Treatment Response in Behaviour Disorders in Rett Syndrome

Ana Roche Martínez, Marc Turon, Laura Callejón-Póo, Elisenda Sole, Judith Armstrong, Mercé Pineda

Child Cardiology Department, Sant Joan de Déu Children’s Hospital, Barcelona, Spain.
Child Neurology Department, Sant Joan de Déu Children’s Hospital, Barcelona, Spain.
Child Neuropsychology Department, Sant Joan de Déu Children’s Hospital, Barcelona, Spain.
Molecular Genetics Laboratory, Sant Joan de Déu Children’s Hospital, Barcelona, Spain.

DOI: 10.4236/jbbs.2013.32023                

Abstract

RTT girls suffer periods of abnormal behavior from early infancy, including irritability and sleep disorders or anxiety in the first years of life, and a more depressed mood after adolescence, all of which influences their quality of life. An association between emotional and behavioral disorders and various neurochemical changes in the synapses of cortical and subcortical brain regions has been established; also, cortisol levels in the blood vary during stress. The main purpose of this study was to improve mood and behavior disorders in RTT patients with venlafaxine (SNRI), and compare the results with citalopram (SSRIs) during 6 - 8 weeks, to determine which drug offered greater efficacy and fewer side effects, as well as to compare them to risperidone, and to correlate cortisol levels in saliva with stress and drug response. Eleven patients, aged 5 to 26 years old, agreed to participate in this study; neuropsychological tests (Mullen and Vineland scales), quality of life and quality of sleep scales, blood tests, EKG and EEG were performed before and after treatment. Only 2 patients completed the three months trial. Improvement in mood and behavior was not statistically significant for patients; differences in neurodevelopment and quality of life or sleep scales were not significant either; no serious adverse effects were observed. Cortisol levels in saliva decreased in 50% of the patients after the first month of treatment, although this was not statistically significant.

Keywords

Cortisol, Mood and Behavior, Rett Syndrome; SSRI; SNRI

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	B. Hagberg, “Clinical Manifestations and Stages of Rett Syndrome,” Mental Retardation and Development Disability Research Review, Vol. 8, No. 2, 2002, pp. 61-65. doi:10.1002/mrdd.10020
[2]	E. Trevathan and S. Naidu, “The Clinical Recognition and Differential Diagnosis of Rett Syndrome,” Journal of Child Neurology, Vol. 3, No. S6, 1988, p. 16.
[3]	P. Moretti, J. M. Levenson, F. Battaglia, R. Atkinson, R. Teague, et al., “Learning and Memory and Synaptic Plasticity Are Impaired in a Mouse Model of Rett Syndrome,” Journal of Neurosciences, Vol. 1, No. 26, 2006, pp. 319-327.
[4]	M. E. Blue, S. Naidu and M. V. Johnston, “Development of Amino Acid Receptors in Frontal Cortex from Girls with Rett Syndrome,” Annals of Neurology, Vol. 45, No. 4, 1999, pp. 541-545. doi:10.1002/1531-8249(199904)45:4<541::AID-ANA21>3.0.CO;2-2
[5]	R. Lappalainen and R. S. Riikonen, “High Levels of CSF Glutamate in Rett Syndrome,” Pediatric Neurology, Vol. 15, No. 3, 1996, pp. 213-216. doi:10.1016/S0887-8994(96)00218-4
[6]	A. Horská, L. Farage, G. Bibat, L. M. Nagae, W. E. Kaufmann, P. B. Barker, et al., “Brain Metabolism in Rett Syndrome: Age, Clinical, and Genotype Correlations,” Annals of Neurology, Vol. 65, No. 1, 2009, pp. 90-97. doi:10.1002/ana.21562
[7]	H. T. Chao, H. Y. Zoghbi and C. Rosenmund, “MeCP2 Controls Excitatory Synaptic Strength by Regulating Glutamatergic Synapse Number,” Neuron, Vol. 56, No. 1, 2007, pp. 58-65. doi:10.1016/j.neuron.2007.08.018
[8]	L. Medrihan, E. Tantalaki, G. Aramuni, V. Sargsyan, I. Dudanova, M. Missler, et al., “Early Defects of GABAergic Synapses in the Brain Stem of a MeCP2 Mouse Model of Rett Syndrome,” Journal of Neurophysiology, No. 99, pp. 112-121.
[9]	J. C. Viemari, “Noradrenergic Modulation of the Respiratory Neural Network,” Respiratory Physiology and Neurobiology, Vol. 1-2, No. 164, 2008, pp. 123-130.
[10]	D. S. Paterson, E. G. Thompson, R. A. Belliveau, B. A. Antalffy, F. L. Trachtenberg, D. D. Armstrong, et al., “Serotonin Transporter Abnormality in the Dorsal Motor Nucleus of the Vagus in Rett Syndrome, Potential Implications for Clinical Autonomic Dysfunction,” Journal of Neuropathology and Experimental Neurology, Vol. 11, No. 64, 2005, pp. 1018-1027. doi:10.1097/01.jnen.0000187054.59018.f2
[11]	C. Chiron, C. Bulteau, C. Loc’h, C. Raynaud, B. Garreau, A. Syrota, et al., “Dopaminergic D2 Receptor SPECT Imaging in Rett Syndrome: Increase of Specific Binding in Striatum,” Journal of Nuclear Medecine, Vol. 10, No. 34, 1993, pp. 1717-1721.
[12]	S. Ide, M. Itoh and Y. Goto, “Defect in Normal Developmental Increase of the Brain Biogenic Amine Concentrations in the Mecp2-Null Mouse,” Neurosciences Letters, Vol. 386, No. 1, 2005, pp. 14-17. doi:10.1016/j.neulet.2005.05.056
[13]	E. Shirazi and J. Alaghband-Rad, “An Open Trial of Citalopram in Children and Adolescents with Depression,” Journal of Child and Adolescent Psychopharmacology, Vol. 15, No. 2, 2005, pp. 233-239. doi:10.1089/cap.2005.15.233
[14]	K. D. Wagner, A. S. Robb, R. L. Findling, J. Jin, M. M. Gutierrez and W. E. Heydorn, “A Randomized, PlaceboControlled Trial of Citalopram for the Treatment of Major Depression in Children and Adolescents,” American Journal of Psychiatry, Vol. 161, No. 6, 2004, pp. 1079-1083. doi:10.1176/appi.ajp.161.6.1079
[15]	L. B. Namerow, P. Thomas, J. Q. Bostic, J. Prince and M. C. Monuteaux, “Use of Citalopram in Pervasive Developmental Disorders,” Journal of Developmental and Behavioral Pediatrics, Vol. 24, No. 2, 2003, pp. 104-108. doi:10.1097/00004703-200304000-00005
[16]	J. L. Couturier and R. Nicolson, “A Retrospective Assessment of Citalopram in Children and Adolescents with Pervasive Developmental Disorders,” Journal of Child and Adolescent Psychopharmacology, Vol. 12, No. 3, 2002, pp. 243-248. doi:10.1089/104454602760386932
[17]	J. L. Baumgartner, G. L. Emslie and M. L. Crismon, “Citalopram in Children and Adolescents with Depression or Anxiety,” Annals of Pharmacotherapy, Vol. 36, No. 11, 2002, pp. 1692-1697. doi:10.1345/aph.1C078
[18]	J. L. Armenteros and J. E. Lewis, “Citalopram Treatment for Impulsive Aggression in Children and Adolescents: An Open Pilot Study,” Journal of the American Academy of Child & Adolescent Psychiatry, Vol. 41, No. 5, 2002, pp. 522-529. doi:10.1097/00004583-200205000-00009
[19]	G. J. Emslie, R. L. Findling, P. P. Yeung, N. R. Kunz and Y. Li, “A Randomized Controlled Trial of Venlafaxine ER versus Placebo in Pediatric Social Anxiety Disorder,” Biological Psychiatry, Vol. 62, No. 10, 2007, pp. 11491154. doi:10.1016/j.biopsych.2007.02.025
[20]	G. J. Emslie, R. L. Findling, P. P. Yeung, N. R. Kunz and Y. Li, “Venlafaxine ER for the Treatment of Pediatric Subjects with Depression: Results of Two Placebo-Controlled Trials,” Journal of the American Academy of Child Adolescent Psychiatry, Vol. 4, No. 46, pp. 479-488.
[21]	G. J. Emslie, P. P. Yeung and N. R. Kunz, “Long-Term, Open-Label Venlafaxine Extended-Release Treatment in Children and Adolescents with Major Depressive Disorder. CNS Spectrums, Vol. 3, No. 12, 2007, pp. 223-233.
[22]	M. A. Rynn, M. A. Riddle, P. P. Yeung and N. R. Kunz, “Efficacy and Safety of Extended-Release Venlafaxine in the Treatment of Generalized Anxiety Disorder in Children and Adolescents: Two Placebo-Controlled Trials,” American Journal of Psychiatry, Vol. 164, No. 2, 2007, pp. 290-300. doi:10.1176/appi.ajp.164.2.290
[23]	E. B. Weller, R. A. Weller and G. P. Davis, “Use of Venlafaxine in Children and Adolescents: A Review of Current Literature,” Depression and Anxiety, Vol. 12, No. S1, 2000, pp. 85-89. doi:10.1002/1520-6394(2000)12:1+<85::AID-DA12>3.0.CO;2-0
[24]	B. E. McGill, S. F. Bundle, M. B. Yaylaoglu, J. P. Carson, C. Thaller and H. Y. Zoghbi, “Enhanced Anxiety and StressInduced Corticosterone Release Are Associated with Increased CRH Expression in Mouse Model of Rett Syndrome,” Proceedings of the National Academy of Sciences of the USA, Vol. 103, No. 48, 2006, pp. 1826718272. doi:10.1073/pnas.0608702103
[25]	K. Greaves-Lord, R. F. Ferdinand, A. J. Oldehinkel, F. E. Sondeijker, J. Ormel and F. C. Verhulst, “Higher Cortisol Awakening Response in Young Adolescents with Persistent Anxiety Problem,” Acta Psychiatrica Scandinavica, Vol. 116, No. 2, 2007, pp 137-144. doi:10.1111/j.1600-0447.2007.01001.x
[26]	L. M. Jansen, C. C. Gispende Wied, M. A. Jansen, R. J. van der Gaag, W. Matthys and H. van Engeland, “Pituitary-Adrenal Reactivity in a Child Psychiatric Population: Salivary Cortisol Response to Stressors,” European Neuropsychopharmacology, Vol. 1-2, No. 9, 1999, pp. 67-75.
[27]	D. Van West, S. Claes, J. Sulon and D. Deboutte, “Hypothalamic-Pituitary-Adrenal Reactivity in Prepubertal Children with Social Phobia,” Journal of Affective Disorders, Vol. 111, No. 2, 2008, pp. 281-290. doi:10.1016/j.jad.2008.03.006
[28]	B. A. Corbett, S. Mendoza, M. Abdullah, J. A. Wegelin and S. Levine, “Cortisol Circadian Rhythms and Response to Stress in Children with Autism,” Psychoneuroendocrinology, Vol. 31, No. 1, 2006, pp. 59-68. doi:10.1016/j.psyneuen.2005.05.011
[29]	J. G. Rosmalen, A. J. Oldehinkel, J. Ormel, A. F. de Winter, J. K. Buitelaar and F. C. Verhulst, “Determinants of Salivary Cortisol Levels in 10-12 Year Old Children; A Population-Based Study of Individual Differences,” Psychoneuroendocrinology, Vol. 30, No. 5, 2005, pp. 483495. doi:10.1016/j.psyneuen.2004.12.007
[30]	D. S. Jessop and J. M. Turner-Cobb, “Measurement and Meaning of Salivary Cortisol: A Focus on Health and Disease in Children,” Stress, Vol. 11, No. 1, 2008, pp. 1-14. doi:10.1080/10253890701365527
[31]	M. Neu, M. Goldstein, D. Gao and M. L. Laudenslager, “Salivary Cortisol in Preterm Infants: Validation of a Simple Method for Collecting Saliva for Cortisol Determination,” Early Human Development, Vol. 1, No. 83, 2007, pp. 4754.
[32]	K. Hanrahan, A. M. McCarthy, C. Kleiber, S. Lutgendorf and E. Tsalikian, “Strategies for Salivary Cortisol Collection and Analysis in Research with Children. Applied Nursing Research, Vol. 19, No. 2, 2006, pp. 95-101. doi:10.1016/j.apnr.2006.02.001
[33]	N. Akshoomoff, “Use of the Mullen Scales of Early Learning for the Assessment of Young Children with Autism Spectrum Disorders,” Child Neuropsychoog, Vol. 12, No. 4-5, 2006, pp. 269-277. doi:10.1080/09297040500473714
[34]	D. Hessl, D. V. Nguyen, C. Green, A. Chavez, F. Tassone, R. J. Hagerman, et al., “A Solution to Limitations of Cognitive Testing in Children with Intellectual Disabilities: The Case of Fragile X Syndrome,” Journal of Neurodevelopment Disorders, Vol. 1, No. 1, 2009, pp. 33-45. doi:10.1007/s11689-008-9001-8
[35]	C. H. Pan and S. Tsai, “Early Intervention with Psychostimulants or Antidepressants to Increase Methyl-CpG-Binding Protein 2 (MeCP2) Expressions: A Potential Therapy for Rett Syndrome,” Medical Sciences Monitor, Vol. 18, No. 1, 2012, pp. 1-3. doi:10.12659/MSM.882183