To the Editor In JAMA Psychiatry, Grant and colleagues 1 demonstrated the efficacy of N-acetylcysteine (NAC) in the treatment of excoriation disorder (ED). The same group had previously reported the benefits of NAC for adults with trichotillomania (TTM). 2 In both studies, NAC was used in monotherapy in otherwise treatment-free patients. In the DSM-5, ED and TTM were included under the umbrella of obsessive-compulsive disorder (OCD) and related disorders because of similarities regarding phenotypic expression and common putative neurobiological underpinnings between these disorders and OCD. When used for treatment-resistant OCD, NAC was not more effective than placebo as a selective serotonin reuptake inhibitor (SSRI) augmentation strategy. 3 In striking contrast with what we know about OCD, SSRIs have not been proved to be superior to placebo in TTM treatment. 2 As for ED, the evidence regarding the efficacy of SSRIs is still scarce. 1 So far, there are no US Food and Drug Administration-approved treatments for ED and TTM. The divergent results of the trials testing either SSRIs or NAC for ED/ TTM and OCD suggest that treatments may not be used interchangeably between OCD and related disorders. Despite the possible methodological issues related to the design of specific trials, do such heterogeneous results regarding treatment response relate to heterogeneous neurobiology between OCD and related disorders?Pathological grooming behaviors in animals are widely used in the literature as a common animal model of ED/TTM and OCD. However, findings derived from animal studies do not always confirm the association between grooming behavior and OCD. For example, no differences were observed in the results of the marble-burying test of rats with different levels of grooming behavior. 4 In addition, results from genetic studies also suggest that the neurobiology of pathological grooming may not be necessarily related to OCD. It had been demonstrated that Sapap3 knockout mice groomed themselves excessively. However, using family-based association analyses, Bienvenu et al 5 found that variation within the human equivalent of the Sapap3 gene appeared associated with ED/TTM, but not with OCD.The conflicting results regarding the efficacy of NAC for ED/TTM and OCD, in addition to the findings of translational studies, suggest that the neural basis of repetitive behaviors observed in patients with these disorders might not be the same. So far, similarities between ED/TTM and OCD do not seem to go beyond the characterization by repetitive behaviors and some degree of familial aggregation.