Altered hypothalamus-pituitary-adrenal axis function: A relevant factor in the comorbidity of atopic eczema and attention deficit/hyperactivity disorder?

Epidemiological data show a significant association between childhood atopic eczema (AE) and an increased risk to develop attention deficit/hyperactivity disorder (ADHD). However, the underlying mechanisms of the comorbidity of AE and ADHD are mostly unknown. We investigated whether alterations of hypothalamus-pituitary-adrenal (HPA) axis function represent a shared feature of AE and ADHD potentiating AE-ADHD comorbidity. Children aged 6-12 years with AE, ADHD, or comorbid AE + ADHD and healthy control (HC) children were examined cross-sectionally (N = 145). To evaluate HPA axis function, salivary cortisol in response to psychosocial stress (Trier Social Stress Test for Children, TSST-C), after awakening (cortisol awakening response, CAR), and throughout the day (short diurnal profile) and hair cortisol capturing long-term HPA axis activity were assessed. Quantile regression analyses showed an attenuated cortisol response (% maximum change) to the TSST-C in children with ADHD compared to HC. A diminished cortisol response to acute stress was also observed in the comorbid AE + ADHD group, in which the reduction was numerically even more pronounced. Contrary to our previous findings, no alteration of the cortisol response to the TSST-C was observed in children with AE. However, in children with AE, increased ADHD-like behavior (i.e., inattention, impulsivity, and overall ADHD symptom severity) was associated with a reduced HPA axis response to acute stress. No such associations were observed in children without AE. Groups did not differ in CAR, short diurnal profile, and hair cortisol. These findings underscore the potential relevance of HPA axis function in the pathophysiology of AE and ADHD with emphasis on stress reactivity. Additional studies are required to further explore the separate and joint role of the HPA axis in the pathophysiology of AE and ADHD.

Increased attention-deficit/hyperactivity symptoms in atopic dermatitis are associated with history of antihistamine use.

BACKGROUND: Epidemiologic evidence indicates a relevant association between atopic dermatitis (AD) and attention-deficit/hyperactivity disorder (ADHD). Underlying mechanisms and ways to best identify subgroups of AD patients at risk for ADHD are poorly understood. AIMS OF THE STUDY: To compare sociodemographic, clinical and psychosocial characteristics of children with AD, ADHD, comorbid AD/ADHD and age-matched healthy controls and to investigate aspects of AD related to ADHD symptoms. METHODS: Applying a factorial design, we investigated 4 groups of children aged 6-12 years: AD-only (ie, without ADHD), ADHD-only (ie, without AD), AD + ADHD and healthy controls (HC; ie, no AD/no ADHD). Using validated instruments, ADHD symptoms and other behavioural problems, quality of life, parenting stress and sleeping problems were compared between groups. In children with AD-only, clinical signs (objective SCORAD), symptoms (POEM, VAS pruritus, VAS sleeping problems) and previous treatment of AD were assessed to investigate disease patterns related to ADHD symptoms. RESULTS: Compared to HC (n = 47), children with AD-only (n = 42), ADHD-only (n = 34) and comorbid AD + ADHD (n = 31) had significantly increased behavioural problems and decreased quality of life. Children with AD-only had significantly higher levels of ADHD symptoms than HC. In children with AD-only, previous use of antihistamines was significantly associated with increased ADHD symptoms (OR 1.88; 95% CI 1.04-3.39). Current clinical signs and AD symptoms were unrelated to the level of ADHD symptoms. CONCLUSIONS: Even if the clinical diagnosis of ADHD is excluded, children with AD show increased levels of ADHD symptoms. Further investigations need to determine whether early antihistamine exposure is a major risk factor for ADHD or a surrogate for previous AD severity and/or associated sleeping problems.

Memory and multitasking performance during acute allergic inflammation in seasonal allergic rhinitis.

BACKGROUND: In previous research, patients with seasonal allergic rhinitis (SAR) showed poorer school and work performance during periods of acute allergic inflammation, supporting the idea of an impact of SAR on cognitive functions. However, the specific cognitive domains particularly vulnerable to inflammatory processes are unclear. OBJECTIVE: In this study, the influence of SAR on memory and multitasking performance, as two potentially vulnerable cognitive domains essential in everyday life functioning, was investigated in patients with SAR. METHODS: Non-medicated patients with SAR (n = 41) and healthy non-allergic controls (n = 42) performed a dual-task paradigm and a verbal learning and memory test during and out of symptomatic allergy periods (pollen vs. non-pollen season). Disease-related factors (e.g. symptom severity, duration of symptoms, duration of disease) and allergy-related quality of life were evaluated as potential influences of cognitive performance. RESULTS: During the symptomatic allergy period, patients showed (1) poorer performance in word list-based learning (P = 0.028) and (2) a general slowing in processing speed (P < 0.001) and a shift in processing strategy (P < 0.001) in multitasking. Yet, typical parameters indicating specific multitasking costs were not affected. A significant negative association was found between learning performance and duration of disease (r = -0.451, P = 0.004), whereas symptom severity (r = 0.326; P = 0.037) and quality of life (r = 0.379; P = 0.015) were positively associated with multitasking strategy. CONCLUSIONS: Our findings suggest that SAR has a differentiated and complex impact on cognitive functions, which should be considered in the management of SAR symptoms. They also call attention to the importance of selecting sensitive measures and carefully interpreting cognitive outcomes.

Altered performance in attention tasks in patients with seasonal allergic rhinitis: seasonal dependency and association with disease characteristics.

BACKGROUND: Seasonal allergic rhinitis (SAR) is a chronic disease affecting about 23% of the European population with increasing prevalence rates. Beside classical symptoms (i.e., sneezing, nasal congestion), patients frequently complain about subjective impairments in cognitive functioning during periods of acute allergic inflammation. However, objective evidence for such deficits or the role of potential modulators and underlying mechanisms is limited. The present study aimed to investigate the effect of SAR on attention-related cognitive processes. In addition, relationships between attention performance, sleep and mood disturbances as well as specific disease characteristics as potential modulators of this link were explored. METHOD: SAR patients (n = 41) and non-allergic healthy controls (n = 42) completed a set of attention tasks during a symptomatic allergy period and during a non-symptomatic period. Influences of sleep, mood, total immunoglobulin E (IgE) levels and individual allergy characteristics on cognitive performance were evaluated. RESULTS: Compared to healthy controls, SAR patients had a slower processing speed during both symptomatic and non-symptomatic allergy periods. Additionally, they showed a more flexible adjustment in attention control, which may serve as a compensatory strategy. Reduction in processing speed was positively associated with total IgE levels whereas flexible adjustment of attention was linked with anxious mood. No association was found between SAR-related attention deficits and allergy characteristics or sleep. CONCLUSIONS: SAR represents a state that is crucially linked to impairments in information processing and changes in attentional control adjustments. These cognitive alterations are more likely to be influenced by mood and basal inflammatory processes than sleep impairments or subjective symptom severity.

Psychoendocrine and psychoneuroimmunological mechanisms in the comorbidity of atopic eczema and attention deficit/hyperactivity disorder.

Epidemiological data indicate that atopic eczema (AE) in infancy significantly increases the risk for attention deficit/hyperactivity disorder (ADHD) in later life. The underlying pathophysiological mechanisms of this comorbidity are unknown. We propose that the release of inflammatory cytokines caused by the allergic inflammation and/or elevated levels of psychological stress as a result of the chronic disease interfere with the maturation of prefrontal cortex regions and neurotransmitter systems involved ADHD pathology. Alternatively, increased stress levels in ADHD patients may trigger AE via neuroimmunological mechanisms. In a third model, AE and ADHD may be viewed as two separate disorders with one or more shared risk factors (e.g., genetics, prenatal stress) that increase the susceptibility for both disorders leading to the co-occurrence of AE and ADHD. Future investigation of these three models may lead to a better understanding of the mechanisms underlying the observed comorbidity between AE and ADHD and further, to targeted interdisciplinary primary prevention and treatment strategies.