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ADHD and stress: Diurnal cortisol levels, early psychosocial adversity and perceived stress
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The Hypothalamus-Pituitary-Adrenal axis (HPA-axis) with its end product cortisol mediates the physiological response to stress thereby promoting mobilization of energy. The cortisol levels follow a diurnal rhythm with a distinct awakening response. Regulation of the HPA-axis differs among persons with certain psychiatric disorders when compared with controls. Some reports concern Attention-Deficit/Hyperactivity Disorder (ADHD) but findings are inconclusive. The main aim of the present thesis was to investigate diurnal levels of saliva cortisol in school aged children with ADHD and age matched non-affected comparisons, also taking early adversity, perceived stress and ADHD-medication into consideration.

Children with ADHD had lower cortisol levels at awakening, 30 minutes later and before going to bed than comparisons. When the study group was split into three different age groups similar results were found only for children above 10 years of age. Within the ADHD group, subtype of ADHD or co-occurring symptoms did not affect the cortisol levels. Furthermore, children in the ADHD group had to a higher degree been exposed to foetal and childhood psychosocial adversity than comparisons.

Since exposure to early adversity has been associated with both ADHD and HPA-axis functioning, such exposures could theoretically explain the low cortisol levels in ADHD via early programming of the HPA-axis. However, no relation was found between exposures to psychosocial adversity and diurnal cortisol levels. Neither did continuous medication with stimulants or atomoxetine explain the low cortisol levels. Possibly, medication may rather increase the levels.

Finally, children with ADHD scored higher on perceived stress, measured by the Pressure-Activation-Stress (PAS) scale, than the comparison group. Female sex was also associated with higher stress in both groups, as well as increasing age in the comparison group. As with psychosocial adversity, no association was found between the higher PAS-scores and the lower cortisol levels, indicating the complexity of the stress regulating system.

The results indicate a down-regulated or displaced HPA-axis with lower cortisol levels in children with ADHD. Stress related fragility – with more exposure to early stressors, higher perceived stress and lower diurnal cortisol levels – seem to accompany ADHD during childhood.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. , 58 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 957
Keyword [en]
ADHD, HPA-axis, cortisol, hypocortisolism, diurnal rhythm, trauma, adversity, medication, perceived stress, gender differences
National Category
Psychiatry
Research subject
Child and Youth Psychiatry
Identifiers
URN: urn:nbn:se:uu:diva-211808ISBN: 978-91-554-8822-2 (print)OAI: oai:DiVA.org:uu-211808DiVA: diva2:668687
Public defence
2014-01-31, Universitetshuset, sal IX, S:t Olofsgatan, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2014-01-09 Created: 2013-12-02 Last updated: 2014-01-24
List of papers
1. Cortisol levels in children with Attention-Deficit/Hyperactivity Disorder
Open this publication in new window or tab >>Cortisol levels in children with Attention-Deficit/Hyperactivity Disorder
Show others...
2012 (English)In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 46, no 11, 1398-1405 p.Article in journal (Refereed) Published
Abstract [en]

Regulation of the Hypothalamus-Pituitary-Adrenal axis (HPA-axis) and its end product cortisol differs among persons with certain psychiatric disorders when compared with controls. Some reports concern Attention-Deficit/Hyperactivity Disorder (ADHD) but findings are inconclusive. In this study we collected four saliva samples during a regular weekday in children, 6-17 years old, with ADHD (n = 201) and non-affected comparisons (n = 221). Saliva cortisol was measured with radioimmunoassay technique. Clinical data were collected for diagnostic information. Subtypes and severity of symptoms were determined using parental rating scales. Children with ADHD had lower saliva cortisol levels than comparisons at waking up Median = 9.1 versus 12.7 nmol/L (p < .001), 30 min later Median = 15.8 versus 20.1 nmol/L (p < .001) and before going to bed Median = 0.8 versus 1.0 nmol/L (p = .015). No difference was found for the afternoon sample. When the study group was split into three different age groups similar results were found only for children above 10 years of age. Subtype of ADHD or co-occurring symptoms did not affect the cortisol levels. Degree of severity of ADHD symptoms was not associated with cortisol levels in the study group, other than a weak negative correlation between the afternoon sample and hyperactivity symptoms. The low cortisol levels in children with ADHD may indicate a dysregulation of the HPA-axis, for instance a down-regulation or a phase delay of the diurnal curve. The low levels may be related to the under-arousal possibly underlying several of the core symptoms of ADHD.

Keyword
ADHD, HPA-axis, Cortisol, Hypocortisolism, Diurnal rhythm
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-187655 (URN)10.1016/j.jpsychires.2012.08.021 (DOI)000310670800003 ()
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2017-12-07Bibliographically approved
2. Early psychosocial adversity and cortisol levels in children with attention-deficit/hyperactivity disorder
Open this publication in new window or tab >>Early psychosocial adversity and cortisol levels in children with attention-deficit/hyperactivity disorder
2013 (English)In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 22, no 7, 425-432 p.Article in journal (Refereed) Published
Abstract [en]

Previous studies suggest a different regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis) with lower diurnal cortisol levels, especially in the morning, in children with attention-deficit/hyperactivity disorder (ADHD) compared with controls. Since exposure to foetal and childhood psychosocial adversity has been associated with both ADHD and HPA-axis functioning, such exposures may explain these low cortisol levels in ADHD via early programming of the HPA-axis. Thus, our main aim was to retrospectively study foetal and early childhood exposures to psychosocial adversity in children with ADHD and to relate these exposures to cortisol levels. Saliva samples were collected during a regular weekday in children, 6-17 years old, with clinically confirmed ADHD (n = 197) and non-affected comparisons (n = 221) for radioimmunoassay analysis of cortisol. Parental rating scales were used for categorising subtypes of ADHD and degree of exposure to adversity. Children with ADHD had more reports of at least one rated foetal adversity (p = 0.041) and childhood adversity (p < 0.001) than comparisons. The association between low morning cortisol levels and ADHD-symptoms remained when analyses were adjusted for adversities, age, sex, sampling time and symptoms of oppositional defiant disorder. No relation was found between exposures to foetal/childhood adversity and cortisol levels except for a positive relation between childhood adversity and cortisol morning increase in children with ADHD. The hypothesis that early adversity may influence the HPA-axis, leading to lower cortisol levels in children with ADHD, was not supported by our findings.

Keyword
ADHD, Trauma, Adversity, HPA-axis, Cortisol, Endocrinology
National Category
Endocrinology and Diabetes Psychiatry
Identifiers
urn:nbn:se:uu:diva-204982 (URN)10.1007/s00787-013-0383-0 (DOI)000321634800006 ()
Available from: 2013-08-16 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved
3. Effects of stimulants and atomoxetine on cortisol levels in children with ADHD
Open this publication in new window or tab >>Effects of stimulants and atomoxetine on cortisol levels in children with ADHD
2013 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 209, no 3, 740-741 p.Article in journal (Refereed) Published
Abstract [en]

Children with attention deficit hyperactivity disorder (ADHD) have lower diurnal cortisol levels than non-ADHD comparison subjects. Aiming at elucidating the effects of medications used to treat ADHD, we investigated saliva cortisol in children with ADHD: 20 without medication, 147 on methylphenidate, and 21 on atomoxetine. The only significant finding was that children on atomoxetine had higher cortisol levels at bedtime than unmedicated children.

National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-210971 (URN)10.1016/j.psychres.2013.06.011 (DOI)000326766300076 ()
Available from: 2013-11-25 Created: 2013-11-18 Last updated: 2017-12-06Bibliographically approved
4. The Pressure-Activation-Stress scale in relation to ADHD and cortisol
Open this publication in new window or tab >>The Pressure-Activation-Stress scale in relation to ADHD and cortisol
2015 (English)In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 24, no 2, 153-161 p.Article in journal (Refereed) Published
Abstract [en]

The Pressure–Activation–Stress (PAS) scale is a self-report questionnaire for children concerning perceived stress. To explore behavioral and physiological correlates, we investigated if scores discriminate between a group prone to perceive high levels of stress [children with attention-deficit/hyperactivity disorder (ADHD)] and a healthy school sample, and if they are associated with diurnal cortisol levels. The PAS scale was filled in at home by children (11–17 years) with clinically confirmed ADHD (n = 102) and non-affected comparisons (n = 146). Saliva samples were collected four times during a regular school day for radioimmunoassay analysis of cortisol. Subtypes and severity of ADHD symptoms were determined using parental rating scales. Children with ADHD scored higher on the PAS scale than a school sample. The PAS scores were similar over ages in the ADHD group while they increased with age in the healthy group. Female sex was associated with higher stress in both groups but no gender interaction was found. No association was found between PAS scores and cortisol levels in neither group. Children in the ADHD group had a lower ratio of cortisol levels/perceived stress on all sampling occasions, built up both by the higher PAS scores and the lower cortisol levels in children with ADHD. The higher PAS scores in children with ADHD support the validity of the scale. The lack of association between PAS scores and diurnal cortisol levels is intriguing and illustrates the complexity of the stress concept. Stress-related fragility seems to accompany ADHD during childhood.

National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-211513 (URN)10.1007/s00787-014-0544-9 (DOI)000351005600004 ()
Available from: 2013-11-25 Created: 2013-11-25 Last updated: 2017-12-06Bibliographically approved

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