Screening for affective dysregulation in school-aged children: relationship with comprehensive measures of affective dysregulation and related mental disorders.

Affective dysregulation (AD) is characterized by irritability, severe temper outbursts, anger, and unpredictable mood swings, and is typically classified as a transdiagnostic entity. A reliable and valid measure is needed to adequately identify children at risk of AD. This study sought to validate a parent-rated screening questionnaire, which is part of the comprehensive Diagnostic Tool for Affective Dysregulation in Children (DADYS-Screen), by analyzing relationships with comprehensive measures of AD and related mental disorders in a community sample of children with and without AD. The sample comprised 1114 children aged 8-12 years and their parents. We used clinical, parent, and child ratings for our analyses. Across all raters, the DADYS-Screen showed large correlations with comprehensive measures of AD. As expected, correlations were stronger for measures of externalizing symptoms than for measures of internalizing symptoms. Moreover, we found negative associations with emotion regulation strategies and health-related quality of life. In receiver operating characteristic (ROC) analyses, the DADYS-Screen adequately identified children with AD and provided an optimal cut-off. We conclude that the DADYS-Screen appears to be a reliable and valid measure to identify school-aged children at risk of AD.

Impact of the COVID-19 pandemic on children with and without affective dysregulation and their families.

Analyzing COVID-19-related stress in children with affective dysregulation (AD) seems especially interesting, as these children typically show heightened reactivity to potential stressors and an increased use of maladaptive emotion regulation strategies. Children in out-of-home care often show similar characteristics to those with AD. Since COVID-19 has led to interruptions in psychotherapy for children with mental health problems and to potentially reduced resources to implement treatment strategies in daily life in families or in out-of-home care, these children might show a particularly strong increase in stress levels. In this study, 512 families of children without AD and 269 families of children with AD reported on COVID-19-related stress. The sample comprised screened community, clinical, and out-of-home care samples. Sociodemographic factors, characteristics of child and caregiver before the pandemic, and perceived change in external conditions due to the pandemic were examined as potential risk or protective factors. Interestingly, only small differences emerged between families of children with and without AD or between subsamples: families of children with AD and families in out-of-home care were affected slightly more, but in few domains. Improvements and deteriorations in treatment-related effects balanced each other out. Overall, the most stable and strongest risk factor for COVID-19-related stress was perceived negative change in external conditions-particularly family conditions and leisure options. Additionally, caregiver characteristics emerged as risk factors across most models. Actions to support families during the pandemic should, therefore, facilitate external conditions and focus on caregiver characteristic to reduce familial COVID-19-related stress. Trial registration: German Clinical Trials Register (DRKS), ADOPT Online: DRKS00014963 registered 27 June 2018, ADOPT Treatment: DRKS00013317 registered 27 September 2018, ADOPT Institution: DRKS00014581 registered 04 July 2018.

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.

Impaired Odor Perception in Autism Spectrum Disorder Is Associated with Decreased Activity in Olfactory Cortex.

Autism Spectrum Disorders (ASDs) are characterized by atypical sensory functioning in the visual, tactile, and auditory systems. Although less explored, olfactory changes have been reported in ASD patients. To explore these changes on a neural level, 18 adults with ASD and 18 healthy neurotypical controls were examined in a 2-phase study. Participants were first tested for odor threshold and odor identification. Then, (i) structural magnetic resonance (MR) images of the olfactory bulb were acquired, and (ii) a functional MR imaging olfaction study was conducted. ASD patients exhibited decreased function for odor thresholds and odor identification; this was accompanied by a relatively decreased activation in the piriform cortex. In conclusion, these findings suggest, that the known alterations in olfaction in ASD are rooted in the primary olfactory cortex.

Diagnostic accuracy of the ADOS and ADOS-2 in clinical practice.

The Autism Diagnostic Observation Schedule is a semi-structured, standardized assessment tool for individuals with suspected autism spectrum disorders (ASD) and is deemed to be part of the gold standard for diagnostic evaluation. Good diagnostic accuracy and interpersonal objectivity have been demonstrated for the ADOS in research setting. The question arises whether this is also true for daily clinical practice and whether diagnostic accuracy depends on specialized experience in the diagnostic evaluation. The present study explores the diagnostic accuracy of the original and the revised version of the ADOS for Modules 1 through 4. Thus, seven cases of ADOS executions were recorded and coded by a group of experts of specialized outpatient clinics for ASD. In an extensive consensus process, including video analysis of every minute of the ADOS executions, a "gold standard" coding for every case was defined. The videos of the ADOS administration were presented to a large group of clinicians (from daily clinical routine care) and their codings (n = 189) were obtained and analysed. Variance of coding and congruence with the expert coding were determined. High variance was found in the codings. The accuracy of the coding depends on the experience of the coder with the ADOS as well as on characteristics of the cases and the quality of the administration of the ADOS. Specialization in the diagnostic of ASD has to be claimed. Specialized outpatient clinics for ASD are required which guarantee a qualified diagnostic/differential diagnostic and case management with the aim of demand-oriented supply of individual cases.

Subliminal and supraliminal processing of reward-related stimuli in anorexia nervosa.

BACKGROUND: Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC). METHODS: fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group × stimulation condition × stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis. RESULTS: AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity. CONCLUSION: Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.

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.

ADHD patients fail to maintain task goals in face of subliminally and consciously induced cognitive conflicts.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) patients have been reported to display deficits in action control processes. While it is known that subliminally and consciously induced conflicts interact and conjointly modulate action control in healthy subjects, this has never been investigated for ADHD. METHOD: We investigated the (potential) interaction of subliminally and consciously triggered response conflicts in children with ADHD and matched healthy controls using neuropsychological methods (event-related potentials; ERPs) to identify the involved cognitive sub-processes. RESULTS: Unlike healthy controls, ADHD patients showed no interaction of subliminally and consciously triggered response conflicts. Instead, they only showed additive effects as their behavioural performance (accuracy) was equally impaired by each conflict and they showed no signs of task-goal shielding even in cases of low conflict load. Of note, this difference between ADHD and controls was not rooted in early bottom-up attentional stimulus processing as reflected by the P1 and N1 ERPs. Instead, ADHD showed either no or reversed modulations of conflict-related processes and response selection as reflected by the N2 and P3 ERPs. CONCLUSION: There are fundamental differences in the architecture of cognitive control which might be of use for future diagnostic procedures. Unlike healthy controls, ADHD patients do not seem to be endowed with a threshold which allows them to maintain high behavioural performance in the face of low conflict load. ADHD patients seem to lack sufficient top-down attentional resources to maintain correct response selection in the face of conflicts by shielding the response selection process from response tendencies evoked by any kind of distractor.

Effects of multisensory integration processes on response inhibition in adolescent autism spectrum disorder.

BACKGROUND: In everyday life it is often required to integrate multisensory input to successfully conduct response inhibition (RI) and thus major executive control processes. Both RI and multisensory processes have been suggested to be altered in autism spectrum disorder (ASD). It is, however, unclear which neurophysiological processes relate to changes in RI in ASD and in how far these processes are affected by possible multisensory integration deficits in ASD. METHOD: Combining high-density EEG recordings with source localization analyses, we examined a group of adolescent ASD patients (n = 20) and healthy controls (n = 20) using a novel RI task. RESULTS: Compared to controls, RI processes are generally compromised in adolescent ASD. This aggravation of RI processes is modulated by the content of multisensory information. The neurophysiological data suggest that deficits in ASD emerge in attentional selection and resource allocation processes related to occipito-parietal and middle frontal regions. Most importantly, conflict monitoring subprocesses during RI were specifically modulated by content of multisensory information in the superior frontal gyrus. CONCLUSIONS: RI processes are overstrained in adolescent ASD, especially when conflicting multisensory information has to be integrated to perform RI. It seems that the content of multisensory input is important to consider in ASD and its effects on cognitive control processes.

Specific cognitive-neurophysiological processes predict impulsivity in the childhood attention-deficit/hyperactivity disorder combined subtype.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders in childhood. Besides inattention and hyperactivity, impulsivity is the third core symptom leading to diverse and serious problems. However, the neuronal mechanisms underlying impulsivity in ADHD are still not fully understood. This is all the more the case when patients with the ADHD combined subtype (ADHD-C) are considered who are characterized by both symptoms of inattention and hyperactivity/impulsivity. METHOD: Combining high-density electroencephalography (EEG) recordings with source localization analyses, we examined what information processing stages are dysfunctional in ADHD-C (n = 20) compared with controls (n = 18). RESULTS: Patients with ADHD-C made more impulsive errors in a Go/No-go task than healthy controls. Neurophysiologically, different subprocesses from perceptual gating to attentional selection, resource allocation and response selection processes are altered in this patient group. Perceptual gating, stimulus-driven attention selection and resource allocation processes were more pronounced in ADHD-C, are related to activation differences in parieto-occipital networks and suggest attentional filtering deficits. However, only response selection processes, associated with medial prefrontal networks, predicted impulsive errors in ADHD-C. CONCLUSIONS: Although the clinical picture of ADHD-C is complex and a multitude of processing steps are altered, only a subset of processes seems to directly modulate impulsive behaviour. The present findings improve the understanding of mechanisms underlying impulsivity in patients with ADHD-C and might help to refine treatment algorithms focusing on impulsivity.

Temporal delay discounting in acutely ill and weight-recovered patients with anorexia nervosa.

BACKGROUND: Patients with anorexia nervosa (AN) are characterized by a very low body weight but readily give up immediate rewards (food) for long-term goals (slim figure), which might indicate an unusual level of self-control. This everyday clinical observation may be quantifiable in the framework of the anticipation-discounting dilemma. METHOD: Using a cross-sectional design, this study compared the capacity to delay reward in 34 patients suffering from acute AN (acAN), 33 weight-recovered AN patients (recAN) and 54 healthy controls. We also used a longitudinal study to reassess 21 acAN patients after short-term weight restoration. A validated intertemporal choice task and a hyperbolic model were used to estimate temporal discounting rates. RESULTS: Confirming the validity of the task used, decreased delay discounting was associated with age and low self-reported impulsivity. However, no group differences in key measures of temporal discounting of monetary rewards were found. CONCLUSIONS: Increased cognitive control, which has been suggested as a key characteristic of AN, does not seem to extend the capacity to wait for delayed monetary rewards. Differences between our study and the only previous study reporting decreased delay discounting in adult AN patients may be explained by the different age range and chronicity of acute patients, but the fact that weight recovery was not associated with changes in discount rates suggests that discounting behavior is not a trait marker in AN. Future studies using paradigms with disorder-specific stimuli may help to clarify the role of delay discounting in AN.

Relationships between platelet MAO-B activity and personality styles in acute and weight-recovered young patients with anorexia nervosa.

OBJECTIVE: Previous studies have shown relationships between personality styles and markers of serotonergic functioning, but data on patients with anorexia nervosa (AN) are scarce. METHODS: The personality styles and disorder inventory was administered to 47 acute patients with anorexia nervosa (acAN), 27 weight-recovered patients (recAN) and 72 healthy controls (HC) aged between 14 and 21 years. Platelet monoamine oxidase (MAO-B) activity was assayed with [14C]-ß-phenylethylamine as substrate. RESULTS: AcAN had significant elevated scores on 9 of the 14 personality style subscales when compared to HC, whereas recAN were largely normal. Platelet MAO-B activity and "ambitious/narcissistic" scores correlated negatively in acAN. In recAN we found positive correlations between MAO-B and personality subscores. CONCLUSIONS: The inverse relationship between a cluster B personality style and MAO-B activity in acAN is in accordance with studies in other patient populations. In contrast, positive associations between problematic personality styles and MAO-B activity in recAN combined with the overall decreased MAO-B activity in this group adds to the existing evidence suggesting a general dysfunction of the serotonergic system as a trait marker for AN.

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.

Tic disorders: administrative prevalence and co-occurrence with attention-deficit/hyperactivity disorder in a German community sample.

Coexistence of tics and attention-deficit/hyperactivity disorder (ADHD) has important clinical and scientific implications. Existing data on the co-occurrence of tic disorders, Tourette Syndrome (TS), and ADHD are largely derived from small-scale studies in selected samples and therefore heterogeneous. The Nordbaden project captures the complete outpatient claims data of more than 2.2 million persons, representing 82% of the regional population in 2003. Based upon the number of diagnosed cases of tic disorders, TS, and ADHD, we determined 12-months administrative prevalence rates as well as rates of co-occurrence. Both tic disorders and ADHD were diagnosed most often in the age group 7-12 years (any tic disorder: 0.8%; ADHD: 5.0%). With increasing age, the administrative prevalence difference in favor of males disappeared, with tic disorders being somewhat more frequently reported in females than males in the age groups above 30 years. The highest rate of ADHD co-occurring with tic disorders was found in adolescents (age 13-18 years, 15.1%). Tic disorders were observed in 2.3% of patients with ADHD. Administrative prevalence rates of tic disorders and TS were substantially lower compared to rates found in community-based epidemiological studies, suggesting that a large number of cases remain undetected and untreated under present conditions of routine outpatient care.

Is atopic disease a risk factor for attention-deficit/hyperactivity disorder? A systematic review.

The increase in prevalence and burden of atopic diseases, i.e. eczema, rhinitis, and asthma over the past decades was paralleled by a worldwide increase in attention-deficit/hyperactivity disorder (ADHD) diagnoses. We systematically reviewed epidemiologic studies investigating the relationship between atopic diseases and ADHD. Electronic literature search in PubMed and PsycINFO (until 02/2010) supplemented by handsearch yielded 20 relevant studies totaling 170,175 individuals. Relevant data were abstracted independently by two reviewers. Six studies consistently reported a positive association between eczema and ADHD with one study suggesting effect modification by sleeping problems. Twelve studies consistently found a positive association between asthma and ADHD, which, however, appeared to be at least partly explained (confounded) by concurrent or previous eczema. Rhinitis and serum-IgE level were not related to ADHD symptomatology. We conclude that not atopic disease in general, but rather that eczema appears to be independently related to ADHD. Conclusions about temporality and whether the observed association constitutes a causal relationship are impossible, as most studies were cross-sectional (n = 14; 70%) or case-control studies without incident exposure measurement (n = 5; 25%). Another methodological concern is that the criteria to define atopic disease and ADHD were inadequate in most studies. A failure to adjust for confounders in the majority of studies was an additional limitation so that meta-analysis was not indicated. Future interdisciplinary high-quality prospective research is needed to better understand the mechanisms underlying the relationship between eczema and ADHD and to eventually establish targeted preventive and treatment strategies.

Methylphenidate normalizes elevated dopamine transporter densities in an animal model of the attention-deficit/hyperactivity disorder combined type, but not to the same extent in one of the attention-deficit/hyperactivity disorder inattentive type.

The spontaneously hypertensive rat (SHR/NCrl) is a validated model of attention-deficit/hyperactivity disorder (ADHD) combined subtype, whereas a recently identified substrain of the Wistar Kyoto rat (WKY/NCrl) is a model of ADHD inattentive subtype. In this study, we first examined the expression of genes involved in dopamine signaling and metabolism in the dorsal striatum and ventral mesencephalon of these two rat strains, as well as three reference control strains (WKY/NHsd, WK/HanTac, and SD/NTac) using quantitative real time RT-PCR. Next, striatal dopamine transporter (DAT) density was determined by ligand binding assay in the two ADHD-like strains at different developmental stages and after methylphenidate treatment. In adult rats, the mRNA expression of DAT and tyrosine hydroxylase was elevated in SHR/NCrl and WKY/NCrl rats compared to control strains, with differences between SHR/NCrl and WKY/NCrl rats also evident. During normal development, changes of striatal DAT densities occurred in both strains with lower densities in WKY/NCrl compared to SHR/NCrl after day 25. Two-weeks methylphenidate treatment during different developmental stages was associated with decreased striatal DAT density in both rat strains compared to the non-treated rats with more pronounced effects followed prepubertal treatment. These results suggest differences in the pathophysiology of the combined versus the predominantly inattentive animal model of ADHD. Finally, treatment with methylphenidate might reduce elevated DAT levels more effectively in the combined subtype especially when applied before puberty.

Voluntary motor drive: possible reduction in Tourette syndrome.

Electrophysiologically, Tourette syndrome (TS) is characterized by shortened cortical silent period (CSP), reflecting decreased motor inhibition. However, voluntary versus involuntary aspects of inhibitory functions in TS are not well understood. Hence, investigating voluntary motor drive (VMD) could help to elucidate this issue. A group of 14 healthy adolescents was compared with subjects of same age suffering from TS with (N = 6) and without (N = 6) presence of distal tics. Basic resting and active motor thresholds (RMT and AMT, respectively) as well as suprathreshold transcranial magnetic stimulation-conditioned RMT and AMT were determined during the CSP. The difference between AMT and RMT was considered as VMD quantum. No group-differences were found in RMT or AMT. Subjects with distal tics showed reduced VMD compared to healthy controls while patients without distal tics did not differ from controls. In the second half of CSP, patients with distal tics showed also diminished VMD compared to tic-patients without distal tics. The findings support the notion, that TS shows possible reduction of VMD and is associated with central motor threshold alterations confined to the very motor networks related to the tics observed.

Color perception deficits in co-existing attention-deficit/hyperactivity disorder and chronic tic disorders.

Preliminary findings suggest that color perception, particularly of blue-yellow stimuli, is impaired in attention-deficit/hyperactivity disorder (ADHD) as well as in chronic tic disorders (CTD). However, these findings have been not replicated and it is unclear what these deficits mean for the comorbidity of ADHD + CTD. Four groups (ADHD, CTD, ADHD + CTD, controls) of children with similar age, IQ and gender distribution were investigated with the Farnsworth-Munsell 100 Hue Test (FMT) and the Stroop-Color-Word Task using a factorial design. Color perception deficits, as indexed by the FMT, were found for both main factors (ADHD and CTD), but there were no interaction effects. A preponderance of deficits on the blue-yellow compared to the red-green axis was detected for ADHD. In the Stroop task only the 'pure' ADHD group showed impairments in interference control and other parameters of Stroop performance. No significant correlations between any FMT parameter and color naming in the Stroop task were found. Basic color perception deficits in both ADHD and CTD could be found. Beyond that, it could be shown that these deficits are additive in the case of comorbidity (ADHD + CTD). Performance deficits on the Stroop task were present only in the 'pure' ADHD group. Hence, the latter may be compensated in the comorbid group by good prefrontal capabilities of CTD. The influence of color perception deficits on Stroop task performance might be negligible.