Am J Psychiatry 162:11, November 2005 2193 LETTERS TO THE EDITOR http://ajp.psychiatryonline.org number of studies have supported the view that response to antidepressant interventions is accompanied by an increase in GABA-ergic neurotransmission. In accordance, there is ev- idence that antidepressant therapeutic brain stimulation techniques, such as vagus nerve stimulation and ECT may act via GABA-ergic pathways (1, 2). Transcranial magnetic stimu- lation is a noninvasive investigational tool that has been ex- tensively used over recent years to assess human motor cor- tex excitability (3). After approval by a local ethics committee and receipt of written informed consent, we tested the motor threshold, postexcitatory inhibition, and intracortical excitability to clarify the influence of vagus nerve stimulation and ECT on motor cortex excitability with transcranial magnetic stimula- tion in two female patients with unipolar major depressive disorder (40 and 65 years old); each received two different an- tidepressant stimulatory interventions. In the premeno- pausal patient, each of the three assessments was performed within the follicular phase of her menstrual cycle. Antidepres- sant medication (tranylcypromine, 40 mg/day, and venlafax- ine, 150 mg/day) was kept constant at least 4 weeks before the first stimulation treatment and throughout the whole treat- ment. Response was defined as a 50% reduction in score on the 21-item Hamilton Depression Rating Scale. Ms. A did not respond to 12 sessions of right unilateral ECT (her Hamilton depression scale score dropped only 1 point, from 27 to 26) and was then successfully treated with vagus nerve stimulation (her Hamilton depression scale score dropped from 26 to 12). Ms. B did not respond to 10 weeks of vagus nerve stimulation (her Hamilton depression scale score increased by 2 points, from 29 to 31) and was then success- fully treated with 12 sessions of ECT (her Hamilton depres- sion scale score dropped from 31 to 10). In both patients, measurements of motor cortical excitability were performed at baseline, after completion of the first unsuccessful inter- vention, and after the completion of the second (successful) intervention. Regardless of the type of intervention, all pa- rameters remained unchanged after the first therapeutic trial. After the second therapeutic intervention (vagus nerve stimu- lation in Ms. A and ECT in Ms. B), both patients showed a treatment response and an increase in cortical silent-period duration and intracortical inhibition. To our knowledge, this is the first report of an increase in motor cortical inhibition in depressed patients receiving va- gus nerve stimulation and ECT. The data suggest that a com- mon GABA-ergic pathway is activated in both vagus nerve stimulation and ECT responders. Furthermore, the data indi- cate that measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of different antidepressant stimulation techniques. In the future, further studies with larger groups are needed. References 1. Sanacora G, Mason GF, Rothman DL, Hyder F, Ciarcia JJ, Ostroff RB, Berman RM, Krystal JH: Increased cortical GABA concentra- tions in depressed patients receiving ECT. Am J Psychiatry 2003; 160:577–579 2. Bajbouj M, Gallinat J, Lang UE, Neu P, Niehaus L: Motorcortical excitability after electroconvulsive therapy in patients with ma- jor depressive disorder. Suppl Clin Neurophysiol 2003; 56:433– 440 3. Siebner HR, Rothwell J: Transcranial magnetic stimulation: new insights into representational cortical plasticity. Exp Brain Res 2003; 148:1–16 MALEK BAJBOUJ, M.D. UNDINE E. LANG, M.D. PETER NEU, M.D. ISABELLA HEUSER, M.D., PH.D. Berlin, Germany Understanding the Heterogeneity of OCD T O THE EDITOR: I read with interest the excellent review of di- mensional approaches to understanding obsessive-compul- sive disorder (OCD) heterogeneity by David Mataix-Cols, Ph.D., and colleagues (1). I agree with the authors that OCD heterogeneity is an important issue and that failure to identify differences within the condition has significantly hindered advances in theory and treatment. My comments focus on the authors’ contention that a dimensional approach to un- derstanding OCD heterogeneity is an inherently superior method. There have been three recent approaches to understanding OCD symptom heterogeneity. Some researchers have focused on patients’ dominant compulsive behavior to form symp- tom subgroups (e.g., washers versus checkers). This approach is limited and fails to capture most cases in which patients are seen with multiple classes of symptoms. In recent investiga- tions, the diversity and complex patterns of symptoms seen in clinical presentations have been characterized with multi- variate statistical analyses. Factor analysis has been used to identify the latent dimensions of several comprehensive OCD symptom measures. Alternatively, symptom measures have been subjected to cluster analysis to form symptom-based subgroups of individuals. In cluster analysis, individuals are assigned to groups created by maximizing between-group differences and minimizing within-group variability on a set of measures (2). Cluster analysis may offer several advantages over factor analysis in characterizing OCD heterogeneity, and this ca- tegorical approach is not limited in some of the ways Dr. Mataix-Cols et al. implied. In cluster analysis, individuals are unambiguously assigned to unique groups, whereas in factor analysis, each individual is assigned a score on all of the iden- tified latent dimensions. Thus, the factor scores estimated for individuals may not connect the person to a specific dimen- sion. As Dr. Mataix-Cols et al. pointed out, hoarding symptoms have emerged as a symptom dimension that predicts unre- sponsiveness to current pharmacotherapy and standard be- havior therapy. Although there has been limited study, similar results have been reported with a cluster analysis approach in which the hoarding subgroup was less responsive to behavior treatment (3). The results of several recent cluster analyses (e.g., reference 4) suggest that complex symptom presenta- tions can be captured with a cluster analysis approach and that resultant clusters are far from monosymptomatic. The relative merits of categorical and dimensional ap- proaches to psychiatric classification have long been debated. The use of each of these approaches to understanding OCD heterogeneity warrants further investigation.