Publications by authors named "Scott Mackey"

51 Publications

Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group.

Transl Psychiatry 2021 May 6;11(1):272. Epub 2021 May 6.

Neuroscience of Addiction & Mental Health Program, Healthy Brain and Mind Research Centre, School of Behavioural & Health Sciences, Faculty of Health Sciences, Australian Catholic University, Melbourne, VIC, Australia.

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, hippocampus, 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 individually tailored neurobiological targets for treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01382-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102553PMC
May 2021

Multimodal brain predictors of current weight and weight gain in children enrolled in the ABCD study ®.

Dev Cogn Neurosci 2021 Mar 30;49:100948. Epub 2021 Mar 30.

Department of Psychiatry, University of Vermont, Burlington, VT, USA; Department of Psychological Science, University of Vermont, Burlington, VT, USA.

Multimodal neuroimaging assessments were utilized to identify generalizable brain correlates of current body mass index (BMI) and predictors of pathological weight gain (i.e., beyond normative development) one year later. Multimodal data from children enrolled in the Adolescent Brain Cognitive Development Study® at 9-to-10-years-old, consisted of structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), resting state (rs), and three task-based functional (f) MRI scans assessing reward processing, inhibitory control, and working memory. Cross-validated elastic-net regression revealed widespread structural associations with BMI (e.g., cortical thickness, surface area, subcortical volume, and DTI), which explained 35% of the variance in the training set and generalized well to the test set (R = 0.27). Widespread rsfMRI inter- and intra-network correlations were related to BMI (R = 0.21; R = 0.14), as were regional activations on the working memory task (R = 0.20; (R = 0.16). However, reward and inhibitory control tasks were unrelated to BMI. Further, pathological weight gain was predicted by structural features (Area Under the Curve (AUC) = 0.83; AUC = 0.83, p < 0.001), but not by fMRI nor rsfMRI. These results establish generalizable brain correlates of current weight and future pathological weight gain. These results also suggest that sMRI may have particular value for identifying children at risk for pathological weight gain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dcn.2021.100948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066422PMC
March 2021

Gender-related neuroanatomical differences in alcohol dependence: findings from the ENIGMA Addiction Working Group.

Neuroimage Clin 2021 Mar 22;30:102636. Epub 2021 Mar 22.

Neuroscience of Addiction and Mental Health Program, Healthy Brain and Mind Research Centre, School of Behavioural & Health Sciences, Faculty of Health Sciences, Australian Catholic University, Melbourne, VIC, Australia. Electronic address:

Gender-related differences in the susceptibility, progression and clinical outcomes of alcohol dependence are well-known. However, the neurobiological substrates underlying such differences remain unclear. Therefore, this study aimed to investigate gender differences in the neuroanatomy (i.e. regional brain volumes) of alcohol dependence. We examined the volume of a priori regions of interest (i.e., orbitofrontal cortex, hippocampus, amygdala, nucleus accumbens, caudate, putamen, pallidum, thalamus, corpus callosum, cerebellum) and global brain measures (i.e., total grey matter (GM), total white matter (WM) and cerebrospinal fluid). Volumes were compared between 660 people with alcohol dependence (228 women) and 326 controls (99 women) recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age and education years. Compared to controls, individuals with alcohol dependence on average had (3-9%) smaller volumes of the hippocampus (bilateral), putamen (left), pallidum (left), thalamus (right), corpus callosum, total GM and WM, and cerebellar GM (bilateral), the latter more prominently in women (right). Alcohol-dependent men showed smaller amygdala volume than control men, but this effect was unclear among women. In people with alcohol dependence, more monthly standard drinks predicted smaller amygdala and larger cerebellum GM volumes. The neuroanatomical differences associated with alcohol dependence emerged as gross and widespread, while those associated with a specific gender may be confined to selected brain regions. These findings warrant future neuroscience research to account for gender differences in alcohol dependence to further understand the neurobiological effects of alcohol dependence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065340PMC
March 2021

COVID-19: A new barrier to treatment for opioid use disorder in the emergency department.

J Am Coll Emerg Physicians Open 2021 Apr 17;2(2):e12403. Epub 2021 Mar 17.

Division of Emergency Medicine, University of Vermont Larner College of Medicine Burlington Vermont USA.

Objective: Start Treatment and Recover (STAR) is an emergency department (ED) program that expands access to medication for opioid use disorder by identifying patients with opioid use disorder and offering ED-initiated buprenorphine/naloxone and rapid access to outpatient treatment. We sought to determine the impacts of the coronavirus disease 2019 pandemic on STAR and the patients with opioid use disorder it serves.

Methods: We conducted a retrospective review of records comparing 2 periods: pre-pandemic (February 1, 2019-February 29, 2020) and pandemic (March 1, 2020-May 31, 2020). Variables evaluated included the number of STAR enrollments, ED census, percentage of census screening positive for opioid use disorder, number and percentage of ED overdose visits, and overdose fatalities by month. All analyses were conducted using 2-sample tests to calculate the mean and 95% confidence intervals (CIs).

Results: Comparing the pre-pandemic to the pandemic period, the mean monthly ED visits decreased from 5126.9 to 3306.7 (difference = -1820.3; 95% CI, -3406.3 to -234.2), STAR mean monthly enrollments decreased from 9.7 to 1.3 (difference = -8.4; 95% CI, -12.8 to -4.0), and statewide monthly opioid-related fatalities increased from 9.4 to 15.3 (difference = 5.9; 95% CI, 0.8 to 11.1). However, the percentage of individuals who presented to the ED with opioid use disorder or overdose remained unchanged.

Conclusion: Although overall ED visits declined during the pandemic period, the percentage of patients presenting with opioid use disorder or overdose remained constant, yet there was a dramatic decline in enrollment in ED-initiated medication for opioid use disorder and an increase in statewide monthly opioid-related fatalities. Strategies to maintain medication for opioid use disorder treatment options must be implemented for this vulnerable population during the ongoing pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/emp2.12403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967916PMC
April 2021

Sex differences in the neuroanatomy of alcohol dependence: hippocampus and amygdala subregions in a sample of 966 people from the ENIGMA Addiction Working Group.

Transl Psychiatry 2021 Mar 4;11(1):156. Epub 2021 Mar 4.

Neuroscience of Addiction & Mental Health Program, Healthy Brain and Mind Research Centre, School of Behavioural & Health Sciences, Faculty of Health Sciences, Australian Catholic University, Melbourne, VIC, Australia.

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 hippocampal and amygdala subregions in a large sample 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 hippocampus and its CA1 and subiculum subfield volumes in both males and females. In summary, hippocampal and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01204-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933136PMC
March 2021

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group.

Addict Biol 2021 Jan 28:e13010. Epub 2021 Jan 28.

BrainPark, Turner Institute for Brain and Mental Health, School of Psychological Sciences, and Monash Biomedical Imaging Facility, Monash University, Melbourne, Victoria, Australia.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.13010DOI Listing
January 2021

Predicting alcohol dependence from multi-site brain structural measures.

Hum Brain Mapp 2020 Oct 16. Epub 2020 Oct 16.

Department of Psychiatry, University of Vermont College of Medicine, Burlington, Vermont, USA.

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 individuals with current AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25248DOI Listing
October 2020

Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study.

J Am Acad Child Adolesc Psychiatry 2021 May 1;60(5):623-636. Epub 2020 Oct 1.

Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.

Objective: It is unclear whether deviations in brain and behavioral development, which may underpin elevated substance use during adolescence, are predispositions for or consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug-naive youths to identify possible predisposing factors for substance use initiation and its possible consequences.

Method: Among 304 drug-naive adolescents at baseline (age 14 years) from the IMAGEN dataset, 83 stayed drug-naive, 133 used alcohol on 1 to 9 occasions, 42 on 10 to 19 occasions, 27 on 20 to 39 occasions, and 19 on >40 occasions at follow-up (age 16 years). Baseline measures included brain activation during the Monetary Incentive Delay task. Data at both baseline and follow-up included measures of trait impulsivity and delay discounting.

Results: From baseline to follow-up, impulsivity decreased in the 0 and 1- to 9-occasions groups (p < .004), did not change in the 10- to 19-occasions and 20- to 29-occasions groups (p > .294), and uncharacteristically increased in the >40-occasions group (p = .046). Furthermore, blunted medial orbitofrontal cortex activation during reward outcome at baseline significantly predicted higher alcohol use frequency at follow-up, above and beyond behavioral and clinical variables (p = .008).

Conclusion: These results suggest that the transition from no use to frequent drinking in early to mid-adolescence may disrupt normative developmental changes in behavioral control. In addition, blunted activity of the medial orbitofrontal cortex during reward outcome may underscore a predisposition toward the development of more severe alcohol use in adolescents. This distinction is clinically important, as it informs early intervention efforts in preventing the onset of substance use disorder in adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaac.2020.08.443DOI Listing
May 2021

Critically Ill Adults With Coronavirus Disease 2019 in New Orleans and Care With an Evidence-Based Protocol.

Chest 2021 01 14;159(1):196-204. Epub 2020 Sep 14.

Section of Pulmonary/Critical Care & Allergy/Immunology, LSU School of Medicine, New Orleans, LA.

Background: Characteristics of critically ill adults with coronavirus disease 2019 (COVID-19) in an academic safety net hospital and the effect of evidence-based practices in these patients are unknown.

Research Question: What are the outcomes of critically ill adults with COVID-19 admitted to a network of hospitals in New Orleans, Louisiana, and what is an evidence-based protocol for care associated with improved outcomes?

Study Design And Methods: In this multi-center, retrospective, observational cohort study of ICUs in four hospitals in New Orleans, Louisiana, we collected data on adults admitted to an ICU and tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 9, 2020 and April 14, 2020. The exposure of interest was admission to an ICU that implemented an evidence-based protocol for COVID-19 care. The primary outcome was ventilator-free days.

Results: The initial 147 patients admitted to any ICU and tested positive for SARS-CoV-2 constituted the cohort for this study. In the entire network, exposure to an evidence-based protocol was associated with more ventilator-free days (25 days; 0-28) compared with non-protocolized ICUs (0 days; 0-23, P = .005), including in adjusted analyses (P = .02). Twenty patients (37%) admitted to protocolized ICUs died compared with 51 (56%; P = .02) in non-protocolized ICUs. Among 82 patients admitted to the academic safety net hospital's ICUs, the median number of ventilator-free days was 22 (interquartile range, 0-27) and mortality rate was 39%.

Interpretation: Care of critically ill COVID-19 patients with an evidence-based protocol is associated with increased time alive and free of invasive mechanical ventilation. In-hospital survival occurred in most critically ill adults with COVID-19 admitted to an academic safety net hospital's ICUs despite a high rate of comorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2020.08.2114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487861PMC
January 2021

Clinical Characteristics and Outcomes Based on Race of Hospitalized Patients With COVID-19 in a New Orleans Cohort.

Open Forum Infect Dis 2020 Sep 13;7(9):ofaa339. Epub 2020 Aug 13.

Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.

Background: In Louisiana, deaths related to COVID-19 have disproportionately occurred in Black persons. Granular data are needed to better understand inequities and develop prevention strategies to mitigate further impact on Black communities.

Methods: We conducted a retrospective study of patients admitted to an urban safety net hospital in New Orleans, Louisiana, with reactive SARS-CoV-2 testing from March 9 to 31, 2020. Clinical characteristics of Black and other racial/ethnic group patients were compared using Wilcoxon rank-sum test and Fisher exact tests. The relationship between race and outcome was assessed using day 14 status on an ordinal scale.

Results: This study included 249 patients. The median age was 59, 44% were male, and 86% were age ≥65 years or had ≥1 comorbidity. Overall, 87% were Black, relative to 55% Black patients typically hospitalized at our center. Black patients had longer symptom duration at presentation (6.41 vs 5.88 days;  = .05) and were more likely to have asthma ( = .008) but less likely to have dementia ( = .002). There were no racial differences in initial respiratory status or laboratory values except for higher lactate dehydrogenase in Black patients. Patient age and initial oxygen requirement, but not race (adjusted proportional odds ratio, 0.92; 95% CI, 0.70-1.20), were associated with worse day 14 outcomes.

Conclusions: Our results demonstrate minor racial differences in comorbidities or disease severity at presentation, and day 14 outcomes were not different between groups. However, Black patients were disproportionately represented in hospitalizations, suggesting that prevention efforts should include strategies to limit SARS-CoV-2 exposures and transmission in Black communities as one step toward reducing COVID-19-related racial inequities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454836PMC
September 2020

Neural Correlates of Adolescent Irritability and Its Comorbidity With Psychiatric Disorders.

J Am Acad Child Adolesc Psychiatry 2020 12 27;59(12):1371-1379. Epub 2020 Aug 27.

Vermont Center on Behavior and Health, University of Vermont, Burlington.

Objective: Irritable mood, a common and impairing symptom in psychopathology, has been proposed to underlie the developmental link between oppositional problems in youth and depression in adulthood. We examined the neural correlates of adolescent irritability in IMAGEN, a sample of 2,024 14-year-old adolescents from 5 European countries.

Method: The Development and Well-Being Assessment (DAWBA) was used to assess attention-deficit/hyperactivity disorder, major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder. Three items from the DAWBA, selected as close matches to the Affective Reactivity Index, were used to assess irritability. Structural magnetic resonance imaging was examined using whole-brain voxel-based morphometry analysis, and functional magnetic resonance imaging was examined during a stop signal task of inhibitory control. Imaging data were included in structural equation models to examine the direct and indirect associations between irritable mood and comorbid DSM diagnoses.

Results: Whole-brain voxelwise analysis showed that adolescent irritable mood was associated with less gray matter volume and less neural activation underlying inhibitory control in frontal and temporal cortical areas (cluster-correction at p < .05). Structural equation models suggested that part of the observed smaller gray matter volume was exclusively driven by irritability separate from direct relationships between generalized anxiety disorder (or attention-deficit/hyperactivity disorder, major depressive disorder, or oppositional defiant disorder) and gray matter volume.

Conclusion: This study identifies adolescent irritability as an independent construct and points to a neurobiological correlate to irritability that is an important contributing feature to many psychopathological disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaac.2019.11.028DOI Listing
December 2020

Common and gender-specific associations with cocaine use on gray matter volume: Data from the ENIGMA addiction working group.

Hum Brain Mapp 2020 Aug 28. Epub 2020 Aug 28.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Gray matter volume (GMV) in frontal cortical and limbic regions is susceptible to cocaine-associated reductions in cocaine-dependent individuals (CD) and is negatively associated with duration of cocaine use. Gender differences in CD individuals have been reported clinically and in the context of neural responses to cue-induced craving and stress reactivity. The variability of GMV in select brain areas between men and women (e.g., limbic regions) underscores the importance of exploring interaction effects between gender and cocaine dependence on brain structure. Therefore, voxel-based morphometry data derived from the ENIGMA Addiction Consortium were used to investigate potential gender differences in GMV in CD individuals compared to matched controls (CTL). T1-weighted MRI scans and clinical data were pooled from seven sites yielding 420 gender- and age-matched participants: CD men (CDM, n = 140); CD women (CDW, n = 70); control men (CTLM, n = 140); and control women (CTLW, n = 70). Differences in GMV were assessed using a 2 × 2 ANCOVA, and voxelwise whole-brain linear regressions were conducted to explore relationships between GMV and duration of cocaine use. All analyses were corrected for age, total intracranial volume, and site. Diagnostic differences were predominantly found in frontal regions (CD < CTL). Interestingly, gender × diagnosis interactions in the left anterior insula and left lingual gyrus were also documented, driven by differences in women (CDW < CTLW). Further, lower right hippocampal GMV was associated with greater cocaine duration in CDM. Given the importance of the anterior insula to interoception and the hippocampus to learning contextual associations, results may point to gender-specific mechanisms in cocaine addiction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25141DOI Listing
August 2020

Declassifying Mobility Classification.

J Endod 2020 Aug 5. Epub 2020 Aug 5.

Department of Endodontics, Case Western Reserve University, School of Dental Medicine, Cleveland, Ohio.

Introduction: Tooth mobility is often discussed among dental health care providers according to a numerical scale (ie, 1, 2, or 3) without a clear understanding of the definition of each category. Thus, a comprehensive review to examine and discuss the various classifications is needed. The aim of this comprehensive review was to discuss the main clinical classifications of tooth mobility.

Methods: The authors conducted electronic searches in MEDLINE, Scopus, and PubMed. Additionally, the authors manually searched the textbooks, gray literature, and bibliographies of all relevant articles.

Results: The most commonly referenced clinical index for mobility was the Miller index; yet, many other mobility classifications exist as well as modifications of those indexes. The literature has been very inconsistent and at times inaccurate when classifying mobility; using various stages of mobility using grades, classes, and scores interchangeably and not defining the meaning of the actual numerical scores/terminologies are common problems.

Conclusions: In order to avoid ambiguity and provide clarity regarding the impact of degrees of mobility when used clinically, this review comprehensively discusses different classifications and definitions of tooth mobility with attention to the importance of using them consistently and accurately. There is a need to standardize 1 classification for mobility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joen.2020.07.030DOI Listing
August 2020

Realization of an intrinsic ferromagnetic topological state in MnBiTe.

Sci Adv 2020 Jul 22;6(30):eaba4275. Epub 2020 Jul 22.

Department of Physics and Astronomy and California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Novel magnetic topological materials pave the way for studying the interplay between band topology and magnetism. However, an intrinsically ferromagnetic topological material with only topological bands at the charge neutrality energy has so far remained elusive. Using rational design, we synthesized MnBi8Te13, a natural heterostructure with [MnBiTe] and [BiTe] layers. Thermodynamic, transport, and neutron diffraction measurements show that despite the adjacent [MnBiTe] being 44.1 Å apart, MnBiTe manifests long-range ferromagnetism below 10.5 K with strong coupling between magnetism and charge carriers. First-principles calculations and angle-resolved photoemission spectroscopy measurements reveal it is an axion insulator with sizable surface hybridization gaps. Our calculations further demonstrate the hybridization gap persists in the two-dimensional limit with a nontrivial Chern number. Therefore, as an intrinsic ferromagnetic axion insulator with clean low-energy band structures, MnBiTe serves as an ideal system to investigate rich emergent phenomena, including the quantized anomalous Hall effect and quantized magnetoelectric effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aba4275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375807PMC
July 2020

How do substance use disorders compare to other psychiatric conditions on structural brain abnormalities? A cross-disorder meta-analytic comparison using the ENIGMA consortium findings.

Hum Brain Mapp 2020 Jul 9. Epub 2020 Jul 9.

Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, CHU Ste-Justine, Montreal, Canada.

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, hippocampus, 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 hippocampus 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25114DOI Listing
July 2020

Toward Inclusion of Youths With Psychiatric Disorders in Brain-Body Research-Reply.

JAMA Pediatr 2020 09;174(9):907-908

Larner College of Medicine, Department of Psychiatry, University of Vermont, Burlington.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2020.1069DOI Listing
September 2020

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

Transl Psychiatry 2020 03 20;10(1):100. Epub 2020 Mar 20.

Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-020-0705-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083923PMC
March 2020

Associations Among Body Mass Index, Cortical Thickness, and Executive Function in Children.

JAMA Pediatr 2020 02;174(2):170-177

Department of Psychiatry, Larner College of Medicine, University of Vermont, Burlington.

Importance: A total of 25.7 million children in the United States are classified as overweight or obese. Obesity is associated with deficits in executive function, which may contribute to poor dietary decision-making. Less is known about the associations between being overweight or obese and brain development.

Objective: To examine whether body mass index (BMI) is associated with thickness of the cerebral cortex and whether cortical thickness mediates the association between BMI and executive function in children.

Design, Setting, And Participants: In this cross-sectional study, cortical thickness maps were derived from T1-weighted structural magnetic resonance images of a large, diverse sample of 9 and 10-year-old children from 21 US sites. List sorting, flanker, matrix reasoning, and Wisconsin card sorting tasks were used to assess executive function.

Main Outcomes And Measures: A 10-fold nested cross-validation general linear model was used to assess mean cortical thickness from BMI across cortical brain regions. Associations between BMI and executive function were explored with Pearson partial correlations. Mediation analysis examined whether mean prefrontal cortex thickness mediated the association between BMI and executive function.

Results: Among 3190 individuals (mean [SD] age, 10.0 [0.61] years; 1627 [51.0%] male), those with higher BMI exhibited lower cortical thickness. Eighteen cortical regions were significantly inversely associated with BMI. The greatest correlations were observed in the prefrontal cortex. The BMI was inversely correlated with dimensional card sorting (r = -0.088, P < .001), list sorting (r = -0.061, P < .003), and matrix reasoning (r = -0.095, P < .001) but not the flanker task. Mean prefrontal cortex thickness mediated the association between BMI and list sorting (mean [SE] indirect effect, 0.014 [0.008]; 95% CI, 0.001-0.031) but not the matrix reasoning or card sorting task.

Conclusions And Relevance: These results suggest that BMI is associated with prefrontal cortex development and diminished executive functions, such as working memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2019.4708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902097PMC
February 2020

Editorial: Alcohol and the Developing Brain: What to Expect Next?

Authors:
Scott Mackey

J Am Acad Child Adolesc Psychiatry 2020 03 21;59(3):346-347. Epub 2019 Nov 21.

University of Vermont, Burlington. Electronic address:

Sometimes anticipation is more fun than the actual event, and sometimes, pleasantly, it's the reverse. The difference between the anticipated value of an action and its actual outcome provides important feedback, which shapes our behavior and future plans and is a central feature of all modern theories of incentivized learning. Contextually adaptive behavior and decision making depends critically on a constantly updated comparison between expectations and outcomes. To clarify the neural substrate of these mental comparisons, there has been an intensive examination of reward-related activity in the brain in the last few decades. Scores of neuroimaging studies have been performed to identify the brain regions involved in the representation of anticipated value and experienced outcomes. Systematic reviews of this neuroimaging literature indicate that a common set of value-coding brain regions are involved across a wide range of tasks..
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaac.2019.09.035DOI Listing
March 2020

Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study.

Addict Biol 2020 11 20;25(6):e12830. Epub 2019 Nov 20.

Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.

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 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, 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 hippocampus, 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 hippocampus 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.12830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237314PMC
November 2020

Low Smoking Exposure, the Adolescent Brain, and the Modulating Role of CHRNA5 Polymorphisms.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 07 15;4(7):672-679. Epub 2019 Mar 15.

Vermont Center on Behavior and Health, Departments of Psychiatry and Psychology, University of Vermont, Burlington, Vermont.

Background: Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may help expose the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents exist, and they include small samples. In addition, the neural mechanism, if one exists, that links nicotinic receptor genes to smoking behavior in adolescents is still unknown.

Methods: Structural and diffusion tensor magnetic resonance imaging data were acquired from a large sample of 14-year-old adolescents who completed an extensive battery of neuropsychological, clinical, personality, and drug-use assessments. Additional assessments were conducted at 16 years of age.

Results: Exposure to smoking in adolescents, even at low doses, is linked to volume changes in the ventromedial prefrontal cortex and to altered neuronal connectivity in the corpus callosum. The longitudinal analyses strongly suggest that these effects are not preexisting conditions in those who progress to smoking. There was a genetic contribution wherein the volume reduction effects were magnified in smokers who were carriers of the high-risk genotype of the alpha 5 nicotinic receptor subunit gene, rs16969968.

Conclusions: These findings give insight into a mechanism involving genes, brain structure, and connectivity underlying why some adolescents find nicotine especially addictive.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpsc.2019.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709448PMC
July 2019

Amygdalar reactivity is associated with prefrontal cortical thickness in a large population-based sample of adolescents.

PLoS One 2019 2;14(5):e0216152. Epub 2019 May 2.

Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.

In structural neuroimaging studies, reduced cerebral cortical thickness in orbital and ventromedial prefrontal regions is frequently interpreted as reflecting an impaired ability to downregulate neuronal activity in the amygdalae. Unfortunately, little research has been conducted in order to test this conjecture. We examine the extent to which amygdalar reactivity is associated with cortical thickness in a population-based sample of adolescents. Data were obtained from the IMAGEN study, which includes 2,223 adolescents. While undergoing functional neuroimaging, participants passively viewed video clips of a face that started from a neutral expression and progressively turned angry, or, instead, turned to a second neutral expression. Left and right amygdala ROIs were used to extract mean BOLD signal change for the angry minus neutral face contrast for all subjects. T1-weighted images were processed through the CIVET pipeline (version 2.1.0). In variable-centered analyses, local cortical thickness was regressed against amygdalar reactivity using first and second-order linear models. In a follow-up person-centered analysis, we defined a "high reactive" group of participants based on mean amygdalar BOLD signal change for the angry minus neutral face contrast. Between-group differences in cortical thickness were examined ("high reactive" versus all other participants). A significant association was revealed between the continuous measure of amygdalar reactivity and bilateral ventromedial prefrontal cortical thickness in a second-order linear model (p < 0.05, corrected). The "high reactive" group, in comparison to all other participants, possessed reduced cortical thickness in bilateral orbital and ventromedial prefrontal cortices, bilateral anterior temporal cortices, left caudal middle temporal gyrus, and the left inferior and middle frontal gyri (p < 0.05, corrected). Results are consistent with non-human primate studies, and provide empirical support for an association between reduced prefrontal cortical thickness and amygdalar reactivity. Future research will likely benefit from investigating the degree to which psychopathology qualifies relations between prefrontal cortical structure and amygdalar reactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216152PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497259PMC
February 2020

Neuroimaging Evidence for Right Orbitofrontal Cortex Differences in Adolescents With Emotional and Behavioral Dysregulation.

J Am Acad Child Adolesc Psychiatry 2019 11 17;58(11):1092-1103. Epub 2019 Apr 17.

University of Vermont, Burlington; Vermont Center on Behavior and Health, University of Vermont, Burlington.

Objective: To characterize the structural and functional neurobiology of a large group of adolescents exhibiting a behaviorally and emotionally dysregulated phenotype.

Method: Adolescents aged 14 years from the IMAGEN study were investigated. Latent class analysis (LCA) on the Strengths and Difficulties Questionnaire (SDQ) was used to identify a class of individuals with elevated behavioral and emotional difficulties ("dysregulated"; n = 233) who were compared to a matched sample from a low symptom class (controls, n = 233). Whole-brain gray matter volume (GMV) images were compared using a general linear model with 10,000 random label permutations. Regional GMV findings were then probed for functional differences from three functional magnetic resonance imaging (fMRI) tasks. Significant brain features then informed mediation path models linking the likelihood of psychiatric disorders (DSM-IV) with dysregulation.

Results: Whole-brain differences were found in the right orbitofrontal cortex (R.OFC; p < .05; k = 48), with dysregulated individuals exhibiting lower GMV. The dysregulated group also exhibited higher activity in this region during successful inhibitory control (F = 7.53, p < .05). Path analyses indicated significant direct effects between the likelihood of psychopathologies and dysregulation. Modeling the R.OFC as a mediator returned modest partial effects, suggesting that the path linking the likelihood of an anxiety or conduct disorder diagnoses to dysregulation is partially explained by this anatomical feature.

Conclusion: A large sample of dysregulated adolescents exhibited lower GMV in the R.OFC relative to controls. Dysregulated individuals also exhibited higher regional activations when exercising inhibitory control at performance levels comparable to those of controls. These findings suggest a neurobiological marker of dysregulation and highlight the role of the R.OFC in impaired emotional and behavioral control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaac.2019.01.021DOI Listing
November 2019

Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence.

J Neurosci 2019 03 14;39(10):1817-1827. Epub 2019 Jan 14.

Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, 01069 Germany.

Rates of cannabis use among adolescents are high, and are increasing concurrent with changes in the legal status of marijuana and societal attitudes regarding its use. Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of Δ-9-tetrahydrocannabinol (THC) on brain structure. In the current study, we used voxel-based morphometry to compare gray matter volume (GMV) in forty-six 14-year-old human adolescents (males and females) with just one or two instances of cannabis use and carefully matched THC-naive controls. We identified extensive regions in the bilateral medial temporal lobes as well as the bilateral posterior cingulate, lingual gyri, and cerebellum that showed greater GMV in the cannabis users. Analysis of longitudinal data confirmed that GMV differences were unlikely to precede cannabis use. GMV in the temporal regions was associated with contemporaneous performance on the Perceptual Reasoning Index and with future generalized anxiety symptoms in the cannabis users. The distribution of GMV effects mapped onto biomarkers of the endogenous cannabinoid system providing insight into possible mechanisms for these effects. Almost 35% of American 10th graders have reported using cannabis and existing research suggests that initiation of cannabis use in adolescence is associated with long-term neurocognitive effects. We understand very little about the earliest effects of cannabis use, however, because most research is conducted in adults with a heavy pattern of lifetime use. This study presents evidence suggesting structural brain and cognitive effects of just one or two instances of cannabis use in adolescence. Converging evidence suggests a role for the endocannabinoid system in these effects. This research is particularly timely as the legal status of cannabis is changing in many jurisdictions and the perceived risk by youth associated with smoking cannabis has declined in recent years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.3375-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407302PMC
March 2019

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

Am J Psychiatry 2019 02 19;176(2):119-128. Epub 2018 Oct 19.

From the Department of Psychiatry and the Department of Mathematics and Statistics, University of Vermont, Burlington; Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Australia; the Department of Psychology, University of Oregon, Eugene; the Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; the Department of Psychiatry and Psychology, University of Barcelona, Barcelona, Spain; the Department of Psychiatry, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands; the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn; the Department of Psychiatry and the MRC Unit on Anxiety and Stress Disorders, University of Cape Town, Cape Town, South Africa; the Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore; the Monash Institute of Cognitive and Clinical Neurosciences and the School of Psychological Sciences, Monash University, Melbourne, Australia; the Departments of Developmental and Experimental Psychology, Utrecht University, Utrecht, the Netherlands; the Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal; the Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London; the Department of Psychiatry, Oregon Health and Science University, Portland; the Department of Neuroscience and the Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; the Department of Psychiatry, University of Amsterdam, Amsterdam; the Amsterdam Institute for Addiction Research and Arkin Mental Health Care, Amsterdam; the Department of Psychiatry, University of Michigan, Ann Arbor; the Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia; the Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder; the Department of Psychiatry, Washington University School of Medicine, St. Louis; the David Geffen School of Medicine, University of California at Los Angeles, Los Angeles; the School of Psychology, Faculty of Health Sciences, Australian Catholic University, Melbourne, Australia; the Department of Psychological Sciences, University of Liverpool, Liverpool, U.K.; the Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands; the Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego; the Clinical Neuroimaging Research Core, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md.; the VA San Diego Healthcare System and the Department of Psychiatry, University of California San Diego, La Jolla; the Laureate Institute for Brain Research, Tulsa, Okla.; the Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia; the Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; the Institute of Psychology, Cognitive Psychology Unit, and the Leiden Institute for Brain and Cognition, Leiden University, Leiden, the Netherlands; the School of Psychology and the Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia; the Department of Psychiatry, University of California San Diego, La Jolla; the Department of Psychiatry, VU University Medical Center, Amsterdam; the Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia; the QIMR Berghofer Medical Research Institute, Brisbane, Australia; the Department of Psychiatry, University of Utah School of Medicine, Salt Lake City; the Imaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey; and the Department of Psychiatry, University of Montreal, CHU Sainte-Justine Hospital, Montreal.

Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes.

Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings.

Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects.

Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1176/appi.ajp.2018.17040415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427822PMC
February 2019

Prevalence and Correlates of Loss of Control Eating among Adults Presenting for Methadone Maintenance Treatment.

Int J Behav Med 2018 Dec;25(6):693-697

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University/The Miriam Hospital, Weight Control and Diabetes Research Center, 196 Richmond Street, Providence, RI, 02903, USA.

Background: Research suggests that substance use disorders and disordered eating are often comorbid. In light of the ongoing opioid epidemic, the purpose of the current study was to understand the prevalence and health-related correlates of loss of control (LOC) eating in adults seeking methadone maintenance treatment primarily for addiction to heroin and/or painkillers.

Methods: Participants were 447 adults surveyed at presentation for methadone maintenance treatment who responded to survey items on LOC eating. Descriptive statistics were used to investigate the prevalence of engaging in LOC eating in the past 2 weeks. Chi-square tests, t tests, and analyses of covariance were used to compare individuals with (LOC+; n = 164) and without (LOC-; n = 283) recent LOC eating on psychosocial, pain-related, and weight-related characteristics.

Results: Approximately one third of respondents endorsed LOC eating in the past 2 weeks. These participants reported greater affective symptoms, interpersonal dysfunction, pain intensity, and pain interference than the LOC- group (Cohen's d effect size range = .24-.94). LOC+ was also more likely to have engaged in recent illicit drug use and to report having concurrent overweight/obesity (φ effect size range = .09-.10).

Conclusion: The prevalence of LOC eating in adults seeking methadone maintenance treatment was more than triple what has been reported in previous studies using community samples. Given its associations with other health-related variables, the presence of LOC eating may be a marker for more severe psychopathology in individuals seeking methadone maintenance treatment. Future research is needed to understand mechanisms explaining this comorbidity and to develop novel ways to prevent and treat their co-occurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12529-018-9750-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360331PMC
December 2018

Ventromedial Prefrontal Volume in Adolescence Predicts Hyperactive/Inattentive Symptoms in Adulthood.

Cereb Cortex 2019 05;29(5):1866-1874

Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France.

Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structure. Herein, we investigate the degree to which vmPFC structure during adolescence predicts hyperactive/inattentive symptomatology at 5-year follow-up. Structural equation modeling was used to test the extent to which adolescent vmPFC volume predicts hyperactive/inattentive symptomatology 5 years later in early adulthood. 1104 participants (M = 14.52 years, standard deviation = 0.42; 583 females) possessed hyperactive/inattentive symptom data at 5-year follow-up, as well as quality controlled neuroimaging data and complete psychometric data at baseline. Self-reports of hyperactive/inattentive symptomatology were obtained during adolescence and at 5-year follow-up using the Strengths and Difficulties Questionnaire (SDQ). At baseline and 5-year follow-up, a hyperactive/inattentive latent variable was derived from items on the SDQ. Baseline vmPFC volume predicted adult hyperactive/inattentive symptomatology (standardized coefficient = -0.274, P < 0.001) while controlling for baseline hyperactive/inattentive symptomatology. These results are the first to reveal relations between adolescent brain structure and adult hyperactive/inattentive symptomatology, and suggest that early structural development of the vmPFC may be consequential for the subsequent expression of hyperactive/inattentive symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhy066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458906PMC
May 2019

The initiation of cannabis use in adolescence is predicted by sex-specific psychosocial and neurobiological features.

Eur J Neurosci 2019 08 15;50(3):2346-2356. Epub 2018 Oct 15.

Baycrest and Departments of Psychology and Psychiatry, Rotman Research Institute, University of Toronto, Toronto, ON, M6A 2E1, Canada.

Cannabis use initiated during adolescence might precipitate negative consequences in adulthood. Thus, predicting adolescent cannabis use prior to any exposure will inform the aetiology of substance abuse by disentangling predictors from consequences of use. In this prediction study, data were drawn from the IMAGEN sample, a longitudinal study of adolescence. All selected participants (n = 1,581) were cannabis-naïve at age 14. Those reporting any cannabis use (out of six ordinal use levels) by age 16 were included in the outcome group (N = 365, males n = 207). Cannabis-naïve participants at age 14 and 16 were included in the comparison group (N = 1,216, males n = 538). Psychosocial, brain and genetic features were measured at age 14 prior to any exposure. Cross-validated regularized logistic regressions for each use level by sex were used to perform feature selection and obtain prediction error statistics on independent observations. Predictors were probed for sex- and drug-specificity using post-hoc logistic regressions. Models reliably predicted use as indicated by satisfactory prediction error statistics, and contained psychosocial features common to both sexes. However, males and females exhibited distinct brain predictors that failed to predict use in the opposite sex or predict binge drinking in independent samples of same-sex participants. Collapsed across sex, genetic variation on catecholamine and opioid receptors marginally predicted use. Using machine learning techniques applied to a large multimodal dataset, we identified a risk profile containing psychosocial and sex-specific brain prognostic markers, which were likely to precede and influence cannabis initiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejn.13989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444673PMC
August 2019

Inattention and Reaction Time Variability Are Linked to Ventromedial Prefrontal Volume in Adolescents.

Biol Psychiatry 2017 Nov 13;82(9):660-668. Epub 2017 Jan 13.

Medical School, University of Tampere, Tampere, Finland.

Background: Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. We investigated the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability-an index of lapses in attention. We also tested for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression.

Methods: Psychopathology and imaging data were available for 1538 youths. Parent ratings of ADHD symptoms were obtained using the Development and Well-Being Assessment and the Strengths and Difficulties Questionnaire (SDQ). Self-reports of ADHD symptoms were assessed using the youth version of the SDQ. Reaction time variability was available in a subset of participants. For each measure, whole-brain voxelwise regressions with gray matter volume were calculated.

Results: Parent ratings of ADHD symptoms (Development and Well-Being Assessment and SDQ), adolescent self-reports of ADHD symptoms on the SDQ, and reaction time variability were each negatively associated with gray matter volume in an overlapping region of the ventromedial prefrontal cortex. Maps of DRD1 and DRD2 gene expression were associated with brain structural correlates of ADHD symptomatology.

Conclusions: This is the first study to reveal relationships between ventromedial prefrontal cortex structure and multi-informant measures of ADHD symptoms in a large population-based sample of adolescents. Our results indicate that ventromedial prefrontal cortex structure is a biomarker for ADHD symptomatology. These findings extend previous research implicating the default mode network and dopaminergic dysfunction in ADHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopsych.2017.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509516PMC
November 2017

Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior.

Biol Psychiatry 2017 08 18;82(4):275-282. Epub 2016 Jan 18.

Department of Psychiatry, University of Vermont, Burlington, Vermont.

Background: Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood.

Methods: Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of temporal discounting in a large cohort (n = 1830) of 14- to 15-year-old children. Mediation analysis was then used to determine whether the volumes of brain regions associated with temporal discounting mediate the relation between adverse life events (e.g., family conflict, serious accidents) and antisocial behaviors (e.g., precocious sexual activity, bullying, illicit substance use).

Results: Greater temporal discounting (more impulsivity) was associated with 1) lower volume in frontomedial cortex and bilateral insula and 2) greater volume in a subcortical region encompassing the ventral striatum, hypothalamus and anterior thalamus. The volume ratio between these cortical and subcortical regions was found to partially mediate the relation between adverse life events and antisocial behavior.

Conclusions: Temporal discounting is related to regions of the brain involved in reward processing and interoception. The results support a developmental imbalance model of impulsivity and are consistent with the idea that negative environmental factors can alter the developing brain in ways that promote antisocial behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopsych.2015.12.027DOI Listing
August 2017