Reduced
Salivary Cortisol in Children with Comorbid Attention Deficit
Hyperactivity Disorder and Oppositional Defiant Disorder
S. Himani
Kariyawasam,1
Frank Zaw, 2
Sheila L. Handley, 3
1
present address: Dept of Pharmacology, University of Columbo
Faculty of Medicine, Sri Lanka.
2 Diana, Princess of Wales Children’s Hospital, Birmingham,
UK.
3 Pharmaceutical Sciences Research Institute, Aston University,
UK.
Submitted:
January 2, 2002
Accepted: January 16, 2002
Key
words:
salivary cortisol, HPA axis, attention deficit hyperactivity
disorder (ADHD), Oppositional-defiant disorder, neuropsychiatric
disorders, D-amphetamine, methyl-phenidate
Abstract
OBJECTIVES: There is growing interest in the role of the hypothalamic-pituitary-adrenal
(HPA) axis in neuropsychiatric disorders and there is some
evidence that the HPA axis may be underfunctional in behaviorally
disturbed children. However, co-morbidity is common in childhood
neuropsychiatric disorders. Stimulant medication is widely
used in the treatment of Attention-deficit hyperactivity disorder
(ADHD) and can increase cortisol secretion when given acutely.
We therefore set out to determine the whether salivary cortisol
would be reduced in a group of children with ADHD/ODD (Oppositional-defiant
disorder) and to examine the effect of stimulant medication
on any such relationship.
DESIGN:
Salivary cortisol was determined in thirty-two children with
co-morbid ADHD and Oppositional-defiant disorder (ODD) according
to DSM-IV criteria, compared to twenty-five healthy controls
of similar age and ethnic background. Data were analysed according
to prescription of stimulant medication in the patient group.
RESULTS: Salivary cortisol was significantly lower in the
ADHD/ODD group than in the controls. Further analysis revealed
that this reduction was restricted to the subgroup of patients
not prescribed stimulant medication.
CONCLUSIONS:
The results support the possibility of a dysfunction of control
of the HPA axis in these behaviorally disturbed children.
A reduction in salivary cortisol could reflect underarousal,
an elevated threshold for detection of stressors or a subsensitivity
of the HPA axis itself. It remains to be determined whether
the ability of stimulant medications to negate the apparent
deficit in cortisol secretion in these ADHD/ODD patients is
an unrelated consequence of increased dopamine release or
a reflection of their therapeutic benefit. The use of stimulant
medication for co-existing ADHD should be taken into account
in future studies of cortisol in behaviorally disturbed children.
Introduction
There
is growing interest in the potential role of the hypothalamic-pituitary-adrenal
(HPA) axis in neuropsychiatric disorders [1,2] and there is
some evidence that behaviorally disturbed children may exhibit
under-functionality of the HPA axis. Salivary cortisol correlates
closely with plasma free cortisol and it is well established
that salivary cortisol levels reflect cortisol secretion [3,4].
In a study of boys with Oppositional-Defiant Disorder (ODD)
[5] it was reported that baseline levels of salivary cortisol
were lower than in a comparison group of normal controls,
but this difference only reached statistical significance
following removal of outliers from the ODD group and the two
groups did not differ significantly in response to stress.
Furthermore, within a group of children referred for disruptive
behavior, those with persistent aggression showed lower single-point
concentrations of salivary cortisol and a smaller stress-induced
elevation than those without this feature [6]. Similarly,
following placement of scalp electrodes, children with substance-abusing
fathers had lower single-point salivary cortisol than those
without [7]. Children with Attention-deficit hyperactivity
disorder (ADHD) persisting over two years exhibited reduced
single-point salivary cortisol and cortisol stress response
to neuropsychiatric testing compared to a group with a more
transient form of the disorder [8].
There is a high degree of co-morbidity among neuropsychiatric
disorders of childhood [9,10]. For example, the incidence
of ODD in ADHD has been variously recorded as 43-93% [9].
The beneficial effect of stimulant medications in ADHD lends
support to the hypothesis that some form of under-arousal
is implicated in ADHD [11,12]. However, these medications
can also elevate circulating cortisol, at least when administered
acutely [13].
We therefore set out to determine the whether single-point
determinations of salivary cortisol would be reduced in a
group of children with ADHD/ODD visiting Diana Princess of
Wales Children’s Hospital for follow-up care, compared
with healthy children of similar age, sex and ethnic background,
and examine the effect of stimulant medication.
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