Neuropsychopharmacology

Associations between the fat mass and obesity-associated (FTO) gene and obesity are well-established. However, recent studies have linked FTO to addiction phenotypes and dopaminergic signaling, thus suggesting broader psychiatric implications. We explored this assumption by conducting a phenome-wide association study (PheWAS) across 4,756 genome-wide association studies (GWASs), identifying 26 psychiatric traits associated with FTO at the multiple-corrected significance level. These traits clust...

Alcohol use disorder (AUD) is known to have a significant genetic component, yet there remains a substantial gap between its heritability and findings from genome-wide association studies. One potential factor contributing to this gap may be genetic interactions, or epistasis, a largely unexplored aspect in the context of AUD. The aim of this study was to investigate the role of epistasis in AUD susceptibility and severity among American Indians, a population that exhibits the highest rates of A...

World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have higher prevalence (23%) of persistent, clinically significant WTC-related post-traumatic stress disorder (WTC-PTSD). Here, we applied eigenvector centrality (EC) metrics and data driven methods on resting state functional magnetic resonance (fMRI) outcomes to investigate neural mechanisms underlying WTC-PTSD and to identify how EC shifts in brain areas relate to WTC-exposu...

Background and AimsCertain symptoms of problematic alcohol use (PAU) show associations with comorbid internalizing and externalizing disorders even after controlling for their common PAU factor. Outsized associations between PAU indicators and comorbid psychopathology may reflect distinct etiologic pathways or measurement characteristics that, if unaccounted for, could bias comorbidity estimates with PAU. Although these issues could represent a source of bias in estimates of genetic correlation ...

BackgroundGenetic influences account for a substantial proportion of individual differences in alcohol use behaviors (AUBs). However, multiple distinct sets of genes are linked to different AUBs, which may explain their dramatic variability in risk factors and manifestations. In this study, we explore whether intermediate neurobiological traits and alcohol-related cognitions mediate the relationship between polygenic scores (PGS) and multiple AUBs, with the aim to better understand processes cap...

As the global burden of addiction intensifies, the neurobiological commonalities and distinctions between substance use disorders (SUDs) and behavioral addictions (BAs) remain poorly characterized. This coordinate-based meta-analysis of 59 fMRI articles (n = 2,951) mapped the neural signatures of visual cue-reactivity across the addictive disorders. Our results revealed a universal core network shared by SUDs and BAs centered in the bilateral opercular inferior frontal gyrus, suggesting a shared...

AimTo determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case-control studies examining gray matter alterations in substance use disorders (SUD) and obsessive-compulsive disorder (OCD). DesignPre-registered voxel-based meta-analysis of grey matter volume (GMV) changes through seed-based d Mapping (SDM), follow-up functional, and network-level characterization of the identified transdiagnostic regions by means of co-activation a...

BackgroundCharting the clinical course of substance use disorders (SUDs) to identify etiologic contributors to milestone onset and progression could inform intervention efforts. MethodsWe calculated polygenic risk scores (PRS) in 5,692 European-ancestry individuals (EUR) (56.2% male) and 4,918 African-ancestry (AFR) individuals (54.9% male) using genome-wide association studies (GWAS) of alcohol use disorder (AUD), opioid use disorder (OUD), and smoking trajectory (SMK). Using Cox regression, w...

ImportanceTraumatic brain injury (TBI) increases the risk of developing psychiatric symptoms such as post-traumatic stress disorder (PTSD), depression and anxiety, however biological risk and resiliency factors that explain the significant heterogeneity in outcomes are limited. Although 5-10% of the population carries natural autoantibodies to the NMDA receptor (anti-NMDAR1) it is unknown if carrying anti-NMDAR1 autoantibodies modifies risk for psychiatric outcomes after TBI. ObjectiveSince TBI...

Novel interventions are urgently needed to treat methamphetamine use disorder (MUD), for which there are no FDA-approved treatments. Previous studies in patients with MUD suggest transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L. dlPFC) decreases craving for methamphetamine. Theta burst stimulation (TBS), which includes intermittent TBS and continuous TBS (cTBS), is increasingly being used for substance use disorders, including MUD. Previous reviews of TMS i...

ObjectivesProblematic sexual behavior (PSB) is defined by recurrent sexual behaviors that are difficult to control, causing social and functional impairments. PSB can co-occur with reward deficiency syndrome (RDS), but this relationship remains unclear. RDS has been associated with the 10/10 genotype of 3 variable number tandem repeat (VNTR) in the dopamine transporter gene SLC6A3, which is implicated in the reward pathway. This study investigates the genetic relationship between PSB and RDS, te...

AimsWe performed a latent class analysis (LCA) in a sample ascertained for addiction phenotypes to investigate cocaine use disorder (CoUD) subgroups related to polysubstance addiction (PSA) patterns and characterized their differences with respect to psychiatric and somatic comorbidities. DesignCross-sectional study SettingUnited States ParticipantsAdult participants aged 18-76, 39% female, 47% African American, 36% European American with a lifetime DSM-5 diagnosis of CoUD (N=7,989) enrolled ...

Meta-analysis shows that sub-clusters defined by affected domains of psychosocial functioning capture PTSD subtypes better than symptom clusters defined in the DSM-IV. This pilot study investigated the association between symptom sub-clusters and brain volume in twelve persons with PTSD (females, mean age 40.9 years). Structural magnetic resonance imaging (MRI) images were acquired, and voxel-based morphometry (VBM) was used to estimate local gray matter volume throughout the brain. Participants...

Despite decades of clinical implementation of medications for opioid use disorder (OUD), overdose mortality rates remain high, underscoring a critical gap in treatments that target brain mechanisms driving addiction. Mindfulness-Oriented Recovery Enhancement (MORE) has demonstrated efficacy in reducing opioid use and craving, hypothetically by restructuring the salience of drug and natural rewards. Yet, to date, MOREs neurobiological mechanisms remain unclear. In this first functional magnetic r...

IntroductionCurrent understanding of the differences in sleep disturbance (SD) and associated risk factors in patients with alcohol use disorders (AUD), major depressive disorders (MDD), and comorbid AUD+MDD is limited. MethodsData from the UK Biobank (UKB) (n=47,825) were utilized to categorize subjects into those with MDD (n=5,991), AUD (n=12,952), both (MDD+AUD)(n=3,219), and controls (n=25,663). We used generalized linear models (GLMs) to test whether rates of SD and sleep duration differed...

BackgroundTranscranial Magnetic, Electrical, and Focused-Ultrasound Stimulation (TMS/tES/tFUS) are major noninvasive brain stimulation (NIBS) techniques used to treat various psychiatric disorders, including substance use disorders (SUDs). Although NIBS with varying stimulation parameters shows promising effects on drug-related behaviors such as craving and consumption/relapse, the question of which protocol is most effective remains unresolved. MethodTo address this gap, we conducted a living ...

ImportanceHeroin addiction is rampant and persistent, with devastating consequences to the public health, necessitating further study into the neurobiological mechanisms of drug cue-reactivity and craving-reducing interventions (e.g., reappraisal and savoring). ObjectiveTo document cortico-striatal reactivity during passive viewing, reappraisal, and savoring, as predictors of heroin craving in individuals with heroin use disorder (iHUD) vs. controls. DesignA cross-sectional study (11/2020-09/2...

Binge drinking is a relatively common pattern of alcohol use among youth with normative frequency trajectories peaking in emerging and early adulthood. Frequent binge drinking is a critical risk factor for not only the development of alcohol use disorders (AUDs) but also increased odds of alcohol-related injury and death, and thus constitutes a significant public health concern. Changes in binge drinking across development are strongly associated with changes in impulsive personality traits (IPT...

Methadone (MET) and buprenorphine (BUP)--mu-opioid receptor (MOR) agonists--are efficacious treatments for opioid use disorder (OUD). Using high-sensitivity, long axial field-of-view PET imaging with [11C]carfentanil, we compared MOR availability in 5 MET and 5 BUP patients and 13 healthy controls (HCs) in five brain regions: ventral tegmentum, thalamus, caudate, putamen, and amygdala. MOR availability differed across groups (F10,34=5.6, p<0.001) and was lower in BUP patients than HCs across all...

Full abstractO_ST_ABSBackgroundC_ST_ABSPrevious studies in people with substance use disorders (SUDs) have implicated both the frontopolar cortex and amygdala in drug cue reactivity and craving, and amygdala-frontopolar coupling is considered a marker of early relapse risk. Accumulating data highlight that the frontopolar cortex can be considered a promising therapeutic target for transcranial magnetic stimulation (TMS) in SUDs. However, one-size-fits-all approaches to TMS targets resulted in su...