Person:

Keuthen, Nancy

Trichotillomania (hair-pulling disorder) is characterized by the repetitive pulling out of one's own hair, and is classified as an Obsessive-Compulsive Related Disorder. Abnormalities of the ventral and dorsal striatum have been implicated in disease models of trichotillomania, based on translational research, but direct evidence is lacking. The aim of this study was to elucidate subcortical morphometric abnormalities, including localized curvature changes, in trichotillomania. De-identified MRI scans were pooled by contacting authors of previous peer-reviewed studies that examined brain structure in adult patients with trichotillomania, following an extensive literature search. Group differences on subcortical volumes of interest were explored (t-tests) and localized differences in subcortical structure morphology were quantified using permutation testing. The pooled sample comprised N = 68 individuals with trichotillomania and N = 41 healthy controls. Groups were well-matched in terms of age, gender, and educational levels. Significant volumetric reductions were found in trichotillomania patients versus controls in right amygdala and left putamen. Localized shape deformities were found in bilateral nucleus accumbens, bilateral amygdala, right caudate and right putamen. Structural abnormalities of subcortical regions involved in affect regulation, inhibitory control, and habit generation, play a key role in the pathophysiology of trichotillomania. Trichotillomania may constitute a useful model through which to better understand other compulsive symptoms. These findings may account for why certain medications appear effective for trichotillomania, namely those modulating subcortical dopamine and glutamatergic function. Future work should study the state versus trait nature of these changes, and the impact of treatment.

Trichotillomania is a functionally impairing, often overlooked disorder with no Food and Drug Administration-approved medications indicated for its treatment. The ability of clinical trials to detect the beneficial effects of pharmacologic treatment in trichotillomania has been hampered by the high placebo response rate. Very little is known about baseline demographic and clinical characteristics that may be predictive of placebo response in such patients. Overall, 104 participants assigned to placebo were pooled from five double-blind trials conducted at three sites in the USA and Canada. Participants were classified as placebo responders or nonresponders on the basis of a cutoff of a 35% reduction in symptom severity on the Massachusetts General Hospital Hair Pulling Scale. Baseline group differences were characterized using t-tests and equivalent nonparametric tests as appropriate. Thirty-one percent of individuals assigned to placebo treatment showed a significant clinical response to placebo. Placebo responders (n=32) and nonresponders (n=72) did not differ significantly on any demographic or clinical variable. Predictors of placebo response for trichotillomania remain elusive and do not appear to be similar to those reported for other mental health disorders.

Trichotillomania is a prevalent but often hidden psychiatric condition, characterized by repetitive hair pulling. The aim of this study was to confirm or refute structural brain abnormalities in trichotillomania by pooling all available global data. De-identified MRI scans were pooled by contacting authors of previous studies. Cortical thickness and sub-cortical volumes were compared between patients and controls. Patients (n = 76) and controls (n = 41) were well-matched in terms of demographic characteristics. Trichotillomania patients showed excess cortical thickness in a cluster maximal at right inferior frontal gyrus, unrelated to symptom severity. No significant sub-cortical volume differences were detected in the regions of interest. Morphometric changes in the right inferior frontal gyrus appear to play a central role in the pathophysiology of trichotillomania, and to be trait in nature. The findings are distinct from other impulsive-compulsive disorders (OCD, ADHD, gambling disorder), which have typically been associated with reduced, rather than increased, cortical thickness. Future work should examine sub-cortical and cerebellar morphology using analytic approaches designed for this purpose, and should also characterize grey matter densities/volumes. Electronic supplementary material The online version of this article (doi:10.1007/s11682-017-9746-3) contains supplementary material, which is available to authorized users.