The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder.

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.

Mindfulness-Based Interventions for the Treatment of Substance and Behavioral Addictions: A Systematic Review.

BACKGROUND: Emotion (dys)regulation as well as the interventions for improving these difficulties are receiving a growing attention in the literature. The aim of the present paper was to conduct a systematic review about the efficacy of mindfulness-based interventions (MBIs) in both substance and behavioral addictions (BAs). METHOD: A literature search was conducted using Cochrane, PubMed, and Web of Science. Fifty-four randomized controlled trials published in English since 2009 to April 2017 were included into a narrative synthesis. RESULTS: Mindfulness-based interventions were applied in a wide range of addictions, including substance use disorders (from smoking to alcohol, among others) and BAs (namely, gambling disorder). These treatments were successful for reducing dependence, craving, and other addiction-related symptoms by also improving mood state and emotion dysregulation. The most commonly used MBI approaches were as follows: Mindfulness-Based Relapse Prevention, Mindfulness Training for Smokers, or Mindfulness-Oriented Recovery Enhancement, and the most frequent control group in the included studies was Treatment as Usual (TAU). The most effective approach was the combination of MBIs with TAU or other active treatments. However, there is a lack of studies showing the maintenance of the effect over time. Therefore, studies with longer follow-ups are needed. CONCLUSION: The revised literature shows support for the effectiveness of the MBIs. Future research should focus on longer follow-up assessments as well as on adolescence and young population, as they are a vulnerable population for developing problems associated with alcohol, drugs, or other addictions.

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis.

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 illness profile and developmental stage. To address these limitations, the authors conducted meta- and mega-analyses of data from OCD sites worldwide. METHOD: T1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta-analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors 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; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. CONCLUSIONS: The results indicate different patterns of subcortical abnormalities in pediatric and 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. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.

Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response.

BACKGROUND: Deep brain stimulation (DBS) has been proposed as an alternative to ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive Disorder (OCD), although with partially discrepant results probably related to differences in anatomical targetting and stimulation conditions. We sought to determine the efficacy and tolerability of DBS in OCD and the existence of clinical predictors of response using meta-analysis. METHODS: We searched the literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and PsycINFO. We performed fixed and random-effect meta-analysis with score changes (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the primary-outcome measure, and the number of responders to treatment, quality of life and acceptability as secondary measures. FINDINGS: Thirty-one studies involving 116 subjects were identified. Eighty-three subjects were implanted in striatal areas--anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate--27 in the subthalamic nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. Better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. Five patients dropped out, but adverse effects were generally reported as mild, transient and reversible. CONCLUSIONS: Our analysis confirms that DBS constitutes a valid alternative to lesional surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome.

Dynamic assessment of the right lateral frontal cortex response to painful stimulation.

The lateral surface of the right frontal lobe has a relevant role in modulating behavioral responses to aversive stimuli and may significantly influence pain experience. Imaging studies suggest that this modulatory role is multifaceted, but no studies have assessed the regional specialization of this cortex on the basis of its response dynamics during pain processing. We aimed to investigate functional specialization within the right lateral frontal cortex using a dynamic fMRI approach. Brain responses to a mechanical painful stimulus and a preceding anticipatory cue (auditory tone) were assessed in 25 healthy subjects. Functional data were decomposed into 15 sequential activation maps covering the full anticipation-painful stimulation cycle using a finite impulse response (FIR) analysis approach. Movie sequences showing the temporal evolution of brain activation illustrate the findings. A region involving premotor-prefrontal cortices was activated soon after the anticipatory cue and showed a significant correlation with both anterior cingulate cortex activation and subjective pain ratings. The frontal operculum also showed a significant anticipatory response, but the most robust activation followed painful stimulation onset and was strongly correlated with insula activation. The anterior prefrontal cortex showed full activation during late painful stimulation and was negatively correlated with pain unpleasantness. In conclusion, different elements within the right lateral frontal cortex showed distinct activation dynamics in response to painful stimulation, which would suggest relevant regional specialization during pain processing. These findings are congruent with the broad functional role of the right frontal cortex and its influence on crucial aspects of human behavior.