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Wild felids are one of the most vulnerable species due to habitat loss caused by fragmentation of ecosystems. We analyzed the effect of a structural corridor, defined as a strip of vegetation connecting two habitat patches, on the richness and habitat occupancy of felids on three sites in Marqués de Comillas, Chiapas, one with two isolated forest patches, the second with a structural corridor, and the third inside the Montes Azules Biosphere Reserve. We found only two species (L. pardalis and H. yagouaroundi) in the isolated forest patches, five species in the structural corridor, and four species inside the Reserve. The corridor did not significantly affect occupancy, but due to the low detection rates, further investigation is needed to rule out differences. Our results highlight the need to manage habitat connectivity in the remaining forests in order to preserve the felid community of Marqués de Comillas, Chiapas, México.

To determine whether untreated grade 3 posterolateral knee injuries contribute to a significant increase in force on a posterior cruciate ligament reconstruction graft, we measured the force on the graft during joint loading of a posterior cruciate ligament-reconstructed knee with otherwise intact structures and then selectively cut the popliteofibular ligament, popliteus tendon, and the fibular collateral ligament. A posterior cruciate ligament reconstruction was performed in eight fresh-frozen cadaveric knees. One end of the graft was fixed to a tensioning jig with a load cell used to measure force in the graft as loads were applied to the knee. The force on the graft was significantly higher with the posterolateral structures cut during varus loading at 30 degrees, 60 degrees, and 90 degrees of flexion than it was in the same joint under the same loading conditions but with the posterolateral structures intact. Additionally, coupled loading of posterior drawer force and external tibial torque at 30 degrees, 60 degrees, and 90 degrees significantly increased force on the graft with the posterolateral structures cut. There was no significant increase in force on the graft under any condition with a posterior force, valgus force, or internal and external tibial torque applied alone. A significant increase in force occurs in a posterior cruciate ligament graft in knees with deficient posterolateral knee structures. We recommend that in knees with grade 3 posterolateral injuries and evidence of varus or coupled posterior-external rotation instability the posterolateral structures be repaired or reconstructed at the time of posterior cruciate ligament reconstruction to decrease the chance of later graft failure. [ABSTRACT FROM AUTHOR]

Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative., Competing Interests: Competing interests statement:The authors declare no competing interest.

PARP1, an established anti-cancer target that regulates many cellular pathways, including DNA repair signaling, has been intensely studied for decades as a poly(ADP-ribosyl)transferase. Although recent studies have revealed the prevalence of mono-ADP-ribosylation upon DNA damage, it was unknown whether this signal plays an active role in the cell or is just a byproduct of poly-ADP-ribosylation. By engineering SpyTag-based modular antibodies for sensitive and flexible detection of mono-ADP-ribosylation, including fluorescence-based sensors for live-cell imaging, we demonstrate that serine mono-ADP-ribosylation constitutes a second wave of PARP1 signaling shaped by the cellular HPF1/PARP1 ratio. Multilevel chromatin proteomics reveals histone mono-ADP-ribosylation readers, including RNF114, a ubiquitin ligase recruited to DNA lesions through a zinc-finger domain, modulating the DNA damage response and telomere maintenance. Our work provides a technological framework for illuminating ADP-ribosylation in a wide range of applications and biological contexts and establishes mono-ADP-ribosylation by HPF1/PARP1 as an important information carrier for cell signaling., Competing Interests: Declaration of interests E.J.L., H.D., J.J.B., T.C., and I.M. declare the following competing financial interests: Max-Planck-Innovation, the technology transfer center of the Max Planck Society, has licensed the antibodies AbD33204, AbD33205, AbD33644, AbD34251, AbD33641, and AbD43647 to Bio-Rad Laboratories., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Wildlife pedigrees provide insights into ecological and evolutionary processes. DNA obtained from noninvasively collected hair is often used to determine individual identities for pedigrees and other genetic analyses. However, detection rates associated with some noninvasive DNA studies can be relatively low, and genetic data do not provide information on individual birth year. Supplementing hair DNA stations with video cameras should increase the individual detection rate, assuming accurate identification of individuals via video data. Video data can also provide birth year information for individuals captured as young of the year, which can enrich population-level pedigrees. We placed video cameras at hair stations and combined genetic and video data to reconstruct an age-specific, population-level pedigree of wild black bears during 2010-2020. Combining individual birth year with mother-offspring relatedness, we also estimated litter size, interlitter interval, primiparity, and fecundity. We used the Cormack-Jolly-Seber model in Program Mark to evaluate the effect of maternal identity on offspring apparent survival. We compared model rankings of apparent survival and parameter estimates based on combined genetic and video data with those based on only genetic data. We observed 42 mother-offspring relationships. Of these, 21 (50%) would not have been detected had we used hair DNA alone. Moreover, video data allowed for the cub and yearling age classes to be determined. Mean annual fecundity was 0.42 (95% CI: 0.27, 0.56). Maternal identity influenced offspring apparent survival, where offspring of one mother experienced significantly lower apparent survival (0.39; SE = 0.15) than that of offspring of four other mothers (0.89-1.00; SE = 0.00-0.06). We video-documented cub abandonment by the mother whose offspring experienced low apparent survival, indicating individual behaviors (e.g., maternal care) may scale up to affect population-level parameters (e.g., cub survival). Our findings provide insights into evolutionary processes and are broadly relevant to wildlife ecology and conservation., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Alcohol use disorder (AUD) is a chronic debilitating disorder with limited treatment options and poorly defined pathophysiology. There are substantial genetic and epigenetic components; however, the underlying mechanisms contributing to AUD remain largely unknown. We conducted the largest DNA methylation epigenome-wide association study (EWAS) analyses currently available for AUD (total N = 625) and employed a top hit replication (N = 4798) using a cross-tissue/cross-phenotypic approach with the goal of identifying novel epigenetic targets relevant to AUD. Results show that a network of differentially methylated regions in glucocorticoid signaling and inflammation-related genes were associated with alcohol use behaviors. A top probe consistently associated across all cohorts was located in the long non-coding RNA growth arrest specific five gene (GAS5) (p < 10 -24 ). GAS5 has been implicated in regulating transcriptional activity of the glucocorticoid receptor and has multiple functions related to apoptosis, immune function and various cancers. Endophenotypic analyses using peripheral cortisol levels and neuroimaging paradigms showed that methylomic variation in GAS5 network-related probes were associated with stress phenotypes. Postmortem brain analyses documented increased GAS5 expression in the amygdala of individuals with AUD. Our data suggest that alcohol use is associated with differential methylation in the glucocorticoid system that might influence stress and inflammatory reactivity and subsequently risk for AUD., (© 2020. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Fear conditioning and extinction (FCE) are vital processes in adaptive emotion regulation and disrupted in anxiety disorders. Despite substantial comorbidity between alcohol dependence (ALC) and anxiety disorders and reports of altered negative emotion processing in ALC, neural correlates of FCE in this clinical population remain unknown. Here, we used a 2-day fear learning paradigm in 43 healthy participants and 43 individuals with ALC at the National Institutes of Health. Main outcomes of this multimodal study included structural and functional brain magnetic resonance imaging, clinical measures, as well as skin conductance responses (SCRs) to confirm differential conditioning. Successful FCE was demonstrated across participants by differential SCRs in the conditioning phase and no difference in SCRs to the conditioned stimuli in the extinction phase. The ALC group showed significantly reduced blood oxygenation level-dependent responses in the right amygdala during conditioning (Cohen's d = .89, P (FWE) = .037) and in the left amygdala during fear renewal (Cohen's d = .68, P (FWE) = .039). Right amygdala activation during conditioning was significantly correlated with ALC severity (r = .39, P (Bonferroni) = .009), depressive symptoms (r = .37, P (Bonferroni) = .015), trait anxiety (r = .41, P (Bonferroni) = .006), and perceived stress (r = .45, P (Bonferroni) = .002). Our data suggest that individuals with ALC have dysregulated fear learning, in particular, dysregulated neural activation patterns, in the amygdala. Furthermore, amygdala activation during fear conditioning was associated with ALC-related clinical measures. The FCE paradigm may be a promising tool to investigate structures involved in negative affect regulation, which might inform the development of novel treatment approaches for ALC., (© Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: Smoking reexposure after a quit attempt (i.e., lapse) increases relapse risk, but lapse recovery is possible. Using a 6-day analogue model of smoking cessation and lapse, this study tested the effect of a single lapse cigarette on the risk of subsequent smoking. Abstinence self-efficacy (ASE) and depressive symptoms (using the Center for Epidemiological Studies Depression Scale, CES-D) were also examined as hypothesized moderators of lapse recovery., Method: After receiving cessation counseling and achieving 2 days of incentivized abstinence, 54 daily smokers (mean age: 41 years, 61% African American, 63% male) were randomly assigned to smoke 1 cigarette or to a no-lapse control condition. Participants were then offered monetary incentives to abstain for 3 more days and smoking was monitored., Results: Compared to the control condition, participants who experienced a lapse had a 2.5 times greater risk of smoking in the first 24 hours Furthermore, a lapse resulted in much greater risk of subsequent smoking compared to the control condition among individuals with lower postquit ASE scores (p = .044) and greater CES-D scores (p = .040)., Conclusions: These findings provide preliminary evidence that a single lapse cigarette after quitting plays a causal role in subsequent smoking and suggest that individuals with lower postquit ASE and greater depressive symptoms are less likely to recover from a lapse. Future research should investigate factors associated with lapse recovery and failure so that effective lapse-responsive strategies can be developed. Laboratory models provide an efficient and controlled method to examine such processes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Alcohol withdrawal syndrome (AWS) is a serious medical condition of high variability in alcohol use disorder (AUD) after drinking cessation. Identification of clinical biomarkers capable of detecting severe AWS is needed. While alcohol consumption and withdrawal are linked with lipid profile dysregulation, the relationship between lipid levels (high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) and AWS is unknown. Therefore, this study investigated whether HDL-C, LDL-C, and triglycerides conferred risk for moderate-to-severe AWS symptoms in treatment-seeking individuals (n = 732) admitted to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) alcohol treatment program. Lipid levels were measured upon admission, and the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) assessed AWS severity for generating a three-level AWS typology (none-to-mild, moderate, and severe). Multivariable multinomial logistic regression examined whether lipid levels were associated with risk for moderate-to-severe AWS. We found significant predictive relationships between AWS and HDL-C, LDL-C, and triglycerides. While extremely high HDL-C (≥100 mg/dL) conferred the highest odds for moderate (4.405, 95% CI, 2.572-7.546, p < 0.001) and severe AWS (5.494, 95% CI, 3.541-8.523, p < 0.001), the lowest odds ratios for moderate AWS (0.493, 95% CI, 0.248-0.981, p = 0.044) and severe AWS (0.303, 95% CI, 0.223-0.411, p < 0.001) were associated with high LDL-C (≥160 mg/dL). The present study demonstrates that altered lipid levels, measured upon admission for inpatient AUD treatment, may help to predict which individuals are at risk for medically relevant moderate-to-severe AWS. This suggests that further research into the role of lipid biomarkers in AWS may be beneficial for identifying biologically determined risk profiles in AUD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Published by Elsevier Inc.)

Aim: High-intensity binge drinking (HIBD), defined as two or more times the gender-specific binge threshold, is rapidly increasing in the USA; however, the underlying contributing factors are poorly understood. This study investigated the relationship of adverse childhood experiences (ACEs) and HIBD., Methods: Two independent, cross-sectional samples were analysed: (a) past 12-month drinkers in the National Epidemiological Survey on Alcohol and Related Conditions-III (NESARC-III; n = 25,552) and (b) the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample (n = 1303). Multinomial logistic regressions were utilized to estimate adjusted odds ratios (AORs) of ACEs on HIBD. Mediation analysis was performed to examine the relationship between the past 12-month psychiatric disorders, ACEs, and HIBD., Results: In the NESARC-III sample, prevalence of ACEs increased across all binge levels with the highest prevalence in extreme HIBD; ACEs were associated with higher odds for HIBD (level II, odds ratio (OR) = 1.2-1.4; P = 0.03-0.001; level III, OR = 1.3-1.9; P < 0.001). Prevalence of DSM-5 diagnoses also increased across all binge levels. Substance use disorders (SUD), mood, personality and post-traumatic stress disorders (PTSD) conferred the highest odds with extreme HIBD (SUD: OR = 21.32; mood: 1.73; personality: 2.84; PTSD: 1.97; all Ps < 0.001). Mediation analyses showed that the association between ACEs and HIBD was fully mediated through SUD (proportion mediated: 70-90%) and partially through other psychiatric disorders (20-80%). In the NIAAA sample, ACEs were 2-5 times more prevalent in extreme HIBD with higher odds (ORs = 3-8, P < 0.001) compared with non-bingers., Conclusion: ACEs were associated with significantly increased odds of HIBD and the relationship may be mediated by psychiatric disorders., (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

To investigate the potential role of alcohol use disorder (AUD) in aging processes, we employed Levine's epigenetic clock (DNAm PhenoAge) to estimate DNA methylation age in 331 individuals with AUD and 201 healthy controls (HC). We evaluated the effects of heavy, chronic alcohol consumption on epigenetic age acceleration (EAA) using clinical biomarkers, including liver function test enzymes (LFTs) and clinical measures. To characterize potential underlying genetic variation contributing to EAA in AUD, we performed genome-wide association studies (GWAS) on EAA, including pathway analyses. We followed up on relevant top findings with in silico expression quantitative trait loci (eQTL) analyses for biological function using the BRAINEAC database. There was a 2.22-year age acceleration in AUD compared to controls after adjusting for gender and blood cell composition (p = 1.85 × 10 -5 ). This association remained significant after adjusting for race, body mass index, and smoking status (1.38 years, p = 0.02). Secondary analyses showed more pronounced EAA in individuals with more severe AUD-associated phenotypes, including elevated gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT), and higher number of heavy drinking days (all ps < 0.05). The genome-wide meta-analysis of EAA in AUD revealed a significant single nucleotide polymorphism (SNP), rs916264 (p = 5.43 × 10 -8 ), in apolipoprotein L2 (APOL2) at the genome-wide level. The minor allele A of rs916264 was associated with EAA and with increased mRNA expression in hippocampus (p = 0.0015). Our data demonstrate EAA in AUD and suggest that disease severity further accelerates epigenetic aging. EAA was associated with genetic variation in APOL2, suggesting potential novel biological mechanisms for age acceleration in AUD.

Importance: The prevalence of high-intensity binge drinking (HIBD), defined as consuming 2 or more times the binge threshold defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), is rapidly increasing in the United States. While the relationship between alcohol consumption and lipid and liver function enzyme (LFT) biomarkers has been previously examined, the associations of HIBD with those biomarkers remain unknown., Objective: To examine associations of HIBD with lipid and LFT levels in a cross-sectional sample enriched with participants who engage in HIBD., Design, Setting, and Participants: Cross-sectional study using data from the NIAAA clinical sample collected from March 3, 2005, to August 21, 2017, with participants recruited for either the NIAAA screening protocols or inpatient alcohol treatment program. For this study, participants were stratified by self-reported alcohol consumption into 4 sex-specific binge levels: nonbinge and 1, 2, and 3 or more times the binge threshold (levels I, II, and III). Multivariable analyses examined the odds of clinically high levels of lipids and LFTs across binge levels. Analyses were performed from December 3, 2018, to January 30, 2019., Main Outcomes and Measures: Serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase., Results: A total of 2065 participants underwent protocol screening; 1519 with data available on alcohol consumption, body mass index, lipid levels, and LFT levels were included in the final analyses. Mean (SD) age was 39.7 (12.1) years; mean (SD) body mass index was 26.6 (5.1); 978 (64.4%) were male; 718 (47.3%) were white; and 578 (31.1%) consumed alcohol at the nonbinge level, 321 (21.2%) at level I, 239 (15.7%) at level II, and 318 (25.1%) at level III. High-intensity binge drinking was associated with 2- to 8-fold increased odds for clinically high levels of HDL-C, total cholesterol, triglycerides, and all LFTs (eg, for HDL-C: level III odds ratio [OR], 8.65; 95% CI, 4.75-15.77 and for γ-glutamyltransferase: level III OR, 8.21; 95% CI, 5.90-11.43). Increased HIBD frequency (days consuming at levels II and III) was associated with increased odds for clinically high levels of HDL-C, total cholesterol, and all LFTs (per unit increase in days consuming at the respective binge level) (eg, for HDL-C: level II OR, 1.025; 95% CI, 1.014-1.036 and level III OR, 1.033; 95% CI, 1.019-1.047 and for γ-glutamyltransferase: level II OR, 1.028; 95% CI, 1.019-1.037 and level III OR, 1.033; 95% CI, 1.019-1.047)., Conclusions and Relevance: High-impact binge drinking was significantly associated with increased odds for clinically high levels of lipids and LFTs. Given that HIBD is increasingly common among US adults, targeted interventions aimed at reducing HIBD may have important health benefits.

Background: Recent studies have shown that alcohol use affects the regulation and expression of proprotein convertase subtilisin/kexin 9 (PCSK9). While a major role of PCSK9 in hepatic function and lipid regulation has been clearly established, other pleiotropic effects remain poorly understood. Existing research suggests a positive association between PCSK9 expression in the brain and psychopathology, with increased levels of PCSK9 in the cerebrospinal fluid (CSF) of individuals with dementia and epigenetic modifications of PCSK9 associated with alcohol use disorder (AUD). In this study, we hypothesized that chronic alcohol use would increase PCSK9 expression in CSF., Methods: PCSK9 levels in CSF were measured in individuals with AUD (n = 42) admitted to an inpatient rehabilitation program and controls (n = 25). CSF samples in AUD were assessed at 2 time points, at day 5 and day 21 after admission. Furthermore, plasma samples were collected and measured from the individuals with AUD., Results: PCSK9 in CSF was significantly increased in the AUD group at day 5 and day 21 compared to the controls (p < 0.0001). Plasma PCSK9 levels were correlated positively with CSF PCSK9 levels in AUD (p = 0.0493)., Conclusions: Our data suggest that PCSK9 is elevated in the CSF of individuals with AUD, which may indicate a potential role of PCSK9 in AUD. Additional studies are necessary to further elucidate the functions of PCSK9 in the brain., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Aims: Differences in DNA methylation of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression and predict brain functions in healthy individuals. This study investigated the association between SLC6A4 promoter methylation and threat-related amygdala activation in individuals with alcohol dependence (AD)., Methods: Methylation of the SLC6A4 promoter region was assessed using peripheral blood DNA from 45 individuals with AD and 45 healthy controls (HCs). All participants completed an emotional face matching task in a 3-T magnetic resonance imaging (MRI) scanner., Results: Results did not reveal any association between SLC6A4 promoter methylation variation and threat-related amygdala activation in HCs or individuals with AD. Furthermore, methylation in the promoter region of SLC6A4 did not significantly differ between the groups., Conclusions: Our results do not replicate a previous finding that increased methylation in the promoter region of SLC6A4 is associated with threat-related amygdala activation in healthy individuals and further show that there is no such association in individuals with AD. Given that the number of imaging epigenetics studies on SLC6A4 is very limited to date, these inconsistent results indicate that future research is needed to clarify its association with amygdala reactivity in both healthy and clinical populations., (Medical Council on Alcohol and Oxford University Press 2019.)

Objective: This study investigated psychological influences on drug withdrawal symptomatology using a caffeine-based model., Methods: Using the 2 × 2 balanced placebo design caffeine dose (given caffeinated vs decaffeinated coffee) was crossed with dose expectancy (told caffeine vs. decaf) among 87 (16-hr abstinent) regular coffee consumers in a 2-day study., Results: There were effects of expectancy and pharmacology that differed depending on the measure. Those told decaf reported greater caffeine cravings than those told caffeine 45 min and 8 hr postmanipulation. There were no expectancy effects on withdrawal symptoms or cognitive performance. There were pharmacological effects on all measures. Those given decaf reported greater withdrawal symptoms and showed poorer cognitive performance 45 min and 8 hr postmanipulation, with effects for headache and flu-like symptoms first emerging 8 hr postmanipulation (i.e., 24 hr abstinence in given decaf conditions). Caffeine readministration alleviated all withdrawal symptoms and cognitive decrements within 45 min. No drug by expectancy interactions were observed., Conclusions: These findings confirm a strong pharmacological basis for caffeine withdrawal and an important role of cognition in drug craving. Future research should investigate the role of expectancy in drug withdrawal and craving and the potential use of expectancy manipulations in symptom prevention and management., (© 2019 John Wiley & Sons, Ltd.)

Alcohol dependence (ALC) is a chronic, relapsing disorder that increases the burden of chronic disease and significantly contributes to numerous premature deaths each year. Previous research suggests that chronic, heavy alcohol consumption is associated with differential DNA methylation patterns. In addition, DNA methylation levels at certain CpG sites have been correlated with age. We used an epigenetic clock to investigate the potential role of excessive alcohol consumption in epigenetic aging. We explored this question in five independent cohorts, including DNA methylation data derived from datasets from blood (n = 129, n = 329), liver (n = 92, n = 49), and postmortem prefrontal cortex (n = 46). One blood dataset and one liver tissue dataset of individuals with ALC exhibited positive age acceleration (p < 0.0001 and p = 0.0069, respectively), whereas the other blood and liver tissue datasets both exhibited trends of positive age acceleration that were not significant (p = 0.83 and p = 0.57, respectively). Prefrontal cortex tissue exhibited a trend of negative age acceleration (p = 0.19). These results suggest that excessive alcohol consumption may be associated with epigenetic aging in a tissue-specific manner and warrants further investigation using multiple tissue samples from the same individuals.

Dopamine transporters (DAT) are implicated in the pathogenesis and treatment of attention-deficit hyperactivity disorder (ADHD) and are upregulated by chronic treatment with methylphenidate, commonly prescribed for ADHD. Methylation of the DAT1 gene in brain and blood has been associated with DAT expression in rodents' brains. Here we tested the association between methylation of the DAT1 promoter derived from blood and DAT availability in the striatum of unmedicated ADHD adult participants and in that of healthy age-matched controls (HC) using Positron Emission Tomography (PET) and [ 11 C]cocaine. Results showed no between-group differences in DAT1 promoter methylation or striatal DAT availability. However, the degree of methylation in the promoter region of DAT1 correlated negatively with DAT availability in caudate in ADHD participants only. DAT availability in VS correlated with inattention scores in ADHD participants. We verified in a postmortem cohort with ADHD diagnosis and without, that DAT1 promoter methylation in peripheral blood correlated positively with DAT1 promoter methylation extracted from substantia nigra (SN) in both groups. In the cohort without ADHD diagnosis, DAT1 gene expression in SN further correlated positively with DAT protein expression in caudate; however, the sample size of the cohort with ADHD was insufficient to investigate DAT1 and DAT expression levels. Overall, these findings suggest that peripheral DAT1 promoter methylation may be predictive of striatal DAT availability in adults with ADHD. Due to the small sample size, more work is needed to validate whether DAT1 methylation in blood predicts DAT1 methylation in SN in ADHD and controls., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Introduction: Many African Americans live in communities with a disproportionately high density of tobacco advertisements compared to Whites. Some research indicates that point-of-sale advertising is associated with impulse purchases of cigarettes and smoking. Ecological Momentary Assessment (EMA) can be used to examine associations between tobacco advertisement exposure and smoking variables in the natural environment., Methods: Non-treatment seeking African American smokers were given a mobile device for 2weeks (N=56). They were prompted four times per day and responded to questions about recent exposure to tobacco advertisements. Participants were also asked to indicate the number of cigarettes smoked, and if they made any purchase, or an impulse purchase, since the last assessment. Linear mixed models (LMMs) analyzed between- and within-subject associations between exposure and outcomes., Results: Participants reported seeing at least one advertisement on 33% of assessments. Of those assessments, they reported seeing menthol advertisements on 87% of assessments. Between-subject analyses revealed that participants who on average saw more advertisements were generally more likely to report purchasing cigarettes and to purchase cigarettes on impulse. Within-subject analyses revealed that when an individual participant reported seeing more advertisements than usual they were more likely to have reported purchasing cigarettes, making an impulse purchase and smoking more cigarettes during the same period, but not the subsequent time period., Conclusions: Many African American smokers are frequently exposed to pro-tobacco marketing. Advertisement exposure is cross-sectionally associated with impulse purchases and smoking. Future research should assess prospective associations in more detail., (Published by Elsevier Ltd.)

Alcohol dependence (AD) frequently co-occurs with major depressive disorder (MDD). While this comorbidity is associated with an increase in disease burden, worse treatment outcomes, and greater economic costs, the underlying neurobiology remains poorly understood. A recent large-scale GWAS of MDD has identified a locus in the TMEM161B-MEF2C region (rs10514299) as a novel risk variant; however, the biological relevance of this variant has not yet been studied. Given previous reports of disrupted reward processing in both AD and MDD, we hypothesized that rs10514299 would be associated with differences in striatal BOLD responses during reward/loss anticipation in AD. DNA samples from 45 recently detoxified patients with AD and 45 healthy controls (HC) were genotyped for rs10514299. Participants performed the Monetary Incentive Delay task in a 3-Tesla MRI scanner. Effects of rs10514299 on striatal activation during anticipation of high/low reward/loss were investigated. Furthermore, we examined associations between rs10514299 and lifetime AD diagnosis in two independent clinical samples [NIAAA: n = 1858 (1123 cases, 735 controls); SAGE: n = 3838 (1848 cases, 1990 controls)], as well as its association with depression severity in a subsample of individuals with a lifetime AD diagnosis (n = 953). Patients carrying the T allele showed significantly greater putamen activation during anticipation of high reward (p = 0.014), low reward (at trend-level; p = 0.081), high loss (p = 0.024), and low loss (p = 0.046) compared to HCs. Association analyses in the NIAAA sample showed a trend-level relationship between rs10514299 and a lifetime AD diagnosis in the European American subgroup (odds ratio = 0.82, p = 0.09). This finding was not replicated in the SAGE sample. In the NIAAA sample, the T allele was significantly associated with greater depression symptom severity in individuals with a lifetime AD diagnosis (β = 1.25, p = 0.02); this association was driven by the African American ancestry subgroup (β = 2.11, p = 0.008). We show for the first time that the previously identified MDD risk variant rs10514299 in TMEM161B-MEF2C predicts neuronal correlates of reward processing in an AD phenotype, possibly explaining part of the shared pathophysiology and comorbidity between the disorders.

Aims: Previous genetic association studies have shown that variation in the GATA4 gene encoding the GATA binding protein 4, a binding protein that binds to the ANA sequence GATA, increase susceptibility for alcohol use disorder (AUD). In this study, we aimed to replicate those findings in an independent sample and analyze their association with anxiety., Methods: Overall, 1044 individuals with AUD [534 European American (EA), 510 African Americans (AA)] and 645 controls [413 EA, 232 AA] were genotyped using 34 markers. Genotype and allele frequencies were compared between cases and controls using chi-square analysis. Other phenotype data were analyzed for possible associations with GATA4 single-nucleotide polymorphisms (SNPs) in individuals with AUD., Results: Rs6601604 was nominally significantly associated with AUD in EA, and 3 SNPs (rs6990313, rs11250159 and rs17153694) showed trend-level significance (P < 0.10) in AA. However, none of the SNPs were significant after correcting for multiple testing. Haplotype analysis of the 34 SNPs did not find a significant association between haplotype blocks and AUD diagnosis after correcting for multiple testing. From the phenotype analysis, anxiety was associated with GATA4 SNP rs10112596 among the AA group with AUD after a correction for multiple testing., Conclusions: Although previous studies have shown a relationship between variants of the GATA4 gene and a diagnosis of AUD, we did not replicate these findings in our sample. Additional studies of variation in this gene are needed to elucidate whether polymorphisms of the GATA4 gene are associated with AUD and other alcohol-related phenotypes., Short Summary: GATA4 variants were not associated with AUD in either the European ancestry or African ancestry groups after correcting for multiple comparisons. Rs10112596 demonstrated a significant relationship with an anxiety measure among the African ancestry group with AUD.