Marked response to VNS in a post-cingulotomy patient: Implications for the mechanism of action of VNS in TRD

AbstractTreatment-resistant major depression (TRMD, major depressive disorder that fails to respond to numerous therapies) is a relatively common and clinically challenging disorder. In many cases, the most severely affected TRMD patients have received surgical intervention (subcaudate tractotomy, limbic leucotomy, anterior capsulotomy, and anterior cingulotomy). New treatments, including vagus nerve stimulation (VNS) and deep brain stimulation, have emerged to treat individuals with TRMD. We describe the case of a woman, 53 years of age, with a long and sustained history of TRMD (33 years), which was unresponsive to numerous treatments (multiple pharmacotherapies, psychotherapy, electroconvulsive therapy [ECT]). Additionally, her TRMD failed to respond to a bilateral anterior cingulotomy. She underwent placement of a cervical vagus nerve stimulator and a brief course of ECT (3 unilateral treatments). Her depression improved markedly, and it has remained in sustained remission for 3.5 years. This case suggests a potential synergistic effect of VNS and ECT, as well as provides possible clues to the neural circuitry of VNS in TRMD.</jats:p

Evaluation of Cortical Thickness after Traumatic Brain Injury in Military Veterans

Military service members frequently sustain traumatic brain injuries (TBI) while on active duty, a majority of which are related to explosive blasts and are mild in severity. Studies evaluating the cortical gray matter in persons with injuries of this nature remain scarce. The purpose of this study was to assess cortical thickness in a sample of military veterans with chronic blast-related TBI. Thirty-eight veterans with mild TBI and 17 veterans with moderate TBI were compared with 58 demographically matched healthy civilians. All veterans with TBI sustained injuries related to a blast and were between 5 and 120 months post-injury (M?=?62.08). Measures of post-traumatic stress disorder (PTSD) and depression were administered, along with a battery of neuropsychological tests to assess cognition. The Freesurfer software package was used to calculate cortical thickness of the participants. Results demonstrated significant clusters of cortical thinning in the right hemispheric insula and inferior portions of the temporal and frontal lobe in both mild and moderate TBI participants. The TBI sample from this study demonstrated a high incidence of comorbid PTSD and depression symptoms, which is consistent with the previous literature. Cortical thickness values correlated with measures of PTSD, depression, and post-concussive symptoms. This study provides evidence of cortical thinning in the context of chronic blast-related mild and moderate TBI in military veterans who have comorbid psychiatric symptoms. Our findings provide important insight into the natural progression of long-term cortical change in this population and may have implications for future clinical evaluation and treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140169/1/neu.2015.3918.pd

Relationship between abuse and neglect in childhood and diabetes in adulthood: Differential effects by sex, national longitudinal study of adolescent health

INTRODUCTION: Few studies have investigated links between child abuse and neglect and diabetes mellitus in nationally representative samples, and none have explored the role of obesity in the relationship. We sought to determine whether child abuse and neglect were associated with diabetes and if so, whether obesity mediated this relationship in a population-representative sample of young adults. METHODS: We used data from 14,493 participants aged 24 to 34 years from Wave IV of the National Longitudinal Study of Adolescent Health to study associations between self-reported child abuse (sexual, physical, or emotional abuse) and neglect as children and diabetes or prediabetes in young adulthood. We conducted sex-stratified logistic regression analyses to evaluate associations in models before and after the addition of body mass index (BMI) as a covariate. RESULTS: Although the prevalence of diabetes was similar for men and women (7.0% vs 6.7%), men were more likely than women to have prediabetes (36.3% vs 24.6%; omnibus P < .001). Among men, recurrent sexual abuse (≥3 lifetime incidents) was significantly associated with diabetes (OR, 3.66; 95% CI, 1.31–10.24), but not with prediabetes. There was no evidence of mediation by BMI. No forms of child abuse or neglect were associated with diabetes or prediabetes among women. CONCLUSIONS: Recurrent sexual abuse is robustly associated with diabetes in young adult men, independently of other forms of child abuse or neglect and BMI. Future research should explore other potential mechanisms for this association to identify avenues for prevention of diabetes among men who have experienced sexual abuse

Computational Discovery of Lanthanide Doped and Co-Doped Y₃Al₅O₁₂ for Optoelectronic Applications

We systematically elucidate the optoelectronic properties of rare-earth doped and Ce co-doped yttrium aluminum garnet (YAG) using hybrid exchange-correlation functional based density functional theory. The predicted optical transitions agree with the experimental observations for single doped Ce:YAG, Pr:YAG, and co-doped Er,Ce:YAG. We find that co-doping of Ce-doped YAG with any lanthanide except Eu and Lu lowers the transition energies; we attribute this behavior to the lanthanide-induced change in bonding environment of the dopant atoms. Furthermore, we find infrared transitions only in case of the Er, Tb, and Tm co-doped Ce:YAG and suggest Tm,Ce:YAG and Tb,Ce:YAG as possible functional materials for efficient spectral up-conversion devices

Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins:a retrospective cohort study

Background: Early and frequent cannabis use are associated with an increased likelihood of major depressive disorder (MDD) as well as suicidal thoughts and behaviours. We identify associations between aspects of cannabis use, MDD, and suicidal thoughts and behaviours and examine whether such associations persist after accounting for those predisposing factors, including genetic liability and early family environment, that are shared by identical twins who are discordant for cannabis exposure. Any residual association in such identical pairs might be indicative of individual-specific pathways that might be of a causal nature. Methods: We did a logistic regression analysis of cannabis use from retrospective data on same-sex male and female twin pairs drawn from 3 studies that had recruited twins from the Australian Twin Registry, 1992–93 (sample 1), 1996–2000 (sample 2), and 2005–09 (sample 3). We studied associations between early use and frequent use of cannabis and MDD, suicidal ideation (ever and persistent), and suicide plan and attempt in the full sample as well as in pairs of monozygotic and dizygotic twins that were discordant for each measure of cannabis involvement at a single timepoint. Significant monozygotic associations were further adjusted for covariates, such as early alcohol or nicotine use, early dysphoric or anhedonic mood, conduct disorder, and childhood sexual abuse. Interactions between each cannabis measure and sex, sample or study effects, and birth year category were also examined as covariates. Findings: In 13 986 twins (6181 monozygotic and 7805 dizygotic), cannabis use ranged from 1345 (30·4%) of 4432 people in sample 1 to 2275 (69·0%) of 3299 in sample 3. Mean age of first cannabis use ranged from 17·9 years (SD 3·3) in sample 3 to 21·1 years (5·2) in sample 1, and frequent use (≥100 times) was reported by 214 (15·9%) of 1345 users in sample 1 and 499 (21·9%) of 2275 in sample 3. The prevalence of suicidal ideation ranged from 1102 (24·9%) of 4432 people in sample 1 to 1644 (26·3%) of 6255 people in sample 2 and 865 (26·2%) of 3299 people in sample 3. Prevalence of MDD ranged from 901 (20·3%) people in sample 1 to 1773 (28·3%) in sample 2. The monozygotic twin who used cannabis frequently was more likely to report MDD (odds ratio 1·98, 95% CI 1·11–3·53) and suicidal ideation (2·47, 1·19–5·10) compared with their identical twin who had used cannabis less frequently, even after adjustment for covariates. For early cannabis use, the monozygotic point estimate was not significant but could be equated to the significant dizygotic estimate, suggesting a possible association with suicidal ideation. Interpretation: The increased likelihood of MDD and suicidal ideation in frequent cannabis users cannot be solely attributed to common predisposing factors

A large-scale genome-wide association study meta-analysis of cannabis use disorder

BACKGROUND: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. METHODS: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. FINDINGS: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10 INTERPRETATION: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. FUNDING: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences

Clinical, environmental, and genetic risk factors for substance use disorders : characterizing combined effects across multiple cohorts

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (N-EUR = 12,659) and African (N-AFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.Peer reviewe

Reconfiguration, contestation, and decline: conceptualizing mature large technical systems

Large technical systems (LTS) are integral to modern lifestyles but arduous to analyze. In this paper, we advance a conceptualization of LTS using the notion of mature “phases,” drawing from insights into innovation studies, science and technology studies, political science, the sociology of infra- structure, history of technology, and governance. We begin by defining LTS as a unit of analysis and explaining its conceptual utility and novelty, situating it among other prominent sociotechnical theories. Next, we argue that after LTS have moved through the (overlapping) phases proposed by Thomas Hughes of invention, expansion, growth, momentum, and style,mature LTS undergo the additional (overlapping) phases of reconfiguration, contestation (subject to pressures such as drift and crisis), and eventually stagnation and decline. We illustrate these analytical phases with historical case studies and the conceptual literature, and close by suggesting future research to refine and develop the LTS framework, particularly related to more refined typologies, temporal dimensions, and a broadening of system users. We aim to contribute to theoretical debates about the coevolution of LTS as well as empirical discussions about system-related use, socio- technical change, and policy-making