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Effects of stimulants and atomoxetine on cortisol levels in children with ADHD
Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Contents lists available at SciVerse ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Effects of stimulants and atomoxetine on cortisol levels in children with ADHD Johan Isaksson a,n, Åsa Hogmark a, Kent W. Nilsson c, Frank Lindblad a,b a
Department of Neuroscience, Child and Adolescent Psychiatry Unit, Uppsala University, Sweden Stress Research Institute, Stockholm University, Sweden c Centre for Clinical Research, County Council of Västmanland/Uppsala University, Sweden b
art ic l e i nf o
a b s t r a c t
Article history: Received 21 November 2012 Received in revised form 10 April 2013 Accepted 12 June 2013
Children with attention deficit hyperactivity disorder (ADHD) have lower diurnal cortisol levels than non-ADHD-comparisons. Aiming at elucidating effects of ADHD-medication 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 non-medicated. & 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: ADHD Cortisol Medication
1. Introduction In a recent study, children with attention deficit hyperactivity disorder (ADHD) had lower saliva cortisol levels than comparisons at waking up, 30 min later and at bedtime (Isaksson et al., 2012). Most of the children were on ADHD-medication; therefore it was not possible to evaluate the impact of this factor in detail. The findings on effects of ADHD-medication on cortisol levels in children with ADHD are inconclusive with reports of elevated levels with either methylphenidate or atomoxetine (Chen et al., 2012), an increase after 1 month of treatment with methylphenidate but then a gradual decrease towards initial levels (Wang et al., 2012) or no effect at all of methylphenidate on cortisol levels (Maayan et al., 2003; Lee et al., 2008). In order to investigate if continuous medication could explain the lower diurnal cortisol levels in children with ADHD reported previously (Isaksson et al., 2012) we recruited a non-medicated group for comparisons.
2. Methods Study groups (6–17 years of age): 1. children (n¼ 20 [15 boys/5 girls]; mean age 10.1 years, 7 2.7) with ADHDsymptoms, not on ADHD-medication (“ADHD/Non-Med”). Referred by a community team—specialized at early identification of children with
n
Corresponding author. Tel.: +46 18 6112540; fax: +46 18 6112565. E-mail address: [email protected] (J. Isaksson).
neuropsychiatric disorders. Symptoms validated by parental SNAP-IV questionnaires (see below). 2. Children (n ¼147 [113 boys/34 girls]; mean age 11.8 years, 72.7) with a clinical diagnosis of ADHD and on medication with central stimulants (“ADHD/Stim”), recruited from four child psychiatry outpatient units. ADHD-diagnosis verified by clinical neuropsychiatric assessment. 3. Children (n¼ 21[17 boys/4 girls]; mean age 12 years, 72.9) with a clinical diagnosis of ADHD and on medication with atomoxetine (“ADHD/Atomox”), in other respects similar to ADHD/Stim. After written informed consent from parents (and child when ≥15 years of age) a questionnaire about any current medication, tubes for saliva samplings and instructions were mailed to the family. Clarifications were given to parents by phone. Information about diagnosis/es and symptom ratings (Swanson, Nolan and Pelham ADHD symptom rating scale [SNAP-IV]) was collected from the records or from parents directly. The version applied has 30 items (nine for inattention, nine for hyperactivity/ impulsivity, eight for ODD, and four control questions), scored by parents on a 4-point scale. Six parental SNAP IV-items for any symptom cluster scored as “quite a bit” or “very much” was applied as a criterion for inclusion in the ADHD/Non-Med-group. Cortisol was analysed in saliva and expressed in nmol/L. Sampling was performed by swabs at home during one ordinary school-day immediately after waking up, 30 min later, at 4 PM (or when coming home from school) and at bedtime. Sampling should be done before brushing teeth, at least 30 min after eating or drinking and at least 1 h after sport activity. The sampling tubes were centrifuged and stored at −70 1C until analysed with the radioimmunoassay technique using the Cortisol (125I) kit from Orion Diagnostica. In 91% (no differences between study groups) of the saliva samples the volume was large enough for carrying out analyses. All analyses were performed with the statistical software programme SPSS (version 20) with log-transformed cortisol data in a general linear model (GLM), adjusting for age, sex, sampling time and symptom scores (attention, hyperactivity, and oppositional behaviour). Interactions had no effects and were removed from the model. Due to unequal group sizes we also performed a Sheffe post-hoc test. We used non-parametric statistical analyses for calculations of differences related to non-ADHD-medication (glucocorticoid inhalation, SSRI, melatonin). Two tailed test with p values o0.05 were considered significant.
0165-1781/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2013.06.011
Please cite this article as: Isaksson, J., et al., Effects of stimulants and atomoxetine on cortisol levels in children with ADHD. Psychiatry Research (2013), http://dx.doi.org/10.1016/j.psychres.2013.06.011i
J. Isaksson et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
2
Table 1 SNAP-IV-scores and saliva cortisol levels of the three study groups: numbers; means and standard deviations; medians and quartiles. Data on individuals in the ADHD/Stim and ADHD/Atomox have previously been included in Isaksson et al. (2012). ADHD-symptoms, not on ADHD-medication “ADHD/Non-Med”
ADHD-diagnosis, on central stimulants “ADHD/Stim”
ADHD-diagnosis, on atomoxetine “ADHD/Atomox”
N
Median (Q1–Q3)
N
Mean (S.D.)
Median (Q1–Q3)
N
Mean (S.D.)
Median (Q1–Q3)
ADHD-symptoms (SNAP-IV; 0.0–3.0 points) Inattention 20 1.84 (0.5) Hyperactivity 20 1.40 (0.7) Oppositional behaviour 20 1.07 (1.0)
1.89 (1.8–2.2) 1.50 (0.7–2.0) 0.75 (0.2–2.1)
134 134 133
1.86 (0.7) 1.50 (0.8) 1.17 (0.8)
2.00 (1.3–2.4) 1.44 (0.9–2.1) 1.13 (0.5–1.8)
19 19 19
1.92 (0.5) 1.91 (0.7) 1.40 (0.6)
1.89 (1.6–2.1) 2.00 (1.2–2.6) 1.50 (1–1.9)
Saliva cortisol levels (nmol/l) Awakening 19 +30 min 18 Afternoon 19 Bedtime 20
7.7 12.4 2.5 0.2
119 134 141 143
10.7 17.9 4.0 2.3
9.0 16.0 3.6 0.8
15 17 20 20
11.7 15.0 4.2 11.0
9.1 15.5 2.8 1.0
Mean (S.D.)
9.6 12.2 2.6 0.9
(4.8) (4.9) (1.6) (1.5)
(5.8–14.1) (7.8–15.6) (1.4–3.4) (0.1–1.1)
The study was approved by the Regional Ethical Review Board in Uppsala, no. 2009/034. All data were re-coded and all identifying information was destroyed.
3. Results SNAP-IV-scores and cortisol data are presented in Table 1. In a GLM adjusted for age, sex, sampling time and symptom scores – where the ADHD/Non-Med group constituted reference – the only significant association between cortisol levels and study group was higher cortisol levels at bedtime in the ADHD/Atomox group (b ¼0.473; p ¼0.031). This association remained significant in a Scheffe post-hoc analysis (p ¼0.045). There was also a trend towards higher cortisol levels 30 min after awakening in the ADHD/Stim group (b¼ 0.129; p ¼0.074). Five children in the ADHD-medicated groups were on inhaled glucocorticoid treatment, eight on SSRI-medication and 20 on melatonin-medication. Neither of these additional treatments influenced the cortisol levels. 4. Discussion In this study of diurnal cortisol levels in children with ADHDmedication (stimulants, atomoxetine), only children on atomoxetine differed from non-medicated with higher cortisol levels at bedtime. These results refute the hypothesis that the lower cortisol levels in children with ADHD than in comparisons are due to ADHD-medication. Contrarily, the findings raise the question if such medication has the opposite effect. This is partly in line with previous findings that stimulants and atomoxetine elevated cortisol levels in children with ADHD (Chen et al., 2012) and that only non-medicated children with ADHD and Oppositional Defiant Disorder had lower cortisol levels than healthy comparisons (Kariyawasam et al., 2002). The dopamine release after stimulant administration correlates positively with a simultaneous cortisol increase (Oswald et al., 2005). Glucocorticoids may enhance the effects of dopamine in the meso-limbic system, thereby contributing to the efficiency of the reward system and facilitating coping (Marinelli and Piazza, 2002). Such types of interplay between cortisol and neurotransmitters may constitute fine-tuned regulatory systems for adaptive procedures (Van Craenenbroeck et al., 2005). One may thus speculate that the low levels of cortisol in children with ADHD may influence such processes. Our findings should be regarded as tentative and need replication in larger study groups, also including more refined data on medication. Children of the ADHD/Non-Med-group had not undergone a child neuropsychiatric examination before inclusion; their symptoms had only been evaluated by parental questionnaires. We had no
(7.4) (16.2) (3.0) (10.9)
(5.6–14.3) (10.3–20.4) (2.1–4.9) (0.3–1.5)
(9.3) (7) (6.4) (30.7)
(6.4–16.2) (9.5–18.2) (2.2–3.8) (0.3–2.0)
objective measure to evaluate coherence to sampling instructions. With the aim of avoiding a “too demanding” approach we refrained from making an evaluation of pubertal development. Instead age was used as a coarse proxy of pubertal stage. We conclude that continuous medication with stimulants or atomoxetine do not explain low cortisol levels in children with ADHD. Possibly, such a medication may rather increase the levels. The interplay between the HPA-axis and neurotransmitters may be a fruitful approach for understanding the development of ADHDsymptoms. Studies measuring cortisol levels before and at different points after start of medication, also controlling for dosage and medication time, are urgent as the next step.
Acknowledgements The study was supported by the Swedish Brain Foundation, (Hjärnfonden), Uppsala University Hospital Research Fund (ALF) and the Swedish Council for Working Life and Social Research, Grant no. 2006-0197 (research position of Frank Lindblad). We want to thank Carl-Johan Törnhage for valuable comments. References Chen, Y.H., Lin, X.X., Chen, H., Liu, Y.Y., Lin, G.X., 2012. Letter to the Editor: the change of the cortisol levels in children with ADHD treated by methylphenidate or atomoxetine. Journal of Psychiatric Research 46, 415–416. Isaksson, J., Nilsson, K.W., Nyberg, F., Hogmark, A., Lindblad, F., 2012. Cortisol levels in children with Attention-Deficit/Hyperactivity Disorder. Journal of Psychiatric Research 46, 1398–1405. Kariyawasam, S.H., Zaw, F., Handley, S.L., 2002. Reduced salivary cortisol in children with comorbid attention deficit hyperactivity disorder and oppositional defiant disorder. Neuroendocrinology Letters 23, 45–48. Lee, M.S., Yang, J.W., Ko, Y.H., Han, C., Kim, S.H., Joe, S.H., Jung, I.K., 2008. Effects of methylphenidate and bupropion on DHEA-S and cortisol plasma levels in attention-deficit hyperactivity disorder. Child Psychiatry and Human Development 39 (2), 201–209. Maayan, R., Yoran-Hagesh, R., Strous, R., Nechmad, A., Averbush, E., Weizman, A., Spivak, B., 2003. Three-month treatment course of methylphenidate increases plasma levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosteronesulfate (DHEA-S) in Attention Deficit Hyperactivity Disorder. Neuropsychobiology 48, 111–115. Marinelli, M., Piazza, P.V., 2002. Interaction between glucocorticoid hormones, stress and psychostimulant drugs. European Journal of Neuroscience 16, 387–394. Oswald, L.M., Wong, D.F., McCaul, M., Zhou, Y., Kuwabara, H., Choi, L., Brasic, J., Wand, G.S., 2005. Relationships among ventral striatal dopamine release, cortisol secretion, and subjective responses to amphetamine. Neuropsychopharmacology 30, 821–832. Van Craenenbroeck, K., De Bosscher, K., Vanden Berghe, W., Vanhoenacker, P., Haegeman, G., 2005. Role of glucocorticoids in dopamine-related neuropsychiatric disorders. Molecular and Cellular Endocrinology 245, 10–22. Wang, L.J., Huang, Y.S., Hsiao, C.C., Chen, C.K., 2012. The trend in morning levels of salivary cortisol in children with ADHD during 6 months of methylphenidate treatment. Journal of Attention Disorders, http://dx.doi.org/10.1177/ 1087054712466139 , in press.
Please cite this article as: Isaksson, J., et al., Effects of stimulants and atomoxetine on cortisol levels in children with ADHD. Psychiatry Research (2013), http://dx.doi.org/10.1016/j.psychres.2013.06.011i
Contents lists available at SciVerse ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Effects of stimulants and atomoxetine on cortisol levels in children with ADHD Johan Isaksson a,n, Åsa Hogmark a, Kent W. Nilsson c, Frank Lindblad a,b a
Department of Neuroscience, Child and Adolescent Psychiatry Unit, Uppsala University, Sweden Stress Research Institute, Stockholm University, Sweden c Centre for Clinical Research, County Council of Västmanland/Uppsala University, Sweden b
art ic l e i nf o
a b s t r a c t
Article history: Received 21 November 2012 Received in revised form 10 April 2013 Accepted 12 June 2013
Children with attention deficit hyperactivity disorder (ADHD) have lower diurnal cortisol levels than non-ADHD-comparisons. Aiming at elucidating effects of ADHD-medication 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 non-medicated. & 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: ADHD Cortisol Medication
1. Introduction In a recent study, children with attention deficit hyperactivity disorder (ADHD) had lower saliva cortisol levels than comparisons at waking up, 30 min later and at bedtime (Isaksson et al., 2012). Most of the children were on ADHD-medication; therefore it was not possible to evaluate the impact of this factor in detail. The findings on effects of ADHD-medication on cortisol levels in children with ADHD are inconclusive with reports of elevated levels with either methylphenidate or atomoxetine (Chen et al., 2012), an increase after 1 month of treatment with methylphenidate but then a gradual decrease towards initial levels (Wang et al., 2012) or no effect at all of methylphenidate on cortisol levels (Maayan et al., 2003; Lee et al., 2008). In order to investigate if continuous medication could explain the lower diurnal cortisol levels in children with ADHD reported previously (Isaksson et al., 2012) we recruited a non-medicated group for comparisons.
2. Methods Study groups (6–17 years of age): 1. children (n¼ 20 [15 boys/5 girls]; mean age 10.1 years, 7 2.7) with ADHDsymptoms, not on ADHD-medication (“ADHD/Non-Med”). Referred by a community team—specialized at early identification of children with
n
Corresponding author. Tel.: +46 18 6112540; fax: +46 18 6112565. E-mail address: [email protected] (J. Isaksson).
neuropsychiatric disorders. Symptoms validated by parental SNAP-IV questionnaires (see below). 2. Children (n ¼147 [113 boys/34 girls]; mean age 11.8 years, 72.7) with a clinical diagnosis of ADHD and on medication with central stimulants (“ADHD/Stim”), recruited from four child psychiatry outpatient units. ADHD-diagnosis verified by clinical neuropsychiatric assessment. 3. Children (n¼ 21[17 boys/4 girls]; mean age 12 years, 72.9) with a clinical diagnosis of ADHD and on medication with atomoxetine (“ADHD/Atomox”), in other respects similar to ADHD/Stim. After written informed consent from parents (and child when ≥15 years of age) a questionnaire about any current medication, tubes for saliva samplings and instructions were mailed to the family. Clarifications were given to parents by phone. Information about diagnosis/es and symptom ratings (Swanson, Nolan and Pelham ADHD symptom rating scale [SNAP-IV]) was collected from the records or from parents directly. The version applied has 30 items (nine for inattention, nine for hyperactivity/ impulsivity, eight for ODD, and four control questions), scored by parents on a 4-point scale. Six parental SNAP IV-items for any symptom cluster scored as “quite a bit” or “very much” was applied as a criterion for inclusion in the ADHD/Non-Med-group. Cortisol was analysed in saliva and expressed in nmol/L. Sampling was performed by swabs at home during one ordinary school-day immediately after waking up, 30 min later, at 4 PM (or when coming home from school) and at bedtime. Sampling should be done before brushing teeth, at least 30 min after eating or drinking and at least 1 h after sport activity. The sampling tubes were centrifuged and stored at −70 1C until analysed with the radioimmunoassay technique using the Cortisol (125I) kit from Orion Diagnostica. In 91% (no differences between study groups) of the saliva samples the volume was large enough for carrying out analyses. All analyses were performed with the statistical software programme SPSS (version 20) with log-transformed cortisol data in a general linear model (GLM), adjusting for age, sex, sampling time and symptom scores (attention, hyperactivity, and oppositional behaviour). Interactions had no effects and were removed from the model. Due to unequal group sizes we also performed a Sheffe post-hoc test. We used non-parametric statistical analyses for calculations of differences related to non-ADHD-medication (glucocorticoid inhalation, SSRI, melatonin). Two tailed test with p values o0.05 were considered significant.
0165-1781/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2013.06.011
Please cite this article as: Isaksson, J., et al., Effects of stimulants and atomoxetine on cortisol levels in children with ADHD. Psychiatry Research (2013), http://dx.doi.org/10.1016/j.psychres.2013.06.011i
J. Isaksson et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
2
Table 1 SNAP-IV-scores and saliva cortisol levels of the three study groups: numbers; means and standard deviations; medians and quartiles. Data on individuals in the ADHD/Stim and ADHD/Atomox have previously been included in Isaksson et al. (2012). ADHD-symptoms, not on ADHD-medication “ADHD/Non-Med”
ADHD-diagnosis, on central stimulants “ADHD/Stim”
ADHD-diagnosis, on atomoxetine “ADHD/Atomox”
N
Median (Q1–Q3)
N
Mean (S.D.)
Median (Q1–Q3)
N
Mean (S.D.)
Median (Q1–Q3)
ADHD-symptoms (SNAP-IV; 0.0–3.0 points) Inattention 20 1.84 (0.5) Hyperactivity 20 1.40 (0.7) Oppositional behaviour 20 1.07 (1.0)
1.89 (1.8–2.2) 1.50 (0.7–2.0) 0.75 (0.2–2.1)
134 134 133
1.86 (0.7) 1.50 (0.8) 1.17 (0.8)
2.00 (1.3–2.4) 1.44 (0.9–2.1) 1.13 (0.5–1.8)
19 19 19
1.92 (0.5) 1.91 (0.7) 1.40 (0.6)
1.89 (1.6–2.1) 2.00 (1.2–2.6) 1.50 (1–1.9)
Saliva cortisol levels (nmol/l) Awakening 19 +30 min 18 Afternoon 19 Bedtime 20
7.7 12.4 2.5 0.2
119 134 141 143
10.7 17.9 4.0 2.3
9.0 16.0 3.6 0.8
15 17 20 20
11.7 15.0 4.2 11.0
9.1 15.5 2.8 1.0
Mean (S.D.)
9.6 12.2 2.6 0.9
(4.8) (4.9) (1.6) (1.5)
(5.8–14.1) (7.8–15.6) (1.4–3.4) (0.1–1.1)
The study was approved by the Regional Ethical Review Board in Uppsala, no. 2009/034. All data were re-coded and all identifying information was destroyed.
3. Results SNAP-IV-scores and cortisol data are presented in Table 1. In a GLM adjusted for age, sex, sampling time and symptom scores – where the ADHD/Non-Med group constituted reference – the only significant association between cortisol levels and study group was higher cortisol levels at bedtime in the ADHD/Atomox group (b ¼0.473; p ¼0.031). This association remained significant in a Scheffe post-hoc analysis (p ¼0.045). There was also a trend towards higher cortisol levels 30 min after awakening in the ADHD/Stim group (b¼ 0.129; p ¼0.074). Five children in the ADHD-medicated groups were on inhaled glucocorticoid treatment, eight on SSRI-medication and 20 on melatonin-medication. Neither of these additional treatments influenced the cortisol levels. 4. Discussion In this study of diurnal cortisol levels in children with ADHDmedication (stimulants, atomoxetine), only children on atomoxetine differed from non-medicated with higher cortisol levels at bedtime. These results refute the hypothesis that the lower cortisol levels in children with ADHD than in comparisons are due to ADHD-medication. Contrarily, the findings raise the question if such medication has the opposite effect. This is partly in line with previous findings that stimulants and atomoxetine elevated cortisol levels in children with ADHD (Chen et al., 2012) and that only non-medicated children with ADHD and Oppositional Defiant Disorder had lower cortisol levels than healthy comparisons (Kariyawasam et al., 2002). The dopamine release after stimulant administration correlates positively with a simultaneous cortisol increase (Oswald et al., 2005). Glucocorticoids may enhance the effects of dopamine in the meso-limbic system, thereby contributing to the efficiency of the reward system and facilitating coping (Marinelli and Piazza, 2002). Such types of interplay between cortisol and neurotransmitters may constitute fine-tuned regulatory systems for adaptive procedures (Van Craenenbroeck et al., 2005). One may thus speculate that the low levels of cortisol in children with ADHD may influence such processes. Our findings should be regarded as tentative and need replication in larger study groups, also including more refined data on medication. Children of the ADHD/Non-Med-group had not undergone a child neuropsychiatric examination before inclusion; their symptoms had only been evaluated by parental questionnaires. We had no
(7.4) (16.2) (3.0) (10.9)
(5.6–14.3) (10.3–20.4) (2.1–4.9) (0.3–1.5)
(9.3) (7) (6.4) (30.7)
(6.4–16.2) (9.5–18.2) (2.2–3.8) (0.3–2.0)
objective measure to evaluate coherence to sampling instructions. With the aim of avoiding a “too demanding” approach we refrained from making an evaluation of pubertal development. Instead age was used as a coarse proxy of pubertal stage. We conclude that continuous medication with stimulants or atomoxetine do not explain low cortisol levels in children with ADHD. Possibly, such a medication may rather increase the levels. The interplay between the HPA-axis and neurotransmitters may be a fruitful approach for understanding the development of ADHDsymptoms. Studies measuring cortisol levels before and at different points after start of medication, also controlling for dosage and medication time, are urgent as the next step.
Acknowledgements The study was supported by the Swedish Brain Foundation, (Hjärnfonden), Uppsala University Hospital Research Fund (ALF) and the Swedish Council for Working Life and Social Research, Grant no. 2006-0197 (research position of Frank Lindblad). We want to thank Carl-Johan Törnhage for valuable comments. References Chen, Y.H., Lin, X.X., Chen, H., Liu, Y.Y., Lin, G.X., 2012. Letter to the Editor: the change of the cortisol levels in children with ADHD treated by methylphenidate or atomoxetine. Journal of Psychiatric Research 46, 415–416. Isaksson, J., Nilsson, K.W., Nyberg, F., Hogmark, A., Lindblad, F., 2012. Cortisol levels in children with Attention-Deficit/Hyperactivity Disorder. Journal of Psychiatric Research 46, 1398–1405. Kariyawasam, S.H., Zaw, F., Handley, S.L., 2002. Reduced salivary cortisol in children with comorbid attention deficit hyperactivity disorder and oppositional defiant disorder. Neuroendocrinology Letters 23, 45–48. Lee, M.S., Yang, J.W., Ko, Y.H., Han, C., Kim, S.H., Joe, S.H., Jung, I.K., 2008. Effects of methylphenidate and bupropion on DHEA-S and cortisol plasma levels in attention-deficit hyperactivity disorder. Child Psychiatry and Human Development 39 (2), 201–209. Maayan, R., Yoran-Hagesh, R., Strous, R., Nechmad, A., Averbush, E., Weizman, A., Spivak, B., 2003. Three-month treatment course of methylphenidate increases plasma levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosteronesulfate (DHEA-S) in Attention Deficit Hyperactivity Disorder. Neuropsychobiology 48, 111–115. Marinelli, M., Piazza, P.V., 2002. Interaction between glucocorticoid hormones, stress and psychostimulant drugs. European Journal of Neuroscience 16, 387–394. Oswald, L.M., Wong, D.F., McCaul, M., Zhou, Y., Kuwabara, H., Choi, L., Brasic, J., Wand, G.S., 2005. Relationships among ventral striatal dopamine release, cortisol secretion, and subjective responses to amphetamine. Neuropsychopharmacology 30, 821–832. Van Craenenbroeck, K., De Bosscher, K., Vanden Berghe, W., Vanhoenacker, P., Haegeman, G., 2005. Role of glucocorticoids in dopamine-related neuropsychiatric disorders. Molecular and Cellular Endocrinology 245, 10–22. Wang, L.J., Huang, Y.S., Hsiao, C.C., Chen, C.K., 2012. The trend in morning levels of salivary cortisol in children with ADHD during 6 months of methylphenidate treatment. Journal of Attention Disorders, http://dx.doi.org/10.1177/ 1087054712466139 , in press.
Please cite this article as: Isaksson, J., et al., Effects of stimulants and atomoxetine on cortisol levels in children with ADHD. Psychiatry Research (2013), http://dx.doi.org/10.1016/j.psychres.2013.06.011i