Eva Real

Clinical implications of insight assessment in obsessive-compulsive disorder

Poor insight has been reported in 15% to 36% of patients with obsessive-compulsive disorder (OCD), but little is known about its clinical correlations. This study examines insight among patients with OCD using a standardized instrument, the Brown Assessment of Beliefs Scale, and analyzes its relationship with clinical factors. Insight was assessed in 132 patients with OCD, before and after pharmacologic treatment, using the Brown Assessment of Beliefs Scale. Differences between patients with good and poor insight on sociodemographic variables, OCD severity, comorbidity, and treatment response were studied. Stability of insight after pharmacologic treatment was also examined. Thirty-nine patients (29.5%) exhibited poor insight. They showed more depressive symptoms (P = .001) and personality disorders (P = .001), especially the schizotypal form, than did good insight subjects, but there were no significant differences in treatment response. Insight significantly improves after treatment (P < .001). Our results suggest that insight in OCD varies widely and constitutes a dynamic phenomenon that can improve after treatment and is influenced by clinical conditions such as affective status or personality.

Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response.

Background Deep brain stimulation (DBS) has been proposed as an alternative to ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive Disorder (OCD), although with partially discrepant results probably related to differences in anatomical targetting and stimulation conditions. We sought to determine the efficacy and tolerability of DBS in OCD and the existence of clinical predictors of response using meta-analysis. Methods We searched the literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and PsycINFO. We performed fixed and random-effect meta-analysis with score changes (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the primary-outcome measure, and the number of responders to treatment, quality of life and acceptability as secondary measures. Findings Thirty-one studies involving 116 subjects were identified. Eighty-three subjects were implanted in striatal areas—anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate—27 in the subthalamic nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. Better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. Five patients dropped out, but adverse effects were generally reported as mild, transient and reversible. Conclusions Our analysis confirms that DBS constitutes a valid alternative to lesional surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome.

Suicide in patients treated for obsessive–compulsive disorder: A prospective follow-up study

BACKGROUND To describe the occurrence of persistent suicidal ideation and suicide attempts in a sample of obsessive-compulsive patients followed-up prospectively during 1 to 6years, and to determine the existence of predictors of suicide behavior. METHOD Two hundred and eighteen outpatients with DSM-IV OCD, recruited from a specialized OCD Unit in Barcelona, Spain, between February 1998 and December 2007, were included in the study. Suicide ideation was assessed by item 3 of the Hamilton Depression Rating Scale. Suicide attempts were evaluated by the Beck Suicide Intent Scale. Patients with and without persistent suicidal thoughts and suicide attempters and non-attempters were compared on sociodemographic and clinical variables. A Cox proportional hazards regression analysis was used to estimate potential predictors of suicide. RESULTS Patients completed a mean follow-up period of treatment of 4.1years (SD: 1.7; range: 1-6years). During this period, eighteen patients (8.2%) reported persistent suicidal ideation, two patients (0.91%) committed suicide and 11 (5.0%) attempted suicide. Being unmarried, presenting higher basal scores in the HDRS, current or previous history of affective disorders and symmetry/ordering obsessions were independently associated with suicidal behaviors. LIMITATIONS Patients were recruited from a specialized OCD clinic and received exhaustive treatment. Influence of variables including social support, life events, hopelessness and substance abuse/dependence was not assessed. CONCLUSIONS Suicide behavior is not a highly common phenomenon in OCD, but it should not be disregarded, especially in unmarried patients, with comorbid depression and symmetry/ordering obsessions and compulsions, who appear to be at a greater risk for suicide acts.

Verbal and nonverbal memory processing in patients with obsessive-compulsive disorder: its relationship to clinical variables.

Memory deficits have been reported in several neuropsychological studies of obsessive-compulsive disorder (OCD). Dysfunction in nonverbal memory has been consistently reported, whereas findings on verbal memory are more heterogeneous. The authors studied 50 patients with OCD who were matched for sex, age, educational level, and hand dominance with 50 healthy controls (HC). Cognitive performance in both groups was assessed on verbal and nonverbal memory tasks, and several clinical variables were also assessed in the patient group. Patients with OCD showed a pattern of cognitive dysfunction with alterations in areas of nonverbal memory (recall and recognition), and verbal memory (learning and recall). Older age at onset of OCD was associated with poorer performance on verbal memory tasks. Low scores on some verbal memory tasks were associated with severity of OCD, and nonverbal memory was influenced by depressive symptoms. The study suggests the existence of dysfunction in the execution of verbal and nonverbal memory tasks in OCD; the influence of clinical variables depends on the specific neuropsychological function.

Amygdala activation and symptom dimensions in obsessive-compulsive disorder

BACKGROUND Despite knowledge of amygdala involvement in fear and anxiety, its contribution to the pathophysiology of obsessive-compulsive disorder (OCD) remains controversial. In the context of neuroimaging studies, it seems likely that the heterogeneity of the disorder might have contributed to a lack of consistent findings. AIMS To assess the influence of OCD symptom dimensions on amygdala responses to a well-validated emotional face-matching paradigm. METHOD Cross-sectional functional magnetic resonance imaging (fMRI) study of 67 patients with OCD and 67 age-, gender- and education-level matched healthy controls. RESULTS The severity of aggression/checking and sexual/religious symptom dimensions were significantly associated with heightened amygdala activation in those with OCD when responding to fearful faces, whereas no such correlations were seen for other symptom dimensions. CONCLUSIONS Amygdala functional alterations in OCD appear to be specifically modulated by symptom dimensions whose origins may be more closely linked to putative amygdala-centric processes, such as abnormal fear processing.

Enhanced brain responsiveness during active emotional face processing in obsessive compulsive disorder.

Abstract Objectives. The abnormal processing of emotional stimuli is common to a variety of psychiatric disorders. Specifically, patients with prominent anxiety symptoms generally overreact to emotional cues, which has been linked to increased amygdala activation. However, in OCD, enhanced responses are predominantly obtained using disease-specific stimuli and preferentially involve frontostriatal systems. Methods. We assessed 21 OCD patients and 21 healthy controls with fMRI during an emotional face-processing paradigm involving active response generation to test for alterations in both brain activation and task-induced functional connectivity of the frontal cortex, the amygdala and the fusiform face area. Results. OCD patients showed significantly greater activation of “face-processing” regions including the amygdala, fusiform gyrus and dorsolateral prefrontal cortex. The reciprocal connectivity between face-processing regions was enhanced in OCD. Importantly, we detected significant correlations between patients’ clinical symptom severity and both task-related region activation and network functional connectivity. Conclusions. The results suggest that OCD patients may show enhanced brain responsiveness during emotional face-processing when tasks involve active response generation. Our findings diverge from previously described alterations in anxiety disorders, as patients showed enhanced amygdala-prefrontal connectivity as opposed to negative reciprocal interaction. This pattern would appear to be disorder-specific and was significantly related to obsessive-compulsive symptom severity.

Genetic susceptibility to obsessive-compulsive hoarding: the contribution of neurotrophic tyrosine kinase receptor type 3 gene1

Recent work suggests that neurotrophic factors may contribute to the genetic susceptibility to obsessive–compulsive disorder (OCD). Among other clinical dimensions, the presence of hoarding obsessions and compulsions has been shown to be correlated with a number of clinical and neuroimaging findings, as well as with a different pattern of genetic inheritance. We used a linkage disequilibrium (LD)‐mapping approach to investigate whether neurotrophic tyrosine kinase receptor type 3 (NTRK3), the high‐affinity receptor of neurotrophin 3 (NT‐3), plays a role in increasing susceptibility to hoarding in OCD. We performed an association study of 52 tag single nucleotide polymorphisms (tagSNPs) covering the whole NTRK3 gene in a sample comprising 120 OCD patients and 342 controls. Single nucleotide polymorphism association and haplotype analysis were performed. Thirty‐six of our patients (30%) exhibited significant hoarding obsessions and compulsions. A significant association of two SNPs in the 3′ downstream region of NTRK3 gene and obsessive–compulsive hoarding was identified: rs1017412 [odds ratio (OR) = 2.16; P = 0.001] and rs7176429 (OR = 2.78; P = 0.0001), although only the latter remained significant after Bonferroni correction. Although the haplotype analysis did not show significant results, a more extended block of LD in the OCD hoarders with respect to the control group was observed, suggesting a lower haplotype diversity in these individuals. Our findings suggest that NTRK3 may contribute to the genetic susceptibility to hoarding in OCD and may constitute an interesting gene to focus on in studies of the genetic basis of obsessive–compulsive hoarding.

Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study

BACKGROUND The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD. METHOD A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed. RESULTS Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r - 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results. CONCLUSIONS OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.

A Brain-Derived Neurotrophic Factor Haplotype Is Associated with Therapeutic Response in Obsessive-Compulsive Disorder

BACKGROUND Several clinical and genetic studies have focused on the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of various mental disorders. Recent lines of evidence regarding the network hypothesis of treatment outcome point towards the involvement of BDNF variants in the pharmacologic response in mood disorders (MD). Furthermore, there is strong evidence of a role for the serotonergic system in the pathophysiology and treatment of OCD, and upregulation of BDNF has been observed with various classes of antidepressants, including selective serotonin reuptake inhibitors (SSRI). Thus, we hypothesized that the BDNF gene might also be associated with treatment outcome in OCD. METHODS We performed a single-marker and haplotype association study of eight tag single nucleotide polymorphisms in the BDNF genomic region and related this to pharmacologic response in a sample of 131 OCD patients. RESULTS We found an association for a haplotype containing two single nucleotide polymorphisms that have previously been reported to be associated with treatment outcome in MD (rs908867 and rs1491850). CONCLUSIONS Our results support the hypothesis that the BDNF gene is involved in the response to psychopharmacologic treatment even though these preliminary findings await replication in a follow-up sample.

The interaction between Comt and Bdnf variants influences obsessive-compulsive-related dysfunctional beliefs.

Cognitive models emphasize the importance of dysfunctional beliefs as overimportance/need to control thoughts, perfectionism, intolerance of uncertainty, responsibility, and overestimation of threat in obsessive-compulsive disorder (OCD). Twin studies suggest that these beliefs are significantly heritable, but candidate genes associated with them have not been analyzed. We genotyped the Val158Met in the COMT gene and Val66Met variant in the BDNF gene in 141 OCD patients and analyzed their single and interactive effects on the obsessive beliefs questionnaire (OBQ-44). Variability in dysfunctional beliefs was not affected by the COMT or BDNF genotype in isolation, but we detected a significant COMT×BDNF interaction effect on responsibility/overestimation of threat and overimportance/need to control thoughts scores. Subjects with the BDNF Met-present and the COMT Met-present genotype showed higher scores on responsibility/overestimation of threat. An interaction between dopaminergic and neurotrophic functional gene variants may influence dysfunctional beliefs hypothesized to contribute to the development of OCD.