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Trichotillomania is more related to Tourette disorder than to obsessive-compulsive disorder

Abstract

Objective:

Trichotillomania (TTM) is characterized by the pulling out of one’s hair. TTM was classified as an impulse control disorder in DSM-IV, but is now classified in the obsessive-compulsive related disorders section of DSM-5. Classification for TTM remains an open question, especially considering its impact on treatment of the disorder. In this review, we questioned the relation of TTM to tic disorder and obsessive-compulsive disorder (OCD).

Method:

We reviewed relevant MEDLINE-indexed articles on clinical, neuropsychological, neurobiological, and therapeutic aspects of trichotillomania, OCD, and tic disorders.

Results:

Our review found a closer relationship between TTM and tic disorder from neurobiological (especially imaging) and therapeutic standpoints.

Conclusion:

We sought to challenge the DSM-5 classification of TTM and to compare TTM with both OCD and tic disorder. Some discrepancies between TTM and tic disorders notwithstanding, several arguments are in favor of a closer relationship between these two disorders than between TTM and OCD, especially when considering implications for therapy. This consideration is essential for patients.

Obsessive-compulsive disorder; trichotillomania; Tourette syndrome; tic disorders; psychiatry


Introduction

As its name implies, obsessive-compulsive disorder (OCD) is defined by obsessions and compulsions.11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. Obsessions are thoughts, images, or urges experienced as unwanted and which cause marked anxiety; compulsions are repetitive behaviors performed to prevent or reduce the anxiety caused by obsessions.11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. In DSM-IV-TR, this disorder was classified within the anxiety disorders,22. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Arlington: American Psychiatric Publishing; 2000. but now, in DSM-5, OCD is included in a specific group called “obsessive-compulsive and related disorder.”11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. This group also includes body dysmorphic disorder and trichotillomania (TTM).11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. TTM is defined by recurrent pulling out of one’s hair, resulting in hair loss,11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. and was classified as an impulse control disorder in DSM-IV-TR.22. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Arlington: American Psychiatric Publishing; 2000. A third disorder – or, rather a group of disorders – is that of tic disorders, which have been linked to OCD in several aspects.33. Zohar AH, Pauls DL, Ratzoni G, Apter A, Dycian A, Binder M, et al. Obsessive-compulsive disorder with and without tics in an epidemiological sample of adolescents. Am J Psychiatry. 1997;154:274-6.

4. Dell'Osso B, Marazziti D, Albert U, Pallanti S, Gambini O, Tundo A, et al. Parsing the phenotype of obsessive-compulsive tic disorder (OCTD): a multidisciplinary consensus. Int J Psychiatry Clin Pract. 2017;21:156-9.

5. Torresan RC, Ramos-Cerqueira AT, Shavitt RG, do Rosario MC, de Mathis MA, Miguel EC, et al. Symptom dimensions, clinical course and comorbidity in men and women with obsessive-compulsive disorder. Psychiatry Res. 2013;209:186-95.

6. Bienvenu OJ, Samuels JF, Wuyek LA, Liang KY, Wang Y, Grados MA, et al. Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med. 2012;42:1-13.

7. Hemmings SM, Kinnear CJ, Lochner C, Niehaus DJ, Knowles JA, Moolman-Smook JC, et al. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates. Psychiatry Res. 2004;128:175-82.
-88. Richter MA, Summerfeldt LJ, Antony MM, Swinson RP. Obsessive-compulsive spectrum conditions in obsessive-compulsive disorder and other anxiety disorders. Depress Anxiety. 2003;18:118-27. A tic is a sudden, rapid, recurrent, nonrhythmic motor movement or vocalization.11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. Some types of tics, especially complex ones, could in fact be considered symptoms of OCD, and some OCD symptoms could conversely be considered complex tics.99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959. Lochner et al.1010. Lochner C, Seedat S, du Toit PL, Nel DG, Niehaus DJ, Sandler R, et al. Obsessive-compulsive disorder and trichotillomania: a phenomenological comparison. BMC Psychiatry. 2005;5:2. have examined the tic disorders vs. OCD relationship, which includes other complex repetitive behaviors, particularly TTM. Evaluating lifetime comorbidities, degree of disability, and response to treatment, these authors noted significant differences between OCD and TTM, and reached the conclusion that these two disorders were obviously different; furthermore, they reached the conclusion that TTM was wrongly classified as an impulse control disorder. But is “obsessive-compulsive related disorder” a better classification for TTM? A review questioning the content of an eventual obsessive-compulsive spectrum grouping of disorders stated that TTM would be better placed in a group of body-focused repetitive disorders than in that of obsessive-compulsive related disorders, unless the former group were not included in DSM-5.1111. Phillips KA, Stein DJ, Rauch SL, Hollander E, Fallon BA, Barsky A, et al. Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V? Depress Anxiety. 2010;27:528-55. And even if TTM were to be classified as an obsessive-compulsive related disorder (as it ultimately was), the authors stated that the overlap between OCD and TTM would be “partial at best.”1111. Phillips KA, Stein DJ, Rauch SL, Hollander E, Fallon BA, Barsky A, et al. Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V? Depress Anxiety. 2010;27:528-55. But what about TTM and tics? Would the tic disorders group be a better group for TTM? Is TTM in fact a complex tic rather than a compulsion?

In this critical review, we will consider different aspects of OCD, tic disorders, and TTM to discuss the possibility of a closer relationship between TTM and tic disorders than between TTM and OCD.

It is worth noting that Tourette syndrome (TS) has been the subject of much more research than simple tic disorders; we will thus refer much more often to TS than to the latter.

Method

Our research question was the following: could TTM be considered a tic disorder rather than an obsessive-compulsive related disorder? To carry out our critical review and answer this question, we searched the MEDLINE database (via PubMed) on November 2018.

We conducted this search across five axes we considered relevant: phenomenological investigation of urges, comorbidities, neuropsychology (especially attention, inhibition, working memory, and flexibility), imaging, and pharmacology. The inclusion criteria were as follows:

  • - Only original studies were considered (case reports, qualitative studies, and qualitative reviews were thus excluded, except for the “antipsychotics and TTM” part, as we found very few original studies);

  • - If meta-analyses existed, we considered only the meta-analysis and not the original studies cited therein;

  • - The reviewed studies should be written in English only;

  • - The populations studied in original research should be patients with OCD, TTM, or tic disorders;

  • - The selected studies should specifically include results concerning the field of interest.

Terms used in the search

The PubMed search queries used for each of the different axes are described below.

Phenomenology

The search query “urges AND (OCD OR “obsessive-compulsive disorder)” yielded 122 results; “urges AND Tourette,”; 124 results; and “urges AND (trichotillomania OR “hair pulling disorder”)” returned 28 results.

Among the OCD results, we found 22 articles potentially relevant for our aim. After full-text reading, 12 of these articles were found to assess OCD phenomenology and thus selected for further analysis (Table 1). Among the articles identified by the urges and TS query, we deemed 78 relevant and selected 20 (Table 1). Finally, among the articles returned by the urges and TTM query, we deemed eight relevant and ultimately selected only two (Table 1).

Comorbidity

The search query “(“hair pulling disorder” OR trichotillomania) AND (OCD OR “obsessive-compulsive disorder”) and comorbidity” yielded 81 articles, of which 19 were ultimately selected; “(“hair pulling disorder” or trichotillomania) and Tourette and comorbidity” yielded 11 articles, of which four studies were ultimately selected (Table 2).

Neuropsychology

Considering the huge numbers of articles found in this part concerning OCD, we considered only two well-done meta-analyses: one in adults1212. Abramovitch A, Abramowitz JS, Mittelman A. The neuropsychology of adult obsessive-compulsive disorder: a meta-analysis. Clin Psychol Rev. 2013;33:1163-71. and one in children.1313. Abramovitch A, Abramowitz JS, Mittelman A, Stark A, Ramsey K, Geller DA. Research review: neuropsychological test performance in pediatric obsessive-compulsive disorder--a meta-analysis. J Child Psychol Psychiatry. 2015;56:837-47.

For TTM, our query was “(TTM or trichotillomania) AND (“working memory” OR “inhibition” OR “attention” OR “flexibility”)”; it returned 181 results, of which 12 were ultimately selected; for TS, “Tourette AND (“working memory” OR “inhibition” OR “attention” OR “flexibility”)” yielded 1,306 results. However, we found a meta-analysis1414. Morand-Beaulieu S, Grot S, Lavoie J, Leclerc JB, Luck D, Lavoie ME. The puzzling question of inhibitory control in Tourette syndrome: a meta-analysis. Neurosci Biobehav Rev. 2017;80:240-62. concerning inhibition, and thus excluded this term from our search. The query was then repeated as follows: “Tourette AND (“working memory” OR “inhibition” OR “attention” OR “flexibility”)”, which returned 1,159 results. We found a well-done recent meta-analysis concerning flexibility (through the Wisconsin Card Sorting Test),1515. Lange F, Seer C, Muller-Vahl K, Kopp B. Cognitive flexibility and its electrophysiological correlates in Gilles de la Tourette syndrome. Dev Cogn Neurosci. 2017;27:78-90. and thus removed that term from the query as well. Finally, we searched for the terms “Tourette AND (“working memory” OR “attention”)”, which yielded 1,155 records; 11 were ultimately selected (Table 3).

Imaging

We found two meta-analyses of voxel-based morphometry (VBM) analysis with magnetic resonance imaging (MRI) in OCD patients.1616. Hu X, Du M, Chen L, Li L, Zhou M, Zhang L, et al. Meta-analytic investigations of common and distinct grey matter alterations in youths and adults with obsessive-compulsive disorder. Neurosci Biobehav Rev. 2017;78:91-103.,1717. Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry. 2017;174:60-9. For TS, the query was “Tourette AND MRI,” yielding 293 results, of which 11 were ultimately selected. For TTM, our query was “(TTM or trichotillomania) AND MRI,” which yielded 55 results; nine were selected for inclusion (Table 4).

Treatment

This final part included six separate queries. The terms “(OCD OR “obsessive-compulsive disorder”) AND (SRI OR “serotonin reuptake inhibitor”)” returned 479 records, 11 of which (all meta-analyses) were ultimately selected. The query “(OCD OR “obsessive-compulsive disorder) AND (antipsychotic OR neuroleptic)” yielded 985 results, seven of which (again, all meta-analyses) were ultimately selected. “Tourette AND (SRI OR “serotonin reuptake inhibitor”)” returned 15 results, only one of which was selected; “Tourette AND (antipsychotic OR neuroleptic)” yielded 767 results, three of which (all meta-analyses) were selected. The query “(trichotillomania or “hair pulling disorder”) AND (antipsychotic OR neuroleptic)” yielded 61 results. Considering the low number of studies, we decided to include case reports as well; 22 articles were ultimately selected. Finally, “(trichotillomania or “hair pulling disorder”) AND (SRI OR “serotonin reuptake inhibitor”)” yielded 20 results, seven of which were selected (Table 5).

Clinical comparison of TTM, OCD, and tic disorders

Phenomenology

TTM is defined by DSM-5 as an obsessive-compulsive related disorder.11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. The two main diagnostic criteria are “recurrent pulling out of one’s hair, resulting in hair loss” and “repeated attempts to decrease or stop hair pulling.”11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. As these diagnostic criteria show, TTM does not involve any obsessions. DSM-5 thus considers TTM as a differential diagnosis of OCD and explains that the one difference from OCD is the absence of obsession in TTM (obsessions are one of the two key diagnostic criteria of OCD, alongside compulsions,11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. even if absence of obsession does not exclude OCD).

The more detailed phenomenology of TTM, as described by DSM-5, involves that hair pulling “may be triggered by feelings of anxiety or boredom (and) may be preceded by an increasing sense of tension (either immediately before pulling out the hair or when attempting to resist the urge to pull).”11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. It is then interesting to notice that some of the phenomenology involved in tics (which are sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013.) bears similarities with those of TTM precisions. Indeed, regarding tics, the DSM-5 explains that “as children get older, they begin to report their tics being associated with a premonitory urge – a somatic sensation that precedes the tic – and a feeling of tension reduction following the expression of the tic” and that “tics are worsened by anxiety.”11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. Hence, tics and TTM are both preceded by urges.

Urges are closer to physical sensations, while obsessions are closer to cognitive processes (e.g., thoughts or images). But obsessions also involve urges, as a subtype of obsessions themselves distinct from thoughts or images.11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013.

Considering the potential importance of urge phenomena for challenging the DSM-5 classification of TTM, we decided to conduct a systematic review concerning this phenomenon (Table 1).

Table 1
Premonitory urges in obsessive-compulsive disorder, Tourette syndrome, and trichotillomania

Articles have reported urges and sensory phenomena in OCD patients,1818. Fornes-Romero G, Belloch A. Induced not just right and incompleteness experiences in OCD patients and non-clinical individuals: an in vivo study. J Behav Ther Exp Psychiatry. 2017;57:103-12.

19. Hirschtritt ME, Darrow SM, Illmann C, Osiecki L, Grados M, Sandor P, et al. Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome. Psychol Med. 2018;48:279-93.

20. Subira M, Sato JR, Alonso P, do Rosario MC, Segalas C, Batistuzzo MC, et al. Brain structural correlates of sensory phenomena in patients with obsessive-compulsive disorder. J Psychiatry Neurosci. 2015;40:232-40.

21. Kano Y, Matsuda N, Nonaka M, Fujio M, Kuwabara H, Kono T. Sensory phenomena related to tics, obsessive-compulsive symptoms, and global functioning in Tourette syndrome. Compr Psychiatry. 2015;62:141-6.

22. Gillan CM, Morein-Zamir S, Urcelay GP, Sule A, Voon V, Apergis-Schoute AM, et al. Enhanced avoidance habits in obsessive-compulsive disorder. Biol Psychiatry. 2014;75:631-8.
-2323. Brandt VC, Hermanns J, Beck C, Baumer T, Zurowski B, Munchau A. The temporal relationship between premonitory urges and covert compulsions in patients with obsessive-compulsive disorder. Psychiatry Res. 2018;262:6-12. with a temporal relationship between these phenomena and the compulsions.2323. Brandt VC, Hermanns J, Beck C, Baumer T, Zurowski B, Munchau A. The temporal relationship between premonitory urges and covert compulsions in patients with obsessive-compulsive disorder. Psychiatry Res. 2018;262:6-12.

24. Rachman S, De Silva P, Roper G. The spontaneous decay of compulsive urges. Behav Res Ther. 1976;14:445-53.
-2525. Likierman H, Rachman SJ. Spontaneous decay of compulsive urges: cumulative effects. Behav Res Ther. 1980;18:387-94. Urges are defined as being distinct phenomena: sensory phenomena, “just-right” sensations, or other phenomena, e.g., a need for the patient to release energy.2626. Prado HS, Rosario MC, Lee J, Hounie AG, Shavitt RG, Miguel EC. Sensory phenomena in obsessive-compulsive disorder and tic disorders: a review of the literature. CNS Spectr. 2008;13:425-32. Studies were divided regarding the association between “just-right”/incompleteness feelings and OCD severity scales: some found no correlation,1818. Fornes-Romero G, Belloch A. Induced not just right and incompleteness experiences in OCD patients and non-clinical individuals: an in vivo study. J Behav Ther Exp Psychiatry. 2017;57:103-12. while others did.2121. Kano Y, Matsuda N, Nonaka M, Fujio M, Kuwabara H, Kono T. Sensory phenomena related to tics, obsessive-compulsive symptoms, and global functioning in Tourette syndrome. Compr Psychiatry. 2015;62:141-6. Furthermore, it is interesting to note that OCD patients with sensory phenomena presented symmetry compulsions more frequently than OCD patients without these phenomena.2020. Subira M, Sato JR, Alonso P, do Rosario MC, Segalas C, Batistuzzo MC, et al. Brain structural correlates of sensory phenomena in patients with obsessive-compulsive disorder. J Psychiatry Neurosci. 2015;40:232-40. Studies also found that urges (sensory phenomena, aggressive urges, or “just-right” phenomena) were more often present in OCD + TS patients than in OCD-only patients.1919. Hirschtritt ME, Darrow SM, Illmann C, Osiecki L, Grados M, Sandor P, et al. Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome. Psychol Med. 2018;48:279-93.,2727. Shavitt RG, de Mathis MA, Oki F, Ferrao YA, Fontenelle LF, Torres AR, et al. Phenomenology of OCD: lessons from a large multicenter study and implications for ICD-11. J Psychiatr Res. 2014;57:141-8.,2828. Miguel EC, do Rosario-Campos MC, Prado HS, do Valle R, Rauch SL, Coffey BJ, et al. Sensory phenomena in obsessive-compulsive disorder and Tourette's disorder. J Clin Psychiatry. 2000;61:150-6; quiz 7. These results (concerning symmetry compulsions and OCD-only vs. OCD + TS) are interesting when compared with the finding of Worbe et al. that symmetry or “just-right” phenomena were more often considered tics than compulsions (the difference between tic and compulsion being the nature of the different repetitive behaviors, based on the absence or presence of anxiety, with tics being unrelated to anxiety).99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959.

Urges are found in TS patients, with a temporal relationship between tics and urges.2929. McGuire JF, McBride N, Piacentini J, Johnco C, Lewin AB, Murphy TK, et al. The premonitory urge revisited: an individualized premonitory urge for tics scale. J Psychiatr Res. 2016;83:176-83.

30. Brandt VC, Beck C, Sajin V, Baaske MK, Baumer T, Beste C, et al. Temporal relationship between premonitory urges and tics in Gilles de la Tourette syndrome. Cortex. 2016;77:24-37.

31. Schunke O, Grashorn W, Kahl U, Schottle D, Haggard P, Munchau A, et al. Quantitative sensory testing in adults with Tourette syndrome. Parkinsonism Relat Disord. 2016;24:132-6.

32. Brabson LA, Brown JL, Capriotti MR, Ramanujam K, Himle MB, Nicotra CM, et al. Patterned changes in urge ratings with tic suppression in youth with chronic tic disorders. J Behav Ther Exp Psychiatry. 2016;50:162-70.

33. McGuire JF, Piacentini J, Scahill L, Woods DW, Villarreal R, Wilhelm S, et al. Bothersome tics in patients with chronic tic disorders: characteristics and individualized treatment response to behavior therapy. Behav Res Ther. 2015;70:56-63.

34. Ganos C, Asmuss L, Bongert J, Brandt V, Munchau A, Haggard P. Volitional action as perceptual detection: predictors of conscious intention in adolescents with tic disorders. Cortex. 2015;64:47-54.

35. Muller-Vahl KR, Riemann L, Bokemeyer S. Tourette patients' misbelief of a tic rebound is due to overall difficulties in reliable tic rating. J Psychosom Res. 2014;76:472-6.

36. Capriotti MR, Brandt BC, Turkel JE, Lee HJ, Woods DW. Negative reinforcement and premonitory urges in youth with Tourette syndrome: an experimental evaluation. Behav Modif. 2014;38:276-96.
-3737. Cohen AJ, Leckman JF. Sensory phenomena associated with Gilles de la Tourette's syndrome. J Clin Psychiatry. 1992;53:319-23. Furthermore, studies have found that TS patients with urges have more severe tics.3838. Sambrani T, Jakubovski E, Muller-Vahl KR. New insights into clinical characteristics of Gilles de la Tourette syndrome: findings in 1032 patients from a single German center. Front Neurosci. 2016;10:415.

39. Eapen V, Robertson MM. Are there distinct subtypes in Tourette syndrome? Pure-Tourette syndrome versus Tourette syndrome-plus, and simple versus complex tics. Neuropsychiatr Dis Treat. 2015;11:1431-6.

40. Ganos C, Garrido A, Navalpotro-Gomez I, Ricciardi L, Martino D, Edwards MJ, et al. Premonitory urge to tic in Tourette's is associated with interoceptive awareness. Mov Disord. 2015;30:1198-202.

41. Reese HE, Scahill L, Peterson AL, Crowe K, Woods DW, Piacentini J, et al. The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults. Behav Ther. 2014;45:177-86.

42. Eddy CM, Cavanna AE. On being your own worst enemy: an investigation of socially inappropriate symptoms in Tourette syndrome. J Psychiatr Res. 2013;47:1259-63.
-4343. Crossley E, Cavanna AE. Sensory phenomena: clinical correlates and impact on quality of life in adult patients with Tourette syndrome. Psychiatry Res. 2013;209:705-10. Considering our aim, it is interesting to note that studies found that urges were associated with symmetry compulsion or “just-right” experiences2121. Kano Y, Matsuda N, Nonaka M, Fujio M, Kuwabara H, Kono T. Sensory phenomena related to tics, obsessive-compulsive symptoms, and global functioning in Tourette syndrome. Compr Psychiatry. 2015;62:141-6.,3838. Sambrani T, Jakubovski E, Muller-Vahl KR. New insights into clinical characteristics of Gilles de la Tourette syndrome: findings in 1032 patients from a single German center. Front Neurosci. 2016;10:415.,4141. Reese HE, Scahill L, Peterson AL, Crowe K, Woods DW, Piacentini J, et al. The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults. Behav Ther. 2014;45:177-86.,4444. Rajagopal S, Cavanna AE. Premonitory urges and repetitive behaviours in adult patients with Tourette syndrome. Neurol Sci. 2014;35:969-71. in TS patients. These findings are similar to those reported for OCD patients above (i.e., urges are more frequent when symmetry compulsions and comorbid tics are present). We can thus remark, as before, that these urges concerned specific repetitive behaviors (not the washing or checking compulsions classically associated with anxiety) that have been more frequently associated with tics than with compulsions.99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959. What highlights the difficulty of determining whether urges are associated with OCD, TS, or both is that some studies found a correlation between level of urges as measured by the Premonitory Urge to Tic Scale (PUTS) and the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS), but not between PUTS and the Yale Global Tic Severity Scale (YGTSS),4545. Gulisano M, Cali P, Palermo F, Robertson M, Rizzo R. Premonitory urges in patients with Gilles de la Tourette syndrome: an Italian translation and a 7-year follow-up. J Child Adolesc Psychopharmacol. 2015;25:810-6.,4646. Steinberg T, Shmuel Baruch S, Harush A, Dar R, Woods D, Piacentini J, et al. Tic disorders and the premonitory urge. J Neural Transm (Vienna). 2010;117:277-84. whereas other studies found the opposite.4040. Ganos C, Garrido A, Navalpotro-Gomez I, Ricciardi L, Martino D, Edwards MJ, et al. Premonitory urge to tic in Tourette's is associated with interoceptive awareness. Mov Disord. 2015;30:1198-202.,4141. Reese HE, Scahill L, Peterson AL, Crowe K, Woods DW, Piacentini J, et al. The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults. Behav Ther. 2014;45:177-86. Unfortunately, among these studies,4040. Ganos C, Garrido A, Navalpotro-Gomez I, Ricciardi L, Martino D, Edwards MJ, et al. Premonitory urge to tic in Tourette's is associated with interoceptive awareness. Mov Disord. 2015;30:1198-202.,4141. Reese HE, Scahill L, Peterson AL, Crowe K, Woods DW, Piacentini J, et al. The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults. Behav Ther. 2014;45:177-86.,4545. Gulisano M, Cali P, Palermo F, Robertson M, Rizzo R. Premonitory urges in patients with Gilles de la Tourette syndrome: an Italian translation and a 7-year follow-up. J Child Adolesc Psychopharmacol. 2015;25:810-6.,4646. Steinberg T, Shmuel Baruch S, Harush A, Dar R, Woods D, Piacentini J, et al. Tic disorders and the premonitory urge. J Neural Transm (Vienna). 2010;117:277-84. none made specific correlations between PUTS scores and different types of OCD to determine whether PUTS scores were associated with specific compulsions (e.g., symmetry) or with symmetry and checking compulsions alike. However, when considering studies which made the distinction between different types of “compulsions,”2020. Subira M, Sato JR, Alonso P, do Rosario MC, Segalas C, Batistuzzo MC, et al. Brain structural correlates of sensory phenomena in patients with obsessive-compulsive disorder. J Psychiatry Neurosci. 2015;40:232-40.,2121. Kano Y, Matsuda N, Nonaka M, Fujio M, Kuwabara H, Kono T. Sensory phenomena related to tics, obsessive-compulsive symptoms, and global functioning in Tourette syndrome. Compr Psychiatry. 2015;62:141-6.,3838. Sambrani T, Jakubovski E, Muller-Vahl KR. New insights into clinical characteristics of Gilles de la Tourette syndrome: findings in 1032 patients from a single German center. Front Neurosci. 2016;10:415.,4141. Reese HE, Scahill L, Peterson AL, Crowe K, Woods DW, Piacentini J, et al. The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults. Behav Ther. 2014;45:177-86.,4444. Rajagopal S, Cavanna AE. Premonitory urges and repetitive behaviours in adult patients with Tourette syndrome. Neurol Sci. 2014;35:969-71. urges were associated with symmetry compulsions or “just-right” perception, phenomena more frequently associated elsewhere with TS than with OCD,99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959. and never specifically with repetitive checking or washing behaviors, which are more frequently associated with OCD.99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959.

As in Tourette and OCD, urges are found in TTM.4747. Lee EB, Homan KJ, Morrison KL, Ong CW, Levin ME, Twohig MP. Acceptance and commitment therapy for trichotillomania: a randomized controlled trial of adults and adolescents. Behav Modif. 2018:145445518794366. The urge to pull was greater in patients who experienced perfectionistic thoughts,4848. Falkenstein MJ, Haaga DA. Symptom accommodation, trichotillomania-by-proxy, and interpersonal functioning in trichotillomania (hair-pulling disorder). Compr Psychiatry. 2016;65:88-97. which could be associated with symmetry or “just-right” phenomena.

Taken together, even if it is impossible to reach a definitive conclusion, it seems that urges are specifically associated with specific repetitive behaviors: tics, symmetry, or “just-right” phenomena. Furthermore, in TTM, urges are associated with perfectionistic thoughts, which could be considered as being close to the “just-right” phenomenon. These phenomenological descriptions could suggest an important overlap between TTM and tic disorders, maybe more so than with OCD – neither TTM nor tics being preceded by thoughts or images, unlike in OCD.11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. Furthermore, one could hypothesize that urges in OCD would in fact precede complex tics, not compulsions, since it has been shown that compulsions can in some cases be considered tics.99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959.

Finally, a very important study on the phenomenology of TTM4949. Rozenman M, Peris TS, Gonzalez A, Piacentini J. Clinical characteristics of pediatric trichotillomania: comparisons with obsessive-compulsive and tic disorders. Child Psychiatry Hum Dev. 2016;47:124-32. found significant differences between TTM and OCD, but not between TTM and tic disorders (chronic tic disorder and TS), particularly when multiple symptoms were taken into consideration, such as anxiety symptoms (as measured by the Multidimensional Anxiety Scale for Children [MASC]), depressive symptoms (as measured by the Children’s Depression Inventory [CDI]), internalizing symptoms, externalizing symptoms, and thoughts (as measured by the Child Behavior Checklist [CBCL]). This study4949. Rozenman M, Peris TS, Gonzalez A, Piacentini J. Clinical characteristics of pediatric trichotillomania: comparisons with obsessive-compulsive and tic disorders. Child Psychiatry Hum Dev. 2016;47:124-32. thus found a more important relationship between tic disorders and TTM when co-symptoms of TTM, OCD, and tic disorders were considered, as our qualitative comparison of DSM-5 diagnostic criteria did.

Comorbidity

Comorbidity results are presented in Table 2.

Table 2
Epidemiological data in obsessive-compulsive disorder, Tourette syndrome, and trichotillomania

Comorbidity rates among TS, OCD, and tic disorder

OCD and TTM are frequently comorbid. The studies included in this review reported a 6 to 11% rate of TTM comorbidity in patients with OCD.55. Torresan RC, Ramos-Cerqueira AT, Shavitt RG, do Rosario MC, de Mathis MA, Miguel EC, et al. Symptom dimensions, clinical course and comorbidity in men and women with obsessive-compulsive disorder. Psychiatry Res. 2013;209:186-95.

6. Bienvenu OJ, Samuels JF, Wuyek LA, Liang KY, Wang Y, Grados MA, et al. Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med. 2012;42:1-13.

7. Hemmings SM, Kinnear CJ, Lochner C, Niehaus DJ, Knowles JA, Moolman-Smook JC, et al. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates. Psychiatry Res. 2004;128:175-82.
-88. Richter MA, Summerfeldt LJ, Antony MM, Swinson RP. Obsessive-compulsive spectrum conditions in obsessive-compulsive disorder and other anxiety disorders. Depress Anxiety. 2003;18:118-27.,5050. Stewart SE, Jenike MA, Keuthen NJ. Severe obsessive-compulsive disorder with and without comorbid hair pulling: comparisons and clinical implications. J Clin Psychiatry. 2005;66:864-9.

51. Brakoulias V, Starcevic V, Sammut P, Berle D, Milicevic D, Moses K, et al. Obsessive-compulsive spectrum disorders: a comorbidity and family history perspective. Australas Psychiatry. 2011;19:151-5.

52. Lochner C, Stein DJ. Obsessive-compulsive spectrum disorders in obsessive-compulsive disorder and other anxiety disorders. Psychopathology. 2010;43:389-96.
-5353. Bienvenu OJ, Samuels JF, Riddle MA, Hoehn-Saric R, Liang KY, Cullen BA, et al. The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry. 2000;48:287-93. However, we found also that OCD patients with TTM have more tics than those without TTM5050. Stewart SE, Jenike MA, Keuthen NJ. Severe obsessive-compulsive disorder with and without comorbid hair pulling: comparisons and clinical implications. J Clin Psychiatry. 2005;66:864-9.; and OCD patients with TTM have an earlier onset of their OCD.5050. Stewart SE, Jenike MA, Keuthen NJ. Severe obsessive-compulsive disorder with and without comorbid hair pulling: comparisons and clinical implications. J Clin Psychiatry. 2005;66:864-9. The same results have been found for OCD patients with tics: they are more likely to have comorbid TTM than OCD patients without tics5454. Jaisoorya TS, Reddy YC, Srinath S, Thennarasu K. Obsessive-compulsive disorder with and without tic disorder: a comparative study from India. CNS Spectr. 2008;13:705-11. and have an earlier age of OCD onset.5454. Jaisoorya TS, Reddy YC, Srinath S, Thennarasu K. Obsessive-compulsive disorder with and without tic disorder: a comparative study from India. CNS Spectr. 2008;13:705-11.

When considering OCD patients with and without “grooming disorders,” we found that the two groups presented the same frequency of tic disorder; however, OCD patients without grooming disorders more often had a family history of tics, while OCD patients with grooming disorder more often had a family history of OCD.5555. Lovato L, Ferrao YA, Stein DJ, Shavitt RG, Fontenelle LF, Vivan A, et al. Skin picking and trichotillomania in adults with obsessive-compulsive disorder. Compr Psychiatry. 2012;53:562-8.

Finally, patients with early-onset OCD have more TS/tics and TTM comorbidity than those with late-onset OCD.77. Hemmings SM, Kinnear CJ, Lochner C, Niehaus DJ, Knowles JA, Moolman-Smook JC, et al. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates. Psychiatry Res. 2004;128:175-82.,5656. Robertson MM. A personal 35 year perspective on Gilles de la Tourette syndrome: prevalence, phenomenology, comorbidities, and coexistent psychopathologies. Lancet Psychiatry. 2015;2:68-87. These data are important from a genetic standpoint (see Genetics section below).

An interesting study looked at the family history of OCD patients and found that 55% of their family members had a history of OCD, 14% had a history of tic disorders, and only 4% had a history of TTM.66. Bienvenu OJ, Samuels JF, Wuyek LA, Liang KY, Wang Y, Grados MA, et al. Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med. 2012;42:1-13. The authors concluded that “it seems reasonable to consider TTM OCD-related,” but also that “OCD and tic disorders are strongly family-related, and from this standpoint, it would be sensible to group these conditions together in DSM-5.”66. Bienvenu OJ, Samuels JF, Wuyek LA, Liang KY, Wang Y, Grados MA, et al. Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med. 2012;42:1-13.

When we searched for studies on comorbid TTM in TS patients, we found that about 3.8-10% of TS patients also have TTM.5757. Greenberg E, Tung ES, Gauvin C, Osiecki L, Yang KG, Curley E, et al. Prevalence and predictors of hair pulling disorder and excoriation disorder in Tourette syndrome. Eur Child Adolesc Psychiatry. 2018;27:569-79.,5858. Frank MC, Piedad J, Rickards H, Cavanna AE. The role of impulse control disorders in Tourette syndrome: an exploratory study. J Neurol Sci. 2011;310:276-8. More importantly, in a multivariable analysis of TTM occurring in TS patients, one of these studies found that only Yale-Global Tic Severity Scale (YGTSS) motor score was associated with occurrence of TTM in comorbidity with TS.5757. Greenberg E, Tung ES, Gauvin C, Osiecki L, Yang KG, Curley E, et al. Prevalence and predictors of hair pulling disorder and excoriation disorder in Tourette syndrome. Eur Child Adolesc Psychiatry. 2018;27:569-79. In this same multivariable analysis, comorbid OCD was not associated with occurrence of TTM in TS patients.5757. Greenberg E, Tung ES, Gauvin C, Osiecki L, Yang KG, Curley E, et al. Prevalence and predictors of hair pulling disorder and excoriation disorder in Tourette syndrome. Eur Child Adolesc Psychiatry. 2018;27:569-79.

Finally, we found that between 2.6 and 20% of TTM patients had a history of OCD,4949. Rozenman M, Peris TS, Gonzalez A, Piacentini J. Clinical characteristics of pediatric trichotillomania: comparisons with obsessive-compulsive and tic disorders. Child Psychiatry Hum Dev. 2016;47:124-32.,5353. Bienvenu OJ, Samuels JF, Riddle MA, Hoehn-Saric R, Liang KY, Cullen BA, et al. The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry. 2000;48:287-93.,5959. Houghton DC, Maas J, Twohig MP, Saunders SM, Compton SN, Neal-Barnett AM, et al. Comorbidity and quality of life in adults with hair pulling disorder. Psychiatry Res. 2016;239:12-9.

60. Greenberg E, Grant JE, Curley EE, Lochner C, Woods DW, Tung ES, et al. Predictors of comorbid eating disorders and association with other obsessive-compulsive spectrum disorders in trichotillomania. Compr Psychiatry. 2017;78:1-8.

61. Grant JE, Redden SA, Leppink EW, Chamberlain SR. Trichotillomania and co-occurring anxiety. Compr Psychiatry 2017;72:1-5.
-6262. Odlaug BL, Grant JE. Trichotillomania and Pathologic Skin Picking: clinical comparison with an examination of comorbidity. Ann Clin Psychiatry. 2008;20:57-63. while 0 to 3% had a history of tic disorders.5353. Bienvenu OJ, Samuels JF, Riddle MA, Hoehn-Saric R, Liang KY, Cullen BA, et al. The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry. 2000;48:287-93.,6060. Greenberg E, Grant JE, Curley EE, Lochner C, Woods DW, Tung ES, et al. Predictors of comorbid eating disorders and association with other obsessive-compulsive spectrum disorders in trichotillomania. Compr Psychiatry. 2017;78:1-8.

When comparing tic comorbidity in OCD and TTM patients, five studies reported that TTM patients have the same level of tic disorders as OCD patients.1010. Lochner C, Seedat S, du Toit PL, Nel DG, Niehaus DJ, Sandler R, et al. Obsessive-compulsive disorder and trichotillomania: a phenomenological comparison. BMC Psychiatry. 2005;5:2.,4949. Rozenman M, Peris TS, Gonzalez A, Piacentini J. Clinical characteristics of pediatric trichotillomania: comparisons with obsessive-compulsive and tic disorders. Child Psychiatry Hum Dev. 2016;47:124-32.,6363. Panza KE, Pittenger C, Bloch MH. Age and gender correlates of pulling in pediatric trichotillomania. J Am Acad Child Adolesc Psychiatry. 2013;52:241-9.

64. King RA, Scahill L, Vitulano LA, Schwab-Stone M, Tercyak KP Jr, Riddle MA. Childhood trichotillomania: clinical phenomenology, comorbidity, and family genetics. J Am Acad Child Adolesc Psychiatry. 1995;34:1451-9.
-6565. Hanna GL. Trichotillomania and related disorders in children and adolescents. Child Psychiatry Hum Dev. 1997;27:255-68. However, another study found distinct results, with TTM patients having much more OCD than tic disorders.6666. Keuthen NJ, Altenburger EM, Pauls D. A family study of trichotillomania and chronic hair pulling. Am J Med Genet B Neuropsychiatr Genet. 2014;165B:167-74. If we consider TTM as a tic, the rate of OCD comorbidity in TTM in this latter study is then close to the one found in TS.6767. Hirschtritt ME, Lee PC, Pauls DL, Dion Y, Grados MA, Illmann C, et al. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry. 2015;72:325-33.

These studies highlight a relationship between tics and TTM, not only in an OCD context (and, possibly, in the specific context of early-onset OCD77. Hemmings SM, Kinnear CJ, Lochner C, Niehaus DJ, Knowles JA, Moolman-Smook JC, et al. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates. Psychiatry Res. 2004;128:175-82.,5454. Jaisoorya TS, Reddy YC, Srinath S, Thennarasu K. Obsessive-compulsive disorder with and without tic disorder: a comparative study from India. CNS Spectr. 2008;13:705-11.), but also directly in TS patients.5757. Greenberg E, Tung ES, Gauvin C, Osiecki L, Yang KG, Curley E, et al. Prevalence and predictors of hair pulling disorder and excoriation disorder in Tourette syndrome. Eur Child Adolesc Psychiatry. 2018;27:569-79. This last study helps us reach the conclusion that the TTM-tic relationship seems stronger than the TTM-OCD relationship, since OCD was not associated with occurrence of TTM in TS patients.

Comorbidity rates of TTM, OCD, and tic disorder with other psychiatric disorders

When we looked at other comorbidities in each of these disorders, we found that: 1) TTM patients have a lifetime rate of comorbid major depressive disorder (MDD) of approximately 43%5959. Houghton DC, Maas J, Twohig MP, Saunders SM, Compton SN, Neal-Barnett AM, et al. Comorbidity and quality of life in adults with hair pulling disorder. Psychiatry Res. 2016;239:12-9.; 2) OCD patients present have a 15 to 55% lifetime rate of comorbid MDD6868. Lochner C, Fineberg NA, Zohar J, van Ameringen M, Juven-Wetzler A, Altamura AC, et al. Comorbidity in obsessive-compulsive disorder (OCD): a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). Compr Psychiatry. 2014;55:1513-9.

69. Hofmeijer-Sevink MK, van Oppen P, van Megen HJ, Batelaan NM, Cath DC, van der Wee NJ, et al. Clinical relevance of comorbidity in obsessive compulsive disorder: the Netherlands OCD association study. J Affect Disord. 2013;150:847-54.
-7070. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15:53-63.; and 3) TS patients have a 13 to 76% lifetime rate of comorbid MDD.5656. Robertson MM. A personal 35 year perspective on Gilles de la Tourette syndrome: prevalence, phenomenology, comorbidities, and coexistent psychopathologies. Lancet Psychiatry. 2015;2:68-87.,6767. Hirschtritt ME, Lee PC, Pauls DL, Dion Y, Grados MA, Illmann C, et al. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry. 2015;72:325-33.

Hence, there are major discrepancies between studies of depressive comorbidity (e.g., some studies reported a 15% rate of comorbid MDD in TS, whereas another reported 60%5656. Robertson MM. A personal 35 year perspective on Gilles de la Tourette syndrome: prevalence, phenomenology, comorbidities, and coexistent psychopathologies. Lancet Psychiatry. 2015;2:68-87.). It is thus very difficult to reach any conclusions. Concerning other psychiatric comorbidities in TTM, OCD, and tic disorders, results also preclude any conclusions.5959. Houghton DC, Maas J, Twohig MP, Saunders SM, Compton SN, Neal-Barnett AM, et al. Comorbidity and quality of life in adults with hair pulling disorder. Psychiatry Res. 2016;239:12-9.,6767. Hirschtritt ME, Lee PC, Pauls DL, Dion Y, Grados MA, Illmann C, et al. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry. 2015;72:325-33.

68. Lochner C, Fineberg NA, Zohar J, van Ameringen M, Juven-Wetzler A, Altamura AC, et al. Comorbidity in obsessive-compulsive disorder (OCD): a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). Compr Psychiatry. 2014;55:1513-9.

69. Hofmeijer-Sevink MK, van Oppen P, van Megen HJ, Batelaan NM, Cath DC, van der Wee NJ, et al. Clinical relevance of comorbidity in obsessive compulsive disorder: the Netherlands OCD association study. J Affect Disord. 2013;150:847-54.

70. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15:53-63.

71. Sallet PC, de Alvarenga PG, Ferrao Y, de Mathis MA, Torres AR, Marques A, et al. Eating disorders in patients with obsessive-compulsive disorder: prevalence and clinical correlates. Int J Eat Disord. 2010;43:315-25.

72. Klobucar A, Folnegovic-Smalc V, Kocijan-Hercigonja D, Sovic S, Gulic L. Clinical characteristics and comorbidity of pediatric trichotillomania: the study of 38 cases in Croatia. Psychiatr Danub. 2018;30:79-84.

73. Roessner V, Becker A, Banaschewski T, Freeman RD, Rothenberger A, Tourette Syndrome International Database C. Developmental psychopathology of children and adolescents with Tourette syndrome--impact of ADHD. Eur Child Adolesc Psychiatry. 2007;16 Suppl 1:24-35.
-7474. Woods DW, Houghton DC. Diagnosis, evaluation, and management of trichotillomania. Psychiatr Clin North Am. 2014;37:301-17. Furthermore, comorbidity studies in patients with OCD or TS are much easier to find than in TTM patients.

Comparison of TTM, OCD, and tic disorder epidemiology

Epidemiological data favor a closer proximity between TTM and OCD than between TTM and tic disorders. Just as OCD (about 55% of patients are female), TTM affects more women than men (about 80-85% of patients are female); this is not the case in TS, which affects males more often females.4949. Rozenman M, Peris TS, Gonzalez A, Piacentini J. Clinical characteristics of pediatric trichotillomania: comparisons with obsessive-compulsive and tic disorders. Child Psychiatry Hum Dev. 2016;47:124-32.,7575. Snorrason I, Belleau EL, Woods DW. How related are hair pulling disorder (trichotillomania) and skin picking disorder? A review of evidence for comorbidity, similarities and shared etiology. Clin Psychol Rev. 2012;32:618-29.

76. Walther MR, Snorrason I, Flessner CA, Franklin ME, Burkel R, Woods DW. The trichotillomania impact project in young children (TIP-YC): clinical characteristics, comorbidity, functional impairment and treatment utilization. Child Psychiatry Hum Dev. 2014;45:24-31.

77. Ko SM. Under-diagnosed psychiatric syndrome. I: Trichotillomania. Ann Acad Med Singapore. 1999;28:279-81.

78. Kichuk SA, Torres AR, Fontenelle LF, Rosario MC, Shavitt RG, Miguel EC, et al. Symptom dimensions are associated with age of onset and clinical course of obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2013;44:233-9.

79. Bebbington PE. Epidemiology of obsessive-compulsive disorder. Br J Psychiatry Suppl. 1998:35:2-6.

80. Knight T, Steeves T, Day L, Lowerison M, Jette N, Pringsheim T. Prevalence of tic disorders: a systematic review and meta-analysis. Pediatr Neurol. 2012;47:77-90.
-8181. Shaw ZA, Coffey BJ. Tics and Tourette syndrome. Psychiatr Clin North Am. 2014;37:269-86. Nonetheless, some studies found a greater proportion of males in OCD.8282. Frare F, Perugi G, Ruffolo G, Toni C. Obsessive-compulsive disorder and body dysmorphic disorder: a comparison of clinical features. Eur Psychiatry. 2004;19:292-8. Age of onset in TTM (about 11 to 13 years) is approximately the same as for early-onset OCD (about 11 years), but onset of tic disorders occurs much earlier (about 4 to 8 years).11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013.,7575. Snorrason I, Belleau EL, Woods DW. How related are hair pulling disorder (trichotillomania) and skin picking disorder? A review of evidence for comorbidity, similarities and shared etiology. Clin Psychol Rev. 2012;32:618-29.,8080. Knight T, Steeves T, Day L, Lowerison M, Jette N, Pringsheim T. Prevalence of tic disorders: a systematic review and meta-analysis. Pediatr Neurol. 2012;47:77-90.,8181. Shaw ZA, Coffey BJ. Tics and Tourette syndrome. Psychiatr Clin North Am. 2014;37:269-86.,8383. Bloch MH. Trichotillomania across the life span. J Am Acad Child Adolesc Psychiatry. 2009;48:879-83.

84. Delorme R, Golmard JL, Chabane N, Millet B, Krebs MO, Mouren-Simeoni MC, et al. Admixture analysis of age at onset in obsessive-compulsive disorder. Psychol Med. 2005;35:237-43.

85. Dell'Osso B, Benatti B, Hollander E, Fineberg N, Stein DJ, Lochner C, et al. 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;20:210-7.
-8686. De Luca V, Gershenzon V, Burroughs E, Javaid N, Richter MA. Age at onset in Canadian OCD patients: mixture analysis and systematic comparison with other studies. J Affect Disord. 2011;133:300-4. On a developmental level, analysis of the age at onset and the course of these illnesses seems to show TTM is closer to OCD (both chronic disorders) than to tic disorders (in which nearly half of patients become tic-free in early adulthood).7575. Snorrason I, Belleau EL, Woods DW. How related are hair pulling disorder (trichotillomania) and skin picking disorder? A review of evidence for comorbidity, similarities and shared etiology. Clin Psychol Rev. 2012;32:618-29.,8181. Shaw ZA, Coffey BJ. Tics and Tourette syndrome. Psychiatr Clin North Am. 2014;37:269-86.,8383. Bloch MH. Trichotillomania across the life span. J Am Acad Child Adolesc Psychiatry. 2009;48:879-83.,8787. Steketee G, Eisen J, Dyck I, Warshaw M, Rasmussen S. Predictors of course in obsessive-compulsive disorder. Psychiatry Res. 1999;89:229-38.

88. Attiullah N, Eisen JL, Rasmussen SA. Clinical features of obsessive-compulsive disorder. Psychiatr Clin North Am. 2000;23:469-91.
-8989. Leckman JF, Zhang H, Vitale A, Lahnin F, Lynch K, Bondi C, et al. Course of tic severity in Tourette syndrome: the first two decades. Pediatrics. 1998;102:14-9. Conversely, however, we could highlight that tic disorders tend to worsen in early adolescence (10-12 years),11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. when OCD and TTM appear.

Hence, even if lifetime prevalences are nearly similar across these disorders (about 1 to 3% for TTM,11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013.,7575. Snorrason I, Belleau EL, Woods DW. How related are hair pulling disorder (trichotillomania) and skin picking disorder? A review of evidence for comorbidity, similarities and shared etiology. Clin Psychol Rev. 2012;32:618-29.,8383. Bloch MH. Trichotillomania across the life span. J Am Acad Child Adolesc Psychiatry. 2009;48:879-83. about 2% for OCD,9090. Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15:410-24. and about 1% for TS8080. Knight T, Steeves T, Day L, Lowerison M, Jette N, Pringsheim T. Prevalence of tic disorders: a systematic review and meta-analysis. Pediatr Neurol. 2012;47:77-90.,9191. Ganos C, Hartmann A. Altered cholinergic neurotransmission in Tourette syndrome. Mov Disord. 2015;30:638.), epidemiological data seem to favor a closer relationship between TTM and OCD than between TTM and tic disorders.

Neuropsychology

Another way to study the proximity between OCD, tic disorders, and TTM is to analyze the neuropsychological particularities of each of these disorders (Table 3).

Table 3
Neuropsychological data in obsessive-compulsive disorder, Tourette syndrome, and trichotillomania

First, when comparing these three disorders, we find that adults with OCD1212. Abramovitch A, Abramowitz JS, Mittelman A. The neuropsychology of adult obsessive-compulsive disorder: a meta-analysis. Clin Psychol Rev. 2013;33:1163-71. seem to show a motor inhibition deficit, but no such deficit was found in children.1313. Abramovitch A, Abramowitz JS, Mittelman A, Stark A, Ramsey K, Geller DA. Research review: neuropsychological test performance in pediatric obsessive-compulsive disorder--a meta-analysis. J Child Psychol Psychiatry. 2015;56:837-47. Results in TTM are divergent; some authors found an inhibition deficit (Stop Signal task, Go-No Go Test9292. Odlaug BL, Chamberlain SR, Derbyshire KL, Leppink EW, Grant JE. Impaired response inhibition and excess cortical thickness as candidate endophenotypes for trichotillomania. J Psychiatr Res. 2014;59:167-73.

93. Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry. 2006;163:1282-4.

94. Bohne A, Savage CR, Deckersbach T, Keuthen NJ, Wilhelm S. Motor inhibition in trichotillomania and obsessive-compulsive disorder. J Psychiatr Res. 2008;42:141-50.
-9595. Grant JE, Odlaug BL, Chamberlain SR. A cognitive comparison of pathological skin picking and trichotillomania. J Psychiatr Res. 2011;45:1634-8.), while others did not (Stop Signal task,9595. Grant JE, Odlaug BL, Chamberlain SR. A cognitive comparison of pathological skin picking and trichotillomania. J Psychiatr Res. 2011;45:1634-8.,9696. Brennan E, Francazio S, Gunstad J, Flessner C. Inhibitory control in pediatric trichotillomania (Hair Pulling Disorder): the importance of controlling for age and symptoms of inattention and hyperactivity. Child Psychiatry Hum Dev. 2016;47:173-82. Go-No Go Test9494. Bohne A, Savage CR, Deckersbach T, Keuthen NJ, Wilhelm S. Motor inhibition in trichotillomania and obsessive-compulsive disorder. J Psychiatr Res. 2008;42:141-50.). Authors found no deficit for the Go-No Go or Stop Signal tasks in TS.1414. Morand-Beaulieu S, Grot S, Lavoie J, Leclerc JB, Luck D, Lavoie ME. The puzzling question of inhibitory control in Tourette syndrome: a meta-analysis. Neurosci Biobehav Rev. 2017;80:240-62. It is thus difficult to compare these three disorders in terms of inhibition, because of the divergent findings in TTM. Second, altered flexibility was found in adults with OCD1212. Abramovitch A, Abramowitz JS, Mittelman A. The neuropsychology of adult obsessive-compulsive disorder: a meta-analysis. Clin Psychol Rev. 2013;33:1163-71. (but not in children1313. Abramovitch A, Abramowitz JS, Mittelman A, Stark A, Ramsey K, Geller DA. Research review: neuropsychological test performance in pediatric obsessive-compulsive disorder--a meta-analysis. J Child Psychol Psychiatry. 2015;56:837-47.) and in TS,1515. Lange F, Seer C, Muller-Vahl K, Kopp B. Cognitive flexibility and its electrophysiological correlates in Gilles de la Tourette syndrome. Dev Cogn Neurosci. 2017;27:78-90. but not in TTM9393. Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry. 2006;163:1282-4.,9595. Grant JE, Odlaug BL, Chamberlain SR. A cognitive comparison of pathological skin picking and trichotillomania. J Psychiatr Res. 2011;45:1634-8.,9797. Flessner CA, Brennan E, Murphy YE, Francazio S. Impaired executive functioning in pediatric trichotillomania (Hair Pulling Disorder). Depress Anxiety. 2016;33:219-28.

98. Chamberlain SR, Fineberg NA, Blackwell AD, Clark L, Robbins TW, Sahakian BJ. A neuropsychological comparison of obsessive-compulsive disorder and trichotillomania. Neuropsychologia. 2007;45:654-62.
-9999. Grant JE, Daws R, Hampshire A, Chamberlain SR. An fMRI pilot study of cognitive flexibility in trichotillomania. J Neuropsychiatry Clin Neurosci. 2018;30:318-24. (except in one study, which found a deficit in the Object Alternation task, but not in the Wisconsin Card Sorting Test [WCST]100100. Bohne A, Savage CR, Deckersbach T, Keuthen NJ, Jenike MA, Tuschen-Caffier B, et al. Visuospatial abilities, memory, and executive functioning in trichotillomania and obsessive-compulsive disorder. J Clin Exp Neuropsychol. 2005;27:385-99.). Attention deficits are found in all three disorders,1212. Abramovitch A, Abramowitz JS, Mittelman A. The neuropsychology of adult obsessive-compulsive disorder: a meta-analysis. Clin Psychol Rev. 2013;33:1163-71.,101101. Stanley MA, Hannay HJ, Breckenridge JK. The neuropsychology of trichotillomania. J Anxiety Disord. 1997;11:473-88. but more mixed results are found in TS (some studies found a deficit,102102. Termine C, Luoni C, Fontolan S, Selvini C, Perego L, Pavone F, et al. Impact of co-morbid attention-deficit and hyperactivity disorder on cognitive function in male children with Tourette syndrome: a controlled study. Psychiatry Res. 2016;243:263-7.

103. Sukhodolsky DG, Landeros-Weisenberger A, Scahill L, Leckman JF, Schultz RT. Neuropsychological functioning in children with Tourette syndrome with and without attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010;49:1155-64.
-104104. Shucard DW, Benedict RH, Tekok-Kilic A, Lichter DG. Slowed reaction time during a continuous performance test in children with Tourette's syndrome. Neuropsychology. 1997;11:147-55. whereas others did not105105. Matsuda N, Kono T, Nonaka M, Shishikura K, Konno C, Kuwabara H, et al. Impact of obsessive-compulsive symptoms in Tourette's syndrome on neuropsychological performance. Psychiatry Clin Neurosci. 2012;66:195-202.

106. Chang SW, McCracken JT, Piacentini JC. Neurocognitive correlates of child obsessive compulsive disorder and Tourette syndrome. J Clin Exp Neuropsychol. 2007;29:724-33.
-107107. Sherman EM, Shepard L, Joschko M, Freeman RD. Sustained attention and impulsivity in children with Tourette syndrome: comorbidity and confounds. J Clin Exp Neuropsychol. 1998;20:644-57.). However, one must keep in mind that attention deficit/hyperactivity disorder (ADHD) is a frequent comorbidity in TS and that the attention deficit results mentioned above seem linked only to comorbid ADHD. Finally, concerning working memory, adult OCD patients presented deficits,1212. Abramovitch A, Abramowitz JS, Mittelman A. The neuropsychology of adult obsessive-compulsive disorder: a meta-analysis. Clin Psychol Rev. 2013;33:1163-71. but children did not.1313. Abramovitch A, Abramowitz JS, Mittelman A, Stark A, Ramsey K, Geller DA. Research review: neuropsychological test performance in pediatric obsessive-compulsive disorder--a meta-analysis. J Child Psychol Psychiatry. 2015;56:837-47. In TTM, no difference from controls was found.9797. Flessner CA, Brennan E, Murphy YE, Francazio S. Impaired executive functioning in pediatric trichotillomania (Hair Pulling Disorder). Depress Anxiety. 2016;33:219-28.,100100. Bohne A, Savage CR, Deckersbach T, Keuthen NJ, Jenike MA, Tuschen-Caffier B, et al. Visuospatial abilities, memory, and executive functioning in trichotillomania and obsessive-compulsive disorder. J Clin Exp Neuropsychol. 2005;27:385-99.,108108. Keuthen NJ, Savage CR, O'Sullivan RL, Brown HD, Shera DM, Cyr P, et al. Neuropsychological functioning in trichotillomania. Biol Psychiatry. 1996;39:747-9. In TS patients, some studies reported deficits106106. Chang SW, McCracken JT, Piacentini JC. Neurocognitive correlates of child obsessive compulsive disorder and Tourette syndrome. J Clin Exp Neuropsychol. 2007;29:724-33.,109109. Jeter CB, Patel SS, Morris JS, Chuang AZ, Butler IJ, Sereno AB. Oculomotor executive function abnormalities with increased tic severity in Tourette syndrome. J Child Psychol Psychiatry. 2015;56:193-202.

110. Eddy CM, Rickards HE, Cavanna AE. Executive functions in uncomplicated Tourette syndrome. Psychiatry Res. 2012;200:46-8.

111. Crawford S, Channon S, Robertson MM. Tourette's syndrome: performance on tests of behavioural inhibition, working memory and gambling. J Child Psychol Psychiatry. 2005;46:1327-36.

112. Channon S, Pratt P, Robertson MM. Executive function, memory, and learning in Tourette's syndrome. Neuropsychology. 2003;17:247-54.
-113113. Bornstein RA. Neuropsychological performance in adults with Tourette's syndrome. Psychiatry Res. 1991;37:229-36. while others did not.114114. Channon S, Gunning A, Frankl J, Robertson MM. Tourette's syndrome (TS): cognitive performance in adults with uncomplicated TS. Neuropsychology. 2006;20:58-65.

Looking at these data, TTM seems closer to TS than to OCD. However, bearing in mind the many divergent findings in these neuropsychological studies and that very few have been conducted in TTM, no definitive conclusion can be drawn as to a close relationship between TTM and either OCD or TS.

Some authors have directly compared OCD and TTM and found that TTM patients have less flexibility dysfunction than OCD patients, as well as a greater impulse control deficiency,9393. Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry. 2006;163:1282-4.,115115. Chamberlain SR, Menzies L, Sahakian BJ, Fineberg NA. Lifting the veil on trichotillomania. Am J Psychiatry. 2007;164:568-74. although the latter is less clear.9494. Bohne A, Savage CR, Deckersbach T, Keuthen NJ, Wilhelm S. Motor inhibition in trichotillomania and obsessive-compulsive disorder. J Psychiatr Res. 2008;42:141-50. Studies based on other neuropsychological tasks, such as response monitoring116116. Roberts K, Stanley EM, Franklin ME, Simons RF. Decreased response monitoring in individuals with symptoms of trichotillomania. Psychophysiology. 2014;51:706-13. and strategy implementation,117117. Chamberlain SR, Blackwell AD, Fineberg NA, Robbins TW, Sahakian BJ. Strategy implementation in obsessive-compulsive disorder and trichotillomania. Psychol Med. 2006;36:91-7. also reached the conclusion that there are differences between OCD and TTM. Direct neurocognitive comparisons between TTM and TS are much harder to find.

In conclusion, from a neurocognitive point of view, TTM seems closer to TS than to OCD, but the many limitations in such research preclude any definitive conclusion.

Neurobiological comparison between TTM, OCD, and tic disorders

Imaging studies

When TTM, TS, and OCD imaging studies1616. Hu X, Du M, Chen L, Li L, Zhou M, Zhang L, et al. Meta-analytic investigations of common and distinct grey matter alterations in youths and adults with obsessive-compulsive disorder. Neurosci Biobehav Rev. 2017;78:91-103.,1717. Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry. 2017;174:60-9.,9292. Odlaug BL, Chamberlain SR, Derbyshire KL, Leppink EW, Grant JE. Impaired response inhibition and excess cortical thickness as candidate endophenotypes for trichotillomania. J Psychiatr Res. 2014;59:167-73.,118118. Roos A, Grant JE, Fouche JP, Stein DJ, Lochner C. A comparison of brain volume and cortical thickness in excoriation (skin picking) disorder and trichotillomania (hair pulling disorder) in women. Behav Brain Res. 2015;279:255-8.

119. Keuthen NJ, Makris N, Schlerf JE, Martis B, Savage CR, McMullin K, et al. Evidence for reduced cerebellar volumes in trichotillomania. Biol Psychiatry. 2007;61:374-81.

120. O'Sullivan RL, Rauch SL, Breiter HC, Grachev ID, Baer L, Kennedy DN, et al. Reduced basal ganglia volumes in trichotillomania measured via morphometric magnetic resonance imaging. Biol Psychiatry 1997;42:39-45.

121. Grachev ID. MRI-based morphometric topogra.phic parcellation of human neocortex in trichotillomania. Psychiatry Clin Neurosci. 1997;51:315-21.

122. Chamberlain SR, Menzies LA, Fineberg NA, Del Campo N, Suckling J, Craig K, et al. Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study. Br J Psychiatry. 2008;193:216-21.

123. Peterson B, Riddle MA, Cohen DJ, Katz LD, Smith JC, Hardin MT, et al. Reduced basal ganglia volumes in Tourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images. Neurology. 1993;43:941-9.

124. Peterson BS, Thomas P, Kane MJ, Scahill L, Zhang H, Bronen R, et al. Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry. 2003;60:415-24.

125. Lee JS, Yoo SS, Cho SY, Ock SM, Lim MK, Panych LP. Abnormal thalamic volume in treatment-naive boys with Tourette syndrome. Acta Psychiatr Scand. 2006;113:64-7.

126. Ludolph AG, Juengling FD, Libal G, Ludolph AC, Fegert JM, Kassubek J. Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry. Br J Psychiatry. 2006;188:484-5.

127. Draganski B, Martino D, Cavanna AE, Hutton C, Orth M, Robertson MM, et al. Multispectral brain morphometry in Tourette syndrome persisting into adulthood. Brain. 2010;133:3661-75.

128. Wittfoth M, Bornmann S, Peschel T, Grosskreutz J, Glahn A, Buddensiek N, et al. Lateral frontal cortex volume reduction in Tourette syndrome revealed by VBM. BMC Neurosci. 2012;13:17.

129. Liu Y, Miao W, Wang J, Gao P, Yin G, Zhang L, et al. Structural abnormalities in early Tourette syndrome children: a combined voxel-based morphometry and tract-based spatial statistics study. PLoS One. 2013;8:e76105.

130. Greene DJ, Williams Iii AC, Koller JM, Schlaggar BL, Black KJ. Brain structure in pediatric Tourette syndrome. Mol Psychiatry. 2017;22:972-80.

131. Forde NJ, Zwiers MP, Naaijen J, Akkermans SEA, Openneer TJC, Visscher F, et al. Basal ganglia structure in Tourette's disorder and/or attention-deficit/hyperactivity disorder. Mov Disord. 2017;32:601-4.

132. Roessner V, Overlack S, Baudewig J, Dechent P, Rothenberger A, Helms G. No brain structure abnormalities in boys with Tourette's syndrome: a voxel-based morphometry study. Mov Disord. 2009;24:2398-403.

133. Muller-Vahl KR, Kaufmann J, Grosskreutz J, Dengler R, Emrich HM, Peschel T. Prefrontal and anterior cingulate cortex abnormalities in Tourette Syndrome: evidence from voxel-based morphometry and magnetization transfer imaging. BMC Neurosci. 2009;10:47.

134. Isobe M, Redden SA, Keuthen NJ, Stein DJ, Lochner C, Grant JE, et al. Striatal abnormalities in trichotillomania: a multi-site MRI analysis. Neuroimage Clin. 2018;17:893-8.

135. Chamberlain SR, Harries M, Redden SA, Keuthen NJ, Stein DJ, Lochner C, et al. Cortical thickness abnormalities in trichotillomania: international multi-site analysis. Brain Imaging Behav. 2018;12:823-8.
-136136. Stein DJ, Coetzer R, Lee M, Davids B, Bouwer C. Magnetic resonance brain imaging in women with obsessive-compulsive disorder and trichotillomania. Psychiatry Res. 1997;74:177-82. were compared (Table 4), striatal abnormalities were found in the three disorders. No other common abnormality is found in OCD and TTM (Table 4). In imaging studies of TS and TTM,122122. Chamberlain SR, Menzies LA, Fineberg NA, Del Campo N, Suckling J, Craig K, et al. Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study. Br J Psychiatry. 2008;193:216-21.,129129. Liu Y, Miao W, Wang J, Gao P, Yin G, Zhang L, et al. Structural abnormalities in early Tourette syndrome children: a combined voxel-based morphometry and tract-based spatial statistics study. PLoS One. 2013;8:e76105. increased precentral gyrus volume has been reported in both disorders (since the supplementary motor area [SMA] is part of the precentral gyrus), not in OCD (Table 4).1616. Hu X, Du M, Chen L, Li L, Zhou M, Zhang L, et al. Meta-analytic investigations of common and distinct grey matter alterations in youths and adults with obsessive-compulsive disorder. Neurosci Biobehav Rev. 2017;78:91-103.,1717. Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry. 2017;174:60-9.

Table 4
Neuroimaging data in obsessive-compulsive disorder, Tourette syndrome, and trichotillomania vs. healthy controls

There is evidence that the SMA is involved in the neurobiology of tics137137. Neuner I, Schneider F, Shah NJ. Functional neuroanatomy of tics. Int Rev Neurobiol. 2013;112:35-71.; hence, the finding of SMA abnormalities in both TS and TTM imaging studies could suggest a neurobiological relationship between TTM and TS. Unfortunately, it is difficult to reach any definitive conclusion, as meta-analyses of VBM studies in TTM and TS are still lacking; nonetheless, the current data seem to favor a closer relationship between TTM and TS than between TTM and OCD.

Concerning diffusion tensor imaging (DTI) studies, we found only one study in TTM,138138. Roos A, Fouche JP, Stein DJ, Lochner C. White matter integrity in hair-pulling disorder (trichotillomania). Psychiatry Res. 2013;211:246-50. which hinders comparisons with DTI meta-analyses in OCD or with the several DTI studies in TS. The same applies to functional connectivity studies (we found only one139139. White MP, Shirer WR, Molfino MJ, Tenison C, Damoiseaux JS, Greicius MD. Disordered reward processing and functional connectivity in trichotillomania: a pilot study. J Psychiatr Res. 2013;47:1264-72. in TTM) and functional MRI in TTM (where we found only three studies on different specific tasks139139. White MP, Shirer WR, Molfino MJ, Tenison C, Damoiseaux JS, Greicius MD. Disordered reward processing and functional connectivity in trichotillomania: a pilot study. J Psychiatr Res. 2013;47:1264-72.

140. Rauch SL, Wright CI, Savage CR, Martis B, McMullin KG, Wedig MM, et al. Brain activation during implicit sequence learning in individuals with trichotillomania. Psychiatry Res. 2007;154:233-40.
-141141. Lee JA, Kim CK, Jahng GH, Hwang LK, Cho YW, Kim YJ, et al. A pilot study of brain activation in children with trichotillomania during a visual-tactile symptom provocation task: a functional magnetic resonance imaging study. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:1250-8.).

Genetic studies

Heritability

Comparing heritability could be a good way to disentangle the TTM-OCD-TS relationship. Heritability in OCD was reported as 40-50% in studies conducted in the 2000s,142142. Browne HA, Gair SL, Scharf JM, Grice DE. Genetics of obsessive-compulsive disorder and related disorders. Psychiatr Clin North Am. 2014;37:319-35. compared to 32-76% in TTM142142. Browne HA, Gair SL, Scharf JM, Grice DE. Genetics of obsessive-compulsive disorder and related disorders. Psychiatr Clin North Am. 2014;37:319-35. and 25-77% in TS.143143. Qi Y, Zheng Y, Li Z, Xiong L. Progress in genetic studies of Tourette's syndrome. Brain Sci. 2017;7. pii: E134. doi: http:/10.3390/brainsci7100134
http:/10.3390/brainsci7100134...
Given the huge differences in heritability across different studies, no conclusion can be reached concerning the relationship of TTM with either OCD or TS in this respect.

Candidate gene studies

Genetic studies – and, more specifically, candidate gene studies – could be useful to compare the neurobiology of TTM, TS, and OCD. Altered genes shared between two of these disorders could suggest that common intracellular pathways are involved.

One study found that a variant of SAPAP3 was associated with TTM, but this result did not withstand correction for multiple comparisons.144144. Boardman L, van der Merwe L, Lochner C, Kinnear CJ, Seedat S, Stein DJ, et al. Investigating SAPAP3 variants in the etiology of obsessive-compulsive disorder and trichotillomania in the South African white population. Compr Psychiatry. 2011;52:181-7. The same study also found that a specific haplotype of SAPAP3 was linked with earlier onset of OCD, but no difference in genotype or allele frequencies for SAPAP3 was found for OCD compared to controls.144144. Boardman L, van der Merwe L, Lochner C, Kinnear CJ, Seedat S, Stein DJ, et al. Investigating SAPAP3 variants in the etiology of obsessive-compulsive disorder and trichotillomania in the South African white population. Compr Psychiatry. 2011;52:181-7. Furthermore, this study did not mention the nature of compulsions, which would have been useful, knowing that tic disorders begin earlier than OCD and that some compulsions are strongly associated with tic disorders (e.g., symmetry compulsions, as noted in the Phenomenology section). Another study found an association between a SAPAP3 variant and TTM, but no association was found between SAPAP3 variants and OCD.145145. Bienvenu OJ, Wang Y, Shugart YY, Welch JM, Grados MA, Fyer AJ, et al. Sapap3 and pathological grooming in humans: results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:710-20. A third study found that two specific variants of SAPAP3 and two specific haplotypes could be linked with TS, but the results were no longer significant after correction.146146. Crane J, Fagerness J, Osiecki L, Gunnell B, Stewart SE, Pauls DL, et al. Family-based genetic association study of DLGAP3 in Tourette syndrome. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:108-14. Hence, the SAPAP3 gene may be linked directly to TS and TTM, but only with the age of onset in OCD.

Another study found that the T102T genotype for 5HTR2A was more frequent in TTM patients than in controls (result remained significant after correction) and OCD patients (result did not remain after correction).147147. Hemmings SM, Kinnear CJ, Lochner C, Seedat S, Corfield VA, Moolman-Smook JC, et al. Genetic correlates in trichotillomania--a case-control association study in the South African Caucasian population. Isr J Psychiatry Relat Sci. 2006;43:93-101. Thus, one might think that 5HTR2A polymorphisms are specific to TTM, but a meta-analysis of genetic association studies in OCD found that 5HTR2A polymorphisms were in fact also associated with OCD.148148. Taylor S. Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol Psychiatry. 2013;18:799-805. Finally, a recent study found no association between 5HTR2A polymorphisms and TS.149149. Xu L, Zheng L, Ma J, Su N, Liu Y, Ma X, et al. Lack of genetic association of 5-HTR2A 102 T/C and -1438A/G polymorphisms with Tourette syndrome in a family-based association study in a Chinese Han population. Asia Pac Psychiatry. 2016;8:87-91. Thus, considering 5HTR2A polymorphisms, one might presume that TTM is closer to OCD than TS.

SLITRK1 variants are associated with OCD,150150. Ozomaro U, Cai G, Kajiwara Y, Yoon S, Makarov V, Delorme R, et al. Characterization of SLITRK1 variation in obsessive-compulsive disorder. PLoS One. 2013;8:e70376.,151151. Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science. 2005;310:317-20. but also with TTM and TS.9090. Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15:410-24.,151151. Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science. 2005;310:317-20.

152. Zuchner S, Cuccaro ML, Tran-Viet KN, Cope H, Krishnan RR, Pericak-Vance MA, et al. SLITRK1 mutations in trichotillomania. Mol Psychiatry. 2006;11:887-9.

153. Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers. 2017;3:16097.
-154154. Padmanabhuni SS, Houssari R, Esserlind AL, Olesen J, Werge TM, Hansen TF, et al. Investigation of SNP rs2060546 immediately upstream to NTN4 in a Danish Gilles de la Tourette syndrome cohort. Front Neurosci. 2016;10:531. This gene seems involved in vulnerability for all three of these disorders.

We did not find any study on links between other candidate genes known to be possibly involved in OCD neurobiology9090. Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15:410-24.,148148. Taylor S. Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol Psychiatry. 2013;18:799-805. and TTM. However, some studies on these genes included patients with both TS and OCD.155155. Stewart SE, Fagerness JA, Platko J, Smoller JW, Scharf JM, Illmann C, et al. Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:1027-33.,156156. Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:769-76. Likewise, we did not find any studies on links between TS candidate genes not mentioned above153153. Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers. 2017;3:16097.,154154. Padmanabhuni SS, Houssari R, Esserlind AL, Olesen J, Werge TM, Hansen TF, et al. Investigation of SNP rs2060546 immediately upstream to NTN4 in a Danish Gilles de la Tourette syndrome cohort. Front Neurosci. 2016;10:531.,157157. Bertelsen B, Melchior L, Groth C, Mol Debes N, Skov L, Holst KK, et al. Association of the CHRNA7 promoter variant -86T with Tourette syndrome and comorbid obsessive-compulsive disorder. Psychiatry Res. 2014;219:710-1.,158158. Sundaram SK, Huq AM, Wilson BJ, Chugani HT. Tourette syndrome is associated with recurrent exonic copy number variants. Neurology. 2010;74:1583-90. and TTM. Among these studies, some included patients with both TS and OCD.158158. Sundaram SK, Huq AM, Wilson BJ, Chugani HT. Tourette syndrome is associated with recurrent exonic copy number variants. Neurology. 2010;74:1583-90.

159. Diaz-Anzaldua A, Joober R, Riviere JB, Dion Y, Lesperance P, Chouinard S, et al. Association between 7q31 markers and Tourette syndrome. Am J Med Genet A. 2004;127A:17-20.
-160160. Verkerk AJ, Mathews CA, Joosse M, Eussen BH, Heutink P, Oostra BA, et al. CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder. Genomics. 2003;82:1-9.

It is difficult to draw any conclusion from these studies. SAPAP3 appears to be somehow associated with TS and TTM, 5THR2A with OCD and TTM, and SLITRK1 with all three disorders. Thus, nothing can be presumed about a relationship between these disorders from a candidate gene standpoint. Furthermore, some of the genes potentially involved in these disorders and mentioned above have also been implicated in schizophrenia161161. Kang H, Han KA, Won SY, Kim HM, Lee YH, Ko J, et al. Slitrk missense mutations associated with neuropsychiatric disorders distinctively impair slitrk trafficking and synapse formation. Front Mol Neurosci. 2016;9:104. and autism.162162. Clarke RA, Lee S, Eapen V. Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism. Transl Psychiatry. 2012;2:e158. The only conclusion we can reach is already well known: OCD, TS, and TTM seem to be genetically related disorders.

Cluster analysis

In terms of genetics, OCD and TS have been considered to be on the same spectrum and genetically linked.163163. Pauls DL, Raymond CL, Stevenson JM, Leckman JF. A family study of Gilles de la Tourette syndrome. Am J Hum Genet. 1991;48:154-63.,164164. Eapen V, Pauls DL, Robertson MM. Evidence for autosomal dominant transmission in Tourette's syndrome. United Kingdom cohort study. Br J Psychiatry. 1993;162:593-6. More recently, a significant genetic correlation has been found between these two disorders, similar to the genetic correlation between bipolar disorder and MDD.165165. Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, Derks EM, et al. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet. 2013;9:e1003864. Different studies that looked at the relationships between TS and OCD in terms of phenotypes found different, complex relationships, which could lead to different TS or OCD subclasses.1010. Lochner C, Seedat S, du Toit PL, Nel DG, Niehaus DJ, Sandler R, et al. Obsessive-compulsive disorder and trichotillomania: a phenomenological comparison. BMC Psychiatry. 2005;5:2.,166166. Huisman-van Dijk HM, Schoot R, Rijkeboer MM, Mathews CA, Cath DC. The relationship between tics, OC, ADHD and autism symptoms: A cross- disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members. Psychiatry Res. 2016;237:138-46.

167. Darrow SM, Hirschtritt ME, Davis LK, Illmann C, Osiecki L, Grados M, et al. Identification of two heritable cross-disorder endophenotypes for Tourette syndrome. Am J Psychiatry. 2017;174:387-96.

168. Nestadt G, Addington A, Samuels J, Liang KY, Bienvenu OJ, Riddle M, et al. The identification of OCD-related subgroups based on comorbidity. Biol Psychiatry. 2003;53:914-20.
-169169. Nestadt G, Di CZ, Riddle MA, Grados MA, Greenberg BD, Fyer AJ, et al. Obsessive-compulsive disorder: subclassification based on co-morbidity. Psychol Med. 2009;39:1491-501. When we analyzed the place of TTM in these different subclasses of OCD or TS, we found only studies on OCD. First, a three-cluster OCD model placed TTM and TS were in the same cluster (called “reward deficiency”)170170. Lochner C, Hemmings SM, Kinnear CJ, Niehaus DJ, Nel DG, Corfield VA, et al. Cluster analysis of obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder: clinical and genetic correlates. Compr Psychiatry. 2005;46:14-9.; second, in a three-subclass OCD model, OCD with tics was more often associated with grooming disorders, which included TTM and pathological skin picking.169169. Nestadt G, Di CZ, Riddle MA, Grados MA, Greenberg BD, Fyer AJ, et al. Obsessive-compulsive disorder: subclassification based on co-morbidity. Psychol Med. 2009;39:1491-501. From the standpoint of these studies, if TTM can be associated with any OCD subclass, it seems that in these cases TTM is also associated with tic disorders. These results may shed light on a potential relationship between tic disorders and TTM in the global context of OCD.

Finally, a key study on latent liability factor found two factors, with the first factor common to all obsessive-compulsive related disorders (but with the strongest loading for OCD, body dysmorphic disorder, and hoarding disorder) and a second factor loaded only by TTM and skin-picking disorder.171171. Monzani B, Rijsdijk F, Harris J, Mataix-Cols D. The structure of genetic and environmental risk factors for dimensional representations of DSM-5 obsessive-compulsive spectrum disorders. JAMA Psychiatry. 2014;71:182-9. Hence, this study highlights the relative distance (essentially genetic) between OCD and TTM.

Treatment

Another potentially relevant approach to distinguishing the tic or OCD nature of TTM is to compare the efficacy of different treatment types in OCD, tic disorder, and TTM (Table 5). It should be noted that not all treatments mentioned below are approved by the U.S. Food and Drug Administration (FDA) for treating the different disorders studied.

Table 5
Studies of pharmacotherapy in obsessive-compulsive disorder, Tourette syndrome, and trichotillomania

When we look at these different data, treatment of TTM appears to resemble that of TS treatment, with antipsychotics172172. Hollis C, Pennant M, Cuenca J, Glazebrook C, Kendall T, Whittington C, et al. Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis. Health Technol Assess. 2016;20:1-450.

173. Zheng W, Li XB, Xiang YQ, Zhong BL, Chiu HF, Ungvari GS, et al. Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis. Hum Psychopharmacol. 2016;31:11-8.

174. Van Ameringen M, Mancini C, Patterson B, Bennett M, Oakman J. A randomized, double-blind, placebo-controlled trial of olanzapine in the treatment of trichotillomania. J Clin Psychiatry. 2010;71:1336-43.

175. Howard AK, Krishnamoorthy A, Leavitt BR, Raymond LA, Weissman CR. Treatment of Huntington disease and comorbid trichotillomania with Aripiprazole. J Neuropsychiatry Clin Neurosci. 2015;27:e211-2.

176. Yasui-Furukori N, Kaneko S. The efficacy of low-dose aripiprazole treatment for trichotillomania. Clin Neuropharmacol. 2011;34:258-9.

177. White MP, Koran LM. Open-label trial of aripiprazole in the treatment of trichotillomania. J Clin Psychopharmacol. 2011;31:503-6.

178. Virit O, Selek S, Savas HA, Kokacya H. Improvement of restless legs syndrome and trichotillomania with aripiprazole. J Clin Pharm Ther. 2009;34:723-5.

179. Jefferys D, Burrows G. Reversal of trichotillomania with aripiprazole. Depress Anxiety. 2008;25:E37-40.

180. Van Ameringen M, Mancini C, Oakman JM, Farvolden P. The potential role of haloperidol in the treatment of trichotillomania. J Affect Disord. 1999;56:219-26.

181. Crescente Junior JA, Guzman CS, Tavares H. Quetiapine for the treatment of trichotillomania. Rev Bras Psiquiatr. 2008;30:402.

182. Khouzam HR, Battista MA, Byers PE. An overview of trichotillomania and its response to treatment with quetiapine. Psychiatry. 2002;65:261-70.

183. Stewart RS, Nejtek VA. An open-label, flexible-dose study of olanzapine in the treatment of trichotillomania. J Clin Psychiatry. 2003;64:49-52.

184. Liu Y, Ni H, Wang C, Li L, Cheng Z, Weng Z. Effectiveness and tolerability of Aripiprazole in children and adolescents with Tourette's disorder: a meta-analysis. J Child Adolesc Psychopharmacol. 2016;26:436-41.

185. Oravecz R, Stuhec M. Trichotillomania successfully treated with risperidone and naltrexone: a geriatric case report. J Am Med Dir Assoc. 2014;15:301-2.

186. Mancini C, Van Ameringen M, Patterson B, Simpson W, Truong C. Trichotillomania in youth: a retrospective case series. Depress Anxiety. 2009;26:661-5.

187. Ashton AK. Olanzapine augmentation for trichotillomania. Am J Psychiatry. 2001;158:1929-30.

188. Senturk V, Tanriverdi N. Resistant trichotillomania and risperidone. Psychosomatics. 2002;43:429-30.

189. Srivastava RK, Sharma S, Tiwari N, Saluja B. Olanzapine augmentation of fluoxetine in trichotillomania: two cases. Aust N Z J Psychiatry. 2005;39:112-3.

190. Potenza MN, Wasylink S, Epperson CN, McDougle CJ. Olanzapine augmentation of fluoxetine in the treatment of trichotillomania. Am J Psychiatry. 1998;155:1299-300.

191. Epperson CN, Fasula D, Wasylink S, Price LH, McDougle CJ. Risperidone addition in serotonin reuptake inhibitor-resistant trichotillomania: three cases. J Child Adolesc Psychopharmacol. 1999;9:43-9.

192. Gabriel A. A case of resistant trichotillomania treated with risperidone-augmented fluvoxamine. Can J Psychiatry. 2001;46:285-6.

193. Ghaziuddin M, Tsai LY, Ghaziuddin N. Brief report: haloperidol treatment of trichotillomania in a boy with autism and mental retardation. J Autism Dev Disord. 1991;21:365-71.

194. Stein DJ, Hollander E. Low-dose pimozide augmentation of serotonin reuptake blockers in the treatment of trichotillomania. J Clin Psychiatry. 1992;53:123-6.
-195195. Pathak S, Danielyan A, Kowatch RA. Successful treatment of trichotillomania with olanzapine augmentation in an adolescent. J Child Adolesc Psychopharmacol. 2004;14:153-4. seemingly effective and selective serotonin reuptake inhibitors (SSRI)196196. Rothbart R, Amos T, Siegfried N, Ipser JC, Fineberg N, Chamberlain SR, et al. Pharmacotherapy for trichotillomania. Cochrane Database Syst Rev. 2013:CD007662.

197. Rothbart R, Stein DJ. Pharmacotherapy of trichotillomania (hair pulling disorder): an updated systematic review. Expert Opin Pharmacother. 2014;15:2709-19.

198. Bloch MH, Landeros-Weisenberger A, Dombrowski P, Kelmendi B, Wegner R, Nudel J, et al. Systematic review: pharmacological and behavioral treatment for trichotillomania. Biol Psychiatry. 2007;62:839-46.

199. Christenson GA, Mackenzie TB, Mitchell JE, Callies AL. A placebo-controlled, double-blind crossover study of fluoxetine in trichotillomania. Am J Psychiatry. 1991;148:1566-71.

200. Streichenwein SM, Thornby JI. A long-term, double-blind, placebo-controlled crossover trial of the efficacy of fluoxetine for trichotillomania. Am J Psychiatry. 1995;152:1192-6.

201. van Minnen A, Hoogduin KA, Keijsers GP, Hellenbrand I, Hendriks GJ. Treatment of trichotillomania with behavioral therapy or fluoxetine: a randomized, waiting-list controlled study. Arch Gen Psychiatry. 2003;60:517-22.
-202202. Scahill L, Riddle MA, King RA, Hardin MT, Rasmusson A, Makuch RW, et al. Fluoxetine has no marked effect on tic symptoms in patients with Tourette's syndrome: a double-blind placebo-controlled study. J Child Adolesc Psychopharmacol. 1997;7:75-85. ineffective (while SSRIs are a well-established treatment for OCD203203. Issari Y, Jakubovski E, Bartley CA, Pittenger C, Bloch MH. Early onset of response with selective serotonin reuptake inhibitors in obsessive-compulsive disorder: a meta-analysis. J Clin Psychiatry. 2016;77:e605-11.

204. Romanelli RJ, Wu FM, Gamba R, Mojtabai R, Segal JB. Behavioral therapy and serotonin reuptake inhibitor pharmacotherapy in the treatment of obsessive-compulsive disorder: a systematic review and meta-analysis of head-to-head randomized controlled trials. Depress Anxiety. 2014;31:641-52.

205. Bloch MH, McGuire J, Landeros-Weisenberger A, Leckman JF, Pittenger C. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol Psychiatry. 2010;15:850-5.

206. Soomro GM, Altman D, Rajagopal S, Oakley-Browne M. Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev. 2008:CD001765.

207. Ivarsson T, Skarphedinsson G, Kornor H, Axelsdottir B, Biedilae S, Heyman I, et al. The place of and evidence for serotonin reuptake inhibitors (SRIs) for obsessive compulsive disorder (OCD) in children and adolescents: views based on a systematic review and meta-analysis. Psychiatry Res. 2015;227:93-103.

208. McGuire JF, Piacentini J, Lewin AB, Brennan EA, Murphy TK, Storch EA. A Meta-analysis of cognitive behavior therapy and medication for child obsessive-compulsive disorder: moderators of treatment efficacy, response, and remission. Depress Anxiety. 2015;32:580-93.

209. Stein DJ, Spadaccini E, Hollander E. Meta-analysis of pharmacotherapy trials for obsessive-compulsive disorder. Int Clin Psychopharmacol. 1995;10:11-8.

210. Sanchez-Meca J, Rosa-Alcazar AI, Iniesta-Sepulveda M, Rosa-Alcazar A. Differential efficacy of cognitive-behavioral therapy and pharmacological treatments for pediatric obsessive-compulsive disorder: a meta-analysis. J Anxiety Disord. 2014;28:31-44.

211. Sharma E, Thennarasu K, Reddy YC. Long-term outcome of obsessive-compulsive disorder in adults: a meta-analysis. J Clin Psychiatry. 2014;75:1019-27.

212. Geller DA, Biederman J, Stewart SE, Mullin B, Martin A, Spencer T, et al. Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessive-compulsive disorder. Am J Psychiatry. 2003;160:1919-28.

213. Piccinelli M, Pini S, Bellantuono C, Wilkinson G. Efficacy of drug treatment in obsessive-compulsive disorder. A meta-analytic review. Br J Psychiatry. 1995;166:424-43.
-214214. Varigonda AL, Jakubovski E, Bloch MH. 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;55:851-9 e2.). A meta-analysis found serotonin reuptake inhibitors (SRI) to be effective in TTM,215215. McGuire JF, Ung D, Selles RR, Rahman O, Lewin AB, Murphy TK, et al. Treating trichotillomania: a meta-analysis of treatment effects and moderators for behavior therapy and serotonin reuptake inhibitors. J Psychiatr Res. 2014;58:76-83. contradicting a previous meta-analysis.198198. Bloch MH, Landeros-Weisenberger A, Dombrowski P, Kelmendi B, Wegner R, Nudel J, et al. Systematic review: pharmacological and behavioral treatment for trichotillomania. Biol Psychiatry. 2007;62:839-46. This difference may be explained by study selection: two clomipramine studies were included in the meta-analysis by McGuire,215215. McGuire JF, Ung D, Selles RR, Rahman O, Lewin AB, Murphy TK, et al. Treating trichotillomania: a meta-analysis of treatment effects and moderators for behavior therapy and serotonin reuptake inhibitors. J Psychiatr Res. 2014;58:76-83. but not in Bloch’s,198198. Bloch MH, Landeros-Weisenberger A, Dombrowski P, Kelmendi B, Wegner R, Nudel J, et al. Systematic review: pharmacological and behavioral treatment for trichotillomania. Biol Psychiatry. 2007;62:839-46. which was limited to SSRI studies. Indeed, clomipramine seems to have a place in the treatment of both TTM and OCD,198198. Bloch MH, Landeros-Weisenberger A, Dombrowski P, Kelmendi B, Wegner R, Nudel J, et al. Systematic review: pharmacological and behavioral treatment for trichotillomania. Biol Psychiatry. 2007;62:839-46.,214214. Varigonda AL, Jakubovski E, Bloch MH. 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;55:851-9 e2. which is not the case for TS.216216. Caine ED, Polinsky RJ, Ebert MH, Rapoport JL, Mikkelsen EJ. Trial of chlorimipramine and desipramine for Gilles de la Tourette syndrome. Ann Neurol. 1979;5:305-6.,224224. Bloch MH, Panza KE, Landeros-Weisenberger A, Leckman JF. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:884-93. Furthermore, antipsychotics also seem to have a place in treatment strategies for OCD217217. Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006;11:622-32.

218. Veale D, Miles S, Smallcombe N, Ghezai H, Goldacre B, Hodsoll J. Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis. BMC Psychiatry. 2014;14:317.

219. Dold M, Aigner M, Lanzenberger R, Kasper S. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials. Int J Neuropsychopharmacol. 2013;16:557-74.

220. Dold M, Aigner M, Lanzenberger R, Kasper S. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: an update meta-analysis of double-blind, randomized, placebo-controlled trials. Int J Neuropsychopharmacol. 2015;18. pii: pyv047. doi: http://10.1093/ijnp/pyv047
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221. Skapinakis P, Papatheodorou T, Mavreas V. Antipsychotic augmentation of serotonergic antidepressants in treatment-resistant obsessive-compulsive disorder: a meta-analysis of the randomized controlled trials. Eur Neuropsychopharmacol. 2007;17:79-93.

222. Maher AR, Maglione M, Bagley S, Suttorp M, Hu JH, Ewing B, et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis. JAMA. 2011;306:1359-69.
-223223. Fineberg NA, Stein DJ, Premkumar P, Carey P, Sivakumaran T, Vythilingum B, et al. Adjunctive quetiapine for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: a meta-analysis of randomized controlled treatment trials. Int Clin Psychopharmacol. 2006;21:337-43. to augment SSRI efficacy. However, this raises diagnostic questions. The fact that some compulsions can be easily confused with tics could explain the efficacy of adjunctive antipsychotic treatment in OCD.99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959. Finally, N-acetylcysteine has been debated for treatment of these conditions, with mixed results across different studies.196196. Rothbart R, Amos T, Siegfried N, Ipser JC, Fineberg N, Chamberlain SR, et al. Pharmacotherapy for trichotillomania. Cochrane Database Syst Rev. 2013:CD007662.,225225. Schumer MC, Panza KE, Mulqueen JM, Jakubovski E, Bloch MH. Long-term outcome in pediatric trichotillomania. Depress Anxiety. 2015;32:737-43.

226. Bloch MH, Panza KE, Grant JE, Pittenger C, Leckman JF. N-Acetylcysteine in the treatment of pediatric trichotillomania: a randomized, double-blind, placebo-controlled add-on trial. J Am Acad Child Adolesc Psychiatry. 2013;52:231-40.

227. Pittenger C. Glutamatergic agents for OCD and related disorders. Curr Treat Options Psychiatry. 2015;2:271-83.

228. Paydary K, Akamaloo A, Ahmadipour A, Pishgar F, Emamzadehfard S, Akhondzadeh S. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther. 2016;41:214-9.

229. Costa DLC, Diniz JB, Requena G, Joaquim MA, Pittenger C, Bloch MH, et al. Randomized, double-blind, placebo-controlled trial of N-Acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry. 2017;78:e766-e73.

230. Sarris J, Oliver G, Camfield DA, Dean OM, Dowling N, Smith DJ, et al. N-Acetyl Cysteine (NAC) in the treatment of obsessive-compulsive disorder: a 16-week, double-blind, randomised, placebo-controlled study. CNS Drugs. 2015;29:801-9.
-231231. Bloch MH, Panza KE, Yaffa A, Alvarenga PG, Jakubovski E, Mulqueen JM, et al. N-Acetylcysteine in the treatment of pediatric Tourette syndrome: randomized, double-blind, placebo-controlled add-on trial. J Child Adolesc Psychopharmacol. 2016;26:327-34.

The efficacy of other treatments used in TS or OCD could not be examined in TTM due to a lack of data. For example, clonidine, which is effective in TS,232232. Whittington C, Pennant M, Kendall T, Glazebrook C, Trayner P, Groom M, et al. Practitioner review: treatments for Tourette syndrome in children and young people – a systematic review. J Child Psychol Psychiatry. 2016;57:988-1004. has not been studied in TTM; amantadine233233. Stryjer R, Budnik D, Ebert T, Green T, Polak L, Weizman S, et al. Amantadine augmentation therapy for obsessive compulsive patients resistant to SSRIs-an open-label study. Clin Neuropharmacol. 2014;37:79-81. and memantine,234234. Haghighi M, Jahangard L, Mohammad-Beigi H, Bajoghli H, Hafezian H, Rahimi A, et al. In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD). Psychopharmacology (Berl). 2013;228:633-40. which have shown adjunctive efficacy in treatment-refractory OCD, have not been studied in TTM to the best of our knowledge. Finally, deep brain stimulation, which has been found highly effective in OCD235235. Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008;359:2121-34. and TS,236236. Schrock LE, Mink JW, Woods DW, Porta M, Servello D, Visser-Vandewalle V, et al. Tourette syndrome deep brain stimulation: a review and updated recommendations. Mov Disord. 2015;30:448-71.,237237. Welter ML, Mallet L, Houeto JL, Karachi C, Czernecki V, Cornu P, et al. Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol. 2008;65:952-7. has not been studied in TTM (although a complex case of Parkinson’s disease with comorbid TTM treated by deep brain stimulation has been reported238238. Machado AG, Hiremath GK, Salazar F, Rezai AR. Fracture of subthalamic nucleus deep brain stimulation hardware as a result of compulsive manipulation: case report. Neurosurgery. 2005;57:E1318; discussion E.).

Concerning psychotherapies, habit reversal training has shown efficacy in TTM198198. Bloch MH, Landeros-Weisenberger A, Dombrowski P, Kelmendi B, Wegner R, Nudel J, et al. Systematic review: pharmacological and behavioral treatment for trichotillomania. Biol Psychiatry. 2007;62:839-46.,239239. Morris SH, Zickgraf HF, Dingfelder HE, Franklin ME. Habit reversal training in trichotillomania: guide for the clinician. Expert Rev Neurother 2013;13:1069-77.

240. Rahman O, McGuire J, Storch EA, Lewin AB. Preliminary randomized controlled trial of habit reversal training for treatment of hair pulling in youth. J Child Adolesc Psychopharmacol. 2017;27:132-9.

241. Grant JE, Chamberlain SR. Trichotillomania. Am J Psychiatry. 2016;173:868-74.

242. Shareh H. A Preliminary investigation of metacognitive therapy and habit reversal as a treatment for trichotillomania. Behav Cogn Psychother. 2018;46:1-20.

243. Lewin AB, Wu MS, McGuire JF, Storch EA. Cognitive behavior therapy for obsessive-compulsive and related disorders. Psychiatr Clin North Am. 2014;37:415-45.

244. Ninan PT, Rothbaum BO, Marsteller FA, Knight BT, Eccard MB. A placebo-controlled trial of cognitive-behavioral therapy and clomipramine in trichotillomania. J Clin Psychiatry. 2000;61:47-50.
-245245. Flessner CA. Cognitive-behavioral therapy for childhood repetitive behavior disorders: tic disorders and trichotillomania. Child Adolesc Psychiatr Clin N Am. 2011;20:319-28. and TS,243243. Lewin AB, Wu MS, McGuire JF, Storch EA. Cognitive behavior therapy for obsessive-compulsive and related disorders. Psychiatr Clin North Am. 2014;37:415-45.,245245. Flessner CA. Cognitive-behavioral therapy for childhood repetitive behavior disorders: tic disorders and trichotillomania. Child Adolesc Psychiatr Clin N Am. 2011;20:319-28.

246. O'Connor KP, Laverdure A, Taillon A, Stip E, Borgeat F, Lavoie M. Cognitive behavioral management of Tourette's syndrome and chronic tic disorder in medicated and unmedicated samples. Behav Res Ther. 2009;47:1090-5.

247. Morand-Beaulieu S, O'Connor KP, Sauve G, Blanchet PJ, Lavoie ME. Cognitive-behavioral therapy induces sensorimotor and specific electrocortical changes in chronic tic and Tourette's disorder. Neuropsychologia. 2015;79:310-21.
-248248. Hartmann A, Martino D, Murphy T. Gilles de la Tourette syndrome – a treatable condition? Rev Neurol (Paris). 2016;172:446-54. while exposure response prevention (ERP) seems to be the most efficient psychotherapy for OCD.243243. Lewin AB, Wu MS, McGuire JF, Storch EA. Cognitive behavior therapy for obsessive-compulsive and related disorders. Psychiatr Clin North Am. 2014;37:415-45.,249249. Wootton BM. Remote cognitive-behavior therapy for obsessive-compulsive symptoms: a meta-analysis. Clin Psychol Rev. 2016;43:103-13.,250250. Ost LG, Havnen A, Hansen B, Kvale G. Cognitive behavioral treatments of obsessive-compulsive disorder. A systematic review and meta-analysis of studies published 1993-2014. Clin Psychol Rev. 2015;40:156-69.

Discussion

TTM is widely and rightly accepted as a part of the OCD spectrum, based in part on its repetitive phenomenology.11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013. However, difficulties in distinguishing OCD and TS in some cases99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959. led us to the question of whether the real nature of TTM is indeed obsessive-compulsive rather than tic-related. We thus examined the literature on TTM, OCD, and tic disorders. We divided this literature review into five different axes (phenomenology, epidemiology, neuropsychology, neurobiology, and treatment), to provide clearer insight into the true nature of TTM.

This review allowed us to go beyond the classical question of “is TTM related to OCD?”251251. Stein DJ, Kogan CS, Atmaca M, Fineberg NA, Fontenelle LF, Grant JE, et al. The classification of obsessive-compulsive and related disorders in the ICD-11. J Affect Disord. 2016;190:663-74. and ask: “is TTM related to tic disorders?” If data from candidate gene studies does not provide clear answers, other information can help. Epidemiological data showed different results concerning age of onset and course of these disorders, but suggesting a closer link between TTM and OCD, while studies of comorbidity (especially rates of TTM, OCD, and TS comorbidity among these conditions) seemed to suggest a closer link between TTM and TS.5757. Greenberg E, Tung ES, Gauvin C, Osiecki L, Yang KG, Curley E, et al. Prevalence and predictors of hair pulling disorder and excoriation disorder in Tourette syndrome. Eur Child Adolesc Psychiatry. 2018;27:569-79. It is difficult to reach a conclusion according to these epidemiological data.

Conversely, clinical, imaging, neuropsychological, cluster-analysis, and, most importantly, treatment studies lead us to think that there is a closer relationship between TTM and tic disorders.

Imaging studies have implicated motor regions, especially the supplementary motor area, in TTM and tic disorders,122122. Chamberlain SR, Menzies LA, Fineberg NA, Del Campo N, Suckling J, Craig K, et al. Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study. Br J Psychiatry. 2008;193:216-21.,129129. Liu Y, Miao W, Wang J, Gao P, Yin G, Zhang L, et al. Structural abnormalities in early Tourette syndrome children: a combined voxel-based morphometry and tract-based spatial statistics study. PLoS One. 2013;8:e76105. but not in OCD.1616. Hu X, Du M, Chen L, Li L, Zhou M, Zhang L, et al. Meta-analytic investigations of common and distinct grey matter alterations in youths and adults with obsessive-compulsive disorder. Neurosci Biobehav Rev. 2017;78:91-103.,1717. Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry. 2017;174:60-9. Even if these findings lack confirmation from meta-analyses, they highlight the motor characteristics of TTM and tic disorders. These aspects are in line with what is seen in clinical practice. OCD patients seem to experience more anxiety than tic-disorder and TTM patients do.4949. Rozenman M, Peris TS, Gonzalez A, Piacentini J. Clinical characteristics of pediatric trichotillomania: comparisons with obsessive-compulsive and tic disorders. Child Psychiatry Hum Dev. 2016;47:124-32. Urges are found in all three disorders; however, in OCD, they seem to pertain more specifically to symmetry or “just-right” compulsions – behaviors that have been associated more frequently with TS than with OCD.99. Worbe Y, Mallet L, Golmard JL, Behar C, Durif F, Jalenques I, et al. Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?PLoS One. 2010;5:e12959. Genetic data, especially from cluster-analysis studies (clusters in which genetic backgrounds are supposed to have a major role), endorse relationships between tics and TTM, since both are found in the same clusters.169169. Nestadt G, Di CZ, Riddle MA, Grados MA, Greenberg BD, Fyer AJ, et al. Obsessive-compulsive disorder: subclassification based on co-morbidity. Psychol Med. 2009;39:1491-501.

170. Lochner C, Hemmings SM, Kinnear CJ, Niehaus DJ, Nel DG, Corfield VA, et al. Cluster analysis of obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder: clinical and genetic correlates. Compr Psychiatry. 2005;46:14-9.
-171171. Monzani B, Rijsdijk F, Harris J, Mataix-Cols D. The structure of genetic and environmental risk factors for dimensional representations of DSM-5 obsessive-compulsive spectrum disorders. JAMA Psychiatry. 2014;71:182-9. Limiting these findings is the fact that these clusters are generated in an OCD context (i.e., from OCD patients), except for one study on latent liability factor which clearly differentiated OCD and TTM.171171. Monzani B, Rijsdijk F, Harris J, Mataix-Cols D. The structure of genetic and environmental risk factors for dimensional representations of DSM-5 obsessive-compulsive spectrum disorders. JAMA Psychiatry. 2014;71:182-9. Results from neuropsychological studies are very divergent depending on study design, neuropsychological processes assessed, and tasks employed.252252. Gruner P, Pittenger C. Cognitive inflexibility in obsessive-compulsive disorder. Neuroscience. 2017;345:243-55. Finally, the strongest evidence leading us to the conclusion of a closer relationship between TTM and tic disorders than between TTM and OCD comes from therapeutic studies. In both TS and TTM, antipsychotic treatment is essential.153153. Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers. 2017;3:16097.,172172. Hollis C, Pennant M, Cuenca J, Glazebrook C, Kendall T, Whittington C, et al. Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis. Health Technol Assess. 2016;20:1-450.

173. Zheng W, Li XB, Xiang YQ, Zhong BL, Chiu HF, Ungvari GS, et al. Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis. Hum Psychopharmacol. 2016;31:11-8.

174. Van Ameringen M, Mancini C, Patterson B, Bennett M, Oakman J. A randomized, double-blind, placebo-controlled trial of olanzapine in the treatment of trichotillomania. J Clin Psychiatry. 2010;71:1336-43.

175. Howard AK, Krishnamoorthy A, Leavitt BR, Raymond LA, Weissman CR. Treatment of Huntington disease and comorbid trichotillomania with Aripiprazole. J Neuropsychiatry Clin Neurosci. 2015;27:e211-2.

176. Yasui-Furukori N, Kaneko S. The efficacy of low-dose aripiprazole treatment for trichotillomania. Clin Neuropharmacol. 2011;34:258-9.

177. White MP, Koran LM. Open-label trial of aripiprazole in the treatment of trichotillomania. J Clin Psychopharmacol. 2011;31:503-6.

178. Virit O, Selek S, Savas HA, Kokacya H. Improvement of restless legs syndrome and trichotillomania with aripiprazole. J Clin Pharm Ther. 2009;34:723-5.

179. Jefferys D, Burrows G. Reversal of trichotillomania with aripiprazole. Depress Anxiety. 2008;25:E37-40.

180. Van Ameringen M, Mancini C, Oakman JM, Farvolden P. The potential role of haloperidol in the treatment of trichotillomania. J Affect Disord. 1999;56:219-26.

181. Crescente Junior JA, Guzman CS, Tavares H. Quetiapine for the treatment of trichotillomania. Rev Bras Psiquiatr. 2008;30:402.
-182182. Khouzam HR, Battista MA, Byers PE. An overview of trichotillomania and its response to treatment with quetiapine. Psychiatry. 2002;65:261-70.,196196. Rothbart R, Amos T, Siegfried N, Ipser JC, Fineberg N, Chamberlain SR, et al. Pharmacotherapy for trichotillomania. Cochrane Database Syst Rev. 2013:CD007662.,197197. Rothbart R, Stein DJ. Pharmacotherapy of trichotillomania (hair pulling disorder): an updated systematic review. Expert Opin Pharmacother. 2014;15:2709-19.,232232. Whittington C, Pennant M, Kendall T, Glazebrook C, Trayner P, Groom M, et al. Practitioner review: treatments for Tourette syndrome in children and young people – a systematic review. J Child Psychol Psychiatry. 2016;57:988-1004.,253253. Kim BN, Lee CB, Hwang JW, Shin MS, Cho SC. Effectiveness and safety of risperidone for children and adolescents with chronic tic or tourette disorders in Korea. J Child Adolesc Psychopharmacol. 2005;15:318-24.

254. Scahill L, Leckman JF, Schultz RT, Katsovich L, Peterson BS. A placebo-controlled trial of risperidone in Tourette syndrome. Neurology. 2003;60:1130-5.

255. Gaffney GR, Perry PJ, Lund BC, Bever-Stille KA, Arndt S, Kuperman S. Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 2002;41:330-6.

256. McCracken JT, Suddath R, Chang S, Thakur S, Piacentini J. Effectiveness and tolerability of open label olanzapine in children and adolescents with Tourette syndrome. J Child Adolesc Psychopharmacol. 2008;18:501-8.

257. Stephens RJ, Bassel C, Sandor P. Olanzapine in the treatment of aggression and tics in children with Tourette's syndrome--a pilot study. J Child Adolesc Psychopharmacol. 2004;14:255-66.

258. Budman CL, Gayer A, Lesser M, Shi Q, Bruun RD. An open-label study of the treatment efficacy of olanzapine for Tourette's disorder. J Clin Psychiatry. 2001;62:290-4.
-259259. Onofrj M, Paci C, D'Andreamatteo G, Toma L. Olanzapine in severe Gilles de la Tourette syndrome: a 52-week double-blind cross-over study vs. low-dose pimozide. J Neurol. 2000;247:443-6. Furthermore, the efficacy of antipsychotics in TTM and TS has been shown for a wide range of agents.153153. Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers. 2017;3:16097.,172172. Hollis C, Pennant M, Cuenca J, Glazebrook C, Kendall T, Whittington C, et al. Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis. Health Technol Assess. 2016;20:1-450.

173. Zheng W, Li XB, Xiang YQ, Zhong BL, Chiu HF, Ungvari GS, et al. Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis. Hum Psychopharmacol. 2016;31:11-8.

174. Van Ameringen M, Mancini C, Patterson B, Bennett M, Oakman J. A randomized, double-blind, placebo-controlled trial of olanzapine in the treatment of trichotillomania. J Clin Psychiatry. 2010;71:1336-43.

175. Howard AK, Krishnamoorthy A, Leavitt BR, Raymond LA, Weissman CR. Treatment of Huntington disease and comorbid trichotillomania with Aripiprazole. J Neuropsychiatry Clin Neurosci. 2015;27:e211-2.

176. Yasui-Furukori N, Kaneko S. The efficacy of low-dose aripiprazole treatment for trichotillomania. Clin Neuropharmacol. 2011;34:258-9.

177. White MP, Koran LM. Open-label trial of aripiprazole in the treatment of trichotillomania. J Clin Psychopharmacol. 2011;31:503-6.

178. Virit O, Selek S, Savas HA, Kokacya H. Improvement of restless legs syndrome and trichotillomania with aripiprazole. J Clin Pharm Ther. 2009;34:723-5.

179. Jefferys D, Burrows G. Reversal of trichotillomania with aripiprazole. Depress Anxiety. 2008;25:E37-40.

180. Van Ameringen M, Mancini C, Oakman JM, Farvolden P. The potential role of haloperidol in the treatment of trichotillomania. J Affect Disord. 1999;56:219-26.

181. Crescente Junior JA, Guzman CS, Tavares H. Quetiapine for the treatment of trichotillomania. Rev Bras Psiquiatr. 2008;30:402.
-182182. Khouzam HR, Battista MA, Byers PE. An overview of trichotillomania and its response to treatment with quetiapine. Psychiatry. 2002;65:261-70.,196196. Rothbart R, Amos T, Siegfried N, Ipser JC, Fineberg N, Chamberlain SR, et al. Pharmacotherapy for trichotillomania. Cochrane Database Syst Rev. 2013:CD007662.,197197. Rothbart R, Stein DJ. Pharmacotherapy of trichotillomania (hair pulling disorder): an updated systematic review. Expert Opin Pharmacother. 2014;15:2709-19.,232232. Whittington C, Pennant M, Kendall T, Glazebrook C, Trayner P, Groom M, et al. Practitioner review: treatments for Tourette syndrome in children and young people – a systematic review. J Child Psychol Psychiatry. 2016;57:988-1004.,253253. Kim BN, Lee CB, Hwang JW, Shin MS, Cho SC. Effectiveness and safety of risperidone for children and adolescents with chronic tic or tourette disorders in Korea. J Child Adolesc Psychopharmacol. 2005;15:318-24.

254. Scahill L, Leckman JF, Schultz RT, Katsovich L, Peterson BS. A placebo-controlled trial of risperidone in Tourette syndrome. Neurology. 2003;60:1130-5.

255. Gaffney GR, Perry PJ, Lund BC, Bever-Stille KA, Arndt S, Kuperman S. Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 2002;41:330-6.

256. McCracken JT, Suddath R, Chang S, Thakur S, Piacentini J. Effectiveness and tolerability of open label olanzapine in children and adolescents with Tourette syndrome. J Child Adolesc Psychopharmacol. 2008;18:501-8.

257. Stephens RJ, Bassel C, Sandor P. Olanzapine in the treatment of aggression and tics in children with Tourette's syndrome--a pilot study. J Child Adolesc Psychopharmacol. 2004;14:255-66.

258. Budman CL, Gayer A, Lesser M, Shi Q, Bruun RD. An open-label study of the treatment efficacy of olanzapine for Tourette's disorder. J Clin Psychiatry. 2001;62:290-4.
-259259. Onofrj M, Paci C, D'Andreamatteo G, Toma L. Olanzapine in severe Gilles de la Tourette syndrome: a 52-week double-blind cross-over study vs. low-dose pimozide. J Neurol. 2000;247:443-6.

Together, these data support a closer relationship between TTM and TS than between TTS and OCD. However, TTM is not exactly a tic disorder. As stated much earlier, TS and OCD are on the same spectrum.163163. Pauls DL, Raymond CL, Stevenson JM, Leckman JF. A family study of Gilles de la Tourette syndrome. Am J Hum Genet. 1991;48:154-63.,260260. Hollander E, Kim S, Braun A, Simeon D, Zohar J. Cross-cutting issues and future directions for the OCD spectrum. Psychiatry Res. 2009;170:3-6. The closer relationship of TTM and OCD in terms of some specific epidemiological data, but not in terms of treatment, suggest that TTM is somewhere on a tic-OCD spectrum, as stated by Hollander et al.260260. Hollander E, Kim S, Braun A, Simeon D, Zohar J. Cross-cutting issues and future directions for the OCD spectrum. Psychiatry Res. 2009;170:3-6. TTM is neither exactly a tic disorder nor an OCD subtype, which is congruent with Phillips’s conclusions that the overlap between TTM and OCD is “partial at best.”1111. Phillips KA, Stein DJ, Rauch SL, Hollander E, Fallon BA, Barsky A, et al. Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V? Depress Anxiety. 2010;27:528-55.

Classifications of psychiatric disorders are only partially based on neurobiological data, which makes them inherently imperfect. Nevertheless, classifications are useful to represent symptoms and support treatment decisions. For these reasons, even if TTM seems to differ from tic disorders in some respects, its phenomenology and treatments (with antipsychotics and/or habit reversal training239239. Morris SH, Zickgraf HF, Dingfelder HE, Franklin ME. Habit reversal training in trichotillomania: guide for the clinician. Expert Rev Neurother 2013;13:1069-77.,240240. Rahman O, McGuire J, Storch EA, Lewin AB. Preliminary randomized controlled trial of habit reversal training for treatment of hair pulling in youth. J Child Adolesc Psychopharmacol. 2017;27:132-9.,248248. Hartmann A, Martino D, Murphy T. Gilles de la Tourette syndrome – a treatable condition? Rev Neurol (Paris). 2016;172:446-54. showing efficacy in TTM) are closer to those of tic disorders than to those of OCD. Thus, we believe it would be more helpful to consider TTM as a tic disorder in clinical practice. Of course, it is still possible that some TTM patients will present with obsessions and anxiety which lead to their hair pulling; each psychiatrist will have to consider specific cases individually.

The potential tic nature of TTM does not exclude a limbic component in this disorder. As in tic disorders, during stressful periods,153153. Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers. 2017;3:16097. the intensity of TTM symptoms can increase7474. Woods DW, Houghton DC. Diagnosis, evaluation, and management of trichotillomania. Psychiatr Clin North Am. 2014;37:301-17. (particularly in male patients, according to some authors261261. Lochner C, Seedat S, Stein DJ. Chronic hair-pulling: phenomenology-based subtypes. J Anxiety Disord. 2010;24:196-202.), which highlights the neurobiological relationship between TTM, tics, and OCD. It is well known that cortico-basal ganglia loops are implicated in OCD and TS,9090. Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15:410-24.,153153. Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers. 2017;3:16097. with participation of the limbic loop in these two disorders,9090. Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15:410-24.,153153. Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers. 2017;3:16097. but probably with a differential impact of limbic, associative, and motor loops. The same loops seem to be implicated in TTM.262262. Flessner CA, Knopik VS, McGeary J. Hair pulling disorder (trichotillomania): genes, neurobiology, and a model for understanding impulsivity and compulsivity. Psychiatry Res. 2012;199:151-8.,263263. Chamberlain SR, Odlaug BL, Boulougouris V, Fineberg NA, Grant JE. Trichotillomania: neurobiology and treatment. Neurosci Biobehav Rev. 2009;33:831-42. These data suggest that OCD, tics, and TTM have to be studied together, as differential or common findings could help improve our understanding of these disorders individually. Furthermore, considering these disorders together could help improve their treatment, particularly in comorbid or complex contexts.

These data could also help develop treatment methods for refractory TTM cases. As in OCD235235. Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008;359:2121-34.,264264. Haynes WI, Mallet L. High-frequency stimulation of deep brain structures in obsessive-compulsive disorder: the search for a valid circuit. Eur J Neurosci. 2010;32:1118-27. and TS,265265. Baldermann JC, Schuller T, Huys D, Becker I, Timmermann L, Jessen F, et al. Deep Brain Stimulation for Tourette-Syndrome: A Systematic Review and Meta-Analysis. Brain Stimul. 2016;9:296-304. deep brain stimulation could be of great help to some patients. In these disorders, stimulation targets play a key role,264264. Haynes WI, Mallet L. High-frequency stimulation of deep brain structures in obsessive-compulsive disorder: the search for a valid circuit. Eur J Neurosci. 2010;32:1118-27.,265265. Baldermann JC, Schuller T, Huys D, Becker I, Timmermann L, Jessen F, et al. Deep Brain Stimulation for Tourette-Syndrome: A Systematic Review and Meta-Analysis. Brain Stimul. 2016;9:296-304. and choosing the most effective one is essential. Our data suggest that regions of the basal ganglia targeted in TS (thalamus, postero-ventro-lateral globus pallidus internus, anteromedial globus pallidus internus, and anterior limb of the internal capsule/nucleus accumbens265265. Baldermann JC, Schuller T, Huys D, Becker I, Timmermann L, Jessen F, et al. Deep Brain Stimulation for Tourette-Syndrome: A Systematic Review and Meta-Analysis. Brain Stimul. 2016;9:296-304.) could be appropriate targets, perhaps more so than OCD targets.

This review has several limitations. Key among them are our qualitative method, without meta-analysis of data, and the lack of studies directly comparing the three disorders in the literature. However, our sample was restricted to original studies and meta-analyses (except for the “antipsychotics in TTM” portion of the pharmacology axis, due to the paucity of original research and absence of meta-analyses).

Much work remains before a truly in-depth understanding of these disorders can be achieved, especially TTM; novel approaches could be helpful. All future research based on neurobiological mechanisms possibly underlying these disorders (e.g., genetic, immunologic, DTI, or animal studies) could help disentangle the relationship between them and, particularly, elucidate the differences in cortico-basal ganglia loop involvement.

In conclusion, despite some discrepancies, we consider that TTM is closer to tic disorders than to OCD, which is confirmed by analysis of phenomenology/symptomatology and treatment efficacy. We believe considering it as such in clinical practice can help psychiatrists better understand and treat patients with TTM.

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Publication Dates

  • Publication in this collection
    26 Sept 2019
  • Date of issue
    Jan-Feb 2020

History

  • Received
    15 July 2018
  • Accepted
    8 June 2019
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