Attention-Deficit/Hyperactivity Disorder in adults. Clinical characteristics and pre- and perinatal risk factors

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is currently a prevalent diagnosis in child psychiatry, typically affecting 2-5 % of school-aged children world-wide. The recent and increasing awareness that ADHD may persist to adulthood for a considerable proportion of the affected children has created a need for more knowledge about ADHD as a lifespan disorder. Aims: The aims of the thesis were to: 1) assess occupational functioning among adults with ADHD; 2) explore the relationship between ADHD and mood disorders; 3) investigate the role of pregnancy- and birth related complications as possible risk factors for persistent ADHD; 4) study the effect of an impaired serotonin production in utero on the development of ADHD symptoms and related behaviour. Material and methods: The thesis is based on four separate articles (Paper I-IV). The first two papers are clinical studies based on questionnaires obtained from 414 and 510 adults with a clinical diagnosis of ADHD, respectively, and controls (n=359/417) from the general population. The third paper is an epidemiologic population-based study using data from the Medical Birth Registry of Norway (MBRN), in which we compared pre- and perinatal risk factors of a national cohort of 2123 adults with ADHD and the rest of the Norwegian adult population born in the same time period (n=1.17 million). The fourth study explores the possible causative role of reduced serotonin production in ADHD related symptoms and behaviour by studying the presence and effects of mutations in the tryptophan hydroxylase 1 gene (TPH1) in adult ADHD patients, their family members and controls. Results: In paper I we showed that only 24 % of adult ADHD patients (mean age 34.5 years) were currently in work, compared to 79 % of controls (mean age 29.9 years). Having been diagnosed and treated for ADHD in childhood was the strongest predictor for being in work as an adult, independently of symptom severity, psychiatric comorbidity, and current treatment (OR 3.2, p=0.014). In the second paper, 51 % of ADHD patients screened positive for a bipolar spectrum disorder (BSD) according to the Mood Disorder Questionnaire (MDQ), compared to 8.3 % of the controls. Patients screening positive for a BSD had lower occupational functioning and significantly more drug problems than patients with low levels of affective symptoms. In the epidemiological population-based study from the MBRN, we found that low birth weight, preterm birth, and low Apgar scores were associated with ADHD in adulthood, with the highest risk for the lowest measures. We also found that maternal epilepsy and infant oral cleft were associated with ADHD in the adult offspring. In the last study, sequencing of TPH1 in 646 adults (patients and controls) resulted in the identification of 7 different missense mutations, of which 6 resulted in reduced enzyme function in vitro compared to wild type TPH1. Family based analyses showed that offspring of mothers with TPH1 mutations had higher levels of ADHD related symptoms and behaviour, compared to offspring of fathers with such mutations or controls, independently of the individuals’ own TPH1 status. Conclusions: Adults with a clinical diagnosis of ADHD had an impaired occupational functioning and a high prevalence of comorbid psychiatric problems. Symptoms of affective disorders were frequent among adults with ADHD, and were associated with lower occupational functioning and more substance abuse. Patients who were diagnosed and treated for ADHD in childhood had a more favourable outcome in adult life compared to patients who were first diagnosed in adulthood. Factors indicating a suboptimal foetal development, such as being born extremely preterm or with very low birth weight, were associated with development of ADHD. Impaired maternal serotonin production in early embryonic life may be a causative pathway in the putative altered brain development, resulting in subsequent ADHD related symptoms and behaviours.