Aripiprazole improves associated comorbid conditions in addition to tics in GTSin addition to tics in GTS

Key findings and significance

11.3 Aripiprazole improves associated comorbid conditions in addition to tics in GTSin addition to tics in GTS

Considering that the drug discovery and development process and is a long and arduous one that may take up to an average of 12 years, it is thus critical to carefully examine the inﬂuence of currently available drugs on the clinical characteristics of the patients.

In this work, we chose to investigate the inﬂuence of aripiprazole on the clinical charac-teristics of the patient sample given its eﬃcacy and its favorable side eﬀect proﬁle [170].

Key findings and significance 155

Although randomized controlled trials including large patient samples are currently lack-ing, aripiprazole is currently considered as a ﬁrst choice drug for the treatment of tics by the European and German societies [6].

Currently, the majority of clinical investigations on aripiprazole have been conducted on child and adolescent populations. Additionally, most studies only explored the inﬂuence of aripiprazole on motor features of GTS, with a small number of reports investigating its inﬂuence on comorbid conditions. In this regard, we aimed at investigating the inﬂuence of aripiprazole on both motor and non-motor features exhibited by GTS, and additionally aimed at further exploring its eﬃcacy and safety in a group of drug-free adult patients.

Given that the patients recruited at baseline were presented with the option of partaking in the longitudinal study design, in which about half elected to undergo treatment, we were also able to investigate the factors that inﬂuence a patients’ decision in electing for or against treatment.

Similar to previous work, our results indicated that aripiprazole leads to signiﬁcant re-ductions of tics in adult patients with GTS. Interestingly, however, we did not ﬁnd any eﬀect on premonitory urges which precede tics, indicating that tics and premonitory urges are not necessarily related events as suggested by other studies [398,399]. We also found that tic severity, premonitory urges and quality of life were not signiﬁcant factors in a patient’s decision in undergoing treatment.

In relation to psychiatric comorbidities, the sample exhibited reductions in some of the associated conditions. Obsessive compulsive disorder (OCD) diagnosis decreased by ap-proximately 50% and no patients developed OCD symptoms following treatment. Simi-larly, the number of patients diagnosed with depression and anxiety decreased by about 10%. Notably, none of the patients developed OCD, depression or anxiety disorder during treatment with aripiprazole. On the other hand, attention deﬁcit/hyperactivity disorder (ADHD) classiﬁcation remained unchanged in the patients that underwent treatment.

While patients with comorbid ADHD tended to elect against undergoing treatment, it is interesting to report that patients with comorbid OCD tended to elect for undergoing treatment. In general, no patients reported any severe side eﬀects. Similar to previous work, our results indicated that aripiprazole is a safe and reliable treatment.

As an atypical second-generation antipsychotic, aripiprazole presents an example of a functionally selective drug that exhibits an adaptive pharmacological proﬁle that pro-duces a mix of eﬀects through the activation or inhibition of a limited number of signal transduction pathways as a result of its ability to induce unique G protein-coupled recep-tor conformations. While it mainly targets the dopaminergic system, recent studies [171]

have indicated it also exhibit potent eﬀects on other systems including the serotonergic, GABAergic and glutamatergic system. In this regard, it may be plausible to suggest

Key findings and significance 156

that eﬃcacy of aripiprazole in treating motor as well as non-motor features are of GTS, are a result of its inﬂuence on the multiple aﬀected systems in GTS. The treatment of motor and non-motor features associated with GTS may stand to be more eﬀective with the design of functionally selective modulators with an adaptive pharmacological proﬁle that targets multiple systems.

11.4 Significance

Our results indicate that patients with GTS exhibit an abnormality in the ﬂux of metabo-lites in the GABA-glutamate-glutamine cycle, thus implying perturbations in astrocytic-neuronal coupling systems that maintain the subtle balance between excitatory and in-hibitory neurotransmission within subcortical nuclei. These abnormalities may be driven or further compounded by abnormalities in iron metabolism. Chronic perturbations in the subcortical GABA-Glu-Gln cycle ﬂux could lead to spatially focalized alterations in excitatory, inhibitory and modulatory subcortical neurochemical ratios that would have a profound inﬂuence on the neuroplastic mechanisms involved in reinforcement learning and habit formation systems. This work sheds a new light on the neurobiological ba-sis of GTS and provides novel clues that may prove critical in the future development of functionally selective pharmacological modulators that target multiple neurochemical systems.

* * *

Part VI

Bibliography

157

Bibliography

[1] Gilles de la Tourette. Étude sur une aﬀection nerveuse caractérisée par de l’incoordination motrice accompagnée d’écholalie et de coprolalie. Arch. Neurol, 9(c):19–42, 1885.

[2] Hugh Rickards, Ian Woolf, and Andrea Eugenio Cavanna. "Trousseau’s disease:" a description of the Gilles de la Tourette syndrome 12 years before 1885. Movement disorders: official journal of the Movement Disorder Society, 25(14):2285–9, oct 2010.

[3] Sheryl Geisler. Une Lecon Clinique a la Salpetriere (A Clinical Lesson at the Salpetriere), Andre Brouillet (1887).The Journal of Physician Assistant Education, 22(3), 2011.

[4] Arthur K Shapiro and E Shapiro. Treatment of Gilles de la Tourette’s Syndrome with Haloperidol.

The British Journal of Psychiatry, 114(508):345–350, mar 1968.

[5] Danielle C Cath, Tammy Hedderly, Andrea G Ludolph, Jeremy S Stern, Tara Murphy, Andreas Hartmann, Virginie Czernecki, Mary May Robertson, Davide Martino, A Munchau, and R Rizzo.

European clinical guidelines for Tourette Syndrome and other tic disorders. Part I: assessment.

European Child & Adolescent Psychiatry, 20(4):155–171, 2011.

[6] Veit Roessner, Kerstin J Plessen, Aribert Rothenberger, Andrea G Ludolph, Renata Rizzo, Liselotte Skov, Gerd Strand, Jeremy S Stern, Cristiano Termine, and Pieter J Hoekstra. Eu-ropean clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. European Child & Adolescent Psychiatry, 20(4):173–96, apr 2011.

[7] Cara Verdellen, Jolande van de Griendt, Andreas Hartmann, and Tara Murphy. European clinical guidelines for Tourette syndrome and other tic disorders. Part III: behavioural and psychosocial interventions. European Child & Adolescent Psychiatry, 20:197–207, 2011.

[8] Kirsten R Müller-Vahl, Danielle C Cath, Andrea E Cavanna, Sandra Dehning, Mauro Porta, Mary M Robertson, and Veerle Visser-Vandewalle. European clinical guidelines for Tourette syn-drome and other tic disorders. Part IV: deep brain stimulation. European Child & Adolescent Psychiatry, 20(4):209–17, apr 2011.

[9] James F Leckman. Tourette’s syndrome. Lancet, 360(9345):1577–86, nov 2002.

[10] Tristan Knight, Thomas Steeves, Lundy Day, Mark Lowerison, Nathalie Jette, and Tamara Pring-sheim. Prevalence of tic disorders: a systematic review and meta-analysis. Pediatric neurology, 47(2):77–90, aug 2012.

[11] Joseph Jankovic. Tourette syndrome. Phenomenology and classiﬁcation of tics.Neurologic Clinics, 15:267–275, 1997.

[12] Michael H Bloch and James F Leckman. Clinical course of Tourette syndrome. Journal of Psy-chosomatic Research, 67:497–501, 2009.

[13] James F. Leckman, Heping Zhang, Amy Vitale, Fatima Lahnin, Kimberly Lynch, Colin Bondi, Young-Shin Kim, and Bradley S. Peterson. Course of tic severity in Tourette syndrome: the ﬁrst two decades. Pediatrics, 102:14–19, 1998.

[14] Carolyn Kwak, Kevin Dat Vuong, and Joseph Jankovic. Premonitory sensory phenomenon in Tourette’s syndrome. Movement disorders official journal of the Movement Disorder Society, 18:1530–1533, 2003.

158

Bibliography 159

[15] Stephanie C Cohen, James F Leckman, and Michael H Bloch. Neuroscience and Biobehavioral Re-views Clinical assessment of Tourette syndrome and tic disorders.Neuroscience and Biobehavioral Reviews, 37(6):997–1007, 2013.

[16] Matthew E Hirschtritt, Paul C Lee, David L Pauls, Yves Dion, Marco A Grados, Cornelia Illmann, Robert A King, Paul Sandor, William M McMahon, Gholson J Lyon, Danielle C Cath, Roger Kurlan, Mary M. Robertson, Lisa Osiecki, Jeremiah M Scharf, and Carol A Mathews. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA psychiatry, 72(4):325–33, 2015.

[17] Nanette M Debes, Helle Hjalgrim, and Liselotte Skov. The presence of attention-deﬁcit hyperac-tivity disorder (ADHD) and obsessive-compulsive disorder worsen psychosocial and educational problems in Tourette syndrome.Journal of child neurology, 25:171–181, 2010.

[18] Mary M Robertson. Tourette syndrome, associated conditions and the complexities of treatment.

Brain: a journal of neurology, 123(3):425–462, mar 2000.

[19] American Psychiatric Association.Diagnostic and statistical manual of mental disorders: DSM-5.

American Psychiatric Association, Washington, D.C., 2013.

[20] Kevin SP McNaught and Jonathan W Mink. Advances in understanding and treatment of Tourette syndrome. Nature reviews. Neurology, 7(12):667–76, dec 2011.

[21] Avshalom Caspi and Terrie E Moﬃtt. Gene-environment interactions in psychiatry: joining forces with neuroscience.Nature reviews. Neuroscience, 7(7):583–90, jul 2006.

[22] Hao Deng, Kai Gao, and Joseph Jankovic. The genetics of Tourette syndrome. Nature reviews.

Neurology, 8(4):203–13, apr 2012.

[23] David L. Pauls, Thomas V. Fernandez, Carol a. Mathews, Matthew W. State, and Jeremiah M.

Scharf. The inheritance of Tourette Disorder: A review. Journal of Obsessive-Compulsive and Related Disorders, 3:380–385, 2014.

[24] Pieter J Hoekstra, Andrea Dietrich, Mark J Edwards, Ishraga Elamin, and Davide Martino. En-vironmental factors in Tourette syndrome. Neuroscience and biobehavioral reviews, 37(6):1040–9, jul 2013.

[25] Carol A Mathews, Brianne Bimson, Thomas L Lowe, Luis Diego Herrera, Cathy L Budman, Gerald Erenberg, Allen Naarden, Ruth D Bruun, Nelson B Freimer, and Victor I Reus. Association Between Maternal Smoking and Increased Symptom Severity in Tourette’s Syndrome. American Journal of Psychiatry, 163(June):1066–1073, 2006.

[26] Douglas L Leslie, Laura Kozma, Andrés Martin, Angeli Landeros, Liliya Katsovich, Robert a King, and James F Leckman. Neuropsychiatric disorders associated with streptococcal infection:

a case-control study among privately insured children.Journal of the American Academy of Child and Adolescent Psychiatry, 47:1166–1172, 2008.

[27] Loren K Mell, Robert L Davis, and David Owens. Association between streptococcal infection and obsessive-compulsive disorder, Tourette’s syndrome, and tic disorder.Pediatrics, 116(1):56–60, 2005.

[28] Ryan J Felling and Harvey S Singer. Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation.The Journal of neuroscience: the official journal of the Society for Neuroscience, 31(35):12387–12395, aug 2011.

[29] Christos Ganos, Veit Roessner, and Alexander Münchau. The functional anatomy of Gilles de la Tourette syndrome. Neuroscience and biobehavioral reviews, 37(6):1050–62, jul 2013.

[30] Deanna J Greene, Kevin J Black, and Bradley L Schlaggar. Neurobiology and functional anatomy of tic disorders. In D. Martino and J Leckman, editors,Tourette Syndrome, pages 238–275. Oxford University Press, 2013.

[31] Harvey Singer. The Neurochemistry of Tourette Syndrome. In Davide Martino and James F.

Leckman, editors,Tourette Syndrome, pages 276–297. Oxford University Press, 2013.

[32] Bogdan Draganski, Davide Martino, Andrea E Cavanna, Chloe Hutton, Michael Orth, Mary M

Bibliography 160

Robertson, Hugo D Critchley, and Richard S Frackowiak. Multispectral brain morphometry in Tourette syndrome persisting into adulthood. Brain: a journal of neurology, 133(Pt 12):3661–75, dec 2010.

[33] Bradley Peterson, Malcolm Riddle, D. J. Cohen, L. D. Katz, J. C. Smith, M. T. Hardin, and J F Leckman. Reduced basal ganglia volumes in Tourette’s syndrome using three-dimensional reconstruction techniques from magnetic resonance images. Neurology, 43(5):941–941, may 1993.

[34] Bradley S Peterson, Prakash Thomas, Michael J Kane, Lawrence Scahill, Heping Zhang, Richard Bronen, Robert a King, James F Leckman, and Lawrence Staib. Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Archives of general psychiatry, 60(4):415–24, apr 2003.

[35] Cherine Fahim, Uicheul Yoon, Samir Das, Oliver Lyttelton, John Chen, Rozie Arnaoutelis, Guy Rouleau, Paul Sandor, Kirk Frey, Catherine Brandner, and Alan C Evans. Somatosensory-motor bodily representation cortical thinning in Tourette: eﬀects of tic severity, age and gender. Cortex;

a journal devoted to the study of the nervous system and behavior, 46(6):750–60, jun 2010.

[36] Elizabeth R Sowell, Eric Kan, June Yoshii, Paul M Thompson, Ravi Bansal, Dongrong Xu, Arthur W Toga, and Bradley S Peterson. Thinning of sensorimotor cortices in children with Tourette syndrome. Nature neuroscience, 11(6):637–9, jun 2008.

[37] Yulia Worbe, Emilie Gerardin, Andreas Hartmann, Romain Valabrégue, Marie Chupin, Léon Tremblay, Marie Vidailhet, Olivier Colliot, and Stéphane Lehéricy. Distinct structural changes underpin clinical phenotypes in patients with Gilles de la Tourette syndrome.Brain: a journal of neurology, 133(Pt 12):3649–60, dec 2010.

[38] James F Leckman, Michael H Bloch, Megan E Smith, Daouia Larabi, and Michelle Hampson.

Neurobiological substrates of Tourette’s disorder. Journal of Child and Adolescent Psychophar-macology, 20(4):237–47, aug 2010.

[39] Michelle Hampson, Fuyuze Tokoglu, Robert A King, R Todd Constable, and James F Leckman.

Brain Areas Coactivating with Motor Cortex During Chronic Motor Tics and Intentional Move-ments.Biological Psychiatry, 65(7):594–599, feb 2009.

[40] Zhishun Wang, TV Maia, and Rachel Marsh. The neural circuits that generate tics in Tourette’s syndrome. American Journal of . . ., pages 1326–1337, 2011.

[41] Bradley S Peterson, Pawel Skudlarski, Adam W Anderson, Heping Zhang, Chris Gatenby, Cheryl M Lacadie, James F Leckman, and John C Gore. A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Archives of general psychiatry, 55(4):326–33, apr 1998.

[42] Stephan Bohlhalter, A Goldﬁne, S Matteson, G Garraux, T Hanakawa, K Kansaku, R Wurz-man, and M Hallett. Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain: a journal of neurology, 129(Pt 8):2029–37, aug 2006.

[43] Luigi Mazzone, Shan Yu, Clancy Blair, Benjamin C Gunter, Zhishun Wang, Rachel Marsh, and Bradley S Peterson. An FMRI study of frontostriatal circuits during the inhibition of eye blinking in persons with Tourette syndrome.The American journal of psychiatry, 167(3):341–9, mar 2010.

[44] Bharat Biswal, John L Ulmer, Robert L Krippendorf, Harold H Harsch, David L Daniels, James S Hyde, and Victor M Haughton. Abnormal cerebral activation associated with a motor task in Tourette syndrome. AJNR. American journal of neuroradiology, 19(8):1509–12, sep 1998.

[45] Nanette M Debes, Adam Hansen, Liselotte Skov, and Henrik Larsson. A functional magnetic resonance imaging study of a large clinical cohort of children with Tourette syndrome.Journal of child neurology, 26(5):560–569, 2011.

[46] Robert A Bornstein, G B Baker, T Bazylewich, and A B Douglass. Tourette syndrome and neuropsychological performance. Acta Psychiatrica Scandinavica, 84:212–216, 1991.

[47] Shelley Channon, Polly Pratt, and Mary M Robertson. Executive function, memory, and learning in Tourette’s syndrome. Neuropsychology, 17:247–254, 2003.

[48] Laura H Watkins, Barbara J Sahakian, Mary M Robertson, David M Veale, Robert D Rogers, Kathryn M Pickard, Michael RF Aitken, and Trevor W Robbins. Executive function in Tourette’s

Bibliography 161

syndrome and obsessive-compulsive disorder. Psychological Medicine, 35:571–582, 2005.

[49] Sally Ozonoﬀ, David L Strayer, William M McMahon, and Francis Filloux. Inhibitory deﬁcits in Tourette syndrome: a function of comorbidity and symptom severity. Journal of child psychology and psychiatry, and allied disciplines, 39(8):1109–18, 1998.

[50] Georgina M Jackson, S C Mueller, K Hambleton, and C P Hollis. Enhanced cognitive control in Tourette Syndrome during task uncertainty. Experimental Brain Research, 182:357–364, 2007.

[51] Sven C Mueller, Georgina M Jackson, Ranu Dhalla, Sophia Datsopoulos, and Chris P Hollis.

Enhanced cognitive control in young people with Tourette’s syndrome. Current Biology, 16:570–

573, 2006.

[52] Rachel Marsh, Hongtu Zhu, Ahishun Wang, Pawel Skudlarski, and Bradley Peterson. A devel-opmental fMRI study of Seld-Regulatory Control in Tourette’s Syndrome. American Journal of Psychiatry, 164(6):955–966, 2007.

[53] Nico Brand, Rinie Geenen, Milo Oudenhoven, Bastiaan Lindenborn, Annette Van Der Ree, Peggy Cohen-Kettenis, and Jan K Buitelaar. Brief report: cognitive functioning in children with Tourette’s syndrome with and without comorbid ADHD.Journal of Pediatric Psychology, 27:203–

208, 2002.

[54] Tamara Hershey, Kevin J Black, Johanna M Hartlein, Deanna M Barch, Todd S Braver, Juanita L Carl, and Joel S Perlmutter. Cognitive-pharmacologic functional magnetic resonance imaging in tourette syndrome: a pilot study. Biological Psychiatry, 55:916–925, 2004.

[55] Amir Raz, Hongtu Zhu, Shan Yu, Ravi Bansal, Zhishun Wang, Gerianne M Alexander, Jason Royal, and Bradley S Peterson. Neural substrates of self-regulatory control in children and adults with Tourette syndrome. Canadian journal of psychiatry. Revue canadienne de psychi-atrie, 54(9):579–588, 2009.

[56] Aaron Alexander-Bloch, Liv Clasen, Michael Stockman, Lisa Ronan, Francois Lalonde, Jay Giedd, and Armin Raznahan. Subtle in-scanner motion biases automated measurement of brain anatomy from in vivo MRI. Human Brain Mapping, 37(7):2385–2397, 2016.

[57] Ludovica Griﬀanti, Gholamreza Salimi-Khorshidi, Christian F Beckmann, Edward J Auerbach, Gwenaëlle Douaud, Claire E Sexton, Eniko Zsoldos, Klaus P Ebmeier, Nicola Filippini, Clare E Mackay, Steen Moeller, Junqian Xu, Essa Yacoub, Giuseppe Baselli, Kamil Ugurbil, Karla L Miller, and Stephen M Smith. ICA-based artefact removal and accelerated fMRI acquisition for improved resting state network imaging.NeuroImage, 95:232–47, jul 2014.

[58] John Muschelli, Mary Beth Nebel, Brian S Caﬀo, Anita D Barber, James J Pekar, and Stew-art H Mostofsky. Reduction of motion-related Stew-artifacts in resting state fMRI using aCompCor.

NeuroImage, 96:22–35, aug 2014.

[59] Ameera X Patel, Prantik Kundu, Mikail Rubinov, P Simon Jones, Petra E Vértes, Karen D Ersche, John Suckling, and Edward T Bullmore. A wavelet method for modeling and despiking motion artifacts from resting-state fMRI time series.NeuroImage, 95:287–304, jul 2014.

[60] Jonathan D Power, Anish Mitra, Timothy O Laumann, Abraham Z Snyder, Bradley L Schlaggar, and Steven E Petersen. Methods to detect, characterize, and remove motion artifact in resting state fMRI.NeuroImage, 84:320–341, aug 2013.

[61] Raimon HR Pruim, Maarten Mennes, Daan van Rooij, Alberto Llera, Jan K Buitelaar, and Christian F Beckmann. ICA-AROMA: A robust ICA-based strategy for removing motion artifacts from fMRI data. NeuroImage, 112:267–277, 2015.

[62] Raimon H R Pruim, Maarten Mennes, Jan K Buitelaar, and Christian F Beckmann. Evaluation of ICA-AROMA and alternative strategies for motion artifact removal in resting state fMRI.

NeuroImage, 112:278–287, 2015.

[63] Theodore D Satterthwaite, Mark a Elliott, Raphael T Gerraty, Kosha Ruparel, James Loughead, Monica E Calkins, Simon B Eickhoﬀ, Hakon Hakonarson, Ruben C Gur, Raquel E Gur, and Daniel H Wolf. An improved framework for confound regression and ﬁltering for control of motion artifact in the preprocessing of resting-state functional connectivity data.NeuroImage, 64:240–56, jan 2013.

Bibliography 162

[64] Ling-Li Zeng, Danhong Wang, Michael D Fox, Mert Sabuncu, Dewen Hu, Manling Ge, Randy L Buckner, and Hesheng Liu. Neurobiological basis of head motion in brain imaging.Proceedings of the National Academy of Sciences of the United States of America, 111(16):6058–62, apr 2014.

[65] Jonathan D Power, Kelly a Barnes, Abraham Z Snyder, Bradley L Schlaggar, and Steven E Petersen. Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage, 59(3):2142–54, feb 2012.

[66] Jonathan D Power, Bradley L Schlaggar, and Steven E Petersen. Recent progress and outstanding issues in motion correction in resting state fMRI, oct 2015.

[67] Martin Reuter, M Dylan Tisdall, Abid Qureshi, Randy L Buckner, André J W van der Kouwe, and Bruce Fischl. Head motion during MRI acquisition reduces gray matter volume and thickness estimates. NeuroImage, 107:107–115, 2015.

[68] Malcolm B Carpenter.Core text of neuroanatomy. Williams & Wilkins, Baltimore, fourth edition, 1991.

[69] Garrett E. Alexander and Michael D. Crutcher. Functional architecture of basal ganglia circuits:

neural substrates of parallel processing.Trends in Neurosciences, 13(7):266–271, 1990.

[70] Mahlon DeLong and Thomas Wichmann. Update on models of basal ganglia function and dys-function. Parkinsonism & related disorders, 15 Suppl 3:S237–40, dec 2009.

[71] Janet M Kemp and T P S Powell. The Connexions of the Striatum and Globus Pallidus: Synthesis and Speculation. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences, 262(845):441–457, sep 1971.

[72] Garret E Alexander, Mahlon R DeLong, and Peter L Strick. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual review of neuroscience, 9:357–381, 1986.

[73] Paul Krack, Marwan I Hariz, Christelle Baunez, Jorge Guridi, and Jose a Obeso. Deep brain stimulation: from neurology to psychiatry? Trends in neurosciences, 33(10):474–84, oct 2010.

[74] Mahlon R DeLong and Thomas Wichmann. Circuits and circuit disorders of the basal ganglia.

Archives of neurology, 64(1):20–24, jan 2007.

[75] Léon Tremblay, Yulia Worbe, Stéphane Thobois, Véronique Sgambato-Faure, and Jean Féger.

Selective dysfunction of basal ganglia subterritories: From movement to behavioral disorders.

Movement disorders: official journal of the Movement Disorder Society, 30(9):1155–70, 2015.

[76] Roger L Albin and Jonathan W Mink. Recent advances in Tourette syndrome research. Trends in Neurosciences, 29(3):175–182, mar 2006.

[77] Kendra Harris and Harvey S Singer. Tic disorders: Neural circuits, neurochemistry, and neuroim-munology. Journal of Child Neurology, 21(8):678–89, 2006.

[78] Jonathan W Mink. Basal ganglia dysfunction in Tourette’s syndrome: A new hypothesis.Pediatric Neurology, 25(3):190–198, 2001.

[79] Jonathan W. Mink. The basal ganglia: Focused selection and inhibition of competing motor programs, 1996.

[80] Yulia Worbe, Véronique Sgambato-Faure, Justine Epinat, Marion Chaigneau, Dominique Tandé, Chantal Francois, Jean Féger, and Léon Tremblay. Towards a primate model of Gilles de la Tourette syndrome: Anatomo-behavioural correlation of disorders induced by striatal dysfunction.

Cortex, 49(4):1126–1140, 2013.

[81] Yulia Worbe, Nicolas Baup, David Grabli, Marion Chaigneau, Stéphanie Mounayar, Kevin Mc-Cairn, Jean Féger, and Léon Tremblay. Behavioral and movement disorders induced by local inhibitory dysfunction in primate striatum.Cerebral Cortex, 19(8):1844–1856, 2009.

[82] Ann M Graybiel. The basal ganglia and chunking of action repertoires. Neurobiology of learning and memory, 70(1-2):119–36, 1998.

Bibliography 163

[83] Jill R Crittenden and Ann M Graybiel. Basal Ganglia disorders associated with imbalances in the striatal striosome and matrix compartments.Frontiers in neuroanatomy, 5(59), sep 2011.

[84] Henry H Yin, Barbara J Knowlton, and Bernard W Balleine. Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning. European Journal of Neuroscience, 19:181–189, 2004.

[85] Carlos Cepeda, N a Buchwald, and M S Levine. Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated. Proceed-ings of the National Academy of Sciences of the United States of America, 90(20):9576–80, oct 1993.

[86] James Surmeier, Jun Ding, Michelle Day, Zhongfeng Wang, and Weixing Shen. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons.

Im Dokument Elemental and neurochemical based analysis of the pathophysiological mechanisms of Gilles de la Tourette syndrome (Seite 175-200)