Psychiatric Comorbidity in Adult Attention Deficit Hyperactivity Disorder: Findings From Multiplex Families

McGough, James J.; Smalley, Susan L.; McCracken, James T.; Yang, May; Del’Homme, Melissa; Lynn, Deborah E.; Loo, Sandra K.

doi:10.1176/appi.ajp.162.9.1621

Cited by 336 publications

(283 citation statements)

References 29 publications

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“…Given the extensive comorbidity between SUDs and many psychiatric disorders such as depression (Tsuang, et al, 2001), anxiety (Mills, et al, 2006), bipolar disorder (Lin, et al, 2006) and attention deficit hyperactivity disorder (ADHD) (McGough, et al, 2005), it is intriguing to speculate that, when SUDs occur in the presence of psychopathology, that psychopathology may reflect the genetic susceptibility to SUDs. This idea is consistent with two bodies of evidence.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, it seems unlikely that there will be a one-to-one correspondence between genetically influenced processes in the brain and the clinical phenomena that define diagnostic categories. Molecular genetic studies may thus be more fruitful if they focus on alternative phenotypes explicitly developed to maximize the power to detect genes.Given the extensive comorbidity between SUDs and many psychiatric disorders such as depression (Tsuang, et al, 2001), anxiety (Mills, et al, 2006), bipolar disorder (Lin, et al, 2006) and attention deficit hyperactivity disorder (ADHD) (McGough, et al, 2005), it is intriguing to speculate that, when SUDs occur in the presence of psychopathology, that psychopathology may reflect the genetic susceptibility to SUDs. This idea is consistent with two bodies of evidence.…”

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confidence: 99%

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Familial transmission of derived phenotypes for molecular genetic studies of substance use disorders

Faraone

Adamson

Wilens

et al. 2008

Drug and Alcohol Dependence

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Although family, twin, and adoption studies indicate that genes play a significant etiologic role in the development of substance use disorders (SUDs), detecting specific genes has been difficult due to uncertainties about how to define SUDs, genetic heterogeneity and variable phenotypic expression of SUD genotypes. We used data from families recruited into six contemporaneous studies of children and adults to derive candidate SUD phenotypes using principle factors factor analysis with varimax rotation. We previously found evidence of two SUD phenotypes in offspring: a psychopathology dimension and a cognitive impairment dimension. We found evidence for one SUD-related phenotype in adults that we term Psychopathology and Cognitive Impairment. Parental factor scores significantly predicted both offspring phenotypes, as well as parental SUD (OR=1.41,p<0.001) and offspring SUD (mother's phenotype: OR=1.34,p=0.04; father's phenotype: OR=1.33,p=0.01). Offspring phenotype predicted offspring SUD (psychopathology phenotype: OR=2.96,p<0.001; cognitive impairment: OR=1.33,p=0.04); in offspring, baseline psychopathology predicted SUD at follow-up assessments (OR=1.55,p=0.01). Results suggest that these candidate SUD phenotypes may be useful for genetic studies of SUD.Correspondence: Dr. Stephen V. Faraone, Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, 750 East Adams St., Syracuse, NY 13210; faraones@upstate.edu, 315-464-3113, (315) 464-3255 (fax). Contributors Stephen V. Faraone participated in study design and execution, planned the analyses, and wrote portions of the manuscript Joel J. Adamson performed data analyses and wrote portions of the manuscript Timothy E. Wilens participated in study design and execution and provided clinical comments on the manuscript Michael C. Monuteaux assisted with the statistical analysis. Participated in study design and execution and provided clinical comments on the manuscript Joseph Biederman participated in study design and execution and provided clinical comments on the manuscript Conflict of Interest Dr. Stephen Faraone receives/d research support from, is/has been a speaker for, or is/has been on the advisory board for the following companies: Eli Lilly & Company, McNeil Consumer & Specialty Pharmaceuticals, Shire US Inc., Noven Pharmaceuticals, Cephalon, National Institute of Mental Health (NIMH), National Institute of Child Health and Human Development (NICHHD), and National Institute of Neurological Disorders and Stroke (NINDS). Dr. Timothy Wilens receives/d research support from, is/has been a speaker for, or is/has been on the advisory board for the following Pharmaceutical Companies: Abbott Laboratories, OrthoMcNeil, Eli Lilly and Company, Novartis Pharmaceuticals, Shire Laboratories Inc. and National Institute on Drug Abuse (NIDA). Dr. Joseph Biederman receives/d research support from, is/has been a speaker for, or is/has been on the advisory board for the following Pharmaceutical Companies: Shire, Eli Lilly, Pfizer, McNeil, Ab...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Familial transmission of derived phenotypes for molecular genetic studies of substance use disorders

Faraone

Adamson

Wilens

et al. 2008

Drug and Alcohol Dependence

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“…Adler et al emphasized that the practice of prescribing a combination of medications is common in adult ADHD and is especially required in cases of partial response, dose-limiting side effects, preexisting or treatment-induced disorders and comorbid diagnoses (21). ADHD is particularly associated with significant lifetime psychiatric comorbidity (22). In the case of comorbid ADHD and MDD, the guidelines recommend the add-on of an antidepressant if the symptoms of depression persist after resolution of ADHD (20).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers

et al. 2016

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ABSTRACT-Purpose:To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers.Methods: An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period I (Reference), each volunteer received a single oral dose of 25 mg atomoxetine, whilst during Period II (Test), a combination of 25 mg atomoxetine and 300 mg bupropion was administered to all volunteers, after a pretreatment regimen with bupropion for 7 days. Next, after determining atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations, their pharmacokinetic parameters were calculated using a noncompartmental method and subsequently compared to determine any statistically significant differences between the two periods. Results: Bupropion intake influenced all the pharmacokinetic parameters of both atomoxetine and its metabolite. For atomoxetine, C max increased from 226±96.1 to 386±137 ng/mL and more importantly, AUC 0-∞ was significantly increased from 1580±1040 to 8060±4160 ng*h/mL, while the mean t 1/2 was prolonged after bupropion pretreatment. For 4-hydroxyatomoxetine-O-glucuronide, C max and AUC 0-∞ were decreased from 707±269 to 212±145 ng/mL and from 5750±1240 to 3860±1220 ng*h/mL, respectively. Conclusions: These results demonstrated that the effect of bupropion on CYP2D6 activity was responsible for an increased systemic exposure to atomoxetine (5.1-fold) and also for a decreased exposure to its main metabolite (1.5-fold). Additional studies are required in order to evaluate the clinical relevance of this pharmacokinetic drug interaction.

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“…These adults are often forgetful, have difficulties completing tasks, struggle with prioritization, and cannot self-monitor their behavior (Culpepper, 2006). These characteristics can lead to difficulties maintaining social and marital relationships (Gudjonsson et al, 2009) and poor educational outcomes (Biederman, 2004;McGough et al, 2005). In addition, ADHD has significant psychiatric comorbidities, such as depression, anxiety, and substance abuse (Biederman, 2004;McGough et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of α4β2 Agonist ABT-894 in Adults with ADHD

Bain

Robieson

Pritchett

et al. 2012

Neuropsychopharmacol

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Dysregulation of the neuronal nicotinic acetylcholine receptor (NNR) system has been implicated in attention-deficit/hyperactivity disorder (ADHD), and nicotinic agonists improve attention across preclinical species and humans. Hence, a randomized, double-blind, placebo-controlled, crossover study was designed to determine the safety and efficacy of a novel a4b2 NNR agonist (ABT-894 (3-(5,6-dichloro-pyridin-3-yl)-1(S),5 (S)-3,6-diazabicyclo[3.2.0]heptane)) in adults with ADHD. Participants (N ¼ 243) were randomized to one of four dose regimens of ABT-894 (1, 2, and 4 mg once daily (QD)) or 4 mg twice daily (BID) or the active comparator atomoxetine (40 mg BID) vs placebo for 28 days. Following a 2-week washout period, participants crossed over to the alternative treatment condition (active or placebo) for an additional 28 days. Primary efficacy was based on an investigator-rated Conners' Adult ADHD Rating Scale (CAARS:Inv) Total score at the end of each 4-week treatment period. Additional secondary outcome measures were assessed. A total of 238 patients were assessed for safety end points, 236 patients were included in the intent-to-treat data set, and 196 were included in the completers data set, which was the prespecified, primary data set for efficacy. Both the 4 mg BID ABT-894 and atomoxetine groups demonstrated significant improvement on the primary outcome compared with placebo. Several secondary outcome measures were also significantly improved with 4 mg BID ABT-894. Overall, ABT-894 was well tolerated at all dose levels. These results provide initial proof of concept for the use of a4b2 agonists in the treatment of adults with ADHD. Further investigation of ABT-894, including higher doses, is therefore warranted.

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Psychiatric Comorbidity in Adult Attention Deficit Hyperactivity Disorder: Findings From Multiplex Families

Abstract: Adult ADHD is associated with significant lifetime psychiatric comorbidity that is not explained by clinical referral bias.

Cited by 336 publications

References 29 publications

Familial transmission of derived phenotypes for molecular genetic studies of substance use disorders

Familial transmission of derived phenotypes for molecular genetic studies of substance use disorders

Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of α4β2 Agonist ABT-894 in Adults with ADHD

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