Factors underlying the neurofunctional domains of the Addictions Neuroclinical Assessment assessed by a standardized neurocognitive battery.

The Addictions Neuroclinical Assessment (ANA) is a neurobiologically-informed framework designed to understand the etiology and heterogeneity of Alcohol Use Disorder (AUD). Previous studies validated the three neurofunctional domains of ANA: Incentive Salience (IS), Negative Emotionality (NE) and Executive Function (EF) using secondary data. The present cross-sectional observational study assessed these domains in an independent, prospective clinical sample. Adults across the drinking spectrum (N = 300) completed the ANA battery, a standardized collection of behavioral tasks and self-report assessments. Factor analyses were used to identify latent factors underlying each domain. Associations between identified domain factors were evaluated using structural equation models. Receiver operating characteristics analyses were used to determine factors with the strongest ability to classify individuals with problematic drinking and AUD. We found (1) two factors underlie the IS domain: alcohol motivation and alcohol insensitivity. (2) Three factors were identified for the NE domain: internalizing, externalizing, and psychological strength. (3) Five factors were found for the EF domain: inhibitory control, working memory, rumination, interoception, and impulsivity. (4) These ten factors showed varying degrees of cross-correlations, with alcohol motivation, internalizing, and impulsivity exhibiting the strongest correlations. (5) Alcohol motivation, alcohol insensitivity, and impulsivity showed the greatest ability in classifying individuals with problematic drinking and AUD. Thus, the present study identified unique factors underlying each ANA domain assessed using a standardized assessment battery. These results revealed additional dimensionality to the ANA domains, bringing together different constructs from the field into a single cohesive framework and advancing the field of addiction phenotyping. Future work will focus on identifying neurobiological correlates and identifying AUD subtypes based on these factors.

The role of resilience in the relationship between stress and alcohol.

Stress plays a well-documented role in alcohol consumption and the risk for developing alcohol use disorder. The concept of resilience - coping with and successfully adapting to stressful life experiences - has received increasing attention in the field of addiction research in recent decades, and there has been an accumulation of evidence for resilience as a protective factor against problematic alcohol consumption, risk for alcohol use disorder, disorder severity, and relapse. The conceptual and methodological approaches used in the generation of this evidence vary considerably across investigations, however. In light of this, we carried out this review in order to provide a more thorough understanding of the meaning and scope of resilience, what factors contribute to resilience, how it is measured, and how it relates to alcohol-associated phenotypes. Implications for treatment through the use of resilience-building interventions are likewise discussed, as well as implications for future research on the role of resilience in the etiology and clinical outcomes of alcohol use disorder.

Gut microbial diversity and functional characterization in people with alcohol use disorder: A case-control study.

Individuals with Alcohol Use Disorder (AUD) typically have comorbid chronic health conditions, including anxiety and depression disorders, increased sleep disruption, and poor nutrition status, along with gut microbial dysbiosis. To better understand the effects of gut dysbiosis previously shown in individuals with AUD, gut microbiome and metabolome were investigated between three cohorts. Two groups of individuals with AUD included treatment-seeking newly abstinent for at least six weeks (AB: N = 10) and non-treatment-seeking currently drinking (CD: N = 9) individuals. The third group was age, gender, and BMI-matched healthy controls (HC: N = 12). Deep phenotyping during two weeks of outpatient National Institutes of Health Clinical Center visits was performed, including clinical, psychological, medical, metabolic, dietary, and experimental assessments. Alpha and beta diversity and differential microbial taxa and metabolite abundance of the gut microbiome were examined across the three groups. Metabolites derived from the lipid super-pathway were identified to be more abundant in the AB group compared to CD and HC groups. The AB individuals appeared to be most clinically different from CD and HC individuals with respect to their gut microbiome and metabolome. These findings highlight the potential long-term effects of chronic alcohol use in individuals with AUD, even during short-term abstinence.

Parosmia Is Positively Associated With Problematic Drinking, as Is Phantosmia With Depressive Symptoms.

OBJECTIVES: Alcohol use disorder (AUD) is a global health problem with significant negative consequences, including preventable deaths. Although olfactory dysfunction is associated with chronic alcohol drinking, the relationship among specific types of olfactory deficits, depressive symptoms, and problematic drinking remains to be explored. Here, we examined the prevalence of olfactory distortion (parosmia) and hallucination (phantosmia) and assessed their associations with problematic drinking and depressive symptoms. METHODS: In April-June 2022, 250 participants across the spectrum of AUD were recruited for assessment in the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol study. Surveys covered self-reported olfactory function, depressive symptoms, and problematic drinking, with key measures assessed, including the Alcohol Use Disorders Identification Test and the Patient Health Questionnaire. Predictors in the analysis included parosmia and phantosmia, with covariates comprising age, sex, socioeconomic status, race, ethnicity, COVID-19 infection status, and smoking status. RESULTS: Among 250 individuals, 5.2% experienced parosmia and 4.4% reported phantosmia. Parosmia was associated with higher Alcohol Use Disorders Identification Test scores (ß = 7.14; 95% confidence interval = 3.31, 10.96; P < 0.001), whereas phantosmia was linked to higher Patient Health Questionnaire scores (ß = 3.32; 95% confidence interval = 0.22, 6.42; P = 0.03). These associations persisted in both the full sample and the subset of participants without COVID-19. CONCLUSIONS: Our study highlights strong existing links among olfactory deficits, problem drinking, and depressive symptoms, underscoring the need to assess smell impairments in clinical settings. Future research should explore these connections further to develop new treatments for individuals with AUD and depression.

Changes in rest-activity rhythms in adolescents as they age: associations with brain changes and behavior in the ABCD study.

Background: Adolescents with disrupted rest-activity rhythms (RAR) including shorter sleep duration, later sleep timing and low physical activity levels have higher risk for mental and behavioral problems. However, it remains unclear whether the same associations can be observed for within-subject changes in RAR. Methods: Our longitudinal investigation on RAR used Fitbit data from the Adolescent Brain Cognitive Development (ABCD) Study at the 2-year (FL2: aged 10-13 years) and 4-year follow-up (FL4: aged 13-16 years). 963 youths had good-quality Fitbit data at both time points. In this study we examined changes in RAR from FL2 to FL4, their environmental and demographic contributors as well as brain and behavioral correlates. Results: From FL2 to FL4, adolescents showed decreases in sleep duration and physical activity as well as delayed sleep timing (Cohen's d .44-.75). The contributions of environmental and demographic factors to RAR changes were greatest to sleep timing (explained 10% variance) and least to sleep duration (explained 1% variance). Delays in sleep timing had stronger correlations with behavioral problems including greater impulsivity and poor academic performance than reductions in sleep duration or physical activity. Additionally, the various brain measures differed in their sensitivity to RAR changes. Reductions in sleep duration were associated with decreased brain functional connectivity between subcortical regions and sensorimotor and cingulo-opercular networks and with enhanced functional connectivity between sensorimotor, visual and auditory networks. Delays in sleep timing were mainly associated with grey matter changes in subcortical regions. Conclusions: The current findings corroborate the role of sleep and physical activity in adolescent's brain neurodevelopment and behavior problems. RAR might serve as biomarkers for monitoring behavioral problems in adolescents and to serve as potential therapeutic targets for mental disorders.

Associations of history of alcohol use disorder with loneliness, social support, and mental health during the COVID-19 pandemic.

This study examined the effects of alcohol use disorder (AUD) and treatment history on changes in loneliness, social support, and mental health symptoms from before to during the pandemic, and tested loneliness and social support as mediators of the AUD-mental health associations. Participants (n = 427) enrolled in the NIAAA COVID-19 Pandemic Impact on Alcohol Study were categorized into three groups: healthy control (62.3%), nontreatment AUD (14.1%), and treatment AUD (23.7%). Multilevel generalized linear models were conducted to examine changes in loneliness, social support, and mental health symptoms by group. Path analyses tested the mediating roles of loneliness and social support. Loneliness increased during the pandemic, especially in the nontreatment AUD group. Social support decreased in the healthy control and AUD treatment group. Anxiety and depressive symptoms increased in the nontreatment AUD group. Individuals with a history of AUD regardless of treatment history reported greater loneliness, which was linked to higher anxiety and depressive symptoms. Loneliness, but not social support, mediated the AUD-mental health associations. Psychosocial interventions aimed at increasing positive social engagement among individuals with AUD may help alleviate feelings of loneliness and mitigate mental health symptoms. Study findings can also help improve preparedness for future public health crises.

Exercising healthy behaviors: A latent class analysis of positive coping during the COVID-19 pandemic and associations with alcohol-related and mental health outcomes.

OBJECTIVE: To identify latent classes of positive coping behaviors during the COVID-19 pandemic and examine associations with alcohol-related and mental health outcomes across participants with and without a history of alcohol use disorder (AUD). METHODS: Baseline data from 463 participants who were enrolled in the NIAAA COVID-19 Pandemic Impact on Alcohol (C19-PIA) Study were analyzed. Latent class analysis (LCA) was applied to five positive coping behaviors during COVID-19: taking media breaks, taking care of their body, engaging in healthy behaviors, making time to relax, and connecting with others. Latent class differences and the moderating role of history of AUD on six alcohol-related and mental health outcomes were examined using multiple regression models. RESULTS: LCA revealed two latent classes: 83.4% High Positive Coping and 16.6% Low Positive Coping. Low Positive Coping was associated with higher levels of perceived stress, anxiety symptoms, and loneliness. A history of AUD was consistently associated with higher levels of alcohol-related and mental health outcomes. Significant interactions between Coping Latent Classes and history of AUD indicated that the associations of Low Positive Coping with problematic alcohol use, depressive symptoms, and drinking to cope motives were either stronger or only significant among individuals with a history of AUD. CONCLUSIONS: Individuals with a history of AUD may be particularly vulnerable to depressive symptoms and alcohol-related outcomes, especially when they do not utilize positive coping strategies. The promotion of positive coping strategies is a promising avenue to address alcohol-related and mental health problems during a public health crisis and warrants future research.

Stress and alcohol-related coping mechanisms linking lifetime suicide ideation and attempt to multidimensional quality of life.

BACKGROUND: Suicide ideation and attempt are linked to adverse mental health outcomes, but few studies have examined their associations with quality of life (QoL). This study examined the impact of lifetime history of suicidal ideation and attempt on four QoL domains via perceived stress and problematic drinking. METHODS: Participants were drawn from the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol (N = 1055), including those with no history of suicidality (78.6 %), suicidal ideation only (15.3 %), and a history of suicide attempt (6.2 %). Structural equation modeling (SEM) was utilized to test perceived stress and drinking as mediational pathways to multidimensional QoL. RESULTS: Individuals with a history of suicide ideation and/or attempt reported higher perceived stress in the past month, more problematic drinking in the past year, and lower QoL domains in the past two weeks. SEM showed significant mediation effects through dimensions of perceived stress (helplessness, lack of self-efficacy) and alcohol problems. When these mediators were considered simultaneously, the mediation effects through alcohol problems were attenuated, while several direct effects of suicidality on physical, psychological, and social QoL were weakened but remained significant. LIMITATIONS: Cross-sectional data with retrospective report of suicidality history. CONCLUSIONS: A lifetime history of suicidality was associated with lower multidimensional QoL. These associations were partially explained by stress and alcohol-related coping mechanisms such as feeling helpless or inadequate when encountering stressors and problematic drinking. Perceived stress and drinking to cope may be important intervention targets to improve QoL among those with a history of suicidality.

Early life stress and body-mass-index modulate brain connectivity in alcohol use disorder.

Early life stress (ELS) significantly increases susceptibility to alcohol use disorder (AUD) by affecting the interplay between the executive and the salience networks (SNs). The link between AUD and higher body-mass index (BMI) is known, but we lack understanding of how BMI impacts the relationship between ELS and brain connectivity in individuals with AUD. To bridge this gap, we investigated the main and interaction effects of ELS and BMI on brain connectivity in individuals with AUD compared to non-AUD participants (n = 77 sex-matched individuals per group). All participants underwent resting-state functional magnetic resonance imaging, revealing intriguing positive functional connectivity between SN seeds and brain regions involved in somatosensory processing, motor coordination and executive control. Examining the relationship of brain connectivity with ELS and BMI, we observed positive associations with the correlations of SN seeds, right anterior insula (RAIns) and supramarginal gyrus (SMG) with clusters in motor [occipital cortex, supplementary motor cortex]; anterior cingulate cortex (ACC) with clusters in frontal, or executive, control regions (middle frontal gyrus; MFG, precentral gyrus) that reportedly are involved in processing of emotionally salient stimuli (all |ß | > 0.001, |p | < 0.05). Interestingly, a negative association of the interaction effect of ELS events and BMI measures with the functional connectivity of SN seeds ACC with decision-making (MFG, precentral gyrus), RAIns and RSMG with visuo-motor control regions (occipital cortex and supplementary motor cortex) (all |ß | = -0.001, |p | < 0.05). These findings emphasize the moderating effect of BMI on ELS-associated SN seed brain connectivity in AUD. Understanding the neural mechanisms linking BMI, ELS and AUD can guide targeted interventions for this population.

Disrupted brain state dynamics in opioid and alcohol use disorder: attenuation by nicotine use.

Substance use disorder (SUD) is a chronic relapsing disorder with long-lasting changes in brain intrinsic networks. While most research to date has focused on static functional connectivity, less is known about the effect of chronic drug use on dynamics of brain networks. Here we investigated brain state dynamics in individuals with opioid use (OUD) and alcohol use disorder (AUD) and assessed how concomitant nicotine use, which is frequent among individuals with OUD and AUD, affects brain dynamics. Resting-state functional magnetic resonance imaging data of 27 OUD, 107 AUD, and 137 healthy participants were included in the analyses. To identify recurrent brain states and their dynamics, we applied a data-driven clustering approach that determines brain states at a single time frame. We found that OUD and AUD non-smokers displayed similar changes in brain state dynamics including decreased fractional occupancy or dwell time in default mode network (DMN)-dominated brain states and increased appearance rate in visual network (VIS)-dominated brain states, which were also reflected in transition probabilities of related brain states. Interestingly, co-use of nicotine affected brain states in an opposite manner by lowering VIS-dominated and enhancing DMN-dominated brain states in both OUD and AUD participants. Our finding revealed a similar pattern of brain state dynamics in OUD and AUD participants that differed from controls, with an opposite effect for nicotine use suggesting distinct effects of various drugs on brain state dynamics. Different strategies for treating SUD may need to be implemented based on patterns of co-morbid drug use.

Dietary linoleic acid lowering alone does not lower arachidonic acid or endocannabinoids among women with overweight and obesity: A randomized, controlled trial.

The linoleic acid (LA)-arachidonic acid (ARA)-inflammatory axis suggests dietary LA lowering benefits health because it lowers ARA and ARA-derived endocannabinoids (ECB). Dietary LA reduction increases concentrations of omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DHA derived ECB. The aim of this study was to examine targeted reduction of dietary LA, with and without EPA and DHA, on plasma EPA and DHA and ECB (2-arachidonoyl glycerol [2-AG], anandamide [AEA], and docosahexaenoyl ethanolamide [DHA-EA]). Healthy, pre-menopausal women (n = 62, BMI 30 ± 3 kg/m2 , age 35 ± 7 years; mean ± SD) were randomized to three 12-week controlled diets: (1) high LA, low omega-3 EPA and DHA (H6L3); (2) low LA, low omega-3 EPA and DHA (L6L3); or (3) low LA, high omega-3 EPA and DHA (L6H3). Baseline plasma fatty acids and ECB were similar between diets. Starting at 4 weeks, L6L3 and L6H3 lowered plasma LA compared to H6L3 (p < 0.001). While plasma ARA changed from baseline by 8% in L6L3 and -8% in L6H3, there were no group differences. After 4 weeks, plasma EPA and DHA increased from baseline in women on the L6H3 diet (ps < 0.001) and were different than the H6L3 and L6L3 diets. No differences were found between diets for AEA or 2-AG, however, in L6L3 and L6H3, AEA increased by 14% (ps < 0.02). L6H3 resulted in 35% higher DHA-EA (p = 0.013) whereas no changes were seen with the other diets. Lowering dietary LA did not result in the expected changes in fatty acids associated with the LA-ARA inflammatory axis in women with overweight and obesity.

Social media addiction as a mediator of the associations between fear of COVID-19, mental health symptoms, and problematic alcohol use.

Background: Fear of COVID-19 is a risk factor for anxiety and depressive symptoms. During the COVID-19 pandemic, drinking to cope with psychological distress has been proposed as a key mechanism leading to problematic drinking. The goal of this study was to test social media addiction as a mediator linking fear of COVID-19 to mental health symptoms and problematic alcohol use. Methods: In between April 6 and July 2 of 2022, 250 participants completed an online survey as part of the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol Study. Path analyses were conducted to test the mediational pathways. Results: Using the polythetic classification scheme, 13.2% (n = 33) of participants were classified as having social media addiction. Compared with participants without social media addiction, participants with social media addiction spent significantly more time on social media platforms and on digital communications with a family member or friend. They also reported greater fear of COVID-19, higher anxiety symptoms, and higher depressive symptoms. Path analyses indicated that social media addiction mediated the associations of fear of COVID-19 with anxiety and depressive symptoms. Furthermore, there were indirect pathways linking fear of COVID-19 to problematic alcohol use through higher social media addiction and higher anxiety and depressive symptoms. Conclusion: Social media addiction may be a maladaptive coping mechanism that individuals with high fear of COVID-19 utilized to deal with uncertainty and perceived risks during the pandemic. Findings underscore the need to examine cognitions related to fear of COVID-19 and address excessive social media use in the context of mental health and alcohol interventions.

Low Dopamine D2 Receptor Expression Drives Gene Networks Related to GABA, cAMP, Growth and Neuroinflammation in Striatal Indirect Pathway Neurons.

Background: A salient effect of addictive drugs is to hijack the dopamine reward system, an evolutionarily conserved driver of goal-directed behavior and learning. Reduced dopamine type 2 receptor availability in the striatum is an important pathophysiological mechanism for addiction that is both consequential and causal for other molecular, cellular, and neuronal network differences etiologic for this disorder. Here, we sought to identify gene expression changes attributable to innate low expression of the Drd2 gene in the striatum and specific to striatal indirect medium spiny neurons (iMSNs). Methods: Cre-conditional, translating ribosome affinity purification (TRAP) was used to purify and analyze the translatome (ribosome-bound messenger RNA) of iMSNs from mice with low/heterozygous or wild-type Drd2 expression in iMSNs. Complementary electrophysiological recordings and gene expression analysis of postmortem brain tissue from human cocaine users were performed. Results: Innate low expression of Drd2 in iMSNs led to differential expression of genes involved in GABA (gamma-aminobutyric acid) and cAMP (cyclic adenosine monophosphate) signaling, neural growth, lipid metabolism, neural excitability, and inflammation. Creb1 was identified as a likely upstream regulator, among others. In human brain, expression of FXYD2, a modulatory subunit of the Na/K pump, was negatively correlated with DRD2 messenger RNA expression. In iMSN-TRAP-Drd2HET mice, increased Cartpt and reduced S100a10 (p11) expression recapitulated previous observations in cocaine paradigms. Electrophysiology experiments supported a higher GABA tone in iMSN-Drd2HET mice. Conclusions: This study provides strong molecular evidence that, in addiction, inhibition by the indirect pathway is constitutively enhanced through neural growth and increased GABA signaling.

Novel paradigms for the gut-brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder.

Introduction: Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Methods: Forty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). Results: CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1ß and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R2 = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). Discussion: The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking. Trial registration: ClinicalTrials.gov, identifier: NCT# 00106106.

Effects of clustering and timing of early life stress exposure on mood problems, ADHD symptoms, and problematic drinking.

OBJECTIVE: Exposure to early life stress (ELS) may lead to long-term health consequences. The Early Life Stress Questionnaire (ELSQ) is a retrospective measure of multiple ELS and their timing. Latent class analysis (LCA) has not been applied to the ELSQ and questions regarding timing are rarely explored. This study examined the effects of clustering and timing of ELS exposure on internalizing and externalizing symptoms. METHOD: Data from 1095 participants in the NIAAA Natural History Protocol were analyzed. LCA was conducted on 18 ELS items. Regression and correlational analyses examined associations of latent classes with sociodemographic variables and clinical outcomes. RESULTS: LCA revealed three classes: Class 1: Minimal ELS (54.2%), Class 2: Moderate ELS (33.2%), and Class 3: Multiple and High ELS (12.6%). Black/African American participants were more likely to be in Class 2, and participants with low household income were more likely to be in Classes 2 and 3. Family history of problematic alcohol use and individual alcohol use disorder diagnosis were linked to Classes with higher ELS exposure. Compared with Class 1, Class 2 reported higher anxiety symptoms, depressive symptoms, ADHD symptoms, and problematic drinking, and Class 3 reported the highest levels across all these outcomes. Regarding timing, earlier exposure to ELS (e.g., sustained family conflict and witnessed domestic violence) was associated with higher psychopathological symptoms. CONCLUSIONS: The ELSQ can effectively capture clustering and timing of exposure to multiple ELS. Greater and earlier exposure to ELS were positively associated with internalizing and externalizing symptoms, underscoring the need for early and well-timed intervention.

Preliminary evidence for changes in frontoparietal network connectivity in the early abstinence period in alcohol use disorder: a longitudinal resting-state functional magnetic resonance imaging study.

The early abstinence period is a crucial phase in alcohol use disorder (AUD) in which patients have to find a new equilibrium and may start recovery, or conversely, relapse. However, the changes in brain functions during this key period are still largely unknown. We set out to study longitudinal changes in large-scale brain networks during the early abstinence period using resting-state scans. We scanned AUD patients twice in a well-controlled inpatient setting, with the first scan taking place shortly after admission and the second scan 4 weeks (±9 days) later near the end of the treatment period. We studied 37 AUD patients (22 males) and 27 healthy controls (16 males). We focused on three networks that are affected in AUD and underly core symptom dimensions in this disorder: the frontoparietal networks (left and right FPN) and default mode network (DMN). Both the whole brain and within network connectivity of these networks were studied using dual regression. Finally, we explored correlations between these brain networks and various neuropsychological and behavioral measures. In contrast to the controls (Z = -1.081, p = 0.280), the AUD patients showed a decrease in within left FPN connectivity (Z = -2.029, p = 0.042). However, these results did not survive a strict Bonferroni correction. The decrease in left FPN connectivity during the early abstinence period in AUD may reflect an initially upregulated FPN, which recovers to a lower resting-state connectivity level during subsequent weeks of abstinence. The AUD patients showed a trend for a positive association between the change in left FPN connectivity and trait anxiety (rs = 0.303, p = 0.068), and a trend for a negative association between the change in left FPN connectivity and delay discounting (rs = -0.283, p = 0.089) (uncorrected for multiple comparisons). This suggests that the FPN might be involved in top-down control of impulsivity and anxiety, which are important risk factors for relapse. Although there were no statistically significant results (after multiple comparison correction), our preliminary findings encourage further research into the dynamic neuroadaptations during the clinically crucial early abstinence period and could inform future study designs.

Early Life Stress and Body-Mass Index Modulate Brain Connectivity in Alcohol Use Disorder.

Early life stress (ELS) significantly increases susceptibility to alcohol use disorder (AUD) by affecting the interplay between executive and salience networks (SN). The link between AUD and higher body-mass index (BMI) is known, but we lack understanding of how BMI impacts the relationship between ELS and brain connectivity in individuals with AUD. To bridge this gap, we investigated the effects of ELS on brain connectivity in AUD participants, taking into account differences in BMI. The cohort included 401 individuals with AUD, with approximately 60% having a BMI ≥ 25. Within the overall cohort, 123 participants underwent resting-state functional magnetic resonance imaging, revealing intriguing anticorrelations between SN seeds and brain regions involved in somatosensory processing, motor coordination, and executive control as an effect of ELS. Examining the relationship between ELS-driven brain connectivity and BMI, we observed negative correlations in connectivity among low BMI (≤ 24.9) vs. high BMI (≥ 25) individuals. For example, the left supramarginal gyrus (SMG) seed exhibited decreased connectivity with emotion regulation and decision-making regions, including the right occipital cortex, posterior cingulate cortex, and precuneus clusters (all |ß| < -0.03, |p| < 0.05). Additionally, the right SMG seed showed reduced connectivity with impulse control and executive function regions, such as the left postcentral/middle frontal gyrus cluster (ß = 0.04, p = 0.02). These findings highlight the role of ELS-induced alterations in SN seed connectivity, influenced by BMI, in the neurobiology of AUD. Understanding the neural mechanisms linking obesity, AUD, and ELS can guide targeted interventions for this population.

Investigating the relationship between early life adversity, inflammation and alcohol use.

Early life adversity (ELA) has long-lasting and potentially harmful effects on adult mental and physical health, including a higher likelihood of developing psychiatric conditions such as depression, anxiety and alcohol use disorder (AUD). It has been suggested that inflammation may play a role in linking ELA to the development of AUD. Here, we evaluated a number of predictive factors of high sensitivity C-reactive protein (hsCRP), a key inflammatory marker, and the potential mediating role of hsCRP in the relationship between ELA and alcohol misuse in adulthood. Data was collected from participants who participated in NIAAA screening protocols between January 2013 and December 2019. In this secondary analysis, we first tested, via multiple linear regression, potential predictors of hsCRP levels among adults with AUD (N = 781) and non-AUD (N = 440) individuals. We subsequently conducted mediation analyses to evaluate the potential role of hsCRP in the relationship between early life stress and alcohol use. Regression analysis showed that stress in early life, but not childhood trauma, significantly predicted increased hsCRP levels in adulthood (p < 0.05). Additionally, a greater amount of alcohol drinking, but not a diagnosis of AUD, significantly predicted increased hsCRP levels (p < 0.05). Furthermore, hsCRP mediated the relationship between early life stress and alcohol consumption. Early life stress and heavier alcohol drinking both predicted increased hsCRP levels; however, an AUD diagnosis did not. Elevated inflammation, due to and/or predicted by greater early life stress, may contribute to the development of unhealthy alcohol use in adulthood.

Chemosensory Alterations and Impact on Quality of Life in Persistent Alcohol Drinkers.

BACKGROUND: Heavy alcohol consumption-associated chemosensory dysfunction is understudied, and early detection can help predict disease-associated comorbidities, especially those related to four quality of life (QOL) domains (physical, psychological, social and environment). We examined self-reports of chemosensory ability of individuals with different alcohol drinking behaviors and their association with changes in QOL domains. METHODS: Participants (n = 466) were recruited between June 2020 and September 2021 into the NIAAA COVID-19 Pandemic Impact on Alcohol study. Group-based trajectory modeling was used to categorize participants without any known COVID-19 infection into three groups (non-drinkers, moderate drinkers and heavy drinkers) based on their Alcohol Use Disorders Identification Test consumption scores at four different time points (at enrollment, week 4, week 8 and week 12). Linear mixed models were used to examine chemosensory differences between these groups. The associations between chemosensory abilities and QOL were determined in each group. RESULTS: We observed significant impairment in self-reported smell ability of heavy drinking individuals compared to non-drinkers. In contrast, taste ability showed marginal impairment between these groups. There were no significant differences in smell and taste abilities between the moderate and non-drinking groups. Heavy drinkers' impairment in smell and taste abilities was significantly associated with deterioration in their physical, psychological, social and environmental QOL. CONCLUSION: Persistent heavy drinking was associated with lower chemosensory ability. Heavy drinkers' reduced smell and taste function and association with poorer QOL indicate that early assessment of chemosensory changes may be crucial in identifying poorer well-being outcomes in heavy drinkers at risk for alcohol use disorder.

A person-centered approach to capture health disparities and multidimensional impact of COVID-related stressors.

The COVID-19 pandemic has influenced people's lives in diverse ways. The authors utilized latent class analysis (LCA), a person-centered approach, to examine distinct patterns of COVID-related stressors and their associations with alcohol-related, mental health, and quality of life outcomes. Participants were 463 adults who completed the baseline assessment of the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol Study from June 2020 to January 2022. Using cross-sectional data, three analytic methods (continuous sum score, categorical grouping, and LCA) were applied to model 17 COVID-related stressors. Regression analyses indicated higher COVID-related stress and endorsement of four or more COVID-related stressors were generally associated with worse health-related outcomes. LCA revealed four classes: Class 1: Minimal COVID-Related Impact (51.6%); Class 2: Work Interruptions (24.8%); Class 3: Family/Friends Affected by COVID (14.5%); and Class 4: Serious Financial Stress (9.1%). Racial/ethnic minorities were more likely to be in Class 3, whereas individuals with more years of education and higher income were less likely to be in Class 4. Individuals with a history of alcohol use disorder were more likely to be in Classes 2 and 4. Compared with Class 1, Class 4 reported highest levels of perceived stress, problematic alcohol use, anxiety symptoms, depressive symptoms, alcohol craving, loneliness, drinking to cope, and lowest levels of physical, psychological, social, and environment quality of life. COVID-related stressors disproportionately affected minority and vulnerable groups. Individuals who experienced multiple financial stressors had the greatest risk for negative health-related outcomes and may benefit from holistic interventions and community outreach. (PsycInfo Database Record (c) 2023 APA, all rights reserved).