Long-term cortisol secretion in attention deficit hyperactivity disorder: roles of sex, comorbidity, and symptom presentation.

Low activity of the hypothalamic-pituitary-adrenal axis (HPAA) has been found in children with attention deficit hyperactivity disorder (ADHD). The condition may be related to the reduced attention regulation capacity and/or to comorbid oppositional defiant or conduct disorder (ODD/CD). Sex differences are probable but not sufficiently studied. We analyzed the HPAA activity and sympathetic nervous system reactivity (SR) in children with ADHD while accounting for ADHD symptom presentation, comorbidity, and sex differences. The sample comprised 205 children, 98 (61 boys, 37 girls) with ADHD and 107 (48 boys, 59 girls) healthy controls. DSM-5 phenotypic symptom presentation and comorbid ODD/CD were assessed using clinical interviews. Hair cortisol concentration (HCC) was used to assess the long-term, cumulative activity of the HPAA. SR was assessed via skin conductance response (SCR). For control purposes, comorbid internalizing symptoms and indicators of adverse childhood experiences (ACE) were assessed. Children were medication naive. Boys presenting with predominantly inattentive symptoms (ADHD-I) showed lower HCC than healthy boys. Girls presenting with combined symptoms (ADHD-C) showed higher HCC than did healthy girls (p's < 0.05, sex-by-group interaction, F (2,194) = 4.09, p = 0.018). Boys with ADHD plus ODD/CD showed a blunted SR (p < 0.001, sex-by-group interaction, F (2,172) = 3.08, p = 0.048). Adjustment for ACE indicators led to non-significant differences in HCC but did not affect differences in SR. HCC constitutes an easily assessable, reliable, and valid marker of phenotypic ADHD-related features (i.e. symptom presentation and comorbidity). It indicates more homogenous subgroups of ADHD and might point to specifically involved pathophysiological processes.

Hair brain-derived neurotrophic factor (BDNF) as predictor of developing psychopathological symptoms in childhood.

BACKGROUND: Dysregulation in the expression of neurotrophins is implicated in the pathophysiology of several mental disorders. Peripheral brain-derived neurotrophic factor (BDNF) can be measured in hair and might represent a marker of adequate neuroplasticity regulation. In early developmental periods, neuroplasticity regulation might be particularly important, but BDNF markers have not yet been analyzed in this regard. We used the hair-BDNF concentration (HBC) to investigate the prediction of emerging symptoms of anxiety/depressive and attention-deficit hyperactivity disorder (ADHD) in the developmentally crucial period from preschool to school age. METHODS: 117 children (58 girls, 59 boys) participated in a longitudinal study at the ages of 4-5 (T1) and 8 (T2) years. At T1, HBC was measured in a 3 cm hair segment. At T1 and T2, symptom domains were assessed using a multi-method (clinical interview, questionnaire) and multi-informant approach. RESULTS: T1 HBC was significantly negatively associated with T1 anxiety/depressive symptoms (r = -0.27) and predicted T2 anxiety disorder symptoms (r = -0.34) after controlling for the T1 symptoms. T1 HBC also predicted T2 depressive disorder symptoms (r = -0.18) but was not associated with ADHD symptom development. LIMITATIONS: BDNF hair analysis is a new method with a not yet large number of studies on methodological issues. Our study adds evidence to the validity of the method. CONCLUSIONS: Prediction of anxiety/depressive symptom development by HBC was shown. As this study was the first to use HBC in this context, cross-validation is necessary and worthwhile. HBC might prove to constitute a useful, non-invasive early marker of risk for anxiety/depressive disorders in childhood.

Increased hair cortisol in mothers of children with ADHD symptoms and psychosocial adversity background.

Parents of children with attention deficit hyperactivity disorder (ADHD) have shown high perceived parenting stress. Hence, physiological adjustment processes, involving the hypothalamic-pituitary-adrenal axis, seem possible. We hypothesized that (1) ADHD symptoms of the child predict an increase of maternal hair cortisol concentration (HCC), and (2) presence of psychosocial adversity amplifies the prediction. We analyzed a preschool-aged sample using a longitudinal design (T1, at the children's age of 4 years; T2, 12 months later). 128 mothers and their children participated in the study. To determine HCC of the previous 3 months, the first scalp-near 3 cm hair segment was used. ADHD symptoms of the child were measured using teacher- and parent-report questionnaires and a clinical interview with the mother. The T1 teacher-reported ADHD symptoms score of the child was significantly positively associated with the mother`s T1 and T2 HCC score. In families with high psychosocial adversity, the prediction of an increase in maternal HCC by the teacher-reported ADHD symptoms of child was significantly stronger than in low-adversity families. In presence of psychosocial family adversity, ADHD symptoms of the child predicted an increase in the mother's HCC. As a continuously high cortisol level implicates health risks and might in turn affect parenting resources, the identifying of caregivers at risk through biological markers of stress could be helpful for planning targeted interventions. As our study is the first on this issue, cross-validation is needed.

Reward-Related Dysfunctions in Children Developing Attention Deficit Hyperactivity Disorder-Roles of Oppositional and Callous-Unemotional Symptoms.

Objectives: Neurocognitive functions might indicate specific pathways in developing attention deficit hyperactivity disorder (ADHD). We focus on reward-related dysfunctions and analyze whether reward-related inhibitory control (RRIC), approach motivation, and autonomic reactivity to reward-related stimuli are linked to developing ADHD, while accounting for comorbid symptoms of oppositional defiant disorder (ODD), and callous-unemotional (CU) traits. Methods: A sample of 198 preschool children (115 boys; age: m = 58, s = 6 months) was re-assessed at age 8 years (m = 101.4, s = 3.6 months). ADHD diagnosis was made by clinical interviews. We measured ODD symptoms and CU traits using a multi-informant approach, RRIC (Snack-Delay task, Gift-Bag task) and approach tendency using neuropsychological tasks, and autonomic reactivity via indices of electrodermal activity (EDA). Results: Low RRIC and low autonomic reactivity were uniquely associated with ADHD, while longitudinal and cross-sectional links between approach motivation and ADHD were completely explained by comorbid ODD and CU symptoms. Conclusion: High approach motivation indicated developing ADHD with ODD and CU problems, while low RRIC and low reward-related autonomic reactivity were linked to developing pure ADHD. The results are in line with models on neurocognitive subtypes in externalizing disorders.

The impact of preschool child and maternal attention-deficit/hyperactivity disorder (ADHD) symptoms on mothers' perceived chronic stress and hair cortisol.

Providing care for a child with attention-deficit/hyperactivity disorder (ADHD) is associated with parenting stress. Moreover, adults with elevated ADHD symptoms report increased perceived stress. Despite this, it has rarely been examined whether and how child and maternal ADHD symptoms may affect maternal perceived stress and the stress-sensitive hypothalamic-pituitary-adrenal axis. This study therefore investigated the possible impact of child and maternal ADHD symptoms on mothers' perceived chronic stress and hair cortisol concentration (HCC), while simultaneously considering the effects of child oppositional defiant/conduct disorder (ODD/CD) and maternal depressive symptomatology. In total, 124 mothers (35.96 ± 5.21 years) of preschool children were included. Maternal perceived stress, ADHD and depressive symptoms were assessed using self-report measures. Child ADHD symptoms were assessed using an interview and questionnaires completed by mothers and teachers. Additionally, mothers provided information about their children's ODD/CD symptoms. Hair samples were taken from mothers to assess HCC. Child and maternal ADHD, child ODD/CD, and maternal depressive symptoms accounted for 50% of the variance in perceived chronic stress (F(4, 119) = 30.24; p < 0.01), with only maternal ADHD (ß = 0.52, p < 0.01) and depressive symptoms (ß = 0.49, p < 0.01) being uniquely significant. Maternal ADHD symptoms did not moderate the relationship between child ADHD symptoms and maternal perceived chronic stress (b = - 0.01; SE b = 0.17; t(5, 118) = - 0.05; p = 0.96). Mother's age became the only significant predictor of maternal HCC (ß = 0.29; p < 0.01). Based on these findings, practitioners are advised to be aware of and take into account possible maternal ADHD and depressive symptomatology and perceived chronic stress when treating children diagnosed with ADHD.

Mother's hair cortisol and symptoms of attention deficit hyperactivity disorder in her preschool child.

Children with attention deficit hyperactivity disorder (ADHD) require increased caregiver assistance and supervision, and their parents have shown high perceived parenting stress. Hence, physiological adjustment processes in the caregivers, involving the hypothalamic-pituitary-adrenal axis, seem plausible. We analyzed the association between maternal hair cortisol concentration (HCC) and symptoms of ADHD in preschool-aged children. 150 mothers of 4-5-year-old children participated in the study. To determine the HCC, the first scalp-near 3 cm hair segment was used. ADHD symptoms of the child were measured using teacher- and parent-report questionnaires and a clinical interview with the mother. When controlling for several putative confounders, teacher-reported ADHD symptoms were significantly positively associated with mothers' HCC. No associations of HCC with the mother-reported ADHD symptoms of the child emerged. It is possible that teacher-reported ADHD symptoms of the child reflect relevant ADHD symptoms more validly. As our study is the first on this issue, cross-validation is needed.

Hair cortisol concentration and neurocognitive functions in preschool children at risk of developing attention deficit hyperactivity disorder.

OBJECTIVE: Sex differences have been shown in the relation between hair cortisol concentration (HCC) and ADHD symptoms. As an extension of these findings, we analyze whether a child's sex modulates the associations between HCC and ADHD-related neurocognitive functions. METHODS: A community-based sample of 122 children was tested at age 4-5 (T1) and 8 (T2) years. At T1 and T2, ADHD symptoms were assessed with clinical parent interviews and parent and teacher questionnaires. Neurocognitive functions (i.e. T1: inhibitory control, working memory (WM), T2: verbal and performance intelligence (IQ-p)) were assessed using (neuro-)psychological tests. At T1, HCC was analyzed in the most proximal 3 cm scalp hair segment using luminescence immunoassay. RESULTS: Exclusively in boys, low HCC correlated with low WM and IQ-p. The sex-by-HCC interaction effect on WM was significant. In boys, HCC completely explained the links of ADHD inattention symptoms with WM and IQ-p, respectively. CONCLUSION: Results suggest a specific neurocognitive/endocrine profile in preschool boys at risk of developing ADHD, comprising hypocortisolism combined with memory and attention deficits.

Parental positive regard and expressed emotion-prediction of developing attention deficit, oppositional and callous unemotional problems between preschool and school age.

Parental expressed emotion and positive reinforcement are assumed to affect the development of oppositional and callous-unemotional behaviors in children at risk of attention deficit hyperactivity disorder (ADHD). As longitudinal research on this issue is scarce, we analyzed the respective links between preschool and school age. 138 five-year-old (m = 58.2, s = 6.2 months) children (59% boys) with elevated ADHD symptoms (according to screening) were assessed at the ages of five and eight years. At 5 years, maternal expressed emotion (using the Five Minute Speech Sample) and positive regard of child (using a standardized at-home observation procedure) were assessed. At 5 and 8 years, symptoms of ADHD, oppositional defiant disorder (ODD), and callous-unemotional (CU) behaviors were measured using a multi-informant approach. Multiple linear regression analyses revealed that positive regard specifically predicted a decrease in ODD symptoms between preschool and school age. The expression of high negative emotion specifically predicted an increase in CU behaviors. The development of ADHD symptoms was not predicted by parenting. Knowledge on these specific links can help to elaborate diagnostic and counseling processes in preschoolers with high ADHD symptoms. Underlying mechanisms and the role of neurocognitive deficits of the preschool child should be further analyzed.

Low hair cortisol concentration predicts the development of attention deficit hyperactivity disorder.

OBJECTIVE: Low activity of the hypothalamic-pituitary-adrenal axis (HPAA) resulting from genetic and early environmental factors has been thought to indicate risk for the development of attention deficit hyperactivity disorder (ADHD) and externalizing disorders. However, longitudinal research on this issue is scarce. We analyzed whether hair cortisol concentration (HCC), i.e. accumulated long-term HPAA activity, predicts the development of ADHD between preschool and school age. METHODS: A community-based sample of 126 children was assessed at the ages of 4, 5 and 8 years. ADHD and symptoms of oppositional defiant and conduct disorder (ODD/CD), callous unemotional (CU) traits, and internalizing symptoms were measured by clinical parent interviews and parent and teacher questionnaires. HCC was analyzed in the most proximal 3-cm scalp hair segment using luminescence immunoassay. RESULTS: Low HCC at preschool age predicted an increase in ADHD symptoms between preschool and school age while adjusting for gender of child, maternal education level, and internalizing symptoms (F(1,119) = 6.5; p = .012). The prediction held after additionally adjusting for ODD/CD symptoms and CU traits (F(1,116) = 4.1; p = .045). The same was true for the prediction of the ADHD diagnosis at the age of 8 years (Chi2(1) = 7.3; p = .007). The prediction of ADHD was mainly based on the presentation of inattention symptoms (F(1,119) = 7.4, p = .008). CONCLUSION: Low HCC in preschool children indicates an increased risk of developing ADHD at school age. In future research, it would be of theoretical and clinical importance to further circumscribe this HCC-related developmental pathway and track its further course of development.

Multiple causal pathways in attention-deficit/hyperactivity disorder - Do emerging executive and motivational deviations precede symptom development?

The multiple causal pathways model on the etiology of attention-deficit/hyperactivity disorder (ADHD) is well established. However, developmental implications of the model are not yet sufficiently analyzed. The model implies that critical neural and neuropsychological deviations from normative development precede secondarily developing ADHD symptoms. Cognitive, "cool" inhibitory control (CIC) and reward-related, "hot" functions (RRF) are regarded as neuropsychological basic deficits that indicate independent causal pathways. Both functions involve top-down control networks that undergo major normative developmental changes in the preschool period. We formalized the following assumptions in a path model: (a) CIC and RRF predict change in ADHD symptoms in the preschool period, (b) the reverse is not true, and (c) CIC and RRF independently contribute to this prediction. A community-based sample of 125 (71 boys) preschoolers was assessed at at age 4 and 5 years. At each assessment wave, CIC and RRF were measured by a battery of age-appropriate valid tasks. ADHD symptoms were measured by a clinical parent interview. Evaluation of model fit using manifest maximum likelihood parameter estimation clearly supported the hypothesized path model while controlling for gender of child and maternal education level. Thus, regarding the basic deficits of CIC and RRF, the results add evidence on the developmental implications of the multiple causal pathways model. Our findings point to the potential significance of these early emerging characteristics as indicators of risk and as targets for preventive interventions.

Hair cortisol concentration in mothers and their children: roles of maternal sensitivity and child symptoms of attention-deficit/hyperactivity disorder.

Associations between mothers' and children's cortisol secretion parameters are well established. According to the bio-behavioral synchrony model, these associations reflect influences of the mother-child relationship, the child's social adjustment, and might also reflect shared genetic dispositions. From the bio-behavioral synchrony model, we predicted a stronger mother-child hair cortisol concentration (HCC) link in mothers showing highly adequate (compared to those showing less adequate) parenting behaviors and in children showing low (compared to those showing high) ADHD symptoms. From a genetic perspective, no such moderator effects, or a stronger mother-child HCC link in children with high ADHD symptoms, can be expected. The study sample consisted of 111 4-5-year-old children (64 of whom screened positive for increased ADHD symptoms) and their mothers. ADHD symptoms were assessed by a clinical interview and parent and teacher questionnaires. Maternal sensitive/responsive parenting behavior was assessed by an at-home behavior observation procedure. In mothers and children, HCC in the most proximal 3-cm scalp hair segment was analyzed using luminescence immunoassay. Overall HCCs of mothers and their children correlated significantly. Maternal sensitivity/responsiveness and child ADHD symptoms proved to be significant moderator variables of this association: High maternal sensitivity/responsiveness and low ADHD symptoms of the child were associated with a stronger mother-child link in HCC. The findings are in line with the bio-behavioral synchrony model in the mother-child relationship, and are less compatible with a genetic perspective. The results might hint at environmental events influencing the development of stress axis functioning in subgroups of preschoolers with high ADHD symptoms.

Low hair cortisol concentration and emerging attention-deficit/hyperactivity symptoms in preschool age.

Previous research demonstrated hypoactivity of the HPA axis in children with attention-deficit/hyperactivity disorder (ADHD) or externalizing symptoms. We analyzed the predictive association between the long-term HPA axis activity and increasing symptoms of ADHD in the preschool period. The sample consisted of n = 125 4-year-old children and their families (including n = 64 children with elevated ADHD symptoms). ADHD symptoms were assessed by a structured clinical interview with the mother and by parent- and teacher-report questionnaires. The long-term HPA axis activity was assessed by the hair cortisol concentration (HCC) (over a 3-month period). After controlling for potential confounders, low HCC predicted an increase in ADHD symptoms between the age of 4 and 5 years. Exploration of gender effects revealed that cross-sectional and predictive associations were significant in boys but not in girls. Low HCC might thus be regarded as an early marker of a possibly gender-related developmental pathway to ADHD.

Maternal Responsiveness as a Predictor of Self-Regulation Development and Attention-Deficit/Hyperactivity Symptoms Across Preschool Ages.

Preschool-age "hot" executive function capacity (i.e. reward-related effortful control) represents an early kind of self-regulation that is involved in social adjustment development as well as the development of subtypes of attention-deficit/hyperactivity disorder (ADHD). Early self-regulation development might be malleable by responsive parenting. We analyzed whether maternal responsiveness/sensitivity predicts reward-related control (RRC) development within the preschool period, and whether RRC mediates a negative link between maternal responsiveness and ADHD symptoms. A sample of 125 preschoolers and their families were seen at the ages of 4 and 5 years. Maternal responsiveness/sensitivity was assessed via home observations, RRC by neuropsychological tasks, and ADHD symptoms by a structured clinical parent interview. Maternal responsiveness/sensitivity predicted RRC development. The negative link between maternal responsiveness/sensitivity at 4 years and ADHD symptoms at 5 years was mediated by RRC performance at 5 years. Preschoolers showing ADHD symptoms combined with low RRC capacity in particular might benefit from responsive/sensitive parenting.

Hair cortisol concentration in preschoolers with attention-deficit/hyperactivity symptoms-Roles of gender and family adversity.

OBJECTIVE: Previous studies on the association between hypothalamic-pituitary-adrenal axis (HPAA) activity and ADHD yielded inconsistent findings, particularly in younger children. This might be due to the heterogeneity of the disorder, making moderator effects of variables probable, which circumscribe more homogenous subgroups. There have been indications of moderator effects on this association by gender of child and exposure to family adversity. Moreover, difficulties in capturing long-term basal HPAA activity in younger children might have contributed to the inconsistencies. We therefore analyzed moderator effects of gender and family adversity while using the hair cortisol concentration (HCC) to assess integrated long-term HPAA. METHODS: The community-based sample consisted of 122 4-5-year-old preschoolers (71 screened positive for elevated ADHD symptoms). ADHD symptoms were measured by a clinical parent interview and parent and teacher questionnaires. HCC in the most proximal 3-cm scalp hair segment was analyzed using luminescence immunoassay. An extended family adversity index was used. RESULTS: Hierarchical linear regression analyses yielded an interaction effect (p<.05) between ADHD symptom groups and gender on HCC, indicating a low HCC in boys with elevated ADHD symptoms. Further exploratory analyses revealed that this interaction effect was most pronounced under the condition of family adversity. The results held after controlling for oppositional, anxiety, and depressive symptoms. CONCLUSION: Low HCC might indicate a specific pathogenic mechanism in boys with elevated ADHD symptoms. This mechanism might further involve an exposure to family adversity. However, the results need to be cross-validated before definitive conclusions can be drawn.

[Expressed emotion, mother-child relationship, and ADHD symptoms in preschool- a study on the validity of the German Preschool Five Minute Speech Sample]. / Expressed Emotion, Mutter-Kind-Beziehung und ADHS-Symptome im Vorschulalter.

An inadequate parent-child relationship with hostility, low warmth, and a lack of responsiveness/sensitivity on the part of the primary caregiver often accompanies a child's externalizing disorders and predicts a negative developmental course. The Preschool Five Minute Speech Sample (PFMSS) was developed to enable an economic assessment of components of an inadequate parent-child relationship. In this article we investigate aspects of the validity of the German version of the PFMSS. We analyze whether the PFMSS scales are associated with observed maternal sensitivity, symptoms of attention deficit-/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and maternal depressive symptoms. The sample consists of n = 114 families with 4- to 5-year-old children, whereof n = 65 (57 %) show heightened ADHD-symptoms. The families were recruited from local kindergardens. Maternal sensitivity was assessed by observing the mother-child interaction at home. ADHD, ODD, and maternal depressive ~symptoms were measured by clinical interviews and questionnaires. Most of the PFMSS scales showed the expected associations with maternal sensitivity, ADHD, and ODD symptoms of the child. The German PFMSS thus validly captures significant components of an inadequate mother-child relationship within the context of preschool externalizing behavior problems.