ORCID Profile
0000-0002-7699-2582
Current Organisations
Erasmus Universiteit Rotterdam
,
Universiteit van Amsterdam
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Publisher: Cold Spring Harbor Laboratory
Date: 23-01-2020
DOI: 10.1101/2020.01.17.20016873
Abstract: The search for neuroimaging biomarkers of alcohol use disorder (AUD) has primarily been restricted to significance testing in small datasets of low ersity. To identify neurobiological markers beyond in idual differences, it may be useful to develop classification models for AUD. The ever-increasing quantity of neuroimaging data demands methods that are robust to the complexities of multi-site designs and are generalizable to data from new scanners. This study represents a mega-analysis of previously published datasets from 2,034 AUD and comparison participants spanning 27 sites, coordinated by the ENIGMA Addiction Working Group. Data were grouped into a training set including 1,652 participants (692 AUD, 24 sites), and test set with 382 participants (146 AUD, 3 sites). A battery of machine learning classifiers was evaluated using repeated random cross-validation (CV) and leave-site-out CV. Area under the receiver operating characteristic curve (AUC) was our base metric of performance. Multi-objective evolutionary search was conducted to identify sparse, generalizable, and high performing subsets of brain measurements. Cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume, appeared most frequently across searches. Restricting a regularized logistic regression model to these four features yielded a test-set AUC of .768. Developing classification models on multi-site data with varied underlying class distributions poses unique challenges. Supplementing datasets with controls from new sites and performing feature selection increases generalizability. Four features identified by evolutionary search may serve as specific biomarkers for in iduals with current AUD.
Publisher: Springer Science and Business Media LLC
Date: 08-06-2013
DOI: 10.1007/S10899-013-9389-2
Abstract: Problem gambling represents a significant public health problem, however, research on effective gambling harm-minimisation measures lags behind other fields, including other addictive disorders. In recognition of the need for consistency between international jurisdictions and the importance of basing policy on empirical evidence, international conventions exist for policy on alcohol, tobacco, and illegal substances. This paper examines the evidence of best practice policies to provide recommendations for international guidelines for harm-minimisation policy for gambling, including specific consideration of the specific requirements for policies on Internet gambling. Evidence indicates that many of the public health policies implemented for addictive substances can be adapted to address gambling-related harms. Specifically, a minimum legal age of at least 18 for gambling participation, licensing of gambling venues and activities with responsible gambling and consumer protection strategies mandated, and brief interventions should be available for those at-risk for and experiencing gambling-related problems. However, there is mixed evidence on the effectiveness of limits on opening hours and gambling venue density and increased taxation to minimise harms. Given increases in trade globalisation and particularly the global nature of Internet gambling, it is recommended that jurisdictions take actions to harmonise gambling public health policies.
Publisher: SAGE Publications
Date: 25-07-2017
Abstract: Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippoc us in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippoc al volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. Twenty heavy cannabis users (mean age 21 years, range 18–24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippoc al volume estimates were obtained from manual tracing the hippoc us on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. Compared to controls, cannabis users did not show hippoc al volume alterations at either baseline or follow-up. Hippoc al volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippoc al volumes. Continued heavy cannabis use did not affect hippoc al neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in s les of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippoc al neuroanatomy.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2021
DOI: 10.1038/S41398-021-01204-1
Abstract: Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippoc al and amygdala subregions in a large s le of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippoc us and its CA1 and subiculum subfield volumes in both males and females. In summary, hippoc al and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.
Publisher: Wiley
Date: 06-09-2022
DOI: 10.1111/ADD.16033
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.EURONEURO.2018.11.1110
Abstract: Cannabis exerts its psychoactive effect through cannabinoid receptors that are widely distributed across the cortical surface of the human brain. It is suggested that cannabis use may contribute to structural alterations across the cortical surface. In a large, multisite dataset of 120 controls and 141 cannabis users, we examined whether differences in key characteristics of the cortical surface - including cortical thickness, surface area, and gyrification index were related to cannabis use characteristics, including (i) cannabis use vs. non-use, (ii) cannabis dependence vs. non-dependence vs. non-use, and (iii) early adolescent vs. late adolescent onset of cannabis use vs. non-use. Our results revealed that cortical morphology was not associated with cannabis use, dependence, or onset age. The lack of effect of regular cannabis use, including problematic use, on cortical structure in our study is contrary to previous evidence of cortical morphological alterations (particularly in relation to cannabis dependence and cannabis onset age) in cannabis users. Careful reevaluation of the evidence on cannabis-related harm will be necessary to address concerns surrounding the long-term effects of cannabis use and inform policies in a changing cannabis regulation climate.
Publisher: Proceedings of the National Academy of Sciences
Date: 15-05-2018
Abstract: Left–right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population and how biological factors such as age, sex, and genetic variation affect these asymmetries. Here, we describe by far the largest-ever study of cerebral cortical asymmetry, based on data from 17,141 participants. We found a global anterior–posterior “torque” pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an online resource that will serve future studies of human brain anatomy in health and disease.
Publisher: Elsevier
Date: 2016
Publisher: Center for Open Science
Date: 05-09-2023
Publisher: Wiley
Date: 16-10-2020
DOI: 10.1002/HBM.25248
Abstract: To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega‐analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case‐ and control‐only sites led to the inadvertent learning of site‐effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary‐based feature selection leveraging leave‐one‐site‐out cross‐validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test‐set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi‐site data with varied underlying class distributions and identify potential biomarkers for in iduals with current AD.
Publisher: Frontiers Media SA
Date: 10-05-2016
Publisher: Bentham Science Publishers Ltd.
Date: 2016
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.ADDBEH.2013.08.011
Abstract: One of the characteristics of people suffering from addictive behaviors is the tendency to be distracted by drug cues. This attentional bias for drug cues is thought to lead to increased craving and drug use, and may draw in iduals into a vicious cycle of drug addiction. In the current study we developed a Dutch version of the cannabis Stroop task and measured attentional bias for cannabis words in a group of heavy cannabis users and matched controls. The classical Stroop task was used as a global measure of cognitive control and we examined the relationship between cognitive control, cannabis-related problems, cannabis craving and cannabis attentional bias. Using our version of the cannabis Stroop task, a group of heavy cannabis users showed attentional bias to cannabis words, whereas a control group of non-users did not. Furthermore, within the group of cannabis users, those who were clinically recognized as dependent showed a stronger attentional bias than the heavy, non-dependent users. Cannabis users who displayed reduced cognitive control (as measured with the classical Stroop task) showed increased session-induced craving. Contrary to expectations, however, cognitive control did not appear to modulate the relationship between attentional bias to cannabis words (cannabis Stroop task) and cannabis dependence. This study confirmed the relationship between cannabis dependence and attentional bias and extends this by highlighting a moderating role for cognitive control, which may make some more vulnerable to craving.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000327682
Abstract: Relapse is the rule rather than the exception in smokers aiming to quit smoking. Recently, evidence has emerged that glutamate transmission plays an important role in relapse. N-acetylcysteine (NAC), a cysteine prodrug, restores glutamate homeostasis and appears to be a potential new treatment for substance dependence. In the current pilot study, the effects of NAC on short-term abstinence of smoking were investigated. Subjects were heavy smokers randomized to receive placebo (n = 12) or NAC 3,600 mg/day (n = 10) in a double-blind fashion during 3.5 days. Subjects were asked to stop smoking and report on nicotine craving, nicotine withdrawal symptoms, and cigarette smoking during treatment. At the end of the treatment, subjects were invited to smoke a cigarette and to rate the rewarding effect of this cigarette. There was no significant effect of NAC on craving (p = 0.23, i d /i = 0.52) and only a statistical trend towards fewer withdrawal symptoms in the NAC condition (p = 0.07, i d /i = 0.80). Interestingly, subjects receiving NAC rated the first cigarette after the abstinence period of 3.5 days as significantly less rewarding than subjects on placebo (p = 0.04, i d /i = 0.85). It is concluded that the results of this pilot study are encouraging and suggest that NAC might be a promising new treatment option for relapse prevention in nicotine dependence.
Publisher: American Psychiatric Association Publishing
Date: 02-2019
Publisher: Wiley
Date: 28-12-2022
DOI: 10.1111/ADD.16109
Abstract: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this h ers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on‐line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts ( n = 54) identified via recommendations from the Steering Committee and a systematic review. Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches (iii) practice, feedback, difficulty‐titration, bias modification, goal‐setting, strategy learning and meta‐awareness as active ingredients and (iv) both addiction treatment work‐force and specialized neuropsychologists facilitating delivery, together with novel digital‐based delivery modalities. Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher‐order cognitive skills via well‐validated intervention approaches qualified with mechanistic techniques and flexible delivery options.
Publisher: Wiley
Date: 18-07-2019
DOI: 10.1111/ADB.12652
Abstract: Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non-dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippoc us, one of the most consistently altered brain regions in cannabis users, in a large multi-site dataset aggregated across four research sites. We compared hippoc al volume and vertex-level hippoc al shape differences (1) between 121 non-using controls and 140 cannabis users (2) between 106 controls, 50 non-dependent users and 70 dependent users and (3) between a subset of 41 controls, 41 non-dependent users and 41 dependent users, matched on s le characteristics and cannabis use pattern (onset age and dosage). Cannabis users did not differ from controls in hippoc al volume or shape. However, cannabis-dependent users had significantly smaller right and left hippoc i relative to controls and non-dependent users, irrespective of cannabis dosage. Shape analysis indicated localized deflations in the superior-medial body of the hippoc us. Our findings support neuroscientific theories postulating dependence-specific neuroadaptations in cannabis users. Future efforts should uncover the neurobiological risk and liabilities separating dependent and non-dependent use of cannabis.
Publisher: Cold Spring Harbor Laboratory
Date: 31-07-2022
DOI: 10.1101/2022.07.28.22278144
Abstract: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this h ers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. Delphi approach with two sequential phases: survey development and iterative surveying of experts. Online study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n=53) identified via recommendations from the Steering Committee and a systematic review. Survey with 67 items covering four key areas of intervention development, i.e., targets, intervention approaches, active ingredients, and modes of delivery. Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions, and social processing as key targets of interventions (ii) cognitive bias modification, contingency management, emotion regulation training, and cognitive remediation as preferred approaches (iii) practice, feedback, difficulty-titration, bias-modification, goal setting, strategy learning, and meta-awareness as active ingredients and (iv) both addiction treatment workforce and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. Expert recommendations on cognitive training and remediation for SUD highlight the relevance of targeting implicit biases, reward, emotion regulation, and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.
Publisher: Wiley
Date: 20-11-2019
DOI: 10.1111/ADB.12830
Abstract: While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance‐specific and substance‐general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 in iduals with dependence on alcohol, nicotine, cocaine, meth hetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex‐level metrics—the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)—that, respectively, describe local thickness and surface area dilation/contraction. Mega‐analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippoc us, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippoc us and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance‐specific relationships with subcortical brain structures.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.PNPBP.2017.07.017
Abstract: Orbitofrontal cortex (OFC) sulcogyral patterns are stable morphological variations established early in life. They consist of three distinct pattern types, with Type III in particular being associated with poor regulatory control (e.g., high sensation seeking and negative emotionality, low constraint), which may confer risk for earlier onset of cannabis (CB) use and greater use in later life. The OFC sulcogyral pattern may therefore be a stable trait marker in understanding in idual differences in substance-use vulnerability and associated affective disturbances in users. In a large multisite cross-sectional study, we compared OFC pattern type distribution between 128 healthy controls (HC) and 146 CB users. Within users (n=140), we explored the association between OFC pattern type and CB use level, and subsequently if level of CB use informed by OFC pattern type may mediate disturbances in affective tone, as indexed by depressive symptoms. While OFC pattern distribution did not distinguish between HC and CB groups, it informed greater lifetime use within users. Specifically, CB users with pattern Type III in the right OFC tended to use more CB over their lifetime, than did CB users with pattern Type I or II. Greater lifetime CB use was subsequently associated with higher depressive symptoms, such that it mediated an indirect association between right OFC pattern Type III and higher depressive symptoms. The present study provides evidence for neurobiological differences, specifically sulcogyral pattern of the OFC, to modulate level of CB use, which may subsequently influence the expression of depressive symptoms.
Publisher: Springer Science and Business Media LLC
Date: 06-2021
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 12-07-2023
DOI: 10.1002/HBM.26404
Abstract: Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole‐brain, voxel‐based, multi‐tissue mega‐analytic approach, thereby extending our recent surface‐based region of interest findings on a nearly matching s le using a complementary methodological approach. T1‐weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel‐based morphometry. The effects of group, sex, group‐by‐sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. In iduals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group‐by‐sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group‐by‐sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo‐occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD.
Publisher: SAGE Publications
Date: 13-05-2013
DOI: 10.5127/JEP.030512
Abstract: Approach Avoidance tasks measure approach bias, a behavioral tendency to be faster at approaching rather than avoiding drug cues. Approach bias has been measured in a number of different drug-using populations and there is evidence to suggest that approach bias measurements correlate with drug use. Little is known, however, about the motivational mechanisms underlying the approach bias. In the current study we assessed whether the approach bias to cigarettes was immediately sensitive to changes in the incentive value of smoking. We examined the change from baseline in a participant group, after half the group had been given the opportunity to smoke. Specifically, we examined whether the approach bias has the characteristics of a cue-elicited behavior or is flexibly modulated by current desire. Results showed that while the baseline approach-bias score in deprived cigarette smokers correlated with craving, smoking a cigarette led to reduced craving but an increased approach bias score. We discuss a possible account of these findings in terms of an ideomotor outcome-response priming mechanism.
Publisher: Elsevier
Date: 2016
Publisher: SAGE Publications
Date: 12-07-2020
Abstract: We aimed to investigate whether severity of cannabis dependence is associated with the neuroanatomy of key brain regions of the stress and reward brain circuits. To examine dependence-specific regional brain alterations, we compared the volumes of regions relevant to reward and stress, between high-dependence cannabis users (CD+, n = 25), low-dependence cannabis users (CD−, n = 20) and controls ( n = 37). Compared to CD− and/or controls, the CD+ group had lower cerebellar white matter and hippoc al volumes, and deflation of the right hippoc us head and tail. These findings provide initial support for neuroadaptations involving stress and reward circuits that are specific to high-dependence cannabis users.
Publisher: Wiley
Date: 25-08-2020
DOI: 10.1002/HBM.25154
Abstract: The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p ‐hacking. Low statistical power in in idual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% ( SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used s le sizes.
Publisher: Center for Open Science
Date: 17-04-2023
Publisher: Springer Science and Business Media LLC
Date: 04-2017
DOI: 10.1007/S00213-017-4606-9
Abstract: Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment. The objective of this study was to investigate the association between CB use and dependence, and the volumes of brain regions critically involved in goal-directed learning and behaviour-the orbitofrontal cortex (OFC) and caudate. In the largest multi-site structural imaging study of CB users vs healthy controls (HC), 140 CB users and 121 HC were recruited from four research sites. Group differences in OFC and caudate volumes were investigated between HC and CB users and between 70 dependent (CB-dep) and 50 non-dependent (CB-nondep) users. The relationship between quantity of CB use and age of onset of use and caudate and OFC volumes was explored. CB users (consisting of CB-dep and CB-nondep) did not significantly differ from HC in OFC or caudate volume. CB-dep compared to CB-nondep users exhibited significantly smaller volume in the medial and the lateral OFC. Lateral OFC volume was particularly smaller in CB-dep females, and reduced volume in the CB-dep group was associated with higher monthly cannabis dosage. Smaller medial OFC volume may be driven by CB dependence-related mechanisms, while smaller lateral OFC volume may be due to ongoing exposure to cannabinoid compounds. The results highlight a distinction between cannabis use and dependence and warrant examination of gender-specific effects in studies of CB dependence.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2016
Publisher: Wiley
Date: 09-07-2020
DOI: 10.1002/HBM.25114
Abstract: Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto‐cerebellar and meso‐cortico‐limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large‐scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case–control differences and to compare brain‐correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta‐analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age‐ and sex‐matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case–control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co‐variates . After correcting for multiple comparisons, AUD case–control meta‐analysis of subcortical regions indicated significant differences in the thalamus, hippoc us, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta‐analysis of CUD case–control studies indicated reliable reductions in amygdala, accumbens and hippoc us volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross‐disorder comparison of brain correlates of substance use disorders and showed alcohol‐related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2021
DOI: 10.1038/S41398-021-01382-Y
Abstract: Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippoc us, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform in idually tailored neurobiological targets for treatment.
Start Date: 2017
End Date: 2021
Funder: National Health and Medical Research Council
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