Marta Subirà

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

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.

Stressful life events at onset of obsessive-compulsive disorder are associated with a distinct clinical pattern.

Background: Environmental stressors are considered to play an important role in the triggering of mental disorders such as obsessive–compulsive disorder (OCD). Although there is extensive literature on traumatic life events, little is known about the role of nontraumatic but nonetheless stressful life events (SLEs) in OCD. The aim of this study was to establish whether OCD preceded by an SLE presents a different clinical pattern compared to non‐SLE‐preceded OCD. Methods: We interviewed 412 OCD patients to assess both SLEs at onset of OCD and other clinical variables, including OCD symptom dimensions. Logistic regression was then applied to explore the relationship between clinical variables and OCD preceded by an SLE. Results: The SLE‐preceded OCD group showed a later onset of the disorder (OR = 1.04, P = .015), a history of complicated birth (OR = 5.54, P<.001), less family history of OCD (OR = 0.42, P = .014), and the presence of contamination/cleaning symptoms (OR = 1.99, P = .01). Conclusions: Patients with OCD onset close to an SLE and those without an SLE close to OCD onset show a distinct clinical pattern. Depression and Anxiety, 2011.

Brain structural alterations in obsessive-compulsive disorder patients with autogenous and reactive obsessions.

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n = 30) and reactive (n = 65) sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally), while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD.

Neural correlates of obsessive-compulsive related dysfunctional beliefs.

There have been few attempts to integrate neurobiological and cognitive models of obsessive-compulsive disorder (OCD), although this might constitute a key approach to clarify the complex etiology of the disorder. Our study aimed to explore the neural correlates underlying dysfunctional beliefs hypothesized by cognitive models to be involved in the development and maintenance of OCD. We obtained a high-resolution magnetic resonance image from fifty OCD patients and 30 healthy controls, and correlated them, voxel-wise, with the severity of OC-related dysfunctional beliefs assessed by the Obsessive Beliefs Questionnaire-44. In healthy controls, significant negative correlations were observed between anterior temporal lobe (ATL) volume and scores on perfectionism/intolerance of uncertainty and overimportance/need to control thoughts. No significant correlations between OBQ-44 domains and regional gray matter volumes were observed in OCD patients. A post-hoc region-of-interest analysis detected that the ATLs was bilaterally smaller in OCD patients. On splitting subjects into high- and low-belief subgroups, we observed that such brain structural differences between OCD patients and healthy controls were explained by significantly larger ATL volumes among healthy subjects from the low-belief subgroup. Our results suggest a significant correlation between OC-related dysfunctional beliefs and morphometric variability in the anterior temporal lobe, a brain structure related to socio-emotional processing. Future studies should address the interaction of these correlations with environmental factors to fully characterize the bases of OC-related dysfunctional beliefs and to advance in the integration of biological and cognitive models of OCD.

Interaction of SLC1A1 gene variants and life stress on pharmacological resistance in obsessive--compulsive disorder

Genetic and environmental factors seem to interact and influence both the onset and the course of obsessive–compulsive disorder (OCD), but the role of glutamate transporter variants (SLC1A1) in pharmacological resistance is not known. We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD. A single-marker association study of several single-nucleotide polymorphisms in the SLC1A1 genomic region was performed in a sample of 238 OCD patients. For the most strongly associated SNP (rs3087879), one copy of the risk allele increased the probability of higher treatment resistance (odds ratio=2.42; 95% confidence interval=1.39–4.21; P=0.0018), but only in OCD patients without life stress at onset of the disorder. These results suggest a gene-by-environment interaction effect on treatment resistance in OCD and strengthen the existing evidence of the role of the glutamatergic system in the phenomenology of OCD.

Predictive value of familiality, stressful life events and gender on the course of obsessive-compulsive disorder

BACKGROUND Familiality, stressful life events (SLE) and gender significantly affect the onset of obsessive-compulsive disorder (OCD). However, their combined impact on the probability of OCD chronicity is largely unknown. With the objective of clarifying their predictive value, we tested a model of interaction effects between these influences. METHODS A sample of 449 patients with OCD was systematically assessed for familial loading, exposure to stressful life events, gender and course of the disease at the OCD referral unit at Bellvitge University Hospital. Multiple ordinal logistic regression was used to test interaction models. RESULTS Familiality presented a main negative association with chronicity (OR=0.83, CI97.5%=0.70-0.98). This association was additively moderated by both exposure to SLE before onset and gender, and showed a positive slope among female patients not exposed to SLE before onset (Familiality*SLEbo: OR=0.69, CI97.5%=0.47-1; Familiality*gender: OR=1.30, CI97.5%=0.91-1.84). LIMITATIONS The findings are based on cross-sectional data. Assessment of course is based on a retrospective measure, which may imply the possibility of overestimation of chronicity. CONCLUSIONS The predictive value of familiality on the course of OCD is only partially informative as both SLEbo and gender modify the association. When other risk factors are included in the model, familiality may predict decreased chances of chronicity. The mediation effects identified could explain the discrepancies found in previous research on this topic. Increased chances of presenting a chronic course of OCD may be found in association with familial vulnerability among female patients not exposed to SLEbo.

Brain structural imaging correlates of olfactory dysfunction in obsessive-compulsive disorder.

Abstract Olfactory dysfunction has been described in obsessive–compulsive disorder (OCD). Brain regions involved in smell processing partially overlap with structures included in the neurobiological models of OCD, although no previous studies have analyzed the neuroanatomical correlates of olfactory dysfunction in this disorder. The aim of our study was to examine the association between regional gray matter volume, as assessed by a voxel-based morphometry analysis of magnetic resonance images (MRI), and olfactory function, as assessed by the Sniffin’ Sticks test (SST). Olfactory function was assessed in 19 OCD patients and 19 healthy volunteers. All participants were also scanned in a 1.5-T magnet to obtain T1-weighted anatomical MRIs, which were pre-processed and analyzed with SPM8. Three different correlation models were used to study the association between regional gray matter volumes and olfactory function in the domains assessed by the SST: detection threshold, discrimination, and identification. OCD patients showed a significant impairment in all the domains assessed by the SST. Voxel-based mapping revealed a positive association in healthy controls between detection threshold and the gray matter content of a left anterior cingulate cortex cluster. In OCD patients, a positive correlation was observed between identification errors and the gray matter volume of the left medial orbital gyrus. In a post hoc analysis, these two gray matter regions were shown to be enlarged in OCD patients. Our findings support the idea that olfactory dysfunction in OCD is associated with volumetric changes in brain areas typically implicated in the neurobiology of the disorder.

Basolateral amygdala-ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive-compulsive disorder.

Background Cognitive behavioural therapy (CBT), including exposure and ritual prevention, is a first-line treatment for obsessive–compulsive disorder (OCD), but few reliable predictors of CBT outcome have been identified. Based on research in animal models, we hypothesized that individual differences in basolateral amygdala–ventromedial prefrontal cortex (BLA–vmPFC) communication would predict CBT outcome in patients with OCD. Methods We investigated whether BLA–vmPFC resting-state functional connectivity (rs-fc) predicts CBT outcome in patients with OCD. We assessed BLA–vmPFC rs-fc in patients with OCD on a stable dose of a selective serotonin reuptake inhibitor who then received CBT and in healthy control participants. Results We included 73 patients with OCD and 84 healthy controls in our study. Decreased BLA–vmPFC rs-fc predicted a better CBT outcome in patients with OCD and was also detected in those with OCD compared with healthy participants. Additional analyses revealed that decreased BLA–vmPFC rs-fc uniquely characterized the patients with OCD who responded to CBT. Limitations We used a sample of convenience, and all patients were receiving pharmacological treatment for OCD. Conclusion In this large sample of patients with OCD, BLA–vmPFC functional connectivity predicted CBT outcome. These results suggest that future research should investigate the potential of BLA–vmPFC pathways to inform treatment selection for CBT across patients with OCD and anxiety disorders.

Brain structural correlates of obsessive–compulsive disorder with and without preceding stressful life events

Abstract Objectives There is growing evidence supporting a role for stressful life events (SLEs) at obsessive–compulsive disorder (OCD) onset, but neurobiological correlates of such effect are not known. We evaluated regional grey matter (GM) changes associated with the presence/absence of SLEs at OCD onset. Methods One hundred and twenty-four OCD patients and 112 healthy controls were recruited. Patients were split into two groups according to the presence (n = 56) or absence (n = 68) of SLEs at disorder’s onset. A structural magnetic resonance image was acquired for each participant and pre-processed with Statistical Parametric Mapping software (SPM8) to obtain a volume-modulated GM map. Between-group differences in sociodemographic, clinical and whole-brain regional GM volumes were assessed. Results SLEs were associated with female sex, later age at disorder’s onset, more contamination/cleaning and less hoarding symptoms. In comparison with controls, patients without SLEs showed GM volume increases in bilateral dorsal putamen and the central tegmental tract of the brainstem. By contrast, patients with SLEs showed specific GM volume increases in the right anterior cerebellum. Conclusions Our findings support the idea that neuroanatomical alterations of OCD patients partially depend on the presence of SLEs at disorder’s onset.