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tricotillomania: Pathopsychology theories and treatment Possibilities

Netta Shoenfeld BA, Oded Rosenberg MD, Moshe Kotler MD and Pinhas N. Dannon* MD
Beer Yaakov Mental Health Hospital, Beer Yaakov, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

In addition, the pulling must not be accounted for by another psychiatric or medical condition [5]. Although the DSM-IV definition requires all of the above criteria, it is plausible that not all of the characteristics are present in all clinically significant cases. It is reported that 17%27% of patients do not complain of rising tension before, during or after the hair pulling. In addition, clinical cases show that the pulling of hair does not necessarily cause hair loss or distress, implying that the behavior occurs on a continuum, ranging from unnoticeable to disfiguring [4]. Therefore, the DSM criteria for the diagnosis of TTM might be overly restrictive and prevents suffering individuals from getting the help they need [2-5]. Due to the inconsistencies in diagnostic criteria, the true IMAJ 2012; 14: 125129 prevalence of TTM is largely unknown. The prevalence of KeY wOrds: trichotillomania, obsessive-compulsive disorder (OCD), TTM varies between different studies, ranging from a lifetime addiction, impulse control, treatment outcome prevalence of 0.6% using the DSM-IV criteria, to 4% of the general population, and 10% having had the habit at some point in their lives. By the time the correct diagnosis is made, it is not uncommon for a patient to have been diagnosed with and already treated for other medical conditions such as tinea capitis or alopecia areata [1,6-8]. he phenomenon of hair pulling has been recognized for centuries, and references to it can be found in the Bible, Gender distribution in the general population is also uncertain, but in the clinical setting there is a higher prevalence among in Homer's The Iliad, and in the plays of William Shakespeare women [9]. This may be explained by the fact that women are (Much Ado About Nothing, Romeo and Juliet, and The Life and more inclined to seek help, that men may blame male pattern Death of King John). In the medical literature the earliest baldness, or that men have the advantage of reference appeared in a work attributed to trichotillomania is more shaving their heads and beards with little Hippocrates. In the literature, the eating of common than thought resultant social stigma [4]. However, addihair, trichophagia, was mentioned before tional data on the differences between men and women might hair pulling. It was not until the 18th century that hair pulling allude to an actual bias in gender. For example, the age at onset was described (by the French physician Baudamant), and in of hair pulling was significantly later for males [8] than for the 19th century it was first described as a medical syndrome females [10-12]. In addition, there are significantly more males [1]. The name trichotillomania was given by Francois Henri than females who present with comorbid obsessive-compulsive Hallopeau in 1889 and was characterized as recurrent hair disorder and tics. Males and females also differed in terms of the pulling that results in noticeable hair loss or distress. According hair pulling site (men pull hair from the stomach/back and the to the current definition, the behavior must be accompanied moustache/beard areas, while women pull from the scalp) [10]. by tension prior to or while attempting to resist pulling the Three subtypes of hair pulling have been distinguished [4]: hair, as well as by gratification, relief or pleasure while pull Early onset, considered the benign form of TTM, occurring ing [1-4] The targeted hair is mostly on the scalp (75%), but in young children (under the age of 8), which receives little may also be from the eyebrows (42%), eyelashes (53%), beard (10%), and pubic area (17%). There is usually more than one DSM-IV = Diagnostic and Statistical Manual, 4th edition target area with the number of sites increasing with age [1,4,5]. TTM = trichotillomania
aBstract: The phenomenon of hair pulling has been recognized for centuries, yet the true prevalence of trichotillomania (TTM) is largely unknown and the topic has been sparsely studied. TTM is classified as an impulse-control disorder despite much debate about its etiology. In this review we summarize the different hypotheses, including impulse-control disorders, obsessive-compulsive disorders, behavioral problems and addiction, and the appropriate treatment methods. The combination of selective serotonin reuptake inhibitors and antipsychotic medications are shown to be most effective. Treatment with anti-addiction drugs seems relevant. Further research is needed to increase our knowledge regarding the etiology of TTM.

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transmission and possibly treatment response. Both OCD and TTM are characterized by repetitive, intentionally performed behaviors that cause significant distress or functional impairment [13]. Although the repetitive behavior of TTM exclusively involves hair pulling, this behavior often follows high anxiety and results in reduced anxiety [14]. In addition, whole-brain magnetic resonance imaging showed that medication-free TTM patients had increased gray matter in the left putamen and multiple cortical regions, similar to the increase in Tourette syndrome and in OCD [15]. In a different study, TTM patients were found to have smaller left putamen volumes than matched controls, thus providing evidence for a link between TTM and Tourette syndrome. Furthermore, TTM patients present with Automatic and focused TTM are usually not exclusive and reduced volumes for the total right and left cerebellum cortex, vary, overlap or co-occur [4]. Still, focused TTM is defined as well as for the autonomic/emotional functional cluster comas pulling with a compulsive quality, which may represent an pared with controls [16]. attempt to regulate negative emotions [9]. TTM may cause additional physical impairments and disThe hypothesis of an OCD spectrum origin of TTM led to tress; sucking and chewing of the pulled hair is observed in 48% the use of SSRIs as a treatment option. However, studies on of patients, and 5%18% of patients ingest the pulled hair. In the potency of SSRIs in TTM have yielded mixed results [17]. addition, skin infections, scalp bleeding or irritation, and carAccording to various studies from the 1990s [18-21], SSRI and pel tunnel syndrome are also prevalent in TTM patients. In the other antidepressants improve some aspects of TTM, although social dimension, 2263% of TTM patients report avoidance placebo-controlled trials have not shown consistent results. In a of common activities. The feeling of isolation and loneliness is study in 2007, some patients with TTM experienced significant common, as are feelings of shame and embarrassment. TTM improvement after treatment with escitalopram [22]. In a 2003 patients tend to have low self-esteem, study, fluoxetine was found ineffectrichotillomania affects primarily tive for the treatment of TTM [23]; feelings of unattractiveness, and body females in every age group dissatisfaction. The use of legal and however, in another study, conducted illegal drugs to cope with those feelings has been reported [4]. in 1991, it was not more effective than a placebo [24]. In two People suffering from TTM will commonly deny the condition studies, one in 1996 and the other in 2000, clomipramine was and may become adept at disguising their hair loss [5]. also found to be ineffective for the treatment of TTM [25,26]. Psychiatric comorbidity is common, with one or more An explanation for the SSRI lack of success in treating TTM lifetime psychiatric diagnoses found in 82%, major depresmight be found in the core assumption that led to the use of sion in 3765%, anxiety disorder in 5560%, and excessive SSRIs in the first place. Although TTM and OCD share some alcohol use in 33% [11]. common ground, there are fundamental differences between the two disorders. For example, in contrast to compulsions in OCD, hair pulling in TTM is not a response to obsessive etiOlOgY and treatment theOries thoughts but is due to an irresistible urge and the promise of gratification after the hair pulling. Also, unlike patients with Although TTM is classified in the DSM-IV-TR [2] and in the OCD whose symptoms change over time in terms of focus ICD-10 [3] as an impulse-control disorder, there has been much and severity, TTM patients usually present with hair pulling debate regarding the etiology of this disorder. Hair-pulling behavwithout evolution to non-self-injurious compulsive rituals [9]. iors have been observed in animals, such as rabbits, sheep, dogs, Moreover, there are no obsessions preceding the compulsions. cats and others; and the analogue behavior of feather-picking has also been noted in birds [4]. Thus, TTM behavior is thought to With regard to demographic variables, TTM is far more be an inappropriately triggered grooming behavior [12]. prevalent in females, whereas OCD is equally common in both genders, and while TTM typically presents an early onset in adolescence, OCD usually appears in childhood Ocd sPectrum etiOlOgY and ssri treatment through early adulthood [9]. It has been suggested that TTM belongs to the OCD spectrum Other clinical observations point to a difference in characand that the use of selective serotonin reuptake inhibitors terization between the two disorders. Patients suffering from could benefit the sufferers. It is believed by some researchers TTM present fewer comorbid obsessive-compulsive symptoms, that OCD and TTM share overlapping comorbidity, familial
OCD = obsessive-compulsive disorder SSRIs = selective serotonin reuptake inhibitors

to no medical intervention. It is believed that the pattern of anxiety and tension followed by relief is not present in this form of TTM. Automatic, thought to occur when the individual is engaged in other activities, such as reading, watching television, listening to the radio, etc., and affects roughly 75% of TTM patients. Focused, thought to occupy the individual's attention, and is associated with more intense urges and thoughts about hair pulling, alluding to the comparison between this subtype of TTM and obsessive-compulsive disorders.

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as well as less depression and anxiety compared to symptoms in patients suffering from OCD. When behavioral techniques such as response prevention are applied in patients suffering from OCD, it eventually leads to anxiety reduction, whereas in people with TTM it may lead to an increase in anxiety. Additional clinical observations included more sexual abuse and more maladaptive cognitive schemas reported by OCD patients, while TTM patients were more novelty seeking [9].
BehaviOral etiOlOgY and cOgnitive BehaviOral theraPY

antiPsYchOtic PharmacOtheraPY and dOPamine theOrY

It has been proposed that TTM occurs through a learning process, similar to the formation of habits [4], and that it might resemble the habit of thumb sucking or nail biting [5]. It may also develop as a coping behavior in response to stress and is reinforced through tension reduction [4]. Habit-reversal training is the preferred behavioral treatment for TTM; it involves three primary components: a) awareness training, b) competing response trainings, and c) social support. Other techniques have been incorporated into the habit-reversal training routine, such addictive sPectrum and reward circuit theOrY as stimulus control, cognitive restructuring, relaxation training Although the similarities between TTM and OCD have been and thought stopping [9]. suggested and studied extensively in recent years, many features The application of behavioral therapy is rooted in learning of TTM are also common with addictive disorders. First, the theories. By interrupting the chain of conditioned and discrimirepetitive or compulsive engagements, despite adverse consenated stimuli, urges, hair-pulling behavior and gratification quences, which are the core of TTM, resemble the nature of following hair pulling, classical and although data on the psychological addiction. Patients suffering from operant conditioning of hair-pulling TTM also exhibit, as in other addicand pharmacological treatments behavior weakens over time [8,10]. tions, diminished control over their of trichotillomania are incomplete, problematic behavior, a growing cravOne study reports these types of cognitive behavioral therapy and treatments to be more useful for the ing prior to engaging in the probopioid antagonist pharmacotherapy treatment of TTM than pharmacolematic behavior, and lastly, a gratiyielded the most promising results therapy [9]. In another study confication during and after engaging ducted in 2000, cognitive behavioral therapy had a dramatic in the problematic behavior. An important difference between effect and achieved statistical significance in reducing TTM compulsions in OCD and hair pulling in TTM is that hair pullsymptoms compared to SSRIs and placebos [26]. The results ing and addiction are usually accompanied by pleasurable or from a 2003 study are similar to other studies, showing that rewarding feelings, while compulsions are executed to decrease behavioral therapy is superior to both fluoxetine treatment and anxiety [31]. postponement of treatment, and 64% of patients in the CBT Reinforcement for the addiction spectrum hypothesis can group showed a significant reduction in the severity of TTM, be found in case reports and studies testing the efficacy of the including actual hair pulling [23]. In a 2006 study, TTM abated medications on dopaminergic and serotonergic neurotransconsiderably immediately after brief behavioral therapy [27]; in mitters in TTM. In a case report from 2004, patients treated a study from 2007, habit-reversal training was found to be the with bupropion at a dosage of 150 mg twice daily noted almost most effective intervention for TTM when practiced by expecomplete remission of TTM symptoms. It is hypothesized rienced clinicians in academic research settings, compared to that bupropion decreases TTM symptoms by diminishing the pharmacotherapy [28]. heightened arousal and pleasurable relief that are involved in hair pulling [32]. Dannon et al. [33] recently completed a study However, despite positive results, the effectiveness of behavwith bupropion XR in the treatment of TTM, showing signifiioral and cognitive strategies varies across clients and involves cant improvement at the 12 week point [33]. significant risk for relapse [21]. In addition, in a study comparing a single modality approach with CBT and pharmacotherapy to a dual modality approach using the two treatments combined, Other treatment POssiBilities: mOOd staBilizers the dual modality was found to be slightly more effective [29]. and FOOd suPPlements Another study found significant reduction in hair pulling following the use of topiramate, which is an antiepileptic drug CBT = cognitive behavioral therapy

Although the role of serotonin has been postulated in TTM and other impulse-control disorders, the use of SSRIs in the treatment of TTM has proven inadequate. One possibility for this shortcoming might be the involvement of other pathways and neurotransmitters, such as opioids and dopamine [30]. In a case report from 2008, pharmacotherapy with fluoxetine led to intolerable side effects. However, when quetiapine was introduced at a dosage of 100 mg/week, both hair pulling and fluoxetine side effects remitted. Cessation of hair pulling lasted for a period of 4 months. This report sheds new light on the combination of SSRIs with antipsychotic medications as a treatment modality for TTM [30]. Yet, in another study conducted in 2008, the use of aripiprazole was associated with the rapid and sustained cessation of hair pulling [11]. The efficacy of the combination of SSRIs and antipsychotic agents has yet to be elucidated.

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known to be effective in the treatment of other impulse-control disorders [10,34]. The use of lamotrigine, a mood stabilizer, also appears to have significant effect in treating TTM [35], as did the mood stabilizer oxcarbazepine [36]. N-acetylcystein, a glutamate modulator (food supplement), was also shown to be effective in TTM on the primary and secondary outcome measures. Its beneficial effects were seen 9 weeks after treatment initiation [37].

etiOlOgY and genetic theOries Genetic factors appear to contribute to the development of TTM. A significantly different concordance rate for TTM was found in monozygotic (38.1%) compared with dizygotic (0%) twins in 34 pairs [38]. Several researchers found mutations of the SLITRK1 gene, which plays a role in cortex development and neuronal growth [39]. Zuckner and colleagues [39] also found that a heterozygous variant of postsynaptic synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP)3, which is involved in the excitatory transmissions at corticostriatal synapses, was present in only 1.1% of the controls, compared with 4.2% of those diagnosed with TTM and OCD. Researchers suggest that SAPAP3 may be involved in the development of obsessive-compulsive spectrum disorders. etiOlOgY and neurOcOgnitive neurOimaging theOries Several authors measured impulsivity with the Stop Signal Task and demonstrated an impaired inhibitory control; however, other studies using the Wisconsin Card Sorting test and the go/no-go task found no significant differences between TTM patients and normal controls [40]. Few brain imaging studies have been performed, and these were with a relatively small number of TTM patients. These studies showed a wide range from no difference to an increased gray matter density in the striatum, left amygdalohippocampal formation, and multiple cortical regions. discussiOn The phenomena of hair pulling, termed trichotillomania, is unique due to the controversy revolving around its etiology and optimal treatment. Officially, and according to the DSM-IV [2] and the ICD-10 [3], TTM is categorized as an impulse-control disorder. Due to the lack of success in treating TTM fully, other explanations regarding the etiology of TTM have been proposed, followed by treatment propositions. Chamberlain [1,6] and others have suggested that TTM is a part of the OCD spectrum, and
ICD = International Classification of Diseases

therefore they treated TTM patients with SSRIs; this method has proven to be only partially effective [24]. A different suggestion attributed TTM to the behavioral disorders spectrum, and accordingly used CBT as the treatment method [10,35]. However, as with SSRIs, the use of CBT did not yield satisfying results [3,9,10,27,30]. The use of dopamine-related medications in TTM patients was chosen due to the opioid and dopamine involvement in the disorder [7]. To date, there have not been sufficient studies to clearly demonstrate the therapeutic effects of these medications. Other treatments, such as mood stabilizers and food supplements, were shown to be somewhat effective but require further larger studies. Our group has been studying the effect of dopaminergic medications in TTM patients (bupropion sustained release and naltrexone) due to the similarities between the two disorders. A few studies have found these medications to be the most useful for treating TTM [1,15].

cOnclusiOns TTM is much more common than believed and seems to be much more complex than the easily categorized impulsecontrol disorder. Although TTM shares similarities with the OCD spectrum, the matching treatment possibilities, such as SSRIs, were proven less effective in TTM. The hypotheses of dopamine, glutamate or GABA (gamma-aminobutyric acid) in TTM have underlined the use of mood stabilizers, antipsychotic and dopamine-related drugs. Currently, CBT seems to be the treatment of choice in psychotherapeutic interventions. To date, the most promising results have been evident when CBT and opioid antagonist pharmacotherapy were implemented.
corresponding author:
dr. P.n. dannon Research Department, Beer Yaakov Mental Health Hospital, P.O. Box 1, Beer Yaakov 60350, Israel Phone: (972-8) 925-8252 Fax: (972-8) 921-2570 email: pinhasd@post.tau.ac.il

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capsule new gene functions in megakaryopoiesis and platelet formation

Platelets are the second most abundant cell type in blood and are essential for maintaining hemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Gieger and coresearchers carried out a high powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. The authors identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, they identified 11 of the genes as novel regulators of blood cell formation. Taken together, their findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.
Nature 2011; 480: 201
Eitan Israeli

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