Background In recent years diffusion tensor imaging (DTI) studies have detected

Background In recent years diffusion tensor imaging (DTI) studies have detected subtle microstructural abnormalities of white matter (WM) in obsessive-compulsive disorder (OCD). and posterior limbs of the internal capsule which are involved LY2484595 in the cortical‐striatal‐thalamic‐cortical loop; the corona radiata and the superior and inferior longitudinal fasciculus which connect frontal to temporal‐parietal‐occipital cortices; and the bundle of corpus callosum which subserves interhemispheric connectivity (Piras et?al. 2013; Koch et?al. 2014; Radua et?al. 2014; Eng et?al. 2015). However the literature remains inconsistent with regard to the direction of effects with some studies reporting significant FA decreases in OCD (Szeszko et?al. 2005; Saito et?al. 2008; Ha et?al. 2009; Garibotto et?al.?2010; Chiu et?al. 2011; Admon et?al. 2012; Oh et?al. 2012) and others reporting increases in the same tracts (Cannistraro et?al. 2007; Yoo et?al. 2007; Nakamae et?al. 2008; Li et?al. 2011). Some of this variation may be attributable to the use of region of interest approaches (Cannistraro et?al. 2007; Saito et?al. 2008; Chiu et?al. 2011; Lochner et?al. 2012; Oh et?al. 2012; Lopez et?al. 2013) which are hypothesis driven but neglect other regions that are potentially affected (Koch et?al. 2014). Other investigations have utilized whole‐brain voxel‐based morphometry (VBM) analysis (Szeszko et?al. 2005; Yoo et?al. 2007; Menzies et?al. 2008b; Nakamae et?al. 2008; Ha et?al. 2009; Garibotto et?al. 2010; Li et?al. 2011; Admon et?al. 2012) which suffers from several methodological limitations when applied to DTI data particularly misregistration and partial volume effects (Jones et?al. 2005). More recently tract‐based spatial statistics (TBSS) have been advanced as a means of overcoming several of these limitations by performing whole‐brain voxel‐wise analysis to provide a more comprehensive measure of WM alterations (Smith et?al. 2006; Koch et?al. 2014). However the studies that have examined adult OCD patients using whole‐brain TBSS so far do not paint a coherent picture (Bora et?al. 2011; Fontenelle et?al. 2011; Nakamae et?al. 2011; Benedetti et?al. 2013; Spalletta et?al. 2014). In addition to structural abnormalities OCD patients show cognitive impairment in executive functions attention visuospatial abilities and nonverbal memory (Nakao et?al. 2014; Eng et?al. 2015) many of which correlate with gray‐matter changes in frontal cortex basal ganglia and thalamus (Eng et?al. 2015). However while correlations between cognition and WM microstructural alterations have been found in healthy subjects (Burzynska et?al. 2011) and patients with schizophrenia and bipolar disorder (Poletti Neurog1 et?al. 2015; Roalf et?al. 2015) this relationship has not been the focus of much investigation in OCD. To our knowledge only one study has examined WM changes related to cognitive dysfunction in OCD identifying a correlation between semantic fluency and FA in the corona radiata and corticospinal tract (Spalletta et?al. 2014). However these regions were not different between OCD and HC groups as a whole; as such the meaning of this relationship is LY2484595 unclear. Nevertheless this type of approach is critically important for understanding the mechanisms by which microstructural alterations impact behavior and may help explain LY2484595 some of the discrepancies in the literature. This study used TBSS to investigate whole‐brain WM microstructure indexed by FA MD and RD in patients with OCD compared with healthy controls (HC). We also explored the relationship of WM alterations with clinical and cognitive variables in OCD in order to investigate the structural correlates of behaviorally relevant features of the disorder. Materials and Methods Subjects and assessments Subjects were recruited from psychiatric clinics at the Icahn School of Medicine at Mount Sinai (ISMMS) and from the greater New York metropolitan area. All subjects provided written informed consent and the research was approved by the Institutional Review Board of the ISMMS. A total of 34 subjects were included in the analysis comprising 16 patients with OCD and 18 HC. All patients met DSM‐IV criteria for current OCD excluding primary hoarding subtypes (A.P.A. LY2484595 1994). Exclusionary comorbid diagnoses for OCD patients included lifetime history of bipolar disorder or psychosis as well as current posttraumatic stress disorder panic disorder or eating disorders. Axis I comorbidities consisted of generalized anxiety disorder (n?=?4) trichotillomania (n?=?1) excoriation (i.e. skin picking) disorder (n?=?3).