Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative.

BACKGROUND: Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2-3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. METHODS: We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. DISCUSSION: Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.

Skin Picking Disorder in a Woman with Polyarteritis Nodosa. Case Report. / Trastorno de excoriación en una mujer con panarteritis nudosa. Reporte de caso.

INTRODUCTION: Excoriation (skin picking) disorder is included in the DSM-5 in the obsessive compulsive and related disorders category. It is defined as the recurrent urge to touch, scratch, scrape, scrub, rub, squeeze, bite or dig in the skin, leading to skin lesions. It is a rare disorder (1.4-5.4% of the population) and occurs mainly in women. CASE REPORT: this article reports the case of a 31-year-old female patient, initially assessed by dermatology and orthopaedics for the presence of infected ulcerated lesions on her lower limbs, with other superficial lesions from scratching on her chest, arms, forearms, back and head. The patient also reported symptoms of anxiety, so was assessed by consultation-liaison psychiatry. DISCUSSION: skin picking, normal behaviour in mammals, becomes pathological from a psychiatric point of view when it is repetitive and persistent, as in the case of excoriation disorder. In view of the reported relationship with the obsessive-compulsive spectrum, use of selective serotonin reuptake inhibitors and cognitive behavioural therapy are recommended.

Caudate volume differences among treatment responders, non-responders and controls in children with obsessive-compulsive disorder.

Treatment response in obsessive-compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7-17 years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14 weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).

Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive-compulsive disorder.

Neurobiological models have provided consistent evidence of the involvement of cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.

Neuroanatomical features and its usefulness in classification of patients with PANDAS.

OBJECTIVE: An obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype. METHODS: Fourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA. RESULTS: The pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls. CONCLUSION: The results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.

Activation of cortical and striatal regions during the expression of a naturalistic compulsive-like behavior in the rabbit.

Nest building behavior in the pregnant rabbit (Oryctolagus cuniculus) can serve as a model for compulsions in obsessive compulsive disorder (OCD). Previous work showed that the "straw carrying" phase of nest building (during which the rabbit repeatedly collects straw in its mouth, carries it into the nest box and deposits it there, and then returns to collect more) is associated with increased c-FOS expression (a marker of neuronal activity) in the orbitofrontal, anterior cingulate, and piriform cortices. In the present study, we quantified c-FOS expression in the caudate and putamen, as well as in the primary motor, somatosensory, and prefrontal cortices of: (1) pregnant rabbits given straw (PREG + STRAW); pregnant rabbits not given straw (PREG); (3) estrous rabbits given straw (ESTROUS + STRAW); and (4) estrous rabbits not given straw (ESTROUS). We found that straw carrying was associated with increased c-FOS expression in the dorsal putamen, ventral caudate, primary motor cortex, and somatosensory cortex. Additionally, a correlational analysis of PREG + STRAW animals revealed that these regions, along with the premotor and prelimbic cortices, were significantly intercorrelated with respect to c-FOS expression, suggesting their "coactivation" during repetitive straw carrying. By contrast, behavioral interactions of non-pregnant (ESTROUS) rabbits with straw (e.g., sniffing, nibbling it) were associated with a distinct pattern of c-FOS expression that included the medial and ventral putamen. c-FOS expression in PREG + STRAW rabbits is similar to patterns of regional brain activity in OCD patients exposed to obsession-provoking stimuli, as well as to those observed in healthy human mothers responding to infant-associated stimuli.

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.

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.

Predicting obsessive-compulsive disorder severity combining neuroimaging and machine learning methods.

BACKGROUND: Recently, machine learning methods have been used to discriminate, on an individual basis, patients from healthy controls through brain structural magnetic resonance imaging (MRI). However, the application of these methods to predict the severity of psychiatric symptoms is less common. METHODS: Herein, support vector regression (SVR) was employed to evaluate whether gray matter volumes encompassing cortical-subcortical loops contain discriminative information to predict obsessive-compulsive disorder (OCD) symptom severity in 37 treatment-naïve adult OCD patients. RESULTS: The Pearson correlation coefficient between predicted and observed symptom severity scores was 0.49 (p=0.002) for total Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) and 0.44 (p=0.006) for total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The regions that contained the most discriminative information were the left medial orbitofrontal cortex and the left putamen for both scales. LIMITATIONS: Our sample is relatively small and our results must be replicated with independent and larger samples. CONCLUSIONS: These results indicate that machine learning methods such as SVR analysis may identify neurobiological markers to predict OCD symptom severity based on individual structural MRI datasets.

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.

Obsessive-compulsive symptom dimensions correlate to specific gray matter volumes in treatment-naïve patients.

BACKGROUND: Clinical and sociodemographic findings have supported that OCD is heterogeneous and composed of multiple potentially overlapping and stable symptom dimensions. Previous neuroimaging investigations have correlated different patterns of OCD dimension scores and gray matter (GM) volumes. Despite their relevant contribution, some methodological limitations, such as patient's previous medication intake, may have contributed to inconsistent findings. METHOD: Voxel-based morphometry was used to investigate correlations between regional GM volumes and symptom dimensions severity scores in a sample of 38 treatment-naïve OCD patients. Several standardized instruments were applied, including an interview exclusively developed for assessing symptom dimensions severity (DY-BOCS). RESULTS: Scores on the "aggression" dimension were positively correlated with GM volumes in lateral parietal cortex in both hemispheres and negatively correlated with bilateral insula, left putamen and left inferior OFC. Scores on the "sexual/religious" dimension were positively correlated with GM volumes within the right middle lateral OFC and right DLPFC and negatively correlated with bilateral ACC. Scores on the "hoarding" dimension were positively correlated with GM volumes in the left superior lateral OFC and negatively correlated in the right parahippocampal gyrus. No significant correlations between GM volumes and the "contamination" or "symmetry" dimensions were found. CONCLUSIONS: Building upon preexisting findings, our data with treatment-naïve OCD patients have demonstrated distinct GM substrates implicated in both cognitive and emotion processing across different OCS dimensions.

Gray matter volumes in obsessive-compulsive disorder before and after fluoxetine or cognitive-behavior therapy: a randomized clinical trial.

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n=38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n=36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n=26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n=13), whereas no significant GM volume changes were observed in CBT-treated patients (n=13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action.

Association between symptom severity and internal capsule volume in obsessive-compulsive disorder.

Neurobiological models support an involvement of white matter tracts in the pathophysiology of obsessive-compulsive disorder (OCD), but there has been little systematic evaluation of white matter volumes in OCD using magnetic resonance imaging (MRI). We investigated potential differences in the volume of the cingulum bundle (CB) and anterior limb of internal capsule (ALIC) in OCD patients (n=19) relative to asymptomatic control subjects (n=15). White matter volumes were assessed using a 1.5T MRI scanner. Between-group comparisons were carried out after spatial normalization and image segmentation using optimized voxel-based morphometry. Correlations between regional white matter volumes in OCD subjects and symptom severity ratings were also investigated. We found significant global white matter reductions in OCD patients compared to control subjects. The voxel-based search for regional abnormalities (with covariance for total white matter volumes) showed no specific white matter volume deficits in brain portions predicted a priori to be affected in OCD (CB and ALIC). However, large clusters of significant positive correlation with OCD severity scores were found bilaterally on the ALIC. These findings provide evidence of OCD-related ALIC abnormalities and suggest a connectivity dysfunction within frontal-striatal-thalamic-cortical circuits. Further studies are warranted to better define the role of such white matter alterations in the pathophysiology of OCD, and may provide clues for a more effectively targeting of neurosurgical treatments for OCD.

Structural magnetic resonance imaging in anxiety disorders: an update of research findings.

OBJECTIVE: The aim of the present report is to present a systematic and critical review of the more recent literature data about structural abnormalities detected by magnetic resonance in anxiety disorders. METHOD: A review of the literature in the last five years was conducted by a search of the Medline, Lilacs and SciELO indexing services using the following key words: "anxiety", "panic", "agoraphobia", "social anxiety", "posttraumatic" and "obsessive-compulsive", crossed one by one with "magnetic resonance", "voxel-based", "ROI" and "morphometry". RESULTS: We selected 134 articles and 41 of them were included in our review. Recent studies have shown significant morphological abnormalities in various brain regions of patients with anxiety disorders and healthy controls. Despite some apparently contradictory findings, perhaps reflecting the variability and limitations of the methodologies used, certain brain regions appear to be altered in a consistent and relatively specific manner in some anxiety disorders. These include the hippocampus and the anterior cingulate cortex in posttraumatic stress disorder and the orbitofrontal cortex in obsessive-compulsive disorder. CONCLUSIONS: The present review indicates that structural neuroimaging has contributed to a better understanding of the neurobiology of anxiety disorders. Further development of neuroimaging techniques, better sample standardization and the integration of data across neuroimaging modalities may extend progress in this area.

Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: a structural MRI pilot prospective study.

OBJECTIVE: The purpose of this study was to investigate regional structural abnormalities in the brains of five patients with refractory obsessive-compulsive disorder (OCD) submitted to gamma ventral capsulotomy. METHODS: We acquired morphometric magnetic resonance imaging (MRI) data before and after 1 year of radiosurgery using a 1.5-T MRI scanner. Images were spatially normalized and segmented using optimized voxel-based morphometry (VBM) methods. Voxelwise statistical comparisons between pre- and post-surgery MRI scans were performed using a general linear model. Findings in regions predicted a priori to show volumetric changes (orbitofrontal cortex, anterior cingulate gyrus, basal ganglia and thalamus) were reported as significant if surpassing a statistical threshold of p<0.001 (uncorrected for multiple comparisons). RESULTS: We detected a significant regional postoperative increase in gray matter volume in the right inferior frontal gyri (Brodmann area 47, BA47) when comparing all patients pre and postoperatively. CONCLUSIONS: Our results support the current theory of frontal-striatal-thalamic-cortical (FSTC) circuitry involvement in OCD pathogenesis. Gamma ventral capsulotomy is associated with neurobiological changes in the inferior orbitofrontal cortex in refractory OCD patients.

Structural magnetic ressonance imaging in anxiety disorders: an update of research findings: [review] / Ressonância magnética estrutural em transtornos de ansiedade: atualização dos achados de pesquisa: [revisão]

OBJECTIVE: The aim of the present report is to present a systematic and critical review of the more recent literature data about structural abnormalities detected by magnetic ressonance in anxiety disorders. METHOD: A review of the literature in the last five years was conducted by a search of the Medline, Lilacs and SciELO indexing services using the following key words: "anxiety", "panic", "agoraphobia", "social anxiety", "posttraumatic" and "obsessive-compulsive", crossed one by one with "magnetic resonance", "voxel-based", "ROI" and "morphometry". RESULTS: We selected 134 articles and 41 of them were included in our review. Recent studies have shown significant morphological abnormalities in various brain regions of patients with anxiety disorders and healthy controls. Despite some apparently contradictory findings, perhaps reflecting the variability and limitations of the methodologies used, certain brain regions appear to be altered in a consistent and relatively specific manner in some anxiety disorders. These include the hippocampus and the anterior cingulate cortex in posttraumatic stress disorder and the orbitofrontal cortex in obsessive-compulsive disorder. CONCLUSIONS: The present review indicates that structural neuroimaging has contributed to a better understanding of the neurobiology of anxiety disorders. Further development of neuroimaging techniques, better sample standardization and the integration of data across neuroimaging modalities may extend progress in this area.

OBJETIVO: Apresentar uma revisão sistemática e crítica dos achados mais recentes da literatura em relação a alterações estruturais avaliados por ressonância magnética nos transtornos de ansiedade. MÉTODO: Uma revisão da literatura dos últimos cinco anos foi realizada utilizando uma busca nos indexadores Medline, Lilacs e SciELO utilizando as seguintes palavras-chave: "anxiety", "panic", "agoraphobia", "social anxiety", "posttraumatic" e "obsessive-compulsive" cruzadas uma a uma com "magnetic ressonance", "voxel-based", "ROI" e "morphometry". RESULTADOS: Foram selecionados 134 artigos, sendo 41 foram incluídos nesta revisão. Estudos recentes mostram alterações morfológicas significativas entre os pacientes com transtorno de ansiedade e os controles saudáveis em várias regiões cerebrais. Apesar de achados contraditórios, sobretudo devido à variabilidade e às limitações nas metodologias utilizadas, algumas estruturas aparecem alteradas de forma mais consistente e relativamente específica em alguns transtornos de ansiedade, como o hipocampo e o córtex cingulado anterior no transtorno de estresse pós-traumático e o córtex orbitofrontal no transtorno obsessivo-compulsivo. CONCLUSÕES: A presente revisão aponta que a neuroimagem estrutural pode ser utilizada na busca de uma maior compreensão da neurobiologia dos transtornos de ansiedade. É possível que o rápido avanço das técnicas de neuroimagem, uma maior padronização das amostras e a associação de dados de diferentes modalidades permitam um maior entendimento deste cenário.

The Wernicke-Kleist-Leonhard "short-circuiting": a missing link between attention deficit hyperactivity disorder, Tourette syndrome, and obsessive-compulsive disorder?

According to the Wernicke-Kleist-Leonhard (WKL) School of Psychiatry, human actions could be categorized into spontaneous, expressive, reflex, and reactive. The so-called short-circuit movements represent a pathological exaggeration of immediate reactions to sensory impressions, such as sudden or threatening stimuli. "Short-circuiting" was deemed of utmost importance for the diagnoses of several WKL endogenous psychoses, such as hyperkinetic motility psychosis, periodic catatonia, and proskinetic catatonia. We suggest that short-circuit movements may be an under-reported behavioral phenotype that may cut across different phenotypes of non-psychotic DSM-IV-TR disorders, such as attention deficit hyperactivity disorder (ADHD), Tourette's syndrome (TS), and obsessive-compulsive disorder (OCD). Several features of a neuropsychiatric syndrome seen in the coarse frontal lobe disease ("complex psychomotor release phenomena") may provide a neurological working model for "short-circuiting" in ADHD, TS, and OCD. Further, short-circuit movements may be associated with different degrees of serotonergic, dopaminergic, and glutamatergic dysfunctions. Indeed, although there are a growing number of studies reporting successful treatment of short-circuit movements with topiramate and other glutamatergic antagonists, treatment response to drugs based on serotonergic or dopaminergic mechanisms of action is more uncertain and, sometimes, detrimental, leading to an aggravation of pathological behavior. A resurgence of the interest on the descriptive psychopathology of the WKL short-circuit movements could provide a new conceptual framework for the studies on the neurobiology of volitional disorders.

Neuromodulation of the inferior thalamic peduncle for major depression and obsessive compulsive disorder.

Neuromodulation of the inferior thalamic peduncle is a new surgical treatment for major depression and obsessive-compulsive disorder. The inferior thalamic peduncle is a bundle of fibers connecting the orbito-frontal cortex with the non-specific thalamic system in a small area behind the fornix and anterior to the polar reticular thalamic nucleus. Electrical stimulation elicits characteristic frontal cortical responses (recruiting responses and direct current (DC)-shift) that confirm correct localization of this anatomical structure. A female with depression for 23 years and a male with obsessive-compulsive disorder for 9 years had stereotactic implantation of electrodes in the inferior thalamic peduncle and were evaluated over a long-term period. Initial OFF stimulation period (1 month) showed no consistent changes in the Hamilton Depression Scale (HAM-D), Yale Brown Obsessive Compulsive Scale (YBOCS), or Global Assessment of Functioning scale (GAF). The ON stimulation period (3-5 V, 130-Hz frequency, 450-msec pulse width in a continuous program) showed significant decrease in depression, obsession, and compulsion symptoms. GAF improved significantly in both cases. The neuropsychological tests battery showed no significant changes except from a reduction in the perseverative response of the obsessive-compulsive patient and better performance in manual praxias of the female depressive patient. Moderate increase in weight (5 kg on average) was observed in both cases.

Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have investigated the presence of brain abnormalities in obsessive-compulsive disorder (OCD) but have not produced consistent findings. This might be partly related to their use of a regions-of-interest approach. We assessed gray matter volumes in 19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM). METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with optimized VBM. Statistical comparisons were performed with the general linear model. RESULTS: Significant findings were detected in regions predicted a priori to be implicated in OCD, including increased gray matter in OCD subjects relative to control subjects in posterior orbitofrontal and parahippocampal regions; decreased gray matter in OCD patients in the left anterior cingulate cortex; and inverse correlations between obsessive-compulsive symptom severity and gray matter in the medial thalamus (p < .001, uncorrected for multiple comparisons). Also, an unpredicted site of gray matter reduction in OCD patients in the right parietal associative cortex approached significance (p = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are consistent with previous studies implicating dysfunction of orbitofrontal, cingulate, thalamic, and temporolimbic regions in OCD and suggest that the involvement of the parietal cortex in the pathophysiology of OCD warrants further investigation.

Impact of age at onset and duration of illness on the expression of comorbidities in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) patients usually experience comorbidities including tics, trichotillomania, body dysmorphic disorder, and mood and anxiety disorders. The present report verifies how age at onset of obsessive-compulsive symptoms and duration of illness are associated with comorbid diagnoses in OCD patients. METHOD: Psychiatric comorbidity was assessed using a structured clinical interview in 161 consecutive outpatients referred for treatment between 1996 and 2001 who met DSM-IV criteria for OCD. Age at onset and duration of illness were retrospectively assessed by direct interviews. RESULTS: An earlier age at onset of obsessive-compulsive symptoms was associated with tic disorders, while longer illness duration was associated with depressive disorder (major depressive disorder or dysthymia) and social phobia. CONCLUSION: Age at onset and duration of OCD illness are meaningful variables affecting the expression of comorbidities in OCD. Tic disorders and OCD may share common etiologic pathways. Depressive disorders, in contrast, may be secondary complications of OCD.