Adult Attention Deficit Hyperactivity Disorder. Beyond the Core Symptoms of the Diagnostic and Statistical Manual of Mental Disorders

Abstract

Background/Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent condition in both children (estimated prevalence of about 5%) and adults (estimated prevalence of about 3%). ADHD is characterized by impairing symptoms of inattention and hyperactivity/impulsivity. However, there are at least two caveats to this symptomatic description. First, as ADHD was initially considered a childhood disorder, these symptoms and their conceptualization may be more applicable to children than adults. Second, ADHD in children, adolescents and adults is comorbid in up to 75% of cases, and can also be understood as an underlying broad regulatory deficit, spanning multiple symptom domains. Thus, to understand and adequately address the needs of adult ADHD patients there is a need to go beyond the core symptoms of ADHD and investigate frequently associated and impairing symptom domains. Aims: The overall aim was to investigate symptom domains in adults with ADHD including and expanding upon the core symptoms described in the Diagnostic and Statistical Manual of Mental Disorders (DSM). In the three papers the thesis investigates 1) the psychometric properties and the clinical utility of self-reported childhood symptoms versus current symptoms using two frequently used symptom checklists for adult ADHD; 2) the prevalence and clinical correlates of insomnia in adult ADHD; and 3) the genetic components of aggressiveness in ADHD. Materials and Methods: This thesis is based on three separate papers. Paper I and II included 268 and 646 clinically diagnosed adult ADHD patients, respectively, as well as 202 and 908 population controls from the Medical Birth Registry of Norway, respectively. Paper III included a total of 1060 adult ADHD patients from three sites within an international multi-centre persistent ADHD collaboration (IMpACT): Germany, Norway, and Spain; and 750 adolescents with ADHD participating in the International Multicentre ADHD Genetics (IMAGE) study across Europe. In Paper I we compared the Adult ADHD Self-Report Scale (ASRS) with the Wender Utah Rating Scale (WURS), testing the discriminatory ability for detecting and separating clinical ADHD patients from population controls. We used Receiver Operating Characteristics Area Under the Curve (AUC), Diagnostic Odds Ratio (DOR) and Likelihood Ratio (LH) as these methods are independent of the disorder prevalence in the sample studied. Principal Component Analysis (PCA) was used to validate the checklists. In Paper II we used the Bergen Insomnia Scale (BIS) to measure insomnia and the Adult ADHD Self-Rating Scale (ASRS) to assess ADHD symptom domains. In Paper III we performed a Genome Wide Association (GWA) study of a childhood aggressiveness phenotype in the adult ADHD sample, and compared this with GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in the adolescent sample. Results: In Paper I we found that both symptom checklists had excellent screening properties, with the WURS having an AUC of .96, (95% CI: .95-.97) and the ASRS an AUC of .90, (95% CI: .89-.92). The WURS factors Learning and Attention Problems and Aggressiveness and Social Problems were found to be the strongest discriminants of ADHD. In Paper II we found that insomnia was far more frequent among adults with ADHD (66.8%) than in a representative control sample (28.8%) (P < 0.001). Insomnia was more common in adults with the combined subtype of ADHD than in those with the inattentive subtype (79.7% and 55.6%, respectively) (P = 0.003). For self-reported current ADHD symptoms, inattention was strongly correlated to insomnia. Patients currently using stimulant treatment for ADHD reported a lower total insomnia score compared to patients without medication (P < 0.05). In Paper III no single polymorphism reached genome-wide significance (P<5.00E- 08). However, we did identify a number of biologically interesting markers (our top hits were rs10826548 within a long noncoding RNA gene; closely followed by rs35974940 in the neurotrimin gene). As these markers possibly represent biological systems involved in childhood aggressiveness, they provide targets for further genetic explorations of aggressiveness across psychiatric disorders. Conclusions: The results in the present thesis suggest that we need to broaden our approach and scope when investigating and treating patients with ADHD. We need to move beyond the classic symptom domains of inattention, hyperactivity and impulsivity, and recognize that patients meeting criteria for the ADHD diagnosis tend to also have other impairing problems across different symptom domains. These domains, such as aggressiveness and insomnia, need to be addressed in order to adequately aid adult ADHD patients’ function in their daily life.