FOCUS POINTS
• Attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are frequently co-occurring disorders in children and adults.
• There is a lack of investigations on the role of ODD and CD in adult patients with ADHD.
• The lifetime history of CD and ODD further increases the significant medical implications of persistent ADHD.
Introduction
Attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) constitute a group of frequently co-occurring externalizing psychiatric disorders.Reference Costello, Mustillo, Erkanli, Keeler and Angold1, Reference Connor, Steeber and McBurnett2 The concept of externalizing (as opposed to internalizing) behavioral dimension derives from a factor analysis of items on the Child Behavioral Checklist.Reference Achenbach and Edelbrock3 Several studies have reinforced the validity of this distinction in children and adults.Reference Kendler, Davis and Kessler4–Reference Hicks, Krueger and Iacono10 A possible common mechanism for the vulnerability to externalizing disorders is linked to deficits in response inhibition that predispose one not only to CD and ODD, but also to substance use disorders and an externalizing temperament profile.Reference Young, Friedman and Miyake11
Longitudinal studies in the last decade revealed that the presence of ODD and CD in children predict different psychiatric outcomes in young adults, supporting the utility and validity of these diagnoses in a lifetime perspective.Reference Young, Friedman and Miyake11–Reference Rowe, Costello and Angold16 However, the role of this group of disorders in adult psychiatry is still under discussion. For example, ODD and CD lack adult age-specific diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).17 A possible reason for these classification caveats is the relative scarcity of clinical studies that have explored the consequences of CD and ODD.
To our knowledge, only one study investigated the role of ODD and CD in referred adult patients with ADHD.Reference Harpold, Biederman and Gignac18 The authors verified that lifetime ODD (and also CD) was associated with increased risk for bipolar disorder, multiple anxiety disorders, and substance use disorders.Reference Harpold, Biederman and Gignac18
The aim of this study is to extend previous findings on a wide range of possible implications for clinical practice of a lifetime history of ODD and CD among adults with ADHD.
Methods
Subjects
The sample comprised 458 ADHD subjects consecutively referred to the adult ADHD outpatient clinic of Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, from September 2002 to October 2010. Subjects were Brazilians of European descent, being at least 18 years old and fulfilling diagnostic criteria for DSM-IV ADHD, both currently and in childhood, based on structured diagnostic interview and confirmed by clinical judgment. Exclusion criteria were the presence of significant neurological disease that might affect cognition, such as epilepsy, sequelae of cerebrovascular accidents and degenerative disorders, current or past history of psychosis, and estimated IQ ≤ 70.Reference Kaplan, Fein, Morris and Delis19 Among patients assessed for eligibility, 11% did not have ADHD and 9% fulfilled exclusion criteria. The project was approved by the Ethics Committee of the hospital, and all patients signed an informed consent.
Diagnostic procedures
The interviewers in this research were all psychiatrists extensively trained in application of all instruments of the research protocol. ADHD and ODD diagnoses were based on DSM-IV criteria using the respective sections of the Portuguese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children – Epidemiological Version (K-SADS-E).Reference Mercadante, Asbahar, Rosário, Ayres, Karman and Ferrari20 The K-SADS-E is a semistructured interview for children and adolescents aged 6 to 18 years that assesses current episodes and the severest episode in the past (lifetime) of DSM-IV psychiatric disorders in children.Reference Ambrosini21 Some descriptions of ADHD symptoms were adapted to make them suitable for adults. In addition, the criterion for onset of symptoms was adjusted to age 12 or earlier instead of age 7 or earlierReference Grevet, Bau and Salgado22 as reported by others, due to operational advantages and diagnostic reliability.Reference Applegate, Lahey and Hart23–Reference Kieling, Kieling and Rohde27 The evaluation of CD and Antisocial personality disorder (ASPD) was performed with the Brazilian Portuguese versionReference Amorim28 of the Mini-International Neuropsychiatric Interview (MINI).Reference Sheehan, Lecrubier and Sheehan29 The assessment of CD is a preliminary and mandatory step in the section of MINI for the diagnosis of ASPD. The diagnosis of CD is based on 6 questions addressing symptoms derived from DSM-IV.
Axis I psychiatric comorbidities were evaluated using the Structured Clinical Interview for DSM Disorders - Axis I Disorders (SCID-I).Reference First, Spitzer, Gibbon and Williams30 The severity of ADHD symptoms was assessed in both samples by the Swanson, Nolan, and Pelham scale—version IV (SNAP-IV).Reference Swanson31 This instrument includes items from DSM-IV criteria for ADHD and ODD. It is based on a 0 to 3 rating scale: Not at All = 0, Just a Little = 1, Quite a Bit = 2, and Very Much = 3. SNAP-IV scores are computed by summing scores in items from each dimension (inattention, hyperactivity/impulsivity, and oppositional defiant), and then dividing by the number of items in the dimension. We applied the validated Portuguese versionReference Mattos, Serra-Pinheiro, Rohde and Pinto32 with a few adaptations to the adult age. Barkley's current and childhood symptoms scales (self-report forms) address impairment due to current and past ADHD symptoms listed in the DSM-IV diagnostic criteria.Reference Barkley and Murphy33 The subset of the scale used in our study asks patients to report how often their symptoms interfere in 10 areas of life activities.
Temperament and character dimension scores were assessed by Cloninger's Temperament and Character Inventory (TCI), version 9,Reference Cloninger, Svrakic and Przybeck34 validated to Portuguese.Reference Fuentes, Tavares, Camargo and Gorenstein35 The TCI employs a list of 240 sentences to be read and rated as true or false. Each sentence is part of 1 out of 7 general scales, comprising 4 temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and 3 character dimensions (self-directedness, cooperativeness, and self-transcendence). The TCI is based on a psychobiological model of temperament and character and is strongly associated with dimensions and subtypes of ADHD in adults.Reference Salgado, Bau and Grevet36 The research protocol also included assessment of demographic and education data, medical history, and social problems.
Statistical analyses
Three groups of patients with ADHD were compared as follows: (1) ADHD without history of CD or ODD (n = 178), (2) ADHD + history of ODD (without CD) (n = 184), and (3) ADHD + history of CD (with or without ODD) (n = 96). Given the neurodevelopmental nature of CD and ODD,17 we considered as cases only those patients with history of childhood symptomatology.
Considering the possibility that the diagnosis of ASPD might entail the same information given by a history of CD and ODD in youth, we performed an additional analysis excluding patients with ASPD.
Categorical variables were analyzed by the Pearson chi-square test followed by post-hoc comparisons provided by Computer Programs for Epidemiologists (WINPEPI).Reference Abramson37 Continuous variables were analyzed by analysis of variance (ANOVA) and Bonferroni ost-hoc comparisons using the SPSS software. All tests were 2-tailed, and the significance level was set at 0.05.
Findings
Developmental history and comorbidities (Table 1)
Patients with CD presented an increased prevalence of fine motor skills problems, year repetition in school, and problems with authority figures in comparison with patients with ODD and patients with ADHD without ODD and CD.
Patients with ODD differ significantly (occupying an intermediate position) in relation to patients without ODD or CD, and in relation to patients with ADHD + CD, in problems with authority figures and school expulsion and/or suspension.
Regarding comorbidities, patients with CD had higher rates of bipolar and substance use disorders (including nicotine use) than patients with ADHD alone. Patients with ODD presented a tendency toward an intermediate position regarding the presence of bipolar disorder.
Severity, impairment, and TCI scores (Table 2)
Compared to patients with ADHD alone, individuals with CD had higher ADHD severity and impairment, higher levels of novelty seeking, and lower self-directedness and cooperativeness.
Patients with ODD also presented higher SNAP-IV hyperactivity scores, higher impairment scores, and lower cooperativeness scores than patients with ADHD alone. These patients presented intermediate scores in novelty seeking.
We repeated all analyses excluding patients with ASPD (data are available upon request). With the exception of substance use disorders, findings did not differ from those presented in Tables 1 and 2. When patients with ASPD were excluded from the CD group, there were no between-group differences in relation to substance use disorders.
Developmental history and comorbidities in adult patients with ADHD
*A = ADHD group; O = ADHD + ODD group; CD = ADHD + CD group.
Severity, impairment, and TCI scores in adult patients with ADHD
*A = ADHD group; O = ADHD + ODD group; CD = ADHD + CD group.
**Barkley's current (last 6 months) scale (self-report form).
Discussion
The results of this study suggest that lifetime CD and/or ODD are associated with a higher burden of psychopathology in adults with ADHD, reinforcing the validity of these diagnoses and justifying the routine evaluation of their past history in adult psychiatry. The presence of childhood or adolescent CD is associated with increased severity and impairment of ADHD, higher prevalence of comorbidities, and a more impulsive personality profile. ODD is also associated with ADHD severity and impairment. Our results fit into a response inhibition deficit model that ranges from neurodevelopmental deficits, various personality traits, and comorbid disorders.Reference Young, Stallings and Corley9, Reference Young, Friedman and Miyake11, Reference Dinn, Aycicegi and Harris38
The presence of ODD and CD in children with ADHD is associated with severe mental health and social problems.Reference Biederman, Petty and Dolan12, Reference Murphy, Barkley and Bush39 It is likely that adult psychiatrists are not trained to actively investigate symptoms of ODD and CD during childhood and adolescence in their patients, even in those with ADHD. Although the lack of appropriate training might explain this issue, two alternative reasons deserve investigation. First, adult psychiatrists might not have sufficient information about the relevance of assessing a childhood history of these conditions in their patients. So, our findings and those from other previous studiesReference Harpold, Biederman and Gignac18 are extremely important to familiarize adult psychiatrists with a more developmental perspective. Second, adult psychiatrists might think that a history of CD and ODD in youth is completely captured by the diagnosis of ASPD in adulthood. In other words, that the history of ODD/CD during youth would only impact on the adult life of their ADHD patients if the psychopathological trajectory ends in an adult diagnosis of ASPD. In fact, only 32 out of 96 patients with a history of CD during youth in our sample had an adult ASPD diagnosis. The analysis we performed that excluded these patients with ASPD showed that, with the exception of substance use disorders, results concerning the influence of CD and ODD did not differ. A history of childhood or adolescent CD and ODD is thus relevant in adult psychiatry, even among patients who do not fulfill criteria for ASPD. This information is even more relevant if we consider the fact that adult ADHD in clinical samples is strongly associated with psychiatric comorbidities.Reference Grevet, Bau and Salgado40
This study presents some limitations that should be considered. The psychiatric profile of ODD and CD patients without ADHD may be different from those ascertained in our ADHD outpatient clinic. Second, it is also important to consider that cross-sectional study designs are not appropriate to establish cause–effect relationships. However, our findings have the strength of being closer to the clinical practice than findings from population-based longitudinal studies. Third, our diagnosis of CD/ODD during childhood and adolescence was based in some but not all DSM-IV symptoms, and was gathered by retrospective self-report. Finally, despite the fact that our sample size is one of the largest ever reported in clinical-referred samples of ADHD, a larger sample size would have made secondary analyses feasible. For example, the small number of women with lifetime CD (n = 25) precluded the analysis of possible gender interactive effects. These are very important issues that demand future studies with significantly larger sample sizes.
Conclusion
The history of CD and ODD further increases the significant medical implications of persistent ADHD, especially for externalizing characteristics, such as comorbid disorders and ADHD severity. There is a need for a more developmental perspective in adult psychiatric research, stressing the inclusion of these evaluations.
Disclosures
Dr. Rohde was on the speakers’ bureau and/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis, and Shire in the last three years (less than U.S. $ 10,000 per year and reflecting less than 5% of his gross income per year). He also received travel awards (air tickets and hotel) for taking part of two child psychiatric meetings from Novartis and Janssen-Cilag. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last three years: Abbott, Bristol-Myers Squibb, Eli-Lilly, Janssen-Cilag, Novartis, and Shire. Dr. Belmonte-de-Abreu is on the speaker's bureau or is a consultant for Janssen-Cilag and Bristol-Myers Squibb. All other authors declare that they have no conflicts of interest.
