Generic placeholder image

Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Diagnostic Issues in Early-Onset Obsessive-Compulsive Disorder and their Treatment Implications

Author(s): Elisabetta Burchi* and Stefano Pallanti

Volume 17, Issue 8, 2019

Page: [672 - 680] Pages: 9

DOI: 10.2174/1570159X16666180426151746

Price: $65


Background: The lifespan approach and recent shift in the conceptualization of Obsessive- Compulsive Disorder (OCD) promoted by the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM5) along with novel insights into the pathogenesis of this heterogeneous disorder are driving the development of new outcome measures and new treatments for a disease that, on the other hand, is characterized by high rates of refractoriness.

Objective and Methods: The aim of this review is to provide a discussion of the translational evidence about Early Onset OCD (EO) in compliance with a neurodevelopmental and RdoC perspective.

Results and Conclusion: EO might be considered the neurodevelopmental subtype of OCD. Indeed there is evidence that different clusters of symptoms and dimensions at an early stage predict different trajectories in phenotype and that distinct neurocircuit pathways underpin the progression of the disorder. Despite the development of high refractoriness in the course of the disorder, evidence suggests that EO may be particularly treatment responsive in the early stages, thus showing the need for early recognition and additional recovery oriented studies in this subgroup.

Consistent with the neurodevelopmental perspective, immunity and glutamate neurotransmission are emerging as novel pathways for parsing out the neurobiology of OCD, the EO form, in particular, supporting the implementation of new multisystemic models of the OCD phenotype. Brain connectivity patterns, immune and microbiome profiles are standing out as promising areas for biomarkers with the potential for targeted personalized therapies in EO.

Keywords: Early-onset OCD, pediatric OCD, neurodevelopmental disorders, neuroinflammation, glutamatergic agents, gut microbiome, RDoC.

Graphical Abstract
Ruscio, A.M.; Stein, D.J.; Chiu, W.T.; Kessler, R.C. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol. Psychiatry, 2010, 15(1), 53-63. []. [PMID: 18725912].
Olesen, J.; Gustavsson, A.; Svensson, M.; Wittchen, H.U.; Jönsson, B. The economic cost of brain disorders in Europe. Eur. J. Neurol., 2012, 19(1), 155-162. [ 03590.x]. [PMID: 22175760].
Geller, D.A. Obsessive-compulsive and spectrum disorders in children and adolescents. Psychiatr. Clin. North Am., 2006, 29(2), 353-370. []. [PMID: 16650713].
Kessler, R.C.; Berglund, P.; Demler, O.; Jin, R.; Merikangas, K.R.; Walters, E.E. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry, 2005, 62(6), 593-602. [http://dx.doi. org/10.1001/archpsyc.62.6.593]. [PMID: 15939837].
Pallanti, S.; Quercioli, L. Treatment-refractory obsessive-compulsive disorder: methodological issues, operational definitions and therapeutic lines. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2006, 30(3), 400-412. [ 11.028]. [PMID: 16503369].
Dell’Osso, B.; Benatti, B.; Hollander, E.; Fineberg, N.; Stein, D.J.; Lochner, C.; Nicolini, H.; Lanzagorta, N.; Palazzo, C.; Altamura, A.C.; Marazziti, D.; Pallanti, S.; Van Ameringen, M.; Karamustafalioglu, O.; Drummond, L.M.; Hranov, L.; Figee, M.; Grant, J.E.; Zohar, J.; Denys, D.; Menchon, J.M. Childhood, adolescent and adult age at onset and related clinical correlates in obsessive-compulsive disorder: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). Int. J. Psychiatry Clin. Pract., 2016, 20(4), 210-217. [ 13651501.2016.1207087]. [PMID: 27433835].
Taylor, S. Early versus late onset obsessive-compulsive disorder: evidence for distinct subtypes. Clin. Psychol. Rev., 2011, 31(7), 1083-1100. []. [PMID: 21820387].
Grünblatt, E.; Oneda, B.; Ekici, A.B.; Ball, J.; Geissler, J.; Uebe, S.; Romanos, M.; Rauch, A.; Walitza, S. High resolution chromosomal microarray analysis in paediatric obsessive-compulsive disorder. BMC Med. Genomics, 2017, 10(1), 68. [ 10.1186/s12920-017-0299-5]. [PMID: 29179725].
Stewart, S.E.; Geller, D.A.; Jenike, M.; Pauls, D.; Shaw, D.; Mullin, B.; Faraone, S.V. Long-term outcome of pediatric obsessive-compulsive disorder: A meta-analysis and qualitative review of the literature. Acta Psychiatr. Scand., 2004, 110(1), 4-13. [http://dx.]. [PMID: 15180774].
Fontenelle, L.F.; Mendlowicz, M.V.; Marques, C.; Versiani, M. Early- and late-onset obsessive-compulsive disorder in adult patients: an exploratory clinical and therapeutic study. J. Psychiatr. Res., 2003, 37(2), 127-133. []. [PMID: 12842166].
Grover, S.; Sarkar, S.; Gupta, G.; Kate, N.; Ghosh, A.; Chakrabarti, S.; Avasthi, A. Factor analysis of symptom profile in early onset and late onset OCD. Psychiatry Res., 2017. [PMID: 29033063].
Delorme, R.; Bille, A.; Betancur, C.; Mathieu, F.; Chabane, N.; Mouren-Simeoni, M.C.; Leboyer, M. Exploratory analysis of obsessive compulsive symptom dimensions in children and adolescents: A prospective follow-up study. BMC Psychiatry, 2006, 6, 1. []. [PMID: 16396684].
Boedhoe, P.S.; Schmaal, L.; Abe, Y.; Ameis, S.H.; Arnold, P.D.; Batistuzzo, M.C.; Benedetti, F.; Beucke, J.C.; Bollettini, I.; Bose, A.; Brem, S.; Calvo, A.; Cheng, Y.; Cho, K.I.; Dallaspezia, S.; Denys, D.; Fitzgerald, K.D.; Fouche, J.P.; Giménez, M.; Gruner, P.; Hanna, G.L.; Hibar, D.P.; Hoexter, M.Q.; Hu, H.; Huyser, C.; Ikari, K.; Jahanshad, N.; Kathmann, N.; Kaufmann, C.; Koch, K.; Kwon, J.S.; Lazaro, L.; Liu, Y.; Lochner, C.; Marsh, R.; Martínez-Zalacaín, I.; Mataix-Cols, D.; Menchón, J.M.; Minuzzi, L.; Nakamae, T.; Nakao, T.; Narayanaswamy, J.C.; Piras, F.; Piras, F.
Pittenger, C.; Reddy, Y.C.; Sato, J.R.; Simpson, H.B.; Soreni, N.; Soriano-Mas, C.; Spalletta, G.; Stevens, M.C.; Szeszko, P.R.; Tolin, D.F.; Venkatasubramanian, G.; Walitza, S.; Wang, Z.; van Wingen, G.A.; Xu, J.; Xu, X.; Yun, J.Y.; Zhao, Q.; Thompson, P.M.; Stein, D.J.; van den Heuvel, O.A.; van den Heuvel, O.A. Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A worldwide meta- and mega-analysis. Am. J. Psychiatry, 2017, 174(1), 60-69. []. [PMID: 27609241].
Ivanov, I.; Bansal, R.; Hao, X.; Zhu, H.; Kellendonk, C.; Miller, L.; Sanchez-Pena, J.; Miller, A.M.; Chakravarty, M.M.; Klahr, K.; Durkin, K.; Greenhill, L.L.; Peterson, B.S. Morphological abnormalities of the thalamus in youths with attention deficit hyperactivity disorder. Am. J. Psychiatry, 2010, 167(4), 397-408. [http://dx.]. [PMID: 20123910].
Miller, A.M.; Bansal, R.; Hao, X.; Sanchez-Pena, J.P.; Sobel, L.J.; Liu, J.; Xu, D.; Zhu, H.; Chakravarty, M.M.; Durkin, K.; Ivanov, I.; Plessen, K.J.; Kellendonk, C.B.; Peterson, B.S. Enlargement of thalamic nuclei in Tourette syndrome. Arch. Gen. Psychiatry, 2010, 67(9), 955-964. [ 102]. [PMID: 20819989].
Gilbert, A.R.; Moore, G.J.; Keshavan, M.S.; Paulson, L.A.; Narula, V.; Mac Master, F.P.; Stewart, C.M.; Rosenberg, D.R. Decrease in thalamic volumes of pediatric patients with obsessive-compulsive disorder who are taking paroxetine. Arch. Gen. Psychiatry, 2000, 57(5), 449-456. []. [PMID: 10807485].
Boileau, B. A review of obsessive-compulsive disorder in children and adolescents. Dialogues Clin. Neurosci., 2011, 13(4), 401-411. [PMID: 22275846].
Mataix-Cols, D.; Rosario-Campos, M.C.; Leckman, J.F. A multidimensional model of obsessive-compulsive disorder. Am. J. Psychiatry, 2005, 162(2), 228-238. [ ajp.162.2.228]. [PMID: 15677583].
Alvarenga, P.G.; Cesar, R.C.; Leckman, J.F.; Moriyama, T.S.; Torres, A.R.; Bloch, M.H.; Coughlin, C.G.; Hoexter, M.Q.; Manfro, G.G.; Polanczyk, G.V.; Miguel, E.C.; do Rosario, M.C. Obsessive-compulsive symptom dimensions in a population-based, cross-sectional sample of school-aged children. J. Psychiatr. Res., 2015, 62, 108-114. []. [PMID: 25702286].
Fullana, M.A.; Mataix-Cols, D.; Caspi, A.; Harrington, H.; Grisham, J.R.; Moffitt, T.E.; Poulton, R. Obsessions and compulsions in the community: prevalence, interference, help-seeking, developmental stability, and co-occurring psychiatric conditions. Am. J. Psychiatry, 2009, 166(3), 329-336. [ appi.ajp.2008.08071006]. [PMID: 19188283].
Alvarenga, P.G.; do Rosario, M.C.; Cesar, R.C.; Manfro, G.G.; Moriyama, T.S.; Bloch, M.H.; Shavitt, R.G.; Hoexter, M.Q.; Coughlin, C.G.; Leckman, J.F.; Miguel, E.C. Obsessive-compulsive symptoms are associated with psychiatric comorbidities, behavioral and clinical problems: A population-based study of Brazilian school children. Eur. Child Adolesc. Psychiatry, 2016, 25(2), 175-182. []. [PMID: 26015374].
Dell’Osso, B.; Camuri, G.; Benatti, B.; Buoli, M.; Altamura, A.C. Differences in latency to first pharmacological treatment (duration of untreated illness) in anxiety disorders: A study on patients with panic disorder, generalized anxiety disorder and obsessive-compulsive disorder. Early Interv. Psychiatry, 2013, 7(4), 374-380. []. [PMID: 23347385].
Dell’Osso, B.; Buoli, M.; Hollander, E.; Altamura, A.C. Duration of untreated illness as a predictor of treatment response and remission in obsessive-compulsive disorder. World J. Biol. Psychiatry, 2010, 11(1), 59-65. []. [PMID: 20001657].
Mancebo, M.C.; Boisseau, C.L.; Garnaat, S.L.; Eisen, J.L.; Greenberg, B.D.; Sibrava, N.J.; Stout, R.L.; Rasmussen, S.A. Long-term course of pediatric obsessive-compulsive disorder: 3 years of prospective follow-up. Compr. Psychiatry, 2014, 55(7), 1498-1504. []. [PMID: 24952937].
Melin, K.; Skarphedinsson, G.; Skärsäter, I.; Haugland, B.S.M.; Ivarsson, T. A solid majority remit following evidence-based OCD treatments: A 3-year naturalistic outcome study in pediatric OCD. Eur. Child Adolesc. Psychiatry, 2018. [ s00787-018-1137-9]. [PMID: 29502315].
Hojgaard, D.; Hybel, K.A.; Ivarsson, T.; Skarphedinsson, G.; Becker Nissen, J.; Weidle, B.; Melin, K.; Torp, N.C.; Valderhaug, R.; Dahl, K.; Mortensen, E.L.; Compton, S.; Jensen, S.; Lenhard, F.; Thomsen, P.H. The relevance of analogue studies for understanding obsessions and compulsions. Clin. Psychol. Rev., 2014, 34(3), 206-217.
Abramowitz, J.S.; Fabricant, L.E.; Taylor, S.; Deacon, B.J.; McKay, D.; Storch, E.A. The relevance of analogue studies for understanding obsessions and compulsions. Clin. Psychol. Rev., 2014, 34(3), 206-217. []. [PMID: 24561743].
Zijlmans, J.; Marhe, R.; van der Ende, J.; Verhulst, F.C.; Popma, A.; Tiemeier, H.; van den Heuvel, O.A. Children with Obsessive-Compulsive Symptomology in the General Population: Different Subtypes? J. Dev. Behav. Pediatr., 2017, 38(7), 476-482. [http://dx.]. [PMID: 28691955].
de Mathis, M.A.; Diniz, J.B.; Hounie, A.G.; Shavitt, R.G.; Fossaluza, V.; Ferrão, Y.; Leckman, J.F.; de Bragança Pereira, C.; do Rosario, M.C.; Miguel, E.C. Trajectory in obsessive-compulsive disorder comorbidities. Eur. Neuropsychopharmacol., 2013, 23(7), 594-601. []. [PMID: 22921470].
Geller, D.A.; Biederman, J.; Faraone, S.V.; Bellordre, C.A.; Kim, G.S.; Hagermoser, L.; Cradock, K.; Frazier, J.; Coffey, B.J. Disentangling chronological age from age of onset in children and adolescents with obsessive-compulsive disorder. Int. J. Neuropsychopharmacol., 2001, 4(2), 169-178. [ S1461145701002395]. [PMID: 11466167].
Selles, R.R.; Storch, E.A.; Lewin, A.B. Variations in symptom prevalence and clinical correlates in younger versus older youth with obsessive-compulsive disorder. Child Psychiatry Hum. Dev., 2014, 45(6), 666-674. []. [PMID: 24549726].
Abramovitch, A.; Dar, R.; Mittelman, A.; Wilhelm, S. Comorbidity between attention deficit/hyperactivity disorder and obsessive-compulsive disorder across the lifespan: A systematic and critical review. Harv. Rev. Psychiatry, 2015, 23(4), 245-262. [http://]. [PMID: 26052877].
Storch, E.A.; Merlo, L.J.; Larson, M.J.; Geffken, G.R.; Lehmkuhl, H.D.; Jacob, M.L.; Murphy, T.K.; Goodman, W.K. Impact of comorbidity on cognitive-behavioral therapy response in pediatric obsessive-compulsive disorder. J. Am. Acad. Child Adolesc. Psychiatry, 2008, 47(5), 583-592. [ e31816774b1]. [PMID: 18356759].
Guzick, A.G.; McNamara, J.P.H.; Reid, A.M.; Balkhi, A.M.; Storch, E.A.; Murphy, T.K.; Goodman, W.K.; Bussing, R.; Geffken, G.R. The link between ADHD-like inattention and obsessions and compulsions during treatment of youth with OCD. J. Obsessive Compuls. Relat. Disord., 2017, 12, 1-8. [ j.jocrd.2016.11.004]. [PMID: 28966908].
Ivarsson, T.; Melin, K. Autism spectrum traits in children and adolescents with obsessive-compulsive disorder (OCD). J. Anxiety Disord., 2008, 22(6), 969-978. [ 2007.10.003]. [PMID: 18053683].
Stewart, E.; Cancilliere, M.K.; Freeman, J.; Wellen, B.; Garcia, A.; Sapyta, J.; Franklin, M. Elevated autism spectrum disorder traits in young children with OCD. Child Psychiatry Hum. Dev., 2016, 47(6), 993-1001. []. [PMID: 26858231].
Tsuchiyagaito, A.; Hirano, Y.; Asano, K.; Oshima, F.; Nagaoka, S.; Takebayashi, Y.; Matsumoto, K.; Masuda, Y.; Iyo, M.; Shimizu, E.; Nakagawa, A. Cognitive-behavioral therapy for obsessive-compulsive disorder with and without autism spectrum disorder: Gray matter differences associated with poor outcome. Front. Psychiatry, 2017, 8, 143. []. [PMID: 28861007].
Tanidir, C.; Adaletli, H.; Gunes, H.; Kilicoglu, A.G.; Mutlu, C.; Bahali, M.K.; Aytemiz, T.; Uneri, O.S. Impact of gender, age at onset, and lifetime tic disorders on the clinical presentation and comorbidity pattern of obsessive-compulsive disorder in children and adolescents. J. Child Adolesc. Psychopharmacol., 2015, 25(5), 425-431. []. [PMID: 26091196].
Conelea, C.A.; Walther, M.R.; Freeman, J.B.; Garcia, A.M.; Sapyta, J.; Khanna, M.; Franklin, M. Tic-related obsessive-compulsive disorder (OCD): phenomenology and treatment outcome in the Pediatric OCD Treatment Study II. J. Am. Acad. Child Adolesc. Psychiatry, 2014, 53(12), 1308-1316. [ 10.1016/j.jaac.2014.09.014]. [PMID: 25457929].
Ferrao, Y.A.D.; Alvarenga, P.G.; Hounie, A.G.; de Mathis, M.A.; de Rosario, M.C.; Miguel, E.C. The phenomenology of obsessive-compulsive symptoms in Tourette Syndrome.Oxford University Press. Vol. Tourette Syndrome, 2013.
Dell’Osso, B.; Marazziti, D.; Albert, U.; Pallanti, S.; Gambini, O.; Tundo, A.; Zanaboni, C.; Servello, D.; Rizzo, R.; Scalone, L.; Benatti, B.; Altamura, A.C.; Porta, M. Parsing the phenotype of obsessive-compulsive tic disorder (OCTD): a multidisciplinary consensus. Int. J. Psychiatry Clin. Pract., 2017, 21(2), 156-159. [http://]. [PMID: 28379724].
Skarphedinsson, G.; Compton, S.; Thomsen, P.H.; Weidle, B.; Dahl, K.; Nissen, J.B.; Torp, N.C.; Hybel, K.; Melin, K.H.; Valderhaug, R.; Wentzel-Larsen, T.; Ivarsson, T. Tics moderate sertraline, but not cognitive-behavior therapy response in pediatric obsessive-compulsive disorder patients who do not respond to cognitive-behavior therapy. J. Child Adolesc. Psychopharmacol., 2015, 25(5), 432-439. []. [PMID: 26091197].
March, J.S.; Franklin, M.E.; Leonard, H.; Garcia, A.; Moore, P.; Freeman, J.; Foa, E. Tics moderate treatment outcome with sertraline but not cognitive-behavior therapy in pediatric obsessive-compulsive disorder. Biol. Psychiatry, 2007, 61(3), 344-347. []. [PMID: 17241830].
Pinto, R.; Monzani, B.; Leckman, J.F.; Rück, C.; Serlachius, E.; Lichtenstein, P.; Mataix-Cols, D. Understanding the covariation of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms: A population-based adult twin study. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2016, 171(7), 938-947. [http://]. [PMID: 26919823].
Turner, C.; O’Gorman, B.; Nair, A.; O’Kearney, R. Moderators and predictors of response to cognitive behaviour therapy for pediatric obsessive-compulsive disorder: A systematic review. Psychiatry Res., 2018, 261, 50-60. [ 12.034]. [PMID: 29287236].
Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. J. Am. Acad. Child Adolesc. Psychiatry, 2012, 51(1), 98-113. [http://dx.doi. org/10.1016/j.jaac.2011.09.019]. [PMID: 22176943].
National Collaborating Centre for Medical Health (UK).In Obsessive-Compulsive Disorder, core interventions in the treatment of obsessive-compulsive disorder and body dysmorphic disorder; Leicester, UK, 2006.
Varigonda, A.L.; Jakubovski, E.; Bloch, M.H. Systematic review and meta-analysis: Early treatment responses of selective serotonin reuptake inhibitors and clomipramine in pediatric obsessive-compulsive disorder. J. Am. Acad. Child Adolesc. Psychiatry, 2016, 55(10), 851-859.
London, A.; Cohen, M.; Schwartz, M. Microglia and monocyte-derived macrophages: Functionally distinct populations that act in concert in CNS plasticity and repair. Front. Cell. Neurosci., 2013, 7, 34. []. [PMID: 23596391].
Swedo, S.E.; Rapoport, J.L.; Cheslow, D.L.; Leonard, H.L.; Ayoub, E.M.; Hosier, D.M.; Wald, E.R. High prevalence of obsessive-compulsive symptoms in patients with Sydenham’s chorea. Am. J. Psychiatry, 1989, 146(2), 246-249. [ ajp.146.2.246]. [PMID: 2912267].
Swedo, S.E.; Leonard, H.L.; Garvey, M.; Mittleman, B.; Allen, A.J.; Perlmutter, S.; Lougee, L.; Dow, S.; Zamkoff, J.; Dubbert, B.K. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am. J. Psychiatry, 1998, 155(2), 264-271. [PMID: 9464208].
Swedo, S.E.L.J.; Rose, N.R. From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). pediatr therapeut 2012.
Calaprice, D.; Tona, J.; Parker-Athill, E.C.; Murphy, T.K. A survey of pediatric acute-onset neuropsychiatric syndrome characteristics and course. J. Child Adolesc. Psychopharmacol., 2017, 27(7), 607-618. [PMID: 28140619].
Chiarello, F.; Spitoni, S.; Hollander, E.; Matucci Cerinic, M.; Pallanti, S. An expert opinion on PANDAS/PANS: Highlights and controversies. Int. J. Psychiatry Clin. Pract., 2017, 21(2), 91-98. [http://]. [PMID: 28498087].
Teixeira, A.L.; Rodrigues, D.H.; Marques, A.H.; Miguel, E.C.; Fontenelle, L.F. Searching for the immune basis of obsessive-compulsive disorder. Neuroimmunomodulation, 2014, 21(2-3), 152-158. []. [PMID: 24557049].
Attwells, S.; Setiawan, E.; Wilson, A.A.; Rusjan, P.M.; Mizrahi, R.; Miler, L.; Xu, C.; Richter, M.A.; Kahn, A.; Kish, S.J.; Houle, S.; Ravindran, L.; Meyer, J.H. Inflammation in the neurocircuitry of obsessive-compulsive disorder. JAMA Psychiatry, 2017, 74(8), 833-840. []. [PMID: 28636705].
Réus, G.Z.; Fries, G.R.; Stertz, L.; Badawy, M.; Passos, I.C.; Barichello, T.; Kapczinski, F.; Quevedo, J. The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience, 2015, 300, 141-154. [ 10.1016/j.neuroscience.2015.05.018]. [PMID: 25981208].
Frick, L.R.; Williams, K.; Pittenger, C. Microglial dysregulation in psychiatric disease. Clin. Dev. Immunol., 2013, 2013608654 []. [PMID: 23690824].
Amantea, D.; Bagetta, G. Drug repurposing for immune modulation in acute ischemic stroke. Curr. Opin. Pharmacol., 2016, 26, 124-130. []. [PMID: 26657075].
Burchi, E.P.S. Antibiotics for PANDAS? Limited evidence. Review and putative mechanisms of action. Prim Care Companion CNS, in press
Stock, M.L.; Fiedler, K.J.; Acharya, S.; Lange, J.K.; Mlynarczyk, G.S.; Anderson, S.J.; McCormack, G.R.; Kanuri, S.H.; Kondru, N.C.; Brewer, M.T.; Carlson, S.A. Antibiotics acting as neuroprotectants via mechanisms independent of their anti-infective activities. Neuropharmacology, 2013, 73, 174-182. [ 10.1016/j.neuropharm.2013.04.059]. [PMID: 23748053].
Rothstein, J.D.; Patel, S.; Regan, M.R.; Haenggeli, C.; Huang, Y.H.; Bergles, D.E.; Jin, L.; Dykes Hoberg, M.; Vidensky, S.; Chung, D.S.; Toan, S.V.; Bruijn, L.I.; Su, Z.Z.; Gupta, P.; Fisher, P.B. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature, 2005, 433(7021), 73-77. []. [PMID: 15635412].
Shmelkov, S.V.; Hormigo, A.; Jing, D.; Proenca, C.C.; Bath, K.G.; Milde, T.; Shmelkov, E.; Kushner, J.S.; Baljevic, M.; Dincheva, I.; Murphy, A.J.; Valenzuela, D.M.; Gale, N.W.; Yancopoulos, G.D.; Ninan, I.; Lee, F.S.; Rafii, S. Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nat. Med., 2010, 16(5), 598-602. [http://dx.].
Welch, J.M.; Lu, J.; Rodriguiz, R.M.; Trotta, N.C.; Peca, J.; Ding, J.D.; Feliciano, C.; Chen, M.; Adams, J.P.; Luo, J.; Dudek, S.M.; Weinberg, R.J.; Calakos, N.; Wetsel, W.C.; Feng, G. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature, 2007, 448(7156), 894-900. [ 10.1038/nature06104]. [PMID: 17713528].
Stewart, S.E.; Mayerfeld, C.; Arnold, P.D.; Crane, J.R.; O’Dushlaine, C.; Fagerness, J.A.; Yu, D.; Scharf, J.M.; Chan, E.; Kassam, F.; Moya, P.R.; Wendland, J.R.; Delorme, R.; Richter, M.A.; Kennedy, J.L.; Veenstra-VanderWeele, J.; Samuels, J.; Greenberg, B.D.; McCracken, J.T.; Knowles, J.A.; Fyer, A.J.; Rauch, S.L.; Riddle, M.A.; Grados, M.A.; Bienvenu, O.J.; Cullen, B.; Wang, Y.; Shugart, Y.Y.; Piacentini, J.; Rasmussen, S.; Nestadt, G.; Murphy, D.L.; Jenike, M.A.; Cook, E.H.; Pauls, D.L.; Hanna, G.L.; Mathews, C.A. Meta-analysis of association between obsessive-compulsive disorder and the 3′ region of neuronal glutamate transporter gene SLC1A1. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2013, 162B(4), 367-379. [ 32137]. [PMID: 23606572].
Alonso, P.; Gratacós, M.; Segalàs, C.; Escaramís, G.; Real, E.; Bayés, M.; Labad, J.; López-Solà, C.; Estivill, X.; Menchón, J.M. Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder. J. Psychiatry Neurosci., 2012, 37(4), 273-281. []. [PMID: 22433450].
Hirschtritt, M.E.; Bloch, M.H.; Mathews, C.A. Obsessive-compulsive disorder: Advances in diagnosis and treatment. JAMA, 2017, 317(13), 1358-1367. [ 2017.2200]. [PMID: 28384832].
Laoutidis, Z.G.; Lekka, G.E.; Kioulos, K.T. Glutamatergic agents as add-on medication for the treatment of obsessive-compulsive disorder: A systematic review and meta-analysis. J. Clin. Psychiatry, 2016, 77(12), e1576-e1583. [ JCP.15r10164]. [PMID: 27780337].
O’Neill, J.; Piacentini, J.; Chang, S.; Ly, R.; Lai, T.M.; Armstrong, C.C.; Bergman, L.; Rozenman, M.; Peris, T.; Vreeland, A.; Mudgway, R.; Levitt, J.G.; Salamon, N.; Posse, S.; Hellemann, G.S.; Alger, J.R.; McCracken, J.T.; Nurmi, E.L. Glutamate in pediatric obsessive-compulsive disorder and response to cognitive-behavioral therapy: Randomized clinical triaL. Neuropsychopharmacology, 2017, 42(12), 2414-2422. []. [PMID: 28409563].
Grant, P.J.; Joseph, L.A.; Farmer, C.A.; Luckenbaugh, D.A.; Lougee, L.C.; Zarate, C.A., Jr; Swedo, S.E. 12-week, placebo-controlled trial of add-on riluzole in the treatment of childhood-onset obsessive-compulsive disorder. Neuropsychopharmacology, 2014, 39(6), 1453-1459. []. [PMID: 24356715].
Storch, E.A.; Wilhelm, S.; Sprich, S.; Henin, A.; Micco, J.; Small, B.J.; McGuire, J.; Mutch, P.J.; Lewin, A.B.; Murphy, T.K.; Geller, D.A. Efficacy of augmentation of cognitive behavior therapy with weight-adjusted d-cycloserine vs. placebo in pediatric obsessive-compulsive disorder: A randomized clinical trial. JAMA Psychiatry, 2016, 73(8), 779-788. [ 2016.1128]. [PMID: 27367832].
Ghanizadeh, A.; Mohammadi, M.R.; Bahraini, S.; Keshavarzi, Z.; Firoozabadi, A.; Alavi Shoshtari, A. Efficacy of N-acetylcysteine augmentation on obsessive compulsive disorder: A multicenter randomized double blind placebo controlled clinical trial. Iran. J. Psychiatry, 2017, 12(2), 134-141. [PMID: 28659986].
Mechler, K.; Häge, A.; Schweinfurth, N.; Glennon, J.C.; Dijkhuizen, R.M.; Murphy, D.; Durston, S.; Williams, S.; Buitelaar, J.K.; Banaschewski, T.; Dittmann, R.W. Tactics Consortium. T. Glutamatergic agents in the treatment of compulsivity and impulsivity in child and adolescent psychiatry: A systematic review of the literature. Z. Kinder Jugendpsychiatr. Psychother., 2018, 46(3), 246-263. []. [PMID: 28922069].
Pasquini, M.; Biondi, M. Memantine augmentation for refractory obsessive-compulsive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2006, 30(6), 1173-1175. [ 1016/j.pnpbp.2006.04.013]. [PMID: 16730870].
Rodriguez, C.I.; Bender, J., Jr; Marcus, S.M.; Snape, M.; Rynn, M.; Simpson, H.B. Minocycline augmentation of pharmacotherapy in obsessive-compulsive disorder: an open-label trial. J. Clin. Psychiatry, 2010, 71(9), 1247-1249. [ 09l05805blu]. [PMID: 20923629].
Dean, O.M.; Data-Franco, J.; Giorlando, F.; Berk, M. Minocycline: therapeutic potential in psychiatry. CNS Drugs, 2012, 26(5), 391-401. []. [PMID: 22486246].
Chakrabarty, K.; Bhattacharyya, S.; Christopher, R.; Khanna, S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology, 2005, 30(9), 1735-1740. []. [PMID: 15841109].
Rao, N.P.; Venkatasubramanian, G.; Ravi, V.; Kalmady, S.; Cherian, A.; Yc, J.R. Plasma cytokine abnormalities in drug-naïve, comorbidity-free obsessive-compulsive disorder. Psychiatry Res., 2015, 229(3), 949-952. [ 2015.07.009]. [PMID: 26187339].
Çolak Sivri, R.; Bilgiç, A.; Kılınç, İ. Cytokine, chemokine and BDNF levels in medication-free pediatric patients with obsessive-compulsive disorder. Eur. Child Adolesc. Psychiatry, 2018. [PMID: 29302747].
Rodríguez, N.; Morer, A.; González-Navarro, E.A.; Serra-Pages, C.; Boloc, D.; Torres, T.; García-Cerro, S.; Mas, S.; Gassó, P.; Lázaro, L. Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder. J. Neuroinflammation, 2017, 14(1), 261. []. [PMID: 29284508].
Nazimek, K.; Strobel, S.; Bryniarski, P.; Kozlowski, M.; Filipczak-Bryniarska, I.; Bryniarski, K. The role of macrophages in anti-inflammatory activity of antidepressant drugs. Immunobiology, 2017, 222(6), 823-830. [ 001]. [PMID: 27453459].
Gobin, V.; Van Steendam, K.; Denys, D.; Deforce, D. Selective serotonin reuptake inhibitors as a novel class of immunosuppressants. Int. Immunopharmacol., 2014, 20(1), 148-156. [http://dx.doi. org/10.1016/j.intimp.2014.02.030]. [PMID: 24613205].
Gałecki, P.; Mossakowska-Wójcik, J.; Talarowska, M. The anti-inflammatory mechanism of antidepressants - SSRIs, SNRIs. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2018, 80(Pt C), 291-294. []. [PMID: 28342944].
Alboni, S.; Poggini, S.; Garofalo, S.; Milior, G.; El Hajj, H.; Lecours, C.; Girard, I.; Gagnon, S.; Boisjoly-Villeneuve, S.; Brunello, N.; Wolfer, D.P.; Limatola, C.; Tremblay, M.E.; Maggi, L.; Branchi, I. Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment. Brain Behav. Immun., 2016, 58, 261-271. [http://dx.doi. org/10.1016/j.bbi.2016.07.155]. [PMID: 27474084].
Sun, Y.; Narayan, V.A.; Wittenberg, G.M. Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders. BMC Pharmacol. Toxicol., 2016, 17(1), 47. [ 10.1186/s40360-016-0090-9]. [PMID: 27765060].
Sayyah, M.; Boostani, H.; Pakseresht, S.; Malayeri, A. A preliminary randomized double-blind clinical trial on the efficacy of celecoxib as an adjunct in the treatment of obsessive-compulsive disorder. Psychiatry Res., 2011, 189(3), 403-406. [ 10.1016/j.psychres.2011.01.019]. [PMID: 21329988].
Shalbafan, M.; Mohammadinejad, P.; Shariat, S.V.; Alavi, K.; Zeinoddini, A.; Salehi, M.; Askari, N.; Akhondzadeh, S. Celecoxib as an adjuvant to fluvoxamine in moderate to severe obsessive-compulsive disorder: A double-blind, placebo-controlled, randomized trial. Pharmacopsychiatry, 2015, 48(4-5), 136-140. [PMID: 25959196].
Strauss, K.I.; Marini, A.M. Cyclooxygenase-2 inhibition protects cultured cerebellar granule neurons from glutamate-mediated cell death. J. Neurotrauma, 2002, 19(5), 627-638. [ 10.1089/089771502753754091]. [PMID: 12042097].
Borre, Y.E.; Moloney, R.D.; Clarke, G.; Dinan, T.G.; Cryan, J.F. The impact of microbiota on brain and behavior: Mechanisms & therapeutic potential. Adv. Exp. Med. Biol., 2014, 817, 373-403. []. [PMID: 24997043].
Cenit, M.C.; Sanz, Y.; Codoñer-Franch, P. Influence of gut microbiota on neuropsychiatric disorders. World J. Gastroenterol., 2017, 23(30), 5486-5498. []. [PMID: 28852308].
Burokas, A.; Arboleya, S.; Moloney, R.D.; Peterson, V.L.; Murphy, K.; Clarke, G.; Stanton, C.; Dinan, T.G.; Cryan, J.F. Targeting the microbiota-gut-brain axis: Prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol. Psychiatry, 2017, 82(7), 472-487. [http://]. [PMID: 28242013].
Turna, J.; Grosman, K.K.; Anglin, R.; Van Ameringen, M. “What’s bugging the gut in Ocd?” a review of the gut microbiome in obsessive-compulsive disorder. Depress. Anxiety, 2016, 33(3), 171-178. []. [PMID: 26629974].
Kantak, P.A.; Bobrow, D.N.; Nyby, J.G. Obsessive-compulsive-like behaviors in house mice are attenuated by a probiotic (Lactobacillus rhamnosus GG). Behav. Pharmacol., 2014, 25(1), 71-79. []. [PMID: 24257436].
Insel, T.; Cuthbert, B.; Garvey, M.; Heinssen, R.; Pine, D.S.; Quinn, K.; Sanislow, C.; Wang, P. Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. Am. J. Psychiatry, 2010, 167(7), 748-751. [http://]. [PMID: 20595427].
Valentin, V.V.; Dickinson, A.; O’Doherty, J.P. Determining the neural substrates of goal-directed learning in the human brain. J. Neurosci., 2007, 27(15), 4019-4026. [ JNEUROSCI.0564-07.2007]. [PMID: 17428979].
Ahmari, S.E.; Dougherty, D.D. Dissecting Ocd Circuits: From animal models to targeted treatments. Depress. Anxiety, 2015, 32(8), 550-562. []. [PMID: 25952989].
Brennan, B. Use of an Individual-Level Approach to Identify Cortical Connectivity Biomarkers of Global and Dimen- sional Symptom Severity and Improvement in Obsessive-Compulsive Disorder. ACNP 56th Annual Meeting, Poster session.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy