No abstract

Objective-Structural brain imaging studies in Obsessive-Compulsive Disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in disease profile and developmental stage.Methods-To address these limitations, we conducted a meta-and mega-analysis of data from OCD sites worldwide. T 1 images from 1,830 OCD patients and 1,759 controls were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ in OCD patients and healthy controls. We additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients.Results-The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=−0.13; p=5.1x10 −3 , % difference −2.80) and larger pallidum volumes (d=0.16; p=1.6x10 −3 , % difference 3.16) compared to adult controls. Both effects were stronger in medicated patients compared to controls (d=−0.29; p=2.4x10 −5 , % difference −4.18 and d=0.29; p=1.2x10 −5 , % difference 4.38, respectively). Unmedicated pediatric patients had larger thalamic volumes (d=0.38, p=2.1x10 −3 ) compared to pediatric controls. None of these findings were mediated by sample characteristics such as mean age or field strength. Overall the mega-analysis yielded similar results. Conclusion-Our study indicates a different pattern of subcortical abnormalities in pediatric versus adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. This highlights the potential importance of neurodevelopmental alterations in OCD, and suggests that further research on neuroplasticity in OCD may be useful. IntroductionObsessive-compulsive disorder (OCD) is a neurodevelopmental disorder that affects 1-3% of the population (1; 2). In more than 50% of all OCD cases, symptoms emerge during Location of work and address for reprints: Premika S.W. Boedhoe, M.Sc.,

Event-related potential (ERP) studies identified the error-related negativity (Ne/ERN) and the error positivity (Pe) to be associated with performance errors. However, the functional significance of these components is not yet resolved. With the present study we intended to further investigate to what extent these components are related to error awareness. ERPs were recorded during an antisaccade task, and error awareness was obtained from accuracy ratings on each trial. In accordance with earlier findings, aware and unaware errors did not differ in Ne/ERN amplitude. Whereas the late Pe (400-600 ms) shows an increased parietal positivity for aware compared with unaware errors, the early Pe (200-300 ms) shows no dissociation between aware and unaware errors. These data lend further support to the view that the Ne/ERN and the (late) Pe reflect different processes in performance monitoring. In fact the present results provide a clear replication of [S. Nieuwenhuis et al. (2001) Psychophysiology, 38, 752-760], showing that the Pe is associated with error awareness and remedial action. Furthermore, it has been shown that this is only true for the late Pe, whereas the early Pe like the Ne/ERN is not modulated by error awareness.

Thyroid hormones (TH) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence THs synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programming of brain development, with implications for early identification of risk, primary prevention and intervention.

The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.

No abstract

Increased error-related brain potentials were observed not only in OCD patients but also in unaffected first-degree relatives. Overactive error monitoring may reflect a trait marker for OCD that is independent of the presence of clinical symptoms. Thus, enhanced error-related brain activity represents a candidate neurocognitive endophenotype for OCD.

No abstract