Lower Ventromedial Prefrontal Cortex Glutamate Levels in Patients With Obsessive-Compulsive Disorder.

Background: Recent studies using magnetic resonance spectroscopy (1H-MRS) indicate that patients with obsessive-compulsive disorder (OCD) present abnormal levels of glutamate (Glu) and gamma aminobutyric acid (GABA) in the frontal and striatal regions of the brain. These abnormalities could be related to the hyperactivation observed in cortico-striatal circuits of patients with OCD. However, most of the previous 1H-MRS studies were not capable of differentiating the signal from metabolites that overlap in the spectrum, such as Glu and glutamine (Gln), and referred to the detected signal as the composite measure-Glx (sum of Glu and Gln). In this study, we used a two-dimensional JPRESS 1H-MRS sequence that allows the discrimination of overlapping metabolites by observing the differences in J-coupling, leading to higher accuracy in the quantification of all metabolites. Our objective was to identify possible alterations in the neurometabolism of OCD, focusing on Glu and GABA, which are key neurotransmitters in the brain that could provide insights into the underlying neurochemistry of a putative excitatory/inhibitory imbalance. Secondary analysis was performed including metabolites such as Gln, creatine (Cr), N-acetylaspartate, glutathione, choline, lactate, and myo-inositol. Methods: Fifty-nine patients with OCD and 42 healthy controls (HCs) underwent 3T 1H-MRS in the ventromedial prefrontal cortex (vmPFC, 30 × 25 × 25 mm3). Metabolites were quantified using ProFit (version 2.0) and Cr as a reference. Furthermore, Glu/GABA and Glu/Gln ratios were calculated. Generalized linear models (GLMs) were conducted using each metabolite as a dependent variable and age, sex, and gray matter fraction (fGM) as confounding factors. GLM analysis was also used to test for associations between clinical symptoms and neurometabolites. Results: The GLM analysis indicated lower levels of Glu/Cr in patients with OCD (z = 2.540; p = 0.011). No other comparisons reached significant differences between groups for all the metabolites studied. No associations between metabolites and clinical symptoms were detected. Conclusions: The decreased Glu/Cr concentrations in the vmPFC of patients with OCD indicate a neurochemical imbalance in the excitatory neurotransmission that could be associated with the neurobiology of the disease and may be relevant for the pathophysiology of OCD.

Cellular and Extracellular White Matter Abnormalities in Obsessive-Compulsive Disorder: A Diffusion Magnetic Resonance Imaging Study.

BACKGROUND: While previous studies have implicated white matter (WM) as a core pathology of obsessive-compulsive disorder (OCD), the underlying neurobiological processes remain elusive. This study used free-water (FW) imaging derived from diffusion magnetic resonance imaging to identify cellular and extracellular WM abnormalities in patients with OCD compared with control subjects. Next, we investigated the association between diffusion measures and clinical variables in patients. METHODS: We collected diffusion-weighted magnetic resonance imaging and clinical data from 83 patients with OCD (56 women/27 men, age 37.7 ± 10.6 years) and 52 control subjects (27 women/25 men, age 32.8 ± 11.5 years). Fractional anisotropy (FA), FA of cellular tissue, and extracellular FW maps were extracted and compared between patients and control subjects using tract-based spatial statistics and voxelwise comparison in FSL Randomise. Next, we correlated these WM measures with clinical variables (age of onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication. RESULTS: Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), lower FA of cellular tissue (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared with control subjects. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures. CONCLUSIONS: Our findings of widespread FA, FA of cellular tissue, and FW abnormalities suggest that OCD is associated with microstructural cellular and extracellular abnormalities beyond the corticostriatothalamocortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory.

Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder.

An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.

Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder.

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

Obsessive-Compulsive Personality Symptoms Predict Poorer Response to Gamma Ventral Capsulotomy for Intractable OCD.

Gamma ventral capsulotomy (GVC) is a radiosurgical procedure which aims to create lesions in the ventral part of the anterior limb of the internal capsule (ALIC). It has been used as a treatment option for patients with intractable obsessive-compulsive disorder (OCD) who do not respond to several first-line treatments attempts. However, changes in personality disorder symptoms after GVC have not been investigated. The aims of this study are to investigate changes in personality disorder symptoms after GVC and to search for baseline personality disorder symptoms that may predict clinical response to GVC. Fourteen treatment-intractable OCD patients who underwent GVC completed the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) at baseline and one year after the procedure. Wilcoxon signed-rank test was performed to investigate personality disorder symptom changes before and after surgery. Linear regression models were utilized to predict treatment response, using baseline personality disorder symptoms as independent variables. We did not observe any quantitative changes in personality disorder symptoms after GVC, compared with baseline. Higher severity of obsessive-compulsive personality disorder symptoms at baseline was correlated with worse treatment response after GVC for OCD (ß = -0.085, t-value = -2.52, p-value = 0.027). These findings advocate for the safety of the GVC procedure in this specific population of intractable OCD patients, in terms of personality disorder symptom changes. They also highlight the importance of taking into account the severity of obsessive-compulsive personality disorder symptoms when GVC is indicated for intractable OCD patients.

Personality measures after gamma ventral capsulotomy in intractable OCD.

BACKGROUND: Neurosurgeries such as gamma ventral capsulotomy (GVC) are an option for otherwise intractable obsessive-compulsive disorder (OCD) patients. In general, clinical and neuropsychological status both improve after GVC. However, its consequences on personality traits are not well-studied. The objective of this study was to investigate personality changes after one year of GVC in intractable OCD patients. METHODS: The personality assessment was conducted using the Revised NEO Personality Inventory (NEO PI-R) and Cloninger's Temperament and Character Inventory (TCI) in 14 intractable OCD patients before and one year after GVC. Comparisons of personality features between treatment responders (n=5) and non-responders (n=9) were performed. Multiple linear regression was also used for predicting changes in clinical and global functioning variables. RESULTS: Overall, no deleterious effect was found in personality after GVC. Responders had a reduction in neuroticism (p=0.043) and an increase in extraversion (p=0.043). No significant changes were observed in non-responders. Increases in novelty seeking and self-directedness, and decreases in persistence and cooperativiness predicted OCD symptom improvement. Similary, improvement in functioning was also predicted by hgher novelty seeking and self-directedness after GVC, whereas better functioning was also associated with lower reward dependence and cooperativeness after surgery. CONCLUSIONS: The pattern of changes in personality traits after GVC was generally towards that observed in nonclinical population, and does not raise safety concerns.

Lateral hypothalamic activity indicates hunger and satiety states in humans.

Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader-Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alpha-frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity.

ORBITOFRONTAL THICKNESS AS A MEASURE FOR TREATMENT RESPONSE PREDICTION IN OBSESSIVE-COMPULSIVE DISORDER.

BACKGROUND: Early prediction of treatment response could reduce exposure to ineffective treatments and optimize the use of medical resources. Neuroimaging techniques have been used to identify biomarkers that are predictive of outcomes. The aims of this study were to investigate orbitofrontal cortex (OFC) thickness as a potential morphometric biomarker to discriminate outcomes in obsessive-compulsive disorder (OCD) and then to reexamine this biomarker in an independent cohort METHODS: Using a logistic regression model based on the mean baseline thickness of subregions of the OFC, we estimated the probability of treatment response in 29 treatment-naïve OCD patients who participated in a clinical trial. That algorithm was then tested in an independent cohort of 12 patients with a confirmed diagnosis of refractory OCD RESULTS: Among the treatment-naïve OCD patients, measures of OFC thickness statistically significantly differentiated responders (n = 13) and nonresponders (n = 16), with an overall classification accuracy of ≈80%, a sensitivity of 77% (10/13), and a specificity of 81% (13/16). Of the refractory OCD patients in the second independent cohort, 67% were correctly classified as nonresponders. The most discriminative measures in the initial cohort of treatment-naïve patients were the thicknesses of the left and right medial OFC (P = .009 and P = .028, respectively) CONCLUSIONS: We found OFC thickness to be a strong predictor of treatment response in treatment-naïve OCD patients. Although there are not yet any brain imaging biomarkers with clinical utility, our results highlight the potential of these measures as tools for predicting treatment outcomes in OCD.

Destaques do VII international symposium of thrombosis and anticoagulation (ISTA) / Highlights of VII international symposium of thrombosis and anticoagulation (ISTA)

O VII Simpósio Internacional de Trombose e Anticoagulação (ISTA) foi realizado em São Paulo, SP, Brasil, nos dias 24 e 25 de outubro de 2014, tendo como principais propósitos a discussão e o compartilhamento de conhecimentos sobre os avanços recentes na abordagem diagnóstica e terapêutica de pacientes com distúrbios trombóticos, nas suas diversas formas de apresentação clínica. O programa científico deste simpósio foi cuidadosamente desenvolvido por líderes de três importantes institutos de pesquisa clínica: o Instituto Brasileiro de Pesquisa Clínica(BCRI), o Duke Clinical Research Institute (DCRI), e Instituto de Pesquisa do Hospital do Coração. Composto por dois dias de apresentações acadêmicas e discussão aberta, o simpósio teve como principal objetivo educar, motivar e inspirar os clínicos, cardiologistas, hematologistas, e outros médicos através de apresentações e discussões de aspectos práticos de condutas que envolvem síndromes relacionadas à trombose e suas respectivas terapias antitrombóticas. Estas atividades possibilitaram uma interação direta entre a plateia e o corpo de palestrantes, composto por médicos de grande experiência clínica e pelos médicos pesquisadores que desenvolveram os principais estudos publicados que guiam nossas condutas em situações relacionadas ao tema "trombose e anticoagulação". Este artigo resume os anais deste simpósio.

The VII International Symposium on Thrombosis and Anticoagulation (ISTA) was held in São Paulo, Brazil, on 24 and 25 October 2014, with the main objectives to discuss and share knowledge on recent advances in the diagnosis and management of patients with thrombotic disorders. The scientific program of this symposium was carefully developed by leaders of three major clinical research institutes: the Brazilian Institute of Clinical Research (BCRI), the Duke Clinical Research Institute from Duke University, and the Research Institute from Hospital do Coração. Comprising two days of academic presentations and open discussion, the symposium aimed to educate, motivate and inspire clinicians, cardiologists, hematologists, and other doctors through presentations and discussions of practical aspects in themes related to thrombosis and anticoagulation. These activities were presented by physicians of great clinical experience and who participated in the main publications that guide our approach on situations related to the theme "thrombosis and anticoagulation". This article summarizes the proceedings of this symposium.

Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients.

Gamma ventral capsulotomy (GVC) radiosurgery is intended to minimize side effects while maintaining the efficacy of traditional thermocoagulation techniques for the treatment of refractory obsessive-compulsive disorder (OCD). Neuropsychological outcomes are not clear based on previous studies and, therefore, we investigated the effects of GVC on cognitive and motor performance. A double-blind, randomized controlled trial (RCT) was conducted with 16 refractory OCD patients allocated to active treatment (n=8) and sham (n=8) groups. A comprehensive neuropsychological evaluation including intellectual functioning, attention, verbal and visuospatial learning and memory, visuospatial perception, inhibitory control, cognitive flexibility, and motor functioning was applied at baseline and one year after the procedure. Secondary analysis included all operated patients: eight from the active group, four from the sham group who were submitted to surgery after blind was broken, and five patients from a previous open pilot study (n=5), totaling 17 patients. In the RCT, visuospatial memory (VSM) performance significantly improved in the active group after GVC (p=0.008), and remained stable in the sham group. Considering all patients operated, there was no decline in cognitive or motor functioning after one year of follow-up. Our initial results after 1 year of follow-up suggests that GVC not only is a safe procedure in terms of neuropsychological functioning but in fact may actually improve certain neuropsychological domains, particularly VSM performance, in treatment refractory OCD patients.

Brain structural correlates of sensory phenomena in patients with obsessive-compulsive disorder.

BACKGROUND: Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, "just-right" perceptions, feelings of incompleteness, or "urge-only" phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive-compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. METHODS: We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. RESULTS: We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. LIMITATIONS: Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. CONCLUSION: We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.

Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial.

IMPORTANCE: Select cases of intractable obsessive-compulsive disorder (OCD) have undergone neurosurgical ablation for more than half a century. However, to our knowledge, there have been no randomized clinical trials of such procedures for the treatment of any psychiatric disorder. OBJECTIVE: To determine the efficacy and safety of a radiosurgery (gamma ventral capsulotomy [GVC]) for intractable OCD. DESIGN, SETTING, AND PARTICIPANTS: In a double-blind, placebo-controlled, randomized clinical trial, 16 patients with intractable OCD were randomized to active (n = 8) or sham (n = 8) GVC. Blinding was maintained for 12 months. After unblinding, sham-group patients were offered active GVC. INTERVENTIONS: Patients randomized to active GVC had 2 distinct isocenters on each side irradiated at the ventral border of the anterior limb of the internal capsule. The patients randomized to sham GVC received simulated radiosurgery using the same equipment. MAIN OUTCOMES AND MEASURES: Scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression-Improvement (CGI-I) Scale. Response was defined as a 35% or greater reduction in Y-BOCS severity and "improved" or "much improved" CGI-I ratings. RESULTS: Three of 8 patients randomized to active treatment responded at 12 months, while none of the 8 sham-GVC patients responded (absolute risk reduction, 0.375; 95% CI, 0.04-0.71). At 12 months, OCD symptom improvement was significantly higher in the active-GVC group than in the sham group (Y-BOCS, P = .046; Dimensional Y-BOCS, P = .01). At 54 months, 2 additional patients in the active group had become responders. Of the 4 sham-GVC patients who later received active GVC, 2 responded by post-GVC month 12. The most serious adverse event was an asymptomatic radiation-induced cyst in 1 patient. CONCLUSIONS AND RELEVANCE: Gamma ventral capsulotomy benefitted patients with otherwise intractable OCD and thus appears to be an alternative to deep-brain stimulation in selected cases. Given the risks inherent in any psychiatric neurosurgery, such procedures should be conducted at specialized centers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01004302.

Hoarding symptoms and prediction of poor response to limbic system surgery for treatment-refractory obsessive-compulsive disorder.

UNLABELLED: OBJECT.: Recent findings have suggested a correlation between obsessive-compulsive disorder (OCD) symptom dimensions and clinical outcome after limbic system surgery for treatment-refractory patients. Based on previous evidence that the hoarding dimension is associated with worse outcome in conventional treatments, and may have a neural substrate distinct from OCD, the authors examined a large sample of patients undergoing limbic surgery (40 with capsulotomy, 37 with cingulotomy) and investigated if symptom dimensions, in particular hoarding, could influence treatment outcome. METHODS: Data from 77 patients from 3 different research centers at São Paulo (n = 17), Boston (n = 37), and Stockholm (n = 23) were analyzed. Dimensional Yale-Brown Obsessive Compulsive Scale (Y-BOCS; São Paulo) or Y-BOCS Symptom Checklist scores (Boston and Stockholm) were used to code the presence of 4 well-established symptom dimensions: forbidden thoughts, contamination/cleaning, symmetry/order, and hoarding. Reductions in YBOCS scores determined clinical outcome. RESULTS: Mean Y-BOCS scores decreased 34.2% after surgery (95% CI 27.2%-41.3%), with a mean follow-up of 68.1 months. Patients with hoarding symptoms had a worse response to treatment (mean Y-BOCS decrease of 22.7% ± 25.9% vs 41.6% ± 32.2%, respectively; p = 0.006), with no significant effect of surgical modality (capsulotomy vs cingulotomy). Patients with forbidden thoughts apparently also had a worse response to treatment, but this effect was dependent upon the co-occurrence of the hoarding dimension. Only the negative influence of the hoarding dimension remained when an ANOVA model was performed, which also controlled for preoperative symptom severity. CONCLUSIONS: The presence of hoarding symptoms prior to surgery was associated with worse clinical outcome after the interventions. Patients with OCD under consideration for ablative surgery should be carefully screened for hoarding symptoms or comorbid hoarding disorder. For these patients, the potentially reduced benefits of surgery need to be carefully considered against potential risks.

Omega-3 fatty acid supplementation reduces resting heart rate of rats with epilepsy.

Since cardiovascular dysfunction may contribute to sudden unexpected death in epilepsy (SUDEP), the consumption of omega-3 fatty acids (omega-3 FAs) might be beneficial as an adjunctive therapy for SUDEP prevention. It is well recognized that omega-3 FAs exert positive effects on the cardiovascular system including heart rate (HR) reduction, a major risk factor to sudden death. Thus, we evaluated the effects of chronic supplementation of omega-3 FAs on the HR of rats with epilepsy. In agreement with our previous investigations, this study also showed that the HR of animals with epilepsy is higher than that of the control group. Quite interestingly, chronic supplementation with omega-3 FAs restored the HR of rats with epilepsy toward control values. In conclusion, although further investigations are still required, our preliminary results showed a potential preventive effect of omega-3 FA supplementation against SUDEP.

Highlights from the fifth international symposium of thrombosis and anticoagulation (ISTA V), October 18-19, 2012, Belo Horizonte, Minas Gerais, Brazil.

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Fifth International Symposium of Thrombosis and Anticoagulation was held in Belo Horizonte, Minas Gerais, Brazil, on October 18-19, 2012. This scientific program was developed by clinicians for clinicians and was promoted by three major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, and Hospital do Coração Research Institute. Comprising 2 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive-compulsive disorder.

Nearly one-third of patients with obsessive-compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naïve OCD patients randomized between trials of fluoxetine or CBT. Treatment-naïve OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetine's effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602.

A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis.

Autoimmunity has been associated with vitamin D deficiency and resistance, with gene polymorphisms related to vitamin D metabolism frequently described in affected patients. High doses of vitamin D3 may conceivably compensate for inherited resistance to its biological effects. This study aimed to assess the efficacy and safety of prolonged high-dose vitamin D3 treatment of patients with psoriasis and vitiligo. Nine patients with psoriasis and 16 patients with vitiligo received vitamin D3 35,000 IU once daily for six months in association with a low-calcium diet (avoiding dairy products and calcium-enriched foods like oat, rice or soya "milk") and hydration (minimum 2.5 L daily). All psoriasis patients were scored according to "Psoriasis Area and Severity Index" (PASI) at baseline and after treatment. Evaluation of clinical response of vitiligo patients required a quartile grading scale. All patients presented low vitamin D status (serum 25(OH)D3 ≤ 30 ng/mL) at baseline. After treatment 25(OH)D3 levels significantly increased (from 14.9 ± 7.4 to 106.3 ± 31.9 ng/mL and from 18.4 ± 8.9 to 132.5 ± 37.0 ng/mL) and PTH levels significantly decreased (from 57.8 ± 16.7 to 28.9 ± 8.2 pg/mL and from 55.3 ± 25.0 to 25.4 ± 10.7 pg/mL) in patients with psoriasis and vitiligo respectively. PTH and 25(OH)D3 serum concentrations correlated inversely. The PASI score significantly improved in all nine patients with psoriasis. Fourteen of 16 patients with vitiligo had 25-75% repigmentation. Serum urea, creatinine and calcium (total and ionized) did not change and urinary calcium excretion increased within the normal range. High-dose vitamin D3 therapy may be effective and safe for vitiligo and psoriasis patients.

Neuropsychological predictors of response to randomized treatment in obsessive-compulsive disorder.

OBJECTIVE: To identify neuropsychological predictors of treatment response to cognitive-behavioral therapy (CBT) and fluoxetine in treatment-naïve adults with obsessive-compulsive disorder (OCD). METHOD: Thirty-eight adult outpatients with OCD underwent neuropsychological assessment, including tasks of intellectual function, executive functioning and visual and verbal memory, before randomization to a 12-week clinical trial of either CBT or fluoxetine. Neuropsychological measures were used to identify predictors of treatment response in OCD. RESULTS: Neuropsychological measures that predicted a better treatment response to either CBT or fluoxetine were higher verbal IQ (Wechsler Abbreviated Scale of Intelligence) (p=0.008); higher verbal memory on the California Verbal Learning Test (p=0.710); shorter time to complete part D (Dots) (p<0.001), longer time to complete part W (Words) (p=0.025) and less errors on part C (Colors) (p<0.001) in the Victoria Stroop Test (VST). Fewer perseverations on the California Verbal Learning Test, a measure of mental flexibility, predicted better response to CBT, but worse response to fluoxetine (p=0.002). CONCLUSION: In general, OCD patients with better cognitive and executive abilities at baseline were more prone to respond to either CBT or fluoxetine. Our finding that neuropsychological measures of mental flexibility predicted response to treatment in opposite directions for CBT and fluoxetine suggests that OCD patients with different neuropsychological profiles may respond preferentially to one type of treatment versus the other. Further studies with larger samples of OCD patients are necessary to investigate the heuristic value of such findings in a clinical context.