
Mark Reinecke,
Rachel Jacobs,
Emily Becker-Weidman,
Elizabeth Weller,
Graham Emslie,
John Walkup, Elizabeth Kastelic,
Barbara Burns,
Karen Wells,
John March
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ABSTRACT: Major depressive disorder in adolescents is common and impairing. Efficacious treatments have been developed, but little is known about longer-term outcomes, including recurrence.
To determine whether adolescents who responded to short-term treatments or who received the most efficacious short-term treatment would have lower recurrence rates, and to identify predictors of recovery and recurrence.
Naturalistic follow-up study.
Twelve academic sites in the United States.
One hundred ninety-six adolescents (86 males and 110 females) randomized to 1 of 4 short-term interventions (fluoxetine hydrochloride treatment, cognitive behavioral therapy, their combination, or placebo) in the Treatment for Adolescents With Depression Study were followed up for 5 years after study entry (44.6% of the original Treatment for Adolescents With Depression Study sample).
Recovery was defined as absence of clinically significant major depressive disorder symptoms on the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version interview for at least 8 weeks, and recurrence was defined as a new episode of major depressive disorder following recovery.
Almost all participants (96.4%) recovered from their index episode of major depressive disorder during the follow-up period. Recovery by 2 years was significantly more likely for short-term treatment responders (96.2%) than for partial responders or nonresponders (79.1%) (P < .001) but was not associated with having received the most efficacious short-term treatment (the combination of fluoxetine and cognitive behavioral therapy). Of the 189 participants who recovered, 88 (46.6%) had a recurrence. Recurrence was not predicted by full short-term treatment response or by original treatment. However, full or partial responders were less likely to have a recurrence (42.9%) than were nonresponders (67.6%) (P = .03). Sex predicted recurrence (57.0% among females vs 32.9% among males; P = .02).
Almost all depressed adolescents recovered. However, recurrence occurs in almost half of recovered adolescents, with higher probability in females in this age range. Further research should identify and address the vulnerabilities to recurrence that are more common among young women.
Archives of general psychiatry 11/2010; 68(3):263-9. · 12.26 Impact Factor
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Jaswinder K Ghuman,
Mark A Riddle,
Benedetto Vitiello,
Laurence L Greenhill,
Shirley Z Chuang,
Sharon B Wigal,
Scott H Kollins,
Howard B Abikoff,
James T McCracken, Elizabeth Kastelic,
Alexander M Scharko,
James J McGough,
Desiree W Murray,
Lori Evans,
James M Swanson,
Tim Wigal,
Kelly Posner,
Charles Cunningham,
Mark Davies,
Anne M Skrobala
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ABSTRACT: The aim of this study was to examine whether demographic or pretreatment clinical and social characteristics influenced the response to methylphenidate (MPH) in the Preschoolers with ADHD Treatment Study (PATS).
Exploratory moderator analyses were conducted on the efficacy data from the PATS 5-week, double-blind, placebo-controlled six-site titration trial. Children (N = 165, age 3-5.5 years) were randomized to 1 week each of four MPH doses (1.25, 2.5, 5, and 7.5 mg) and placebo administered three times per day (t.i.d.). We assessed the fixed effects on the average slope in the regression outcome on moderators, weight-adjusted dose, and the moderator-by-dose interaction using SAS PROC GENMOD.
A significant interaction effect was found for a number of co-morbid disorders diagnosed in the preschoolers at baseline (p = 0.005). Preschoolers with three or more co-morbid disorders did not respond to MPH (Cohen's d at 7.5 mg dose relative to placebo = -0.37) compared to a significant response in the preschoolers with 0, 1, or 2 co-morbid disorders (Cohen's d = 0.89, 1.00, and 0.56, respectively). Preschoolers with more co-morbidity were found to have more family adversity. No significant interaction effect was found with the other variables.
In preschoolers with ADHD, the presence of no or one co-morbid disorder (primarily oppositional defiant disorder) predicted a large treatment response at the same level as has been found in school-aged children, and two co-morbid disorders predicted moderate treatment response; whereas the presence of three or more co-morbid disorders predicted no treatment response to MPH.
Journal of Child and Adolescent Psychopharmacology 11/2007; 17(5):563-80. · 2.88 Impact Factor
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Kelly Posner,
Glenn A Melvin,
Desiree W Murray,
S Sonia Gugga,
Prudence Fisher,
Anne Skrobala,
Charles Cunningham,
Benedetto Vitiello,
Howard B Abikoff,
Jaswinder K Ghuman, [......],
Tim Wigal,
James T McCracken,
James J McGough, Elizabeth Kastelic,
Roy Boorady,
Mark Davies,
Shirley Z Chuang,
James M Swanson,
Mark A Riddle,
Laurence L Greenhill
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ABSTRACT: The aim of this study was to describe the clinical presentation of preschoolers diagnosed with moderate to severe attention-deficit/hyperactivity disorder (ADHD) recruited for the multisite Preschool ADHD Treatment Study (PATS). The diagnosis and evaluation process will also be described.
A comprehensive multidimensional, multi-informant assessment protocol was implemented including the semistructured PATS Diagnostic Interview. Parent and teacher-report measures were used to supplement information from interviews. Consensus agreement by a cross-site panel on each participant's diagnoses was required. Analyses were conducted to describe the sample and to test associations between ADHD severity and demographic and clinical variables.
The assessment protocol identified 303 preschoolers (3-5.5 years) with moderate to severe ADHD Hyperactive/Impulsive or Combined type. The majority of participants (n = 211, 69.6%) experienced co-morbid disorders, with oppositional defiant disorder, communication disorders, and anxiety disorders being the most common. Participants with co-morbid communication disorders were found to be more anxious and depressed. ADHD severity was found to correlate with more internalizing difficulties and lower functioning. Although boys and girls had similar symptom presentations, younger children had significantly higher ADHD severity.
Preschoolers with moderate to severe ADHD experience high co-morbidity and impairment, which have implications for both assessment and treatment.
Journal of Child and Adolescent Psychopharmacology 11/2007; 17(5):547-62. · 2.88 Impact Factor
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Howard B Abikoff,
Benedetto Vitiello,
Mark A Riddle,
Charles Cunningham,
Laurence L Greenhill,
James M Swanson,
Shirley Z Chuang,
Mark Davies, Elizabeth Kastelic,
Sharon B Wigal,
Lori Evans,
Jaswinder K Ghuman,
Scott H Kollins,
James T McCracken,
James J McGough,
Desiree W Murray,
Kelly Posner,
Anne M Skrobala,
Tim Wigal
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ABSTRACT: The purpose of this study was to examine the effects of methylphenidate (MPH) on functional outcomes, including children's social skills, classroom behavior, emotional status, and parenting stress, during the 4-week, double-blind placebo controlled phase of the Preschoolers with Attention Deficit/Hyperactivity Disorder (ADHD) Treatment Study (PATS).
A total of 114 preschoolers who had improved with acute MPH treatment, were randomized to their best MPH dose (M = 14.22 mg/day; n = 63) or placebo (PL; n = 51). Assessments included the Clinical Global Impression-Severity (CGI-S), parent and teacher versions of the Strengths and Weaknesses of ADHD-Symptoms and Normal Behaviors (SWAN), Social Competence Scale (SCS), Social Skills Rating System (SSRS), and Early Childhood Inventory (ECI), and Parenting Stress Index (PSI).
Medication effects varied by informant and outcome measure. Parent measures and teacher SWAN scores did not differentially improve with MPH. Parent-rated depression (p < 0.02) and dysthymia (p < 0.001) on the ECI worsened with MPH, but scores were not in the clinical range. Significant medication effects were found on clinician CGI-S (p < 0.0001) and teacher social competence ratings (SCS, p < 0.03).
Preschoolers with ADHD treated with MPH for 4 weeks improve in some aspects of functioning. Additional improvements might require longer treatment, higher doses, and/or intensive behavioral treatment in combination with medication.
Journal of Child and Adolescent Psychopharmacology 10/2007; 17(5):581-92. · 2.88 Impact Factor
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James McGough,
James McCracken,
James Swanson,
Mark Riddle,
Scott Kollins,
Laurence Greenhill,
Howard Abikoff,
Mark Davies,
Shirley Chuang,
Tim Wigal,
Sharon Wigal,
Kelly Posner,
Anne Skrobala, Elizabeth Kastelic,
Jaswinder Ghuman,
Charles Cunningham,
Sharon Shigawa,
Robert Moyzis,
Benedetto Vitiello
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ABSTRACT: The authors explored genetic moderators of symptom reduction and side effects in methylphenidate-treated preschool-age children diagnosed with attention-deficit/hyperactivity disorder (ADHD).
DNA was isolated from 81 subjects in a double-blind, placebo-controlled, crossover methylphenidate titration. Parents and teachers completed ADHD symptom scales and side effect ratings for each of five randomly administered weekly conditions that included immediate-release methylphenidate 1.25, 2.5, 5.0, 7.5 mg and placebo given three times daily. Candidate genes hypothesized to influence stimulant effects or individual risks for ADHD were genotyped.
Although the primary analysis did not indicate significant genetic effects, secondary analyses revealed associations between symptom response and variants at the dopamine receptor (DRD4) promoter (p=.05) and synaptosomal-associated protein 25 (SNAP25) allelesT1065G (p=.03) andT1069C (p=.05). SNAP25 variants were also associated with tics (p=.02), buccal-lingual movements (p=.01), and irritability (p=04). DRD4 variants were also associated with picking (p=.03). Increasing dose predicted irritability (p=.05) and social withdrawal (p=.03) with DRD4 variants. There were no significant effects for the dopamine transporter (DAT1).
Emerging evidence suggests the potential for understanding the individual variability of response to and side effects of ADHD medications from the study of genetics, although additional research is required before these findings are proven to have clinical utility.
Journal of the American Academy of Child & Adolescent Psychiatry 12/2006; 45(11):1314-22. · 6.44 Impact Factor
