Physiological and psychological stress responses in adults with attention-deficit/hyperactivity disorder (ADHD)
Introduction
Although attention-deficit/hyperactivity disorder (ADHD) was initially conceptualized as a disorder of childhood and adolescence, it is acknowledged today that for many patients, the syndrome persists into adulthood. A recent large-scale epidemiological study carried out in 10 countries reported an average prevalence estimate for DSM-IV adult ADHD of 3.4% (range 1.2–7.3%) (Fayyad et al., 2007); other authors found prevalence rates of current adult ADHD of 2.9% (Faraone and Biederman, 2005) and 4.4% (Kessler et al., 2006) for the United States. As ADHD patients often suffer from serious educational, occupational and interpersonal role impairments, and negative consequences in various areas of their lives (see Weiss and Hechtman, 1993; Barkley, 1996; Wilens et al., 1998; Mannuzza and Klein, 2000) an improved understanding of the disorder's underlying mechanisms is of great importance, particularly as it may facilitate advancements in therapeutic intervention.
The three main symptom clusters of the disorder are inattention, hyperactivity, and impulsivity (American Psychiatric Association, 1994). The symptoms must emerge before the age of 7 years and cause significant impairments in more than one setting. The DSM-IV subdivides ADHD into a predominantly inattentive, a predominantly hyperactive-impulsive, and a combined diagnostic subtype. According to several theorists and researchers, poor behavioral or response inhibition is the central characteristic of ADHD (Schachar et al., 1993; Barkley, 1997a; Quay, 1997), and vast amount of supporting empirical evidence has been reported (Barkley, 1997b; Quay, 1997). In reference to Gray's (1987) theory of anxiety disorders, Quay, 1988, Quay, 1997 postulated an underreactive behavioral inhibition system (BIS) in individuals with ADHD symptoms. The BIS is monoaminergically mediated and activated by conditioned stimuli for punishment, nonreward and novelty, resulting in response inhibition, an enhanced focusing of attention to relevant environmental cues, and an increase in nonspecific arousal which leads to an elevated level of cortisol (Ryan, 1998) and heightened autonomic arousal (Rogeness et al., 1990). A potential dysfunction of the BIS in ADHD patients should thus be measurable not only via behavioral observations but also by examination of various physiological indicators of the stress response. In fact, a number of studies on children with ADHD reported abnormalities in function and reactivity of the hypothalamic–pituitary–adrenal (HPA) axis. Kaneko et al. (1993) found dysfunctions in diurnal cortisol release in ADHD children, compared to autistic children and healthy adult controls, as well as nonsuppression in the dexamethasone suppression test (DST) in 46.7% of the ADHD subjects. Children with ADHD who retained their diagnosis over 2 years showed blunted cortisol responses to mental stressors compared to children with a more transient form of the disorder (King et al., 1998). Kariyawasam et al. (2002) observed significantly reduced single-point salivary cortisol levels in children with ADHD and comorbid oppositional-defiant disorder (ODD), compared to healthy controls of similar age. In seeming contradiction to these results, Snoek et al. (2004) found similar cortisol levels in ADHD children and normal controls not only under baseline, but also under stressful conditions. However, most children in the ADHD group were on stimulant (methylphenidate) medication which may have altered the cortisol response (Kariyawasam et al., 2002).
Hong et al. (2003) found an association between HPA axis underreactivity and impulsivity in a sample of ADHD boys after a computerized Continuous Performance Test (CPT), although it should be noted that ADHD diagnoses were not made via structured clinical interviews in the study. In a survey by Schulz et al. (1997), the hypothesized inverse relationship between basal plasma cortisol levels and aggression in prepubertal boys with DSM-III-R ADHD was not confirmed. The authors did not test possible associations between cortisol and separate ADHD symptom clusters (inattention, impulsivity). Also, since no healthy control subjects were included in the study, it is unclear whether ADHD boys, as a group, showed diminished basal cortisol levels.
While all these studies examined ADHD children, so far no investigations have been conducted on HPA axis function or reactivity in adults with ADHD. Drawing on the results of King et al. (1998), it can be assumed that adult subjects with disorder persistence since childhood display an attenuated cortisol response to mental stress when compared to healthy controls.
With regard to autonomic arousal, several studies indicated abnormal patterns in children with ADHD symptoms. Typically, skin conductance (SCL), blood pressure (BP), HRV or HR levels were measured and comparisons drawn between children with different psychopathology or between ADHD children and healthy controls. Boyce and Quas (2001) found reduced autonomic arousal in the sympathetic and parasympathetic branch of the autonomic nervous system (ANS) in children with externalizing problems and attention deficits when responding to standard psychological stressors. In a study examining epinephrine excretion, an endocrine marker of the sympathetic nervous system, Hanna et al. (1996) discovered significantly (at least 40%) lower urinary epinephrine levels in response to a standardized intelligence test in ADHD boys than in normal controls. Electrodermal activity, which is an indicator of sympathetic nervous activity, was consistently attenuated in ADHD subjects compared to normal controls in a number of studies (Shibagaki et al., 1993; Zahn and Kruesi, 1993; Mangina et al., 2000; Beauchaine et al., 2001; O’Connell et al., 2004). In contrast, Van Lang et al. (2007) found comparable SCL, but lower HR reactivity to a stress task in ADHD children than in children with anxiety disorders. No group of normal controls was included in the study. Since HR levels are influenced by both sympathetic and parasympathetic activity, while SCL is determined by sympathetic modulation alone, the authors hypothesized a stronger parasympathetic than sympathetic activation during stress in children with ADHD than in children with anxiety disorders. However, no exclusively parasympathetic parameter was included in the study design. It is noteworthy that the expectation of an attenuated HR stress response in ADHD children is in line with Lacey (1967) and Lacey and Lacey, 1970, Lacey and Lacey, 1974, whose theoretical and empirical work relates changes in cardiovascular function with different modes of information processing. The authors found sensory intake of external stimuli to be associated with HR deceleration, whereas environmental rejection, a process of filtering out distracting stimuli and selectively focusing relevant cues to enhance cognitive performance, was related to HR acceleration. Changes in cardiovascular function may facilitate or impair cortical information processing. It seems plausible to expect less pronounced HR increases during psychosocial and mental stress in ADHD patients with symptoms of inattentiveness than in healthy individuals.
HRV is increasingly being used as a noninvasive tool to gain detailed insight into the balance between the sympathetic and the parasympathetic branch or division of the ANS. This is relevant as there is evidence indicating that this balance may be affected by various psychiatric conditions as well as by the presence of stressful stimuli (Berntson and Cacioppo, 2004). Behaviorally inhibited children have repeatedly been shown to be under enhanced sympathetic influence when exposed to stressful tasks (Kagan et al., 1987, Kagan et al., 1988). Börger et al. (1999) found a significantly greater 0.10-Hz component of the HRV in ADHD children than in healthy children during a CPT, designed to measure sustained attention. The 0.10-Hz component is parasympathetically determined and considered to be a psychophysiological index of effort allocation. In another study, preschool children with ADHD and ODD exhibited comparable parasympathetically influenced cardiac activity, but attenuated sympathetically influenced cardiac activity in comparison to normal controls during baseline conditions and a reward task (Crowell et al., 2006). Although the cited results on stress reactivity in ADHD patients may seem contradictory, it must be taken into account that neuroendocrine stress response patterns are known to be influenced by type of stressor (stimulus–response–specifity) and contextual factors of the experiment (Garralda et al., 1991; Zahn and Kruesi, 1993; Biondi and Picardi, 1999; Berntson and Cacioppo, 2004). Berntson and Cacioppo (2004) pointed out that laboratory tasks involving active cognitive processing and response, such as mental arithmetics or reaction time, lead to parasympathetic withdrawal and sympathetic activation, whereas more passive cognitive tasks (e.g. focused attention, response inhibition) are associated with either parasympathetic activation or coactivation of both ANS branches. In an extensive meta-analysis covering 208 original studies on HPA axis response to acute stressors in laboratory settings, Dickerson and Kemeny (2004) found public speaking/cognitive task combinations to elicit significantly greater cortisol changes than all other laboratory task types (cognitive tasks, public speaking/verbal interaction tasks, emotion induction procedures, or noise exposure). The empirical evidence supported the authors’ social self-preservation theory insofar as performance tasks characterized by social-evaluative threat and/or uncontrollability reliably elicited significant cortisol increases. Social-evaluative threat is present when a core aspect of the self-identity (e.g. intelligence, competence) is or could be negatively judged by other persons. Uncontrollability occurs in situations of forced failure where participants cannot succeed, despite their best efforts. The largest cortisol effects were found for performance tasks that contained both elements. It can be concluded that implementing an appropriate stressor is a crucial factor in laboratory stress experiments. An established standardized laboratory stress paradigm that includes both social-evaluative threat and uncontrollability, but has not yet been employed in adult ADHD patients, is the Trier Social Stress Test (TSST; Kirschbaum et al., 1993).
So far, few studies have investigated autonomic arousal in adults with ADHD. Hermens et al. (2004) reported reduced SCL in ADHD adults compared to normal controls under resting conditions. A detailed data analysis showed, however, that only ADHD females, but not males, were autonomically hypo-aroused (although males, but not females, showed enhanced global theta EEG activity). In a pilot study, Schubiner et al. (2006) explored ANS function in ADHD adults who were receiving stimulant medication. Compared with a normal control group, ADHD patients showed significantly higher resting HRs. However, since stimulants may increase HR, and the study did not include medication-free ADHD adults, the results cannot be easily interpreted. To date, not a single study examining HRV in ADHD adults in order to determinate the relative contributions of the two ANS branches under various conditions has been conducted.
To our knowledge, the psychological dimension of the stress response in ADHD adults has also not yet been investigated systematically. Nevertheless, it seems noteworthy that many authors mention an elevation in perceived or subjective stress in adult patients with ADHD, compared to healthy subjects (e.g. Krause et al., 1998; Resnick, 2000; Kordon and Kahl, 2004). Stress intolerance is even postulated as an additional characteristic of the disorder in the Wender Utah criteria for adult ADHD (Wender, 1995). Moreover, cognitive–behavioral treatments for adult patients with ADHD often include stress management techniques (e.g. Hesslinger et al., 2002). However, it is still uncertain whether the subjective stress experience in ADHD adults is significantly different from healthy subjects. Knowledge of associations between psychological and physiological stress measures in ADHD is also lacking.
The aim of the present study was to investigate physiological aspects of the stress response (salivary cortisol, HR, HRV) as well as the subjective stress experience in adult ADHD patients compared to healthy controls under laboratory conditions. In accordance with the majority of the cited theoretical and empirical work, it was hypothesized that ADHD adults and healthy controls would show comparable baseline levels of HPA and ANS activity, as well as similar subjective stress ratings. In response to a laboratory psychosocial stressor, however, an attenuated HPA and HR reaction and an elevated subjective stress experience were expected in the patient group. For HRV, significant differences between the ADHD and the control group were proposed regarding the relative influence of the two divisions of the ANS.
Section snippets
Design of study
To test the hypotheses that ADHD patients may exhibit altered reactivity in physiological and psychological stress parameters, a quasi-experimental research design was deemed appropriate, with a sample consisting of a clinical group of adult ADHD patients and a control group of healthy adults. Subjects were matched in regard to age, gender, and educational background.
Subjects
Eighteen adult subjects (10 females, 8 males) who met the DSM-IV diagnosis of ADHD and ranged in age from 20 to 57 years and 18
Pre-stress baselines
Means and S.D.s for age as well as baseline levels for physiological and self-report data for both study groups are presented in Table 1. There were no significant group differences in regard to mean age and pre-TSST subjective stress experience, ANS parameters, or cortisol levels.
Subjective stress experience
The nonparametric analysis with the F1_LD_F1 macro with group as between-subjects factor and time as within-subjects factor revealed a significant main effect of time, indicating significant increases in subjective
Discussion
The current study is the first report on psychological and physiological stress responses to a standardized psychosocial stressor (TSST) in adult ADHD patients and healthy controls. Special emphasis was placed on the careful selection of subjects for the ADHD group. Potential subjects underwent an elaborate stepwise diagnostic process prior to the laboratory session to ensure a high reliability of the ADHD diagnoses. The experimental results show considerably elevated subjective stress levels
Role of the funding sources
No funding was received for this study.
Conflict of interest
All authors declare that they have no conflicts of interest related to this work.
Acknowledgments
We would like to thank Christine Agel, Annika Kolle, Anna Peiser, and Irene Warnecke for help with the diagnostic procedures and collection of the data. We are also indebted to Uta Engelhardt for her invaluable assistance in the processing of the cortisol data, and to Lisette Morris for helpful comments on an earlier version of the manuscript. Finally, our gratitude goes to all the women and men who took the time to participate in our research.
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