Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review

Recently, the abuse of ketamine has soared. Therefore, it is of great importance to study its potential risks. The effects of prolonged ketamine on the brain can be observationally studied in chronic recreational users. We performed a systematic review of studies reporting functional and structural brain changes after repeated ketamine abuse. We searched the following electronic databases: Medline, Embase and PsycINFO We screened 11,438 records and 16 met inclusion criteria, totaling 440 chronic recreational ketamine users (2-9.7 years; mean use 2.4 g/day), 259 drug-free controls and 44 poly-drug controls. Long-term recreational ketamine use was associated with lower gray matter volume and less white matter integrity, lower functional thalamocortical and corticocortical connectivity. The observed differences in both structural and functional neuroanatomy between ketamine users and controls may explain some of its long-term cognitive and psychiatric side effects, such as memory impairment and executive functioning. Given the effect that long-term ketamine exposure may yield, an effort should be made to curb its abuse

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 T-1-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

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

Objective Higher 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. Method Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2,649 OCD patients and 2,774 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 preregistered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Results 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. Conclusion 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

Obsessive-compulsive symptoms and resting-state functional characteristics in pre-adolescent children from the general population

While functional brain characteristics of obsessive-compulsive disorder have been extensively studied, literature on network topology and subnetwork connectivity related to obsessive-compulsive symptoms (OCS) is sparse. Here we investigated the functional brain characteristics of OCS in children from the general population using a multiscale approach. Since we previously observed OCS-related differences in thalamus morphology, we also focused on the network participation of thalamic subregions. The study included 1701 participants (9–12 years) from the population-based Generation R study. OCS were measured using the Short Obsessive-Compulsive Disorder Screener. We studied the brain network at multiple scales: global network topology, subnetwork connectivity and network participation of thalamic nodes (pre-registration: https://osf.io/azr9c). Modularity, small-worldness and average participation coefficient were calculated on the global scale. We used a data-driven consensus community approach to extract a partition of five subnetworks involving thalamic subregions and calculate the within- and between-subnetwork functional connectivity and topology. Multiple linear regression models were fitted to model the relationship between OCS and functional brain measures. No significant associations were found when using our preregistered definition of probable OCS. However, post-hoc analyses showed that children endorsing at least one OCS (compared with controls) had higher modularity, lower connectivity between frontoparietal, limbic and visual networks as well as altered participation of the lateral prefrontal thalamus node. Our results suggest that network characteristics of OCS in children from the general population are partly symptom-specific and severity-dependent. Thorough assessment of symptom dimensions can deepen our understanding of OCS-related brain networks

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

Brain Morphology Associated With Obsessive-Compulsive Symptoms in 2,551 Children From the General Population

Objective: Obsessive-compulsive (OC) symptoms are common in the general population, but it is unclear whether subclinical OC symptoms and obsessive-compulsive disorder (OCD) are part of a neuroanatomical continuum. The goal of this study was to investigate the relation between OC symptoms and subcortical and cortical morphology in a population-based sample of children. Method: The study included 2,551 participants, aged 9–12 years, from the population-based Generation R Study. OC symptoms were measured using the 7-item caregiver-rated Short Obsessive-Compulsive Disorder Screener (SOCS). Structural (3T) magnetic resonance imaging scans were processed using FreeSurfer to study the thalamus and other subcortical volumes, intracranial volume, vertexwise cortical thickness, and surface area. We used linear regression models to investigate the association between OC symptoms and brain morphology. Emulating case-control studies from the literature, we compared children scoring above the clinical cutoff of the SOCS (probable OCD cases, n = 164) with matched children without symptoms. Results: Children with probable OCD had larger thalami compared with the control group (d 0.16, p = .044). Vertexwise analysis showed a positive association between OC symptoms and thickness of the right inferior parietal cortex, which disappeared after adjusting for total behavioral problems. SOCS scores correlated negatively with intracranial volume (B = −2444, p = .038). Conclusion: Children with probable OCD showed thalamus alterations similar to those previously reported in unmedicated children with OCD. OC symptoms showed a stronger association with total intracranial volume than regional brain measures. Longitudinal studies are needed to further elucidate similarities and distinctions between neural correlates of subclinical and clinical OC symptoms

Thalamic Subregions and Obsessive-Compulsive Symptoms in 2,500 Children From the General Population

Objective: Pediatric obsessive-compulsive disorder (OCD) and clinically relevant obsessive-compulsive symptoms in the general population are associated with increased thalamic volume. It is unknown whether this enlargement is explained by specific thalamic subregions. The relation between obsessive-compulsive symptoms and volume of thalamic subregions was investigated in a population-based sample of children. Method: Obsessive-compulsive symptoms were measured in children (9-12 years of age) from the Generation R Study using the Short Obsessive-Compulsive Disorder Screener (SOCS). Thalamic nuclei volumes were extracted from structural 3T magnetic resonance imaging scans using the ThalamicNuclei pipeline and regrouped into anterior, ventral, intralaminar/medial, lateral, and pulvinar subregions. Volumes were compared between children with symptoms above clinical cutoff (probable OCD cases, SOCS ≥ 6, n = 156) and matched children without symptoms (n = 156). Linear regression models were fitted to investigate the association between continuous SOCS score and subregional volume in the whole sample (N = 2500). Results: Children with probable OCD had larger ventral nuclei compared with children without symptoms (d = 0.25, p =.025, false discovery rate adjusted p =.126). SOCS score showed a negative association with pulvinar volume when accounting for overall thalamic volume (β = −0.057, p =.009, false discovery rate adjusted p =.09). However, these associations did not survive multiple testing correction. Conclusion: The results suggest that individual nuclei groups contribute in varying degrees to overall thalamic volume in children with probable OCD, although this did not survive multiple comparisons correction. Understanding the role of thalamic nuclei and their associated circuits in pediatric OCD could lead toward treatment strategies targeting these circuits

Structural assessment of thalamus morphology in brain disorders: A review and recommendation of thalamic nucleus segmentation and shape analysis

The thalamus is a central brain structure crucially involved in cognitive, emotional, sensory, and motor functions and is often reported to be involved in the pathophysiology of neurological and psychiatric disorders. The functional subdivision of the thalamus warrants morphological investigation on the level of individual subnuclei. In addition to volumetric measures, the investigation of other morphological features may give additional insights into thalamic morphology. For instance, shape features offer a higher spatial resolution by revealing small, regional differences that are left undetected in volumetric analyses. In this review, we discuss the benefits and limitations of recent advances in neuroimaging techniques to investigate thalamic morphology in vivo, leading to our proposed methodology. This methodology consists of available pipelines for volume and shape analysis, focussing on the morphological features of volume, thickness, and surface area. We demonstrate this combined approach in a Parkinson's disease cohort to illustrate their complementarity. Considering our findings, we recommend a combined methodology as it allows for more sensitive investigation of thalamic morphology in clinical populations

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