|Year : 2016 | Volume
| Issue : 1 | Page : 41-45
Cortisol and its effects on cognitive function in a sample of Egyptian school-aged children with attention-deficit hyperactivity disorder
Omneya Ibrahim, Wafaa El-lithy, Khaled Abd El-Moez MD
Department of Neuropsychiatry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
|Date of Submission||19-Nov-2015|
|Date of Acceptance||25-Jan-2016|
|Date of Web Publication||13-Apr-2016|
Khaled Abd El-Moez
Assistant Professor of Psychiatry, Faculty of Medicine, Suez Canal University, Ismailia
Source of Support: None, Conflict of Interest: None
Several studies have suggested that cortisol level influences the development and functioning of the brain in children and that it is implicated in a variety of processes including memory and attention.
This study was conducted to investigate the relation between cortisol level in children with attention-deficit/hyperactivity disorder (ADHD) and their cognitive function profile.
The participants of the study, held in Suez Canal University Hospital in Ismailia, were recruited from among those attending the childhood and adolescent psychiatry clinic. They were divided into two groups, the ADHD group [diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR) through a structured clinical interview], composed of 43 children (pure ADHD children with no comorbid conditions), and the control group, composed of 31 typically developing children. All of them participated voluntarily in this study. The participants' ages ranged from 6 to 12 years; both sexes were included. Early morning awakening salivary cortisol levels were collected on two different days 2 months apart. The Stanford-Binet intelligence test 4th edition, the Wisconsin Card Sorting Test, Conner's test, and the child behavioral checklist were administered on all participants.
Early morning salivary cortisol levels in both groups showed a statistically significant difference. Comparison shows that there was a statistically significant difference in the mean total score and the mean subdomain score of Stanford-Binet intelligence test 4th edition and Wisconsin Card Sorting Test (total number of errors, perseverative errors) between ADHD children and the comparison group. These results were positively correlated with decrease in mean cortisol awakening response.
There are significant associations between salivary cortisol levels and cognitive and executive function impairment in children with ADHD.
Keywords: attention-deficit/hyperactivity disorder, cortisol, executive functions, school-aged children
|How to cite this article:|
Ibrahim O, El-lithy W, El-Moez KA. Cortisol and its effects on cognitive function in a sample of Egyptian school-aged children with attention-deficit hyperactivity disorder. Egypt J Psychiatr 2016;37:41-5
|How to cite this URL:|
Ibrahim O, El-lithy W, El-Moez KA. Cortisol and its effects on cognitive function in a sample of Egyptian school-aged children with attention-deficit hyperactivity disorder. Egypt J Psychiatr [serial online] 2016 [cited 2022 Aug 14];37:41-5. Available from: http://new.ejpsy.eg.net/text.asp?2016/37/1/41/180270
| Introduction|| |
The definition of executive function was based on the description of two central conceptual themes. The first associates executive function with 'higher' cognitive functions, such as insight, will, abstraction, and judgment, which are mostly dependent on functioning of the frontal lobe. The second emphasizes behavioral regulation of nonexecutive processes by frontal control systems (American Psychiatric Association, 1994, 2000; Royall et al., 2005).
The term executive function seems to incorporate the following: volition, planning, and purposive, goal-directed, or intentional action; inhibition and resistance to distraction; problem-solving and strategy development, selection, and monitoring; flexible shifting of actions to meet task demands; maintenance of persistence toward attaining a goal; and self-awareness across time (Barkley, 2000).
No single etiology has been identified yet for attention-deficit/hyperactivity disorder (ADHD), and findings are much more consistent with a 'multifactorial hypothesis'(Hoza et al., 2001), but ADHD behavioral symptoms have been also explained by deviations from an optimal arousal level (Sonuga-Barke et al., 2010).
Such deficits in arousal modulation in ADHD have been studied by examining cortisol levels in saliva, which is a reliable peripheral measure for evaluating hypothalamic-pituitary-adrenal (HPA) axis functioning (Kirschbaum and Hellhammer, 1989).
The HPA axis plays an important role in regulating central nervous system neurotransmitters and behavior, such as attention, emotion, learning, memory, and movement (Pariante and Lihtman, 2008; Marques et al., 2010).
Cortisol influences the development and functioning of the brain in children (Goodyer et al., 2001) and is implicated in a variety of mental processes including regulation of attention, behavior, and emotion exerted through affecting processes within the prefrontal cortex and hippocampus (Prudhomme and Mulligan, 2005).
ADHD, among other neurodevelopmental disorders, is implicated in the frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia structures), which is responsible for our adaptive responses (initiation, execution, or withholding) to environmental situations, and the above disorders, involving effectively excessive release or withholding of various types of response, are all a consequence of changes in specific frontostriatal regions (Bradshow and Sheppard, 2007).
Levels of cortisol are often regarded as a better biomarker, as catecholamine is more immediate and transient, more sensitive to exercise, and more expensive to analyze (Vanaelst et al., 2012).
A significant proportion of ADHD children will experience failure in school. As a result, the burden of ADHD on affected individuals, on their families, and on society is considerable (Barkley, 2000). Evidence shows a broad range of negative effects one changes made to the affected individuals and a serious financial burden on families and society; hence, it is considered a major public health problem (Polanczyk et al., 2007; Karama et al., 2008).
The goal of this study was to determine the relationship between cortisol level in ADHD children and their cognitive function. The results might also provide a foundation for future research focused on interventions based on the impact of cortisol level.
| Methods|| |
This study was a cross-sectional comparative case-control trial held at the Child and Adolescent Psychiatry Clinic, Suez Canal University Hospital, in Ismailia.
Consecutive attendees to the 'Child and Adolescent Psychiatry clinic' who were diagnosed with ADHD (44 children) with no comorbid conditions were enrolled. The control group (31 children) comprised matched healthy, typically developing children who were recruited from Ismailia primary schools.
The ADHD diagnosis was made before inclusion into the study. The diagnosis of ADHD and of other psychiatric disorders was based on Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR) criteria using a standardized, structured child psychiatric interview.
A physical/neurological assessment was made on all participants in the study before inclusion, and a standardized battery of psychological assessments was applied on all participants.
All children participated voluntarily in the study. Assent from the child and written consent from the parents with regard to the aim, the tools used in the research, benefits, risks, confidentiality, and voluntary participation were prerequisites. The tools for diagnosis carried less than the minimal accepted risk. The research plan was approved by the 'Faculty of Medicine's Scientific Research Ethical Committee'.
The ages of the children under study ranged from 6 to 12 years. Both boys and girls with intelligence quotient (IQ) more than or equal to 80 were included. Children with any comorbid psychiatric condition, any neurological condition, serious medical illness that could have affected the HPA axis function or those on hormonal and dental treatments during the trial or girls who experienced menarche or those who have a history of any sensory or motor disability were excluded.
Saliva was collected two times on two different days (at early morning awakening and before morning breakfast).
The following tools and instruments were applied in this work.
Child behavioral checklist: to aid in the recognition of the comorbid conditions for exclusion.
Conners 3 - Parent version: to assess ADHD symptoms and comorbid conditions.
Wisconsin Card Sorting Test (WCST): to assess the executive functions of the children in both groups.
Stanford-Binet 4th edition: to determine the IQ of the children.
Unpaired t-test and analysis of variance test was used for comparison between quantitative variables.
| Results|| |
There was no statistically significant difference between the two studied groups regarding residence and parental educational level.
The mean age of children in the ADHD group was 7.3 ± 0.7 years, and was 7.0 ± 0.7 years in the typically developing (control) group (P < 0.05, no statistically significant difference) ([Figure 1]).
There was no statistically significant difference between the two groups regarding sex distribution (P > 0.05). Most of the studied participants in the two groups were male (statistically significant difference P < 0.05) ([Figure 2]).
Comparison between the control group and the ADHD group regarding the mean and SD of the salivary cortisol levels
Early morning awakening cortisol levels were lower in the ADHD group in comparison with controls, with a statistically significant difference (P < 0.01) ([Figure 3]).
Mean and SD for early morning awakening salivary cortisol levels between the three ADHD subtypes
There was no statistically significant difference between ADHD subtypes regarding early morning awakening salivary cortisol levels on days 1 and 2, nor in the average cortisol level indices (P > 0.01).
Comparison between the ADHD group and the control group regarding mean and SD of the Stanford-Binet intelligence scale scores
t -Test results were lower in the ADHD group in comparison with the control group, and differences were statistically significant (P < 0.01) for all subscales of the Stanford-Binet intelligence Scale.
Comparison between boys and girls of the ADHD group regarding mean and SD of the Wisconsin Card Sorting Test scores
Independent-sample t-test results for the mean and SD between ADHD boys and girls showed statistically significant differences in total number of errors, perseverative responses, and perseverative errors in addition to the number of categories completed and responses to the first category, with boys displaying lower performance.
Correlation between salivary cortisol and Wisconsin Card Sorting Test between the two groups
There was significant positive correlation between early morning salivary cortisol level and WCST domains ([Table 1]).
|Table 1 Correlation between Salivary cortisol and Wisconsin Card Sorting Test between the two studied groups|
Click here to view
| Discussion|| |
In this study, in the ADHD group, boys outnumbered girls by three-fold, similar to the results of a large body of research (Gozal and Molfese, 2005; Polanczyk et al., 2007; Farah et al., 2009; Roufaele et al., 2012; Abdel-Hamid et al., 2013; El Missiry et al., 2013; Sciberras et al., 2013; Richa et al., 2014).
Here early morning awakening cortisol levels were assessed in noncomorbid ADHD children compared with healthy controls, similar to some other studies.
Bäumler et al. (2014) studied 35 preschool children (aged 36 years) in good mental and physical health who were not taking any medication. The children's postawakening cortisol levels were estimated. Results revealed mean and SD of 15.05 and 3.89 nmol/l, respectively, and these results were somehow different from those of the current research (as the mean and SD in our control group were 11.4 and 1.7 nmol/l, respectively).
Ma et al. (2011) investigated the relationship between the HPA axis and ADHD in ordinary, nonstressful states, as we did in our research. In that study, they recruited only 128 boys with ADHD with ages ranging between 6 and 14 years and compared them with 30 healthy boys. The diagnosis was also based on DSM-IV, but they did not clarify whether children with comorbid psychiatric conditions were included.
Isaksson (2014) investigated the effect of stress and ADHD in school-aged children (aged 6-12 years) by exploring diurnal levels of saliva cortisol and comparing with age-matched healthy controls. His results were consistent with ours regarding the lower cortisol levels in children with ADHD, especially the morning levels.
Although the IQ scores, estimated by the Stanford-Binet 4th edition , for all ADHD children were above 80 (mean and SD for the total score of intelligence was 105.9 ± 10.4), it was still lower than that of the control group of normal children (128.8 ± 8.7); the scores for Short-term memory, Verbal reasoning, Quantitative reasoning, and Abstract/visual reasoning subscales yielded statistically significant results. These results were consistent with the findings from many other studies (Abdeldayem and Selim, 2005; Yanez-Tellez et al., 2012; Marusiak and Janzen, 2013) reporting significantly lower cognitive abilities in ADHD children as estimated through IQ tests and compared with matched controls. With regard to the results of the WCST, results showed statistically significant differences between the ADHD group and the control group, indicating lower executive performance on WCST in all the test domains, a finding that was concluded by multiple other studies (Oosterlaan et al., 2005; Royall et al., 2005; Barkley et al., 2007; Zorcec and Pop-Jordanova, 2010).
The authors are grateful to Dr Muhammed Fouad, consultant at the Clinical Pathology Department, for helping with cortisol level assessment. They also thank physician Ahmad Fouad and Muhammed Alaa for their help with the statistics, and pay a special tribute to the ADHD children to whom this study is dedicated.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Abdel-Hamid A, Safwat R, Raafat O, Hamed H, Farouk A (2013). Central auditory processing and audio-vocal psycholinguistic abilities in children with attention deficit-hyperactivity disorder. Egypt J Psychiatry 34:98-103.
Abdeldayem H, Selim O (2005). Cognitive function and skills′ performance of children with attention deficit disorder. Int J Ch Neuropsychiatry 2: 119-126.
American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders (DSM-IV)
. 4th ed. Washington, DC: American Psychiatric Association.
American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (DSM-II), text revision
. 4th ed. Washington, DC: American Psychiatric Association.
Barkley AR (2000). Genetics of childhood disorders; ADHD, part 1: the executive functions and ADHD; development and neurobiology. J Am Acad Child Adolesc Psychiatry 39:8.
Barkley RA, Fischer M, Edelbrock CS, Smallish L (2007). The adolescent outcome of hyperactive children diagnosed by research criteria:II. Academic, attentional and neuropsychological status. J Consult Clin Psychol 58:580-588.
Bäumler D, Voigt B, Miller R, Stalder T, Kirschbaum K, Kliegel M (2014). The relation of the cortisol awakening response and prospective memory functioning in young children. Biol Psychol 99:41-46.
Bradshow JL, Sheppard DM (2007). The neurodevelopmental frontostriatal disorders: evolutionary adaptiveness and anomalous lateralization. Brain Lang 73:297-320.
Farah LG, Fayyaad JA, Eapen V, Cassir Y, Salamoun MM,Tablet CC, et al.
(2009). ADHD in the Arab World; a review of epidemiologic studies. J Att Dis 13:211-222.
Fernández de la Cruz L, Simonoff E, McGough JJ, Halperin JM, Arnold LE, Stringaris A (2015). Treatment of children with attention-deficit/hyperactivity disorder (ADHD) and irritability: results from the multimodal treatment study of children with ADHD (MTA). J Am Acad Child Adolesc Psychiatry 54:62-70.
Freitag CM, Hänig S, Palmason H, Meyer J, Wüst S, Seitz C (2009). Cortisol awakening response in healthy children and children with ADHD: Impact of comorbid disorders and psychosocial risk factors. Psych Neuroendocrinol 34:1019-1028.
Goodyer IM, Park RJ, Netherton CM, Herbert J (2001). Possible role of cortisol and dehydroepiandrosterone in human development and psychopathology. Br J Psychiatry 179:243-249.
Gozal D, Molfese DL (2005). Attention deficit hyperactivity disorder from genes to patients
. Totowa, NJ: Humana Press Inc.:1-40.
Hoza B, Vallano G, Pelham Jr WE (2001). Attention deficit/hyperactivity disorder. In: Ammerman RT, Hersen M, eds Handbook of child behavior therapy in the psychiatric setting
. New York, NY: John Wiley & Sons: 181-199.
Imeraj L, Sonuga-Barke E, Antrop I, Roeyers H, Wiersema R, Bal B, Deboutte D (2012). Altered circadian profiles in attention-deficit/hyperactivity disorder: an integrative review and theoretical framework for future studies. Neurosci Biobehav Rev 36:1897-1919.
Isaksson J (2014). ADHD and stress diurnal cortisol levels, early psychosocial adversity and perceived stress
. Uppsala, Sweden: Acta Universitatis Upsaliensis.
Karama, S, Grizenko, N, Sonuga-Barke, E, Doyle, A, Biederman, J, Mbekou, V, et al.
(2008). Dopamine transporter 3¢UTR VNTR genotype is a marker of performance on executive function tasks in children with ADHD. BMC Psychiatry 8:45.
Kirschbaum C, Hellhammer DH (1989). Salivary cortisol in psychobiological research: an overview. Neuropsychobiology 22:150-169.
Ma L, Chen YH, Chen H, Liu YY, Wang YX (2011). The function of hypothalamus-pituitary-adrenal axis in children with ADHD. Brain Res 1368:159-162.
Marques AH, Silverman MN, Sternberg EM (2010). Evaluation of stress systems by applying noninvasive methodologies: measurements of neuroimmune biomarkers in the sweat, heart rate variability and salivary cortisol, Neuroimmunomodulation 17:205-208.
Marusiak CW, Janzen HL (2013). Assessing the working memory abilities of ADHD children using the Stanford-Binet intelligence scales, fifth edition. Can J Sch Psychol 20:84-97.
Oosterlaan J, Scheres A, Sergeant JA (2005). Which executive functioning deficits are associated with AD/HD, ODD/CD and Comorbid AD/HD+ODD/CD?. J Abnorm Child Psychol 33:69-85.
Pariante CM, Lihtman SL (2008). The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31:464-468.
Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007). The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164:942-948.
Prudhomme W, Mulligan SE (2005). Behavioral and physiologic response measures of occupational task performance: a preliminary comparison between typical children and children with attention disorder. Am J Occup Ther 59:426-436.
Richa S, Rohayem J, Chammai R, Kazour F, Haddad R, Hleis S, et al.
(2014). ADHD prevalence in Lebanese school-age population. J Atten Disord 18:242-246.
Roufaele R, El Bakry A, Amer D, Refaat O, Emad-Eldin M (2012). Gender differences in executive functions and reading abilities in children with attention deficit hyperactivity disorder. Egypt J Psychiatry 33:63-73.
Schillerstrom JE, Horton MS,Royall DR (2005). The impact of medical illness on executive function. Psychosomatics 46:6.
Sciberras E, Efron DE, Schilpzand EJ, Anderson V, Jongeling B, Hazel P, et al.
(2013). The Children′s Attention Project: a community based longitudinal study of children with ADHD and non-ADHD controls. BMC Psychiatry 13:18.
Sonuga-Barke E, Banaschewski T, Asherson P, Buitelaar J, Chen W, Franke B, et al.
(2010). Emotional liability in children and adolescents with attention deficit/hyperactivity disorder (ADHD): clinical correlates and familial prevalence. J Child Psychol Psychiatry 51:915-923.
Vanaelst B, Huybrechts I, Bammann K, Michels N, de Vriendt T, Vyncke K, et al.
(2012). Intercorrelations between serum, salivary, and hair cortisol and child-reported estimates of stress in elementary school girls. Psychophysiology 49:1072-1081.
Willcutt EG (2012). The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics 9:490-499.
Yanez-Tellez G, Romero-Romero H,Rivera-García L,Prieto-Corona B,Bernal-Hernández J,Marosi-Holczberger E,et al.
(2012). Cognitive and executive functions in ADHD. Actas Esp Psiquiatr 40:293-298.
Zorcec T, Pop-Jordanova N (2010). ADHD as an executive dysfunction. Sec Biol Med Sci 31:171-181.
[Figure 1], [Figure 2], [Figure 3]