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Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder

Castellanos, F Xavier; Margulies, Daniel S; Kelly, Clare; Uddin, Lucina Q; Ghaffari, Manely; Kirsch, Andrew; Shaw, David; Shehzad, Zarrar; Di Martino, Adriana; Biswal, Bharat; Sonuga-Barke, Edmund J S; Rotrosen, John; Adler, Lenard A; Milham, Michael P
BACKGROUND: Pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) have focused on frontal-striatal circuitry with alternative hypotheses relatively unexplored. On the basis of evidence that negative interactions between frontal foci involved in cognitive control and the non-goal-directed 'default-mode' network prevent attentional lapses, we hypothesized abnormalities in functional connectivity of these circuits in ADHD. METHODS: Resting-state blood oxygen level-dependent functional magnetic resonance imaging (fMRI) scans were obtained at 3.0-Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers. RESULTS: Examination of healthy control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x = 8, y = 7, z = 38) and in default-mode network components. Group analyses revealed ADHD-related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions (p < .0004, corrected). Secondary analyses revealed an extensive pattern of ADHD-related decreases in connectivity between precuneus and other default-mode network components, including ventromedial prefrontal cortex (p < 3 x 10(-11), corrected) and portions of posterior cingulate (p < .02, corrected). CONCLUSIONS: Together with prior unbiased anatomic evidence of posterior volumetric abnormalities, our findings suggest that the long-range connections linking dorsal anterior cingulate to posterior cingulate and precuneus should be considered as a candidate locus of dysfunction in ADHD
PMCID:2745053
PMID: 17888409
ISSN: 0006-3223
CID: 76108

Gender differences in 2 clinical trials of adults with attention-deficit/hyperactivity disorder: a retrospective data analysis

Robison, Reid J; Reimherr, Frederick W; Marchant, Barrie K; Faraone, Stephen V; Adler, Lenard A; West, Scott A
INTRODUCTION: Studies show that, in childhood attention-deficit/hyperactivity disorder (ADHD), boys have the combined type with externalizing behaviors more frequently, and girls have the inattentive type with increased internalizing disorders more frequently. METHOD: This study explored gender differences in adults with ADHD in 2 large, placebo-controlled, multicenter studies conducted from 2000 to 2001. Information collected included 2 measures of ADHD, multiple psychological measures, general physical symptoms, and treatment response. RESULTS: Thirty-four percent of the subjects were female. Women were rated as more impaired on every measure of ADHD symptoms including total Conners' Adult ADHD Rating Scale-Investigator Format (CAARS-INV), total Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), and most subscales of both measures. More women (75%) had combined type compared with men (62%). Women showed a more complex presentation, with higher scores on the Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Rating Scale for Depression, 17-item version (HAM-D(17)), more sleep problems, and more past DSM-IV Axis I diagnoses. Both sexes displayed substantial impairment on 3 Psychological General Well-Being Schedule factors: tension-anxiety, life satisfaction, and vitality-drive. Women experienced significantly (p = .003) greater rates of emotional dysregulation (37%) versus men (29%) as defined by a cluster of symptoms on the WRAADDS. The emotional dysregulation factor is derived by combining 3 symptoms--temper control, mood lability, and emotional overreactivity--from the Utah Criteria for ADHD in adults. These symptoms are considered associated symptoms in the DSM-IV description of ADHD. Women also experienced greater improvement (p = .011) on this symptom factor. CONCLUSION: In contrast to the results from childhood studies, women were more impaired than men on ADHD scales in our study. The higher level of emotional symptoms and more complicated presentation in women may obscure the diagnosis of ADHD. Thus, the assessments of adults with ADHD should include an exploration of the emotional dimensions of the illness
PMID: 18211131
ISSN: 1555-2101
CID: 93892

Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature

Wilens, Timothy E; Adler, Lenard A; Adams, Jill; Sgambati, Stephanie; Rotrosen, John; Sawtelle, Robert; Utzinger, Linsey; Fusillo, Steven
OBJECTIVE: Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed and prescribed stimulant medications in adolescent and young adult populations. The purpose of this systematic review of the literature is to evaluate the extent and characteristics of stimulant misuse and diversion in attention-deficit/hyperactivity disorder (ADHD) and non-ADHD individuals. METHOD: We conducted a systematic review of the literature of available studies looking at misuse and diversion of prescription ADHD medications using misuse, diversion, stimulants, illicit use, and ADHD medications as key words for the search. RESULTS: We identified 21 studies representing 113,104 subjects. The studies reported rates of past year nonprescribed stimulant use to range from 5% to 9% in grade school- and high school-age children and 5% to 35% in college-age individuals. Lifetime rates of diversion ranged from 16% to 29% of students with stimulant prescriptions asked to give, sell, or trade their medications. Recent work suggests that whites, members of fraternities and sororities, individuals with lower grade point averages, use of immediate-release compared to extended-release preparations, and individuals who report ADHD symptoms are at highest risk for misusing and diverting stimulants. Reported reasons for use, misuse, and diversion of stimulants include to concentrate, improve alertness, 'get high,' or to experiment. CONCLUSIONS: The literature suggests that individuals both with and without ADHD misuse stimulant medications. Recent work has begun to document the context, motivation, and demographic profile of those most at risk for using, misusing, and diverting stimulants. The literature highlights the need to carefully monitor high-risk individuals for the use of nonprescribed stimulants and educate individuals with ADHD as to the pitfalls of the misuse and diversion of the stimulants
PMID: 18174822
ISSN: 0890-8567
CID: 93597

Familial transmission of ADHD and psychoactive substance use disorders [Editorial]

Adler, Lenard A
PMID: 18178750
ISSN: 0002-953x
CID: 93893

Adult ADHD pharmacotherapy

Adler L.A.
EMBASE:2009007170
ISSN: 1523-5998
CID: 92149

Atomoxetine alleviates executive function impairments in adults with ADHD [Meeting Abstract]

Brown, T; Kelsey, D; Holdnack, J; Saylor, K; Adler, L; Spencer, T; Paczkowski, M; Schuh, K; Trzepacz, P
ISI:000252745500040
ISSN: 1044-5463
CID: 75951

Atomoxetine treatment of adults with ADHD and comorbid alcohol abuse [Meeting Abstract]

Wilens, TE; Adler, LA; Weiss, MD; Ramsey, JL; Moore, RJ; Renard, D; Levine, LR
ISI:000252745500041
ISSN: 1044-5463
CID: 75952

Introduction [Preface]

Adler, LA; Newcorn, JH
ISI:000252701800001
ISSN: 1092-8529
CID: 75964

The impact, identification, and management of attention-deficit/hyperactivity disorder in adults. Introduction

Adler, Lenard A; Newcorn, Jeffrey H
PMID: 18163042
ISSN: 1092-8529
CID: 78636

From childhood into adulthood: the changing face of ADHD

Adler, Lenard A
PMID: 18396510
ISSN: 1092-8529
CID: 78640