Euripides C. Miguel

Multicenter Voxel-Based Morphometry Mega-Analysis of Structural Brain Scans in Obsessive-Compulsive Disorder

OBJECTIVE Results from structural neuroimaging studies of obsessive-compulsive disorder (OCD) have been only partially consistent. The authors sought to assess regional gray and white matter volume differences between large samples of OCD patients and healthy comparison subjects and their relation with demographic and clinical variables. METHOD A multicenter voxel-based morphometry mega-analysis was performed on 1.5-T structural T1-weighted MRI scans derived from the International OCD Brain Imaging Consortium. Regional gray and white matter brain volumes were compared between 412 adult OCD patients and 368 healthy subjects. RESULTS Relative to healthy comparison subjects, OCD patients had significantly smaller volumes of frontal gray and white matter bilaterally, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula. Patients also showed greater cerebellar gray matter volume bilaterally compared with healthy subjects. Group differences in frontal gray and white matter volume were significant after correction for multiple comparisons. Additionally, group-by-age interactions were observed in the putamen, insula, and orbitofrontal cortex (indicating relative preservation of volume in patients compared with healthy subjects with increasing age) and in the temporal cortex bilaterally (indicating a relative loss of volume in patients compared with healthy subjects with increasing age). CONCLUSIONS These findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction.

Tourette's Disorder and Related Problems: A Review and Update

&NA; Tourettes disorder is a complex, multifaceted condition of neurological origin with psychiatric symptomatology characterized by multiple motor and vocal tics. It begins during childhood and has a waxing and waning course. Coexisting obsessive‐compulsive symptoms, attentional problems, and other behavioral features are common. Pathophysiology involves dysfunction in basal ganglia and related corticothalamic circuits. Many patients who present in clinical settings have mild to moderate symptoms and require only education, monitoring, and long‐term follow‐up. Those with more‐severe symptoms require treatment, typically including both pharmacotherapy and nonmedication approaches. In addition to traditional neuroleptic treatment, a variety of agents such as clonidine, serotonin‐reuptake inhibitors, and tricyclic antidepressants can be used. Further investigation is needed in a variety of areas, including longitudinal follow‐up studies of children, adolescents, and adults with Tourettes disorder; systematic investigation of psychiatric comorbidity and the heterogeneity of the disorder; clarification of the phenomenological similarities and differences between Tourettes disorder and obsessive‐compulsive disorder; and neuroimaging and neuropsychological studies of Tourettes disorder and related problems.

DBS for Obesity

Obesity is a chronic, progressive and prevalent disorder. Morbid obesity, in particular, is associated with numerous comorbidities and early mortality. In patients with morbid obesity, pharmacological and behavioral approaches often have limited results. Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects. In the last decades, deep brain stimulation (DBS) has been investigated as a neurosurgical modality to treat various neuropsychiatric disorders. In this article we review the rationale for selecting different brain targets, surgical results and future perspectives for the use of DBS in medically refractory obesity.

Coordinated brain development: exploring the synchrony between changes in grey and white matter during childhood maturation

Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7–14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.

Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways

Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein–protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10−8 per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions.

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

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

Comorbidity, age of onset and suicidality in obsessive–compulsive disorder (OCD): An international collaboration

OBJECTIVES To collate data from multiple obsessive-compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive-compulsive and related disorders. METHODS Researchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. RESULTS Data from 3711 adult patients with primary OCD came from Brazil (n=955), India (n=802), Italy (n=750), South Africa (n=565), Japan (n=322), Australia (n=219), and Spain (n=98). The most common current comorbid disorders were major depressive disorder (28.4%; n=1055), obsessive-compulsive personality disorder (24.5%, n=478), generalized anxiety disorder (19.3%, n=716), specific phobia (19.2%, n=714) and social phobia (18.5%, n=686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n=1874). OCD generally had an age of onset in late adolescence (mean=17.9years, SD=1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n=200) of patients with OCD and 9.0% (n=314) reported a lifetime history of suicide attempt. CONCLUSIONS In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.

NEUROPSYCHOLOGICAL PREDICTORS OF TREATMENT RESPONSE TO COGNITIVE BEHAVIORAL GROUP THERAPY IN OBSESSIVE-COMPULSIVE DISORDER.

The available research on the relationship between neuropsychological functioning and the therapeutic outcome of obsessive–compulsive disorder (OCD) has yielded inconsistent results. In this study, our aim was twofold. First, we sought to evaluate the effects of cognitive behavioral group therapy (CBGT) on neurocognitive functions in OCD patients. Second, we assessed the viability of neuropsychological test performance as a predictor of treatment response to CBGT.

Obsessive–compulsive symptoms in adults with rheumatic fever

DOI: 10.1111/j.1600-0447.2006.00806.xWe would appreciate the opportunity to further discussthe intriguing findings of Asbahr’s manuscript Obsessive–compulsive symptoms in adults with history of rheumaticfever, Sydenham’s chorea and type I diabetes mellitus: prelim-inary results (1). This research consists of an original inves-tigation of later development of obsessive–compulsivesymptoms (OCS) in adults who suffered from rheumaticfever (RF) in childhood (in the non-active phase of RF) withnegative findings suggesting that OCS are restricted to theactive phase of RF and do not seem to predispose theappearance of OCS in adulthood (1). These findings, however,contrast with several studies (2, 3) describing higher frequencyof OCS in patients with RF (with and without Sydenham’sChorea) in non-active phase of RF.Using a larger sample, blind interviews and the best estimatediagnosis (4) method, Alvarenga et al. (2) assessed 97 adultsfrom a heart disease out-patient clinic of the same academichospital (51 with non-active RF and 46 controls) and reportedincreased frequencies of OCS in RF (P

205 Tractography Characterizing Lesions Differentiating Responders to Stereotactic Capsulotomy for Obsessive-Compulsive Disorder.

INTRODUCTION: It has been increasingly recognized that the insular cortex plays an important role in frontotemporal epilepsy (FTE) in children. The insula, however, cannot properly by monitored with conventional subdural grids, and open surgical resection of the insula is technically difficult and often associated with significant morbidity. Stereotactically placed insular depth electrodes allow direct and comprehensive monitoring of this region, and can easily be replaced with a laser applicator for minimally invasive treatment via thermo-ablation.