Gamma Ventral Capsulotomy in Intractable Obsessive-Compulsive Disorder.

BACKGROUND: Despite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD. METHODS: Fifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging. RESULTS: Thirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state. CONCLUSIONS: Gamma Knife ventral capsulotomy is an effective radiosurgical procedure for many treatment-refractory OCD patients. A minority of patients developed cysts at long-term follow-up, 1 of whom had permanent neurological sequelae.

Integrating evolutionary and regulatory information with a multispecies approach implicates genes and pathways in obsessive-compulsive disorder.

Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 × 10-11) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with symptoms including intrusive thoughts and time-consuming repetitive behaviors. Here Noh and colleagues identify genes enriched for functional variants associated with increased risk of OCD.

LOWER POSTERIOR CINGULATE CORTEX GLUTATHIONE LEVELS IN OBSESSIVE-COMPULSIVE DISORDER.

BACKGROUND: Several lines of evidence support the hypothesis that lower cerebral levels of glutathione (GSH), associated with increased oxidative stress, may contribute to obsessive-compulsive disorder (OCD). However, no studies to date have investigated brain GSH levels in individuals with OCD. METHODS: Twenty-nine individuals with OCD and 25 age-, sex-, and race-matched comparison individuals without OCD underwent single voxel 2D J-resolved proton magnetic resonance spectroscopy (MRS) to examine GSH levels in the posterior cingulate cortex (PCC). MRS data were analyzed using LCModel and a simulated basis set. Group metabolite differences referenced to total creatine (Cr), as well as relationships between metabolite ratios and symptom severity as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), were analyzed using linear regression with adjustment for age, sex, and race. RESULTS: One OCD participant failed to produce usable PCC MRS data. We found significantly lower PCC GSH/Cr in OCD participants compared with non-OCD participants (ß = -0.027 [95% CI: -0.049 to -5.9 × 10-3]; P = 0.014). PCC GSH/Cr was not significantly associated with total Y-BOCS score in the OCD group (ß = 5.7 × 10-4 [95% CI: -4.8 × 10-3 to 5.9 × 10-3]; P = 0.83). CONCLUSIONS: Lower PCC GSH/Cr may be indicative of increased oxidative stress secondary to hypermetabolism in this brain region in OCD. Future MRS studies are warranted to investigate GSH levels in other brain regions that comprise the cortico-striato-thalamo-cortical circuit thought to be abnormal in OCD.

Open-label study of duloxetine for the treatment of obsessive-compulsive disorder.

BACKGROUND: This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder (DSM-IV). METHODS: Twenty individuals were enrolled in a 17-week, open-label trial of duloxetine at Massachusetts General Hospital. Data were collected between March 2007 and September 2012. Study measures assessing obsessive-compulsive disorder symptoms, quality of life, depression, and anxiety were administered at baseline and weeks 1, 5, 9, 13, and 17. The primary outcome measures were the Yale-Brown Obsessive Compulsive Scale and Clinical Global Improvement scale. RESULTS: For the 12 study completers, pre- and posttreatment analyses revealed significant improvements (P<.05) on clinician- and self-rated measures of obsessive-compulsive disorder symptoms and quality of life. Among the 12 completers, more than one-half (n=7) satisfied full medication response criteria. Intention-to-treat analyses (n=20) showed similar improvements (P<.05) on primary and secondary study outcome measures. CONCLUSION: The results of this study suggest that duloxetine may provide a significant reduction in symptoms for patients with obsessive-compulsive disorder. ClinicalTrials.gov NCT00464698; http://clinicaltrials.gov/ct2/show/NCT00464698?term=NCT00464698&rank=1.

An Examination of Rostral Anterior Cingulate Cortex Function and Neurochemistry in Obsessive-Compulsive Disorder.

The anterior cingulate cortex is implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, few studies have examined functional and neurochemical abnormalities specifically in the rostral subdivision of the ACC (rACC) in OCD patients. We used functional magnetic resonance imaging (fMRI) during an emotional counting Stroop task and single-voxel J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) in the rACC to examine the function and neurochemistry of the rACC in individuals with OCD and comparison individuals without OCD. Between-group differences in rACC activation and glutamine/glutamate ratio (Gln/Glu), Glu, and Gln levels, as well as associations between rACC activation, Gln/Glu, Glu, Gln, behavioral, and clinical measures were examined using linear regression. In a sample of 30 participants with OCD and 29 age- and sex-matched participants without OCD, participants with OCD displayed significantly reduced rACC deactivation compared with those without OCD in response to OCD-specific words versus neutral words on the emotional counting Stroop task. However, Gln/Glu, Glu, and Gln in the rACC did not differ between groups nor was there an association between reduced rACC deactivation and Gln/Glu, Glu, or Gln in the OCD group. Taken together, these findings strengthen the evidence for rACC dysfunction in OCD, but weigh against an underlying association with abnormal rACC glutamatergic neurotransmission.

REDUCED DISGUST PROPENSITY IS ASSOCIATED WITH IMPROVEMENT IN CONTAMINATION/WASHING SYMPTOMS IN OBSESSIVE-COMPULSIVE DISORDER.

OBJECTIVES: Disgust is a well-established phenomenon with known neurobiological correlates. However, it remains unclear how or whether disgust changes with clinical treatment, because few longitudinal studies have tracked the association of disgust vulnerability and clinical symptoms in patient populations. METHODS: We assessed disgust propensity and symptoms of obsessive-compulsive disorder (OCD) in 134 patients receiving intensive residential treatment for OCD. Using linear regression with adjustment for age, sex, and depression severity, we tested the association between change in disgust propensity and change in OCD symptoms from admission to discharge. RESULTS: Change in disgust propensity was significantly associated with improvement in contamination/washing symptoms (ß = 0.25 [95% confidence interval: 0.11-0.39]; P = .001). No significant association was found between change in disgust propensity and change in other OCD symptom dimensions. CONCLUSIONS: In patients with OCD undergoing intensive residential treatment, disgust propensity appears to improve in parallel with contamination/washing symptoms.

Brain white matter integrity and association with age at onset in pediatric obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common and debilitating neuropsychiatric illness thought to involve abnormal connectivity of widespread brain networks, including frontal-striatal-thalamic circuits. At least half of OCD cases arise in childhood and their underlying neuropathology may differ at least in part from that of adult-onset OCD. Yet, only a few studies have examined brain white matter (WM) integrity in childhood-onset OCD using diffusion tensor imaging (DTI), and none have examined potential associations with age at onset. RESULTS: In this study, 17 youth with OCD and 19 healthy control subjects, ages 10 to 19 years, underwent DTI on a 3T Siemens scanner. DSM-IV diagnoses were established with standardized interviews, and OCD symptom severity was evaluated using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Voxel-wise analyses were conducted on data processed with tract-based spatial statistics (TBSS) to derive measures of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). OCD patients had significantly lower FA in seven WM clusters, with over 80% of significant voxels in bilateral frontal cortex and corpus callosum (CC). There were no regions of significantly higher FA in patients compared with controls. Patients also had significantly higher RD in right frontal cortex and right body of the CC. Earlier age at onset of OCD correlated significantly with lower FA in the right thalamus and with higher RD in the right CC. FA and RD were not significantly associated with symptom severity. CONCLUSIONS: These findings point to compromised WM integrity and reduced myelination in some brain regions of children with OCD, particularly the CC and fiber tracts that connect the frontal lobes to widespread cortical and subcortical targets. They also suggest that age at onset may be a moderator of some of the WM changes in pediatric OCD.

Intensive residential treatment for severe obsessive-compulsive disorder: characterizing treatment course and predictors of response.

BACKGROUND: Intensive residential treatment (IRT) is effective for severe, treatment-resistant obsessive-compulsive disorder (OCD). We sought to characterize predictors and course of response to IRT. METHODS: Admission, monthly, and discharge data were collected on individuals receiving IRT. We examined the association between baseline characteristics and percent change in OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) using linear regression. We compared baseline characteristics of IRT responders (≥35% reduction in Y-BOCS) versus non-responders, and of patients who did versus those who did not achieve wellness (Y-BOCS ≤ 12) using non-parametric tests. To examine the course of OCD severity over time, we used linear mixed-effects models with randomly varying intercepts and slopes. RESULTS: We evaluated 281 individuals admitted to an IRT program. Greater baseline Y-BOCS scores were associated with a significantly greater percent reduction in Y-BOCS scores (ß = -1.49 ([95% confidence interval: -2.06 to -0.93]; P < .001)). IRT responders showed significantly greater baseline Y-BOCS scores than non-responders (mean (SD) 28 (5.2) vs. 25.6 (5.8); P = .003) and lower past-year alcohol use scores than non-responders (1.4 (1.9) vs. 2.1 (2.2); P = .01). Participants who achieved wellness displayed lower hoarding factor scores than those who did not (5 (4.6) vs. 9.53 (6.3); P = .03). OCD symptoms declined rapidly over the first month but more slowly over the remaining two months. CONCLUSIONS: Higher baseline OCD severity, lower past-year alcohol use, and fewer hoarding symptoms predicted better response to IRT. IRT yielded an initial rapid reduction in OCD symptoms, followed by a slower decline after the first month.

DBT-enhanced cognitive-behavioral treatment for trichotillomania: A randomized controlled trial.

Background and aims Limited treatment options are available for trichotillomania (TTM) and most have modest outcomes. Suboptimal treatment results may be due to the failure of existing approaches to address all TTM styles. Methods Thirty-eight DSM-IV TTM participants were randomly assigned across two study sites to Dialectical Behavior Therapy (DBT) -enhanced cognitive-behavioral treatment (consisting of an 11-week acute treatment and 3-month maintenance treatment) or a minimal attention control (MAC) condition. MAC participants had active treatment after the 11-week control condition. Follow-up study assessments were conducted three and six months after the maintenance period. Results Open trial treatment resulted in significant improvement in TTM severity, emotion regulation (ER) capacity, experiential avoidance, anxiety and depression with changes generally maintained over time. In the randomized controlled trial, those with active treatment had greater improvement than those in the MAC condition for both TTM severity and ER capacity. Correlations between changes in TTM severity and ER capacity were not reported at post-treatment but did occur in maintenance and follow-up indicating reduced TTM severity with improved ER capacity. Conclusions DBT-enhanced cognitive-behavioral treatment is a promising treatment for TTM. Future studies should compare this approach to other credible treatment interventions and investigate the efficacy of this approach in more naturalistic samples with greater comorbidity.

DBT-enhanced habit reversal treatment for trichotillomania: 3-and 6-month follow-up results.

BACKGROUND: Maintenance of gains with cognitive-behavioral treatment for trichotillomania (TTM) has historically been problematic. METHODS: We conducted follow-up assessments 3 and 6 months after completion of a 3-month maintenance phase on 10 individuals with DSM-IV-TR TTM who participated in an open trial of a dialectical behavior therapy (DBT)-enhanced habit reversal treatment (HRT). RESULTS: Significant improvement from baseline was reported at 3-and 6-month follow-up on all measures of hair pulling severity and emotion regulation, although some worsening was reported on some measures from earlier study time points. At 6-month follow-up, five and four participants were full and partial responders, respectively. Significant correlations were reported at both follow-up time points between changes in hair pulling severity and emotion regulation capacity. CONCLUSIONS: DBT-enhanced HRT offers promise for improved long-term treatment results in TTM. Changes in TTM severity from baseline to 3-and 6-month follow-up is correlated with changes in emotion regulation capacity.

Depression in comorbid obsessive-compulsive disorder and posttraumatic stress disorder.

Previous findings suggested a unique role that depression symptoms might play in the comorbid relationship between obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). However, the nature of this role remains unclear. Thus, the current study examined ways in which OCD and PTSD symptoms vary as a function of depression, as well as the mediating role of depression in the OCD-PTSD relationship, in 104 individuals seeking treatment for refractory OCD. Findings revealed that depressed individuals in the treatment-refractory OCD sample report higher levels of overall obsessing and greater severity of PTSD. In addition, depression appeared to mediate the relation between OCD and PTSD. Implications of findings are discussed.

Double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant obsessive-compulsive disorder.

BACKGROUND: From 40% to 60% of obsessive-compulsive disorder (OCD) patients fail to tolerate or respond to selective serotonin reuptake inhibitors (SSRIs). Preclinical and neuroimaging studies have shown abnormally high glutamatergic concentrations in OCD patients and an association between decreased caudate glutamatergic concentrations and reduced OCD symptom severity after SSRI treatment. Topiramate inhibits glutamatergic conduction. METHOD: Thirty-six adult patients with DSM-IV-defined OCD were randomly assigned to topiramate (n = 18) and placebo (n = 18) groups in this 12-week, double-blind, placebo-controlled, parallel-groups trial. Subjects were taking the maximum SSRI dose they could tolerate for at least 12 weeks and their current dose for at least 6 weeks, which was maintained throughout the study. Primary outcome measures were changes in the Yale-Brown Obsessive Compulsive Scale (YBOCS) total score and compulsions and obsessions subscores. Patients were recruited and followed up between April 1, 2003, and April 13, 2006. RESULTS: Using mixed regression models (time [weeks] × treatment), we found a significant treatment effect on the YBOCS compulsions (P = .014) subscale, but not the obsessions (P = .99) subscale or the total score (P = .11). Over the 12-week trial, the topiramate group (mean endpoint dose = 177.8 ± 134.2 mg/d; range, 50-400 mg/d) showed an average linear decrease of 5.38 points on the compulsions subscale compared to 0.6 points in the placebo group. Thirteen topiramate and 14 placebo subjects completed the study. Topiramate was not well tolerated in this trial: 28% (5/18) of the subjects discontinued the drug for adverse effects, and 39% (7/18) had a dose reduction for this reason. CONCLUSIONS: The results of this first double-blind, placebo-controlled trial of topiramate augmentation for treatment-resistant OCD suggest that topiramate may be beneficial for compulsions, but not obsessions. Modifications in glutamatergic function may be responsible, at least in part, for the improved response in compulsions seen with topiramate. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00211744.

Latent class analysis of the Yale-Brown Obsessive-Compulsive Scale symptoms in obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous, and findings of underlying structure classification based on symptom grouping have been ambiguous to date. Variable-centered approaches, primarily factor analysis, have been used to identify homogeneous groups of symptoms; but person-centered latent methods have seen little use. This study was designed to uncover sets of homogeneous groupings within 1611 individuals with OCD based on symptoms. METHOD: Latent class analysis models using 61 obsessive-compulsive symptoms collected from the Yale-Brown Obsessive-Compulsive Scale were fit. Relationships between latent class membership and treatment response, sex, symptom severity, and comorbid tic disorders were tested for relationship to class membership. RESULTS: Latent class analysis models of best fit yielded 3 classes. Classes differed only in frequency of symptom endorsement. Classes with higher symptom endorsement were associated with earlier age of onset, being male, higher Yale-Brown Obsessive-Compulsive Scale symptom severity scores, and comorbid tic disorders. There were no differences in treatment response between classes. CONCLUSIONS: These results provide support for the validity of a single underlying latent OCD construct, in addition to the distinct symptom factors identified previously via factor analyses.

Cognitive inflexibility and frontal-cortical activation in pediatric obsessive-compulsive disorder.

OBJECTIVE: Deficits in cognitive flexibility and response inhibition have been linked to perturbations in cortico-striatal-thalamic circuitry in adult obsessive-compulsive disorder (OCD). Although similar cognitive deficits have been identified in pediatric OCD, few neuroimaging studies have been conducted to examine its neural correlates in the developing brain. In this study, we tested hypotheses regarding group differences in the behavioral and neural correlates of cognitive flexibility in a pediatric OCD and a healthy comparison (HC) sample. METHOD: In this functional magnetic resonance imaging (fMRI) study, a pediatric sample of 10- to 17-year-old subjects, 15 with OCD and 20 HC, completed a set-shifting task. The task, requiring an extradimensional shift to identify a target, examines cognitive flexibility. Within each block, the dimension (color or shape) that identified the target either alternated (i.e., mixed) or remained unchanged (i.e., repeated). RESULTS: Compared with the HC group, the OCD group tended to be slower to respond to trials within mixed blocks. Compared with the HC group, the OCD group exhibited less left inferior frontal gyrus/BA47 activation in the set-shifting contrast (i.e., HC > OCD, mixed versus repeated); only the HC group exhibited significant activation in this region. The correlation between set shifting-induced right caudate activation and shift cost (i.e., reaction time differential in response to mixed versus repeated trials) was significantly different between HC and OCD groups, in that we found a positive correlation in HC and a negative correlation in OCD. CONCLUSIONS: In pediatric OCD, less fronto-striatal activation may explain previously identified deficits in shifting cognitive sets.

Pilot trial of dialectical behavior therapy-enhanced habit reversal for trichotillomania.

BACKGROUND: Not all hair pullers improve acutely with cognitive-behavioral treatment (CBT) and few maintain their gains over time. METHODS: We conducted an open clinical trial of a new treatment that addresses affectively triggered pulling and emphasizes relapse prevention in addition to standard CBT approaches. Ten female participants satisfying DSM-IV criteria for trichotillomania (TTM) at two study sites received Dialectical Behavior Therapy (DBT)-enhanced CBT consisting of 11 weekly sessions and 4 maintenance sessions over the following 3 months. Independent assessors rated hair pulling impairment and global improvement at several study time points. Participants completed self-report measures of hair pulling severity and emotion regulation. RESULTS: Significant improvement in hair pulling severity and emotion regulation, as well as hair pulling impairment and anxiety and depressive symptoms, occurred during acute treatment and were maintained during the subsequent 3 months. Significant correlations were reported between changes in emotion regulation and hair pulling severity during both the acute treatment and maintenance phases. CONCLUSIONS: This study offers preliminary evidence for the efficacy of DBT-enhanced CBT for TTM and suggests the importance of addressing emotion regulation during TTM treatment.

Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder.

BACKGROUND: Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison (HC) subjects. However, the profile of amygdala activation in response to facial expressions in obsessive-compulsive disorder (OCD) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation [Cannistraro et al. (2004). Biological Psychiatry 56:916-920]. METHODS: In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N=12) and a HC sample (N=17) performed a gender discrimination task while viewing emotional faces (happy, fearful, disgusted) and neutral faces. RESULTS: Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. CONCLUSIONS: Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder specific.

Symptom dimensions in OCD: item-level factor analysis and heritability estimates.

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.

A single-blinded case-control study of memantine in severe obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common debilitating psychiatric illness that typically improves but does not remit with first-line medication and behavioral treatments. Serotonergic agents including selective serotonin reuptake inhibitors and clomipramine have provided the mainstay of OCD medication management for decades. Combined dopamine/serotonergic agents such as atypical antipsychotics are presently the only OCD-augmenting strategies proven effective via randomized controlled trials. Despite increasing evidence for a pathogenic role of glutamate in OCD, no controlled trials of glutamatergic augmenting agents have been reported. METHODS: An intent-to-treat sample included 44 subjects receiving standard treatment at the McLean/Massachusetts General Hospital Intensive Residential Treatment (IRT) program, 22 of whom also received memantine augmentation. Admission, monthly and discharge measures of OCD, depression, and psychosocial functioning were collected by raters blinded to augmentation status. Matched controls were selected based on sex, initial OCD severity, psychosocial functioning, and timing of admission. The Clinical Global Improvement Scale captured global clinical change. RESULTS: Mean (SD) Yale-Brown Obsessive Compulsive Scale score decreases were 7.2 (6.4) among the cases and 4.6 (5.9) among the matched controls, reflecting mean clinical improvement among the cases (27.0% decrease) but not the controls (16.5% decrease). Mean (SD) depression severity score decreases were 5.8 (9.5) among the cases and 4.7 (9.9) among the controls. Initial intrusive obsessions were significantly more severe among marked responders compared with limited response or nonresponse cases (4.4 vs 2.9; t = 2.15; P = 0.048). CONCLUSIONS: This study provides preliminary supportive evidence for the effectiveness of memantine as a glutamatergic augmenting agent in severe OCD. Future randomized double-blind placebo-controlled trials are warranted.

Long-term outcome following Intensive Residential Treatment of Obsessive-Compulsive Disorder.

BACKGROUND: IRT has been demonstrated as an effective treatment for severe, refractory OCD. METHODS: Consecutive IRT subjects were ascertained over a 12 month period (female N=26, male N=35). Psychometric measures were completed at admission and discharge from the McLean/MGH OCD Institute IRT, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory (BDI) and the Work and Social Adjustment Scale (WSA)(N=61). These measures were repeated at one (N=57), three (N=42) and six months (N=36) following discharge. This study was IRB approved. RESULTS: OCD mean severity did not significantly worsen from discharge to the one (17.4, SD 6.5), three (16.5, SD 7.4) or six month (16.2, SD 7.3) follow-up (p>0.25). Furthermore, the significant improvement from admission was maintained at each of the one (17.4, SD 6.5), three (16.5, SD 7.4) and six month (16.2, SD SD 7.3) follow-up time points (p<0.001). Relapsers were significantly more likely to be living alone following discharge (p=0.01), and were less likely to have comorbid illnesses (p=0.02). There were no significant differences found between study dropouts and completers with regards to YBOCS scores (P>0.47). CONCLUSION: In the first OCD IRT long-term follow-up study to date, findings have indicated that mean treatment gains were maintained at one, three, and six months post-discharge. This finding is important as it suggests that improvements of OCD severity were subsequently retained in home and work environments. Improvement of depression severity from admission was also maintained.

Four-factor structure of obsessive-compulsive disorder symptoms in children, adolescents, and adults.

OBJECTIVE: To determine whether the four-factor category-based obsessive-compulsive disorder (OCD) symptom structure from a previous confirmatory factor analysis (CFA) may be appropriately used in child, adolescent, and adult groups. Symptom dimensions are increasingly used as quantitative traits in genetic, neuroimaging, and treatment studies of OCD across all ages. Identification of a category-based OCD symptom dimension structure that is validated for use across child, adolescent, and adult age groups is necessary to guide ongoing translational research. METHOD: Four OCD samples comprising 356 individuals were divided into child, adolescent, and adult groups. The fit of the only CFA-defined four-factor model was compared across these independent age group samples. Multiple-group CFA using maximum likelihood estimation assessed adequacy of fit comparing unconstrained and measurement weight-constrained models. The fit of previous exploratory factor analysis-defined three- and five-factor models on adults was also examined using CFA. RESULTS: A four-factor solution provided adequate but imperfect fit across age groups, with comparable indices to the only previous OCD CFA: factor 1 (aggressive/sexual/religious/somatic/checking); factor 2 (symmetry/ordering/counting/repeating); factor 3 (contamination/cleaning), and factor 4 (hoarding). Models in which factor loadings were constrained and unconstrained across the three age groups yielded comparable model fit. Factors were highly correlated and were not mutually exclusive. The four-factor solution provided an improved fit to both three- and five-factor solutions using CFA across the three age groups. CONCLUSIONS: A four-factor, CFA-defined, category-based model of OCD symptom dimensions is adequate for use in children, adolescents, and adult age groups. The factor structure of this multiple age group sample has limitations and is imperfect, but current findings support the comparability of the defined latent OCD dimensions across age groups. Further work is needed to optimize a comprehensive symptom dimension model reflecting clinical heterogeneity for use in emergent translational studies.