搜索结果：Addiction neuroscience

Addiction is a brain disorder marked by profound inter-individual heterogeneity, a factor that limits the clinical utility of group-level neuroimaging findings. To address this, we constructed a precision neuroimaging framework to capture individual variability. We quantified gray matter volume (GMV) deviations in 464 individuals with five substance-related and addictive disorders using a normative model derived from over 1000 healthy controls. Subsequently, we applied a dimensionality reduction technique to decompose these individual deviations into distinct spatial patterns. We observe a shared pattern involving the insula and prefrontal cortex that reflects common underlying biology across different addictions. In contrast, a pattern centered on the basal ganglia captures the differences between specific addiction types. Importantly, only transdiagnostic factors correlated with clinical measures, whereas the heterogeneity factor did not. By resolving neurobiological heterogeneity into distinct, structural atrophy subtypes, this framework offers insights into understanding structural heterogeneity as a local effect of common networks. Addiction affects the brain differently in every person. This study aimed to map these individualized brain changes. We compared brain scans of 464 people with various addictions against over 1000 healthy individuals to measure personalized patterns of brain shrinkage. We found that addiction involves both shared and highly specific physical brain changes. Recognizing these subtypes helps the public understand that addiction is a biologically diverse condition.

Digitalisation and rapid technological advancements have intensified socio-cultural pressures surrounding body ideals and performance, contributing to the increased use of Image and Performance Enhancing Drugs (IPED). Body dissatisfaction, muscularity-oriented concerns, and distorted self-perception represent key drivers of this phenomenon and are further amplified by digital media, which increasingly promote IPED use. Although IPED use has been consistently associated with body image disturbances and eating-related psychopathology, its relationship with behavioural addictions remains largely underexplored. This represents a critical knowledge gap, given that IPEDs are often used to shape the body, regulate mood, sustain productivity, sharpen cognition, and intensify sexual experiences, all of which may contribute to compulsive patterns of behaviour. This narrative review synthesises existing literature examining IPED use in relation to behavioural addictions, including exercise addiction, eating disorders, work addiction, gaming disorder, gambling disorder, and compulsive sexual behaviour disorder. Moving beyond traditional doping frameworks, it examines how IPED use is shaped by appearance-related disorders, compulsive behaviours, and social validation pressures. Particular attention is given to the role of digital environments and online fora in facilitating access to IPEDs, normalising their use, and interacting with reinforcement processes in these conditions. By integrating previously fragmented lines of research, the review proposes a novel framework that conceptualises IPED use as recurring across diverse behavioural addictions rather than an isolated phenomenon confined to sport. Understanding the mechanisms linking IPED use, behavioural addictions, and digital contexts is crucial for informing targeted public health strategies and the development of effective prevention and intervention approaches.

Opioid use disorder is associated with high relapse risk and a persistent mismatch between intention and behavior. Contemporary neurobiological models have clarified the roles of reward learning, reinforcement, habit formation, salience attribution, stress adaptation, and executive-control dysfunction in relapse vulnerability. However, these mechanisms are not always translated into a clinically usable framework that links neurobiology with lived experience and relapse-prevention planning. The Informational Dysregulation Framework of Addiction (IDFA) was developed in response to this translational need, through structured integrative synthesis of addiction neuroscience, computational psychiatry, information theory, and clinical relapse research. IDFA conceptualizes relapse vulnerability in opioid use disorder as dysregulation in how the brain predicts, updates, and integrates information under uncertainty. The framework organizes relapse processes across three interacting domains: precision dysregulation, entropy and complexity disruption, and awareness and integration impairment. Together, these processes form a self-reinforcing loop that narrows informational bandwidth and behavioral flexibility across relapse trajectories. Alongside established reward- and habit-based accounts, IDFA provides an integrative information-processing perspective on how prediction, updating, and action selection become dysregulated during relapse vulnerability. This approach also generates clinically relevant hypotheses regarding relapse prediction, individualized case formulation, and mechanism-informed intervention planning across pharmacologic and psychosocial treatments.

The striatum plays a central role in the pathophysiology of addiction. Studies report that cannabis use is associated with greater striatal gray matter volume (GMV), while tobacco use is associated with both greater and lower striatal GMV. However, their combined effects on striatal GMV remain unclear. Using two MRI processing methods, we investigated associations between these substances and striatal GMV. Men and women from eight ENIGMA Addiction sites (N = 302) were parsed into 4 groups; individuals with: co-use (CT, n = 38); cannabis-only use (CO, n = 34); tobacco-only use (TO, n = 61), and controls (CTL, n = 169). Striatal GMV was assessed using (1) Freesurfer-extracted region-specific estimates and (2) voxel-based morphometry using FSL within a striatal mask. Analyses employed 2 × 2 ANCOVAs. With Freesurfer, a main effect of cannabis use (CT and CO) emerged in the right nucleus accumbens, and was replicated using FSL (ps ≤ 0.05). With FSL, main effects of cannabis use were found in the putamen and caudate (ps ≤ 0.01), and were modulated by tobacco use (cannabis-tobacco interaction ps ≤ 0.02). Post-hoc comparisons revealed: CT =  CTL >  TO in the putamen and caudate (ps ≤ 0.04); and CTL >  CO (ps ≤ 0.06) and CT >  CO (p = 0.03) in the caudate. Results demonstrate that in the putamen and caudate, individuals who co-use have greater GMV compared to those who use either substance alone, whereas individuals using either substance alone have lower GMV compared to controls. Future research should replicate our novel findings and investigate the clinical correlates of this unique pattern to clarify the functional significance of these findings.

Although opioids are effective analgesics, they can lead to problematic drug use behaviors that underlie opioid use disorder (OUD). Opioids also cause gut microbiota dysbiosis, which is linked to altered opioid responses. We used a longitudinal paradigm of voluntary oral morphine self-administration to capture multiple facets of drug seeking and preserve both individual behavioral responses and individual gut microbiota variation to investigate the role of the gut microbiota in a mouse model of OUD. Although all the mice consumed morphine, only a subset of the mice that transitioned to a state we defined statistically as compulsive. In compulsive mice, morphine constricted natural variability and fragmented the microbiota community networks, which convergently reorganized to form robust novel connections post-morphine. In contrast, the more variable communities of non-compulsive mice were highly interconnected during morphine disturbance and displayed more continuity post-morphine, suggesting greater flexibility and adaptability. Compulsive mice displayed a greater loss of functional diversity and a shift in favor of potential pathobionts, whereas non-compulsive mice better preserved genera associated with gut health and broader functional diversity. These findings highlight the potential role of persistent and stable opioid-induced microbiota dysbiosis in long-term behavioral changes underlying OUD and contributing to vulnerability to relapse.

Addiction is a heterogeneous disorder, and the specific psychological processes and neural mechanisms involved are hard to parse in humans. Animal models are useful in this regard, as biological substrates of addiction-relevant behaviors can be examined one at a time. Ventral pallidum GABAergic neurons (VPGABA), are key players in circuits underlying natural and drug reward, but the exact behavioral processes to which they contribute are still not precisely defined. Here we systematically examined the necessity of VPGABA neurons for opioid and food reward seeking and taking behaviors, using reversible chemogenetic inhibition in GAD1:Cre, predominately female, rats. We found that VPGABA inhibition revealed their preferential roles in highly-motivated pursuit and choice of heroin, but lesser involvement in unconditioned heroin effects, or in similarly motivated pursuit and choice of another rewarding opioid drug, remifentanil. Specifically, inhibiting VPGABA decreased cued- but not heroin-primed reinstatement of heroin seeking, decreased progressive ratio heroin pursuit, and increased selection of heroin over food when rats were forced to choose. In contrast, VPGABA inhibition did not alter remifentanil progressive ratio or choice of remifentanil over food, nor did it affect locomotion or food intake after heroin, or general arousal or anxiety-like states. These findings reveal a previously underappreciated specificity in the functions of VPGABA neurons, and show they may play distinct roles in overtly similar behaviors rewarded by different classes of opioid drugs. Results also highlight the usefulness, when investigating the biological substrates of addiction, of parsing heterogeneities not just in neural circuits, but also in the specific behavioral processes they mediate.Significance Statement Opioid addiction is a heterogeneous disorder, which makes it difficult to pinpoint the neural processes underlying its various components. Here we show that VPGABA neurons play surprisingly specific roles in behaviors relevant to opioid use disorder. VPGABA inhibition selectively reduced choice of heroin over food, highly-motivated heroin progressive ratio self-administration, and cue-triggered reinstatement, yet spared other heroin-induced behaviors. In contrast, closely matched behaviors motivated by the similarly-reinforcing fentanyl derivative remifentanil including choice of remifentanil over food, were spared. These results reveal unexpected reward- and process-specific functions of VPGABA neurons, highlighting the importance of comprehensive behavioral profiling in such experiments for identifying how neural mechanisms depend upon particular drugs and behavioral models-an essential step toward developing effective addiction interventions.

The entopeduncular nucleus (EP) is a major output nucleus of the basal ganglia and plays a critical role in integrating motor, emotional, and behavioral processes. Although traditionally linked to motor control, accumulating evidence indicates that the EP is deeply involved in psychiatric disorders, sleep regulation, addiction, and mood-related behaviors. As the rodent homolog of the human internal Globus pallidus (GP) the EP represents a key translational structure bridging preclinical and clinical neuroscience. This narrative review was conducted following established narrative review methodology. Relevant literature was identified through a structured search of major biomedical databases. Peer-reviewed experimental and clinical studies investigating EP anatomy, connectivity, neurotransmitter systems, and functional roles were included. The review synthesizes findings from mouse and rat models employing optogenetic and chemogenetic manipulation, electrophysiological recording, neuroanatomical tracing, molecular approaches, and behavioral assays, alongside human neuroimaging, lesion, and deep brain stimulation studies. Evidence from rodent models demonstrates that the EP functions as a convergence hub integrating GABAergic, glutamatergic, dopaminergic, serotonergic, and endocannabinoid signaling. EP projections to the lateral habenula regulate aversive processing, addiction-related behaviors, and mood states. Cell-type-specific mouse studies identify entopeduncular circuits implicated in anxiety regulation. Dysregulation of EP circuits is implicated in depression, anxiety, and Parkinsonian motor dysfunction. Clinical and preclinical neuromodulation studies further support the therapeutic relevance of targeting EP circuits. The EP is a multifunctional neural hub extending beyond motor control. Integrating evidence from rodent and human studies highlights its importance in psychiatric and sleep disorders and supports its potential as a translational therapeutic target. The entopeduncular nucleus (EP) functions extend beyond motor control to psychiatric regulation and sleep modulation.EP-lateral habenula projections are crucial for addiction and aversive behaviors.EP’s endocannabinoid system plays a vital role in sleep regulation and mood control.Deep brain stimulation of EP shows therapeutic potential for Parkinson’s disease and treatment-resistant depression.Novel therapeutic approaches targeting EP circuits are emerging for psychiatric disorders, including anxiety, Obsessive-compulsive disorder (OCD), and schizophrenia.Translation of preclinical findings to human applications remains a key challenge.

The difference between neuroimaging-predicted brain age and chronological age, the predicted age difference (PAD), has been studied as a potential biomarker reflecting individual brain health. Although previous large-scale studies have shown that brain age deviations occur across multiple disorders, cross-disorder comparisons of PAD within a unified framework, together with identification of the neuroimaging features associated with these differences and their related gene expression profiles, remain limited. Our aims are to systematically compare brain aging across multiple common brain disorders and explore the brain patterns and biological processes underlying these differences. In this study, structural MRI data from 45,900 healthy controls (HCs) and 2,698 patients with developmental disorders (attention-deficit/hyperactivity disorder [ADHD] and autism spectrum disorder [ASD]), addiction (alcohol use disorder [AUD], tobacco use disorder [TUD], and AUD&TUD-A&TUD), dementia (Alzheimer's disease [AD], and mild cognitive impairment [MCI]) or other psychiatric disorders (schizophrenia [SZ], bipolar disorder [BP], and major depressive disorder [MDD]), were collected to generate PAD, along with transcriptome data. Then, we calculated the PAD difference between patient and HC as Cohen's d effect sizes, derived from a linear model that accounted for age, age2, sex, and site, and further identified the interpretable brain patterns associated with the PAD difference for each diagnostic group. Finally, enrichment analyses was conducted to identify the biological function of genes relatively over- or underexpressed in association with these patterns. Results showed that while PAD was consistently greater across disorders, different brain disorders showed different degrees of abnormality, the highest effects in dementia (AD: d&#x2009;=&#x2009;0.97, 95% confidence interval (CI) [0.82,1.13]; p&#x2009;<&#x2009;0.001 and MCI: d&#x2009;=&#x2009;0.45, 95% CI [0.34,0.56]; p&#x2009;<&#x2009;0.001), followed by addiction (A&TUD: d&#x2009;=&#x2009;0.84, 95% CI [0.44,1.23]; p&#x2009;<&#x2009;0.001, TUD: d&#x2009;=&#x2009;0.72, 95% CI [0.49,0.96]; p&#x2009;<&#x2009;0.001, and AUD d&#x2009;=&#x2009;0.62, 95% CI [0.39,0.84]; p&#x2009;<&#x2009;0.001) and psychiatric disorders (SZ: d&#x2009;=&#x2009;0.53, 95% CI [0.30,0.76]; p&#x2009;<&#x2009;0.001, BP: d&#x2009;=&#x2009;0.46, 95% CI [0.22,0.69]; p&#x2009;<&#x2009;0.001 and MDD: d&#x2009;=&#x2009;0.28, 95% CI [0.11,0.46]; p&#x2009;<&#x2009;0.001), but not different from expected in developmental disorders (ASD: d&#x2009;=&#x2009;0.06, 95% CI [-0.04,0.16]; p&#x2009;=&#x2009;0.36) and ADHD: d&#x2009;=&#x2009;0.01, 95% CI [-0.14,0.15]; p&#x2009;=&#x2009;0.98). Furthermore, higher PAD values in patient groups were linked to specific spatial brain patterns, including the frontotemporal network in psychiatric disorders, default mode network-salience network-putamen-thalamus in addiction and fronto-occipital network in dementia. Prefrontal cortex involvement was common across disorders, and disorder-specific brain patterns associated genes were enriched in different biological processes. A limitation of our study is that psychiatric disorders and addiction have high comorbidity, and these potential confounders were not considered. In summary, the different brain aging patterns, each based around specific underlying circuits, may serve as neuroimaging biomarkers for understanding the neural aging mechanisms in commonly occurring brain disorders. Future studies should test whether these disorder-specific brain aging patterns can serve as useful biomarkers to guide critical clinical decision-making.

The Adolescent Brain Cognitive Development (ABCD) Study has substantially advanced developmental neuroscience through its large scale and open-science framework. This review synthesizes the study's significant statistical and methodological contributions over its first ten years, organized around the pillars of population neuroscience, longitudinal modeling, and causal inference. We first examine how ABCD's population-based design has prompted a reconsideration of how effect sizes are interpreted, helping to establish new benchmarks for distinguishing stable, biologically relevant signals from trivial associations in large-N contexts. We detail the computational innovations required to process high-dimensional data at scale, specifically highlighting new analytic tools like the Fast and Efficient Mixed Effects Algorithm (FEMA) framework for mass-univariate modeling and advanced strategies for managing selective attrition and missing data in large-scale longitudinal cohorts. In the domain of longitudinal and multilevel modeling, we discuss the transition from traditional cross-lagged designs to sophisticated frameworks - such as random-intercept cross-lagged panel models, latent growth curves, and parallel process models - that disentangle within-person developmental trajectories from stable between-person traits. We further highlight the study's role in advancing causal inference in observational research through "G-methods", marginal structural models, and quasi-experimental family-based designs. Finally, we explore how ABCD serves as a critical bridge for cross-cohort generalizability and lifespan validation using datasets like the UK Biobank. By contributing to new standards for reproducibility and methodological rigor, the ABCD Study has helped move neuroscience toward a "big data" era, providing a comprehensive statistical foundation for understanding the complex interplay between biology and environment during the transition to adulthood.

Opioid use disorder (OUD) remains a critical global health challenge. The nucleus accumbens (NAc), a key region of the brain reward system, plays an essential role in opioid-induced neuroadaptations. Characterizing gene expression alterations in reward-system regions, such as the NAc, is essential for elucidating the molecular mechanisms underlying addiction. In recent years, bioinformatics has emerged as a rapidly advancing field and has played a pivotal role in elucidating molecular mechanisms and in advancing computational biology. This study aimed to characterize transcriptomic changes in the NAc of mice following chronic morphine administration using RNA sequencing and bioinformatic analysis. RNA sequencing (RNA-Seq) data from morphine- and saline-treated mice were obtained from the Gene Expression Omnibus database via the Sequence Read Archive. Following quality control and alignment, differentially expressed genes (DEGs) were identified using the DESeq2 package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, as well as protein-protein interaction (PPI) network analyses, were performed to evaluate the functional implications of these genes. Principal component analysis (PCA) revealed distinct transcriptomic profiles between the morphine and control groups. A total of 143 DEGs were identified, including 125 up-regulated and 18 down-regulated genes. Enrichment analyses indicated significant involvement in synaptic signaling, ion transport, and neurodegenerative pathways. Protein-protein interaction (PPI) network analysis identified several hub genes, including fgf3 (fibroblast growth factor 3), mki67 (marker of proliferation Ki-67), grin2a/grin2b (glutamate receptor NMDA subunits 2A/2B), gli1 (GLI family zinc finger 1), and ago2 (argonaute RISC catalytic component 2), which are associated with synaptic plasticity, neurogenesis, and epigenetic regulation. Chronic morphine exposure induces widespread gene expression changes in the NAc, engaging pathways associated with synaptic remodeling, neuronal excitability, and addiction-related neuroplasticity. These findings provide a molecular framework for understanding opioid-induced adaptations and identify candidate targets, including N-methyl-D-aspartate (NMDA) receptor subunits, fgf3, and ago2, for potential therapeutic intervention. Future studies should functionally validate these targets and evaluate their translational relevance in the context of OUD.

Tobacco use remains the leading cause of preventable death in the United States (U.S.) and worldwide. The U.S. Food and Drug Administration (FDA) has proposed a product standard to reduce nicotine in cigarettes and other combustible tobacco products to minimally or non-addictive levels, specifically, 0.7 milligrams of nicotine per gram of tobacco. To inform implementation of this standard and future policy directions, the American Thoracic Society's Tobacco Action Committee convened a multidisciplinary workshop that included experts in tobacco treatment, behavioral science, pharmacology, toxicology, pulmonology, cardiology, policy, public health, and advocacy from the U.S., United Kingdom, Lebanon, and Australia. Panelists reviewed the evidence and supported the proposed nicotine standard, citing its potential to reduce addiction, lower daily consumption of smoked tobacco, and increase smoking cessation rates. The panel emphasized that the policy's success depends on a comprehensive rollout strategy that includes complementary measures to protect public health and avoid unintended consequences. These include clear public messaging to prevent misperceptions about product safety, robust surveillance systems to monitor behavioral change and industry responses, and equitable access to FDA-approved cessation support, particularly for disproportionately affected populations. Panelists also addressed the anticipated shift toward non-combustible products, recommending harm minimization strategies, stronger monitoring and enforcement of industry marketing activities, and expanded regulatory authority over emerging products, including nicotine analogues and other addiction-enhancing substances. The panel highlighted the need for improved tools to assess real-world tobacco dependence and toxicant exposure to help ensure that evolving product landscapes are effectively regulated to protect public health.

Psilocybin has been granted breakthrough therapy status in the United States, speeding its advancement from research to clinical care. Due to the controversial nature of psilocybin, psychiatrists may not be fully prepared to incorporate it into clinical practice. The current study aimed to evaluate the opinions toward psilocybin among practicing psychiatrists in Louisiana. Louisiana serves as a representative state, modeling other areas with limited exposure to psychedelic research. A 30-question survey was distributed via mail and digital newsletter to all registered Louisiana psychiatrists. The survey consisted of demographic questions and questions pertaining to how strongly respondents agreed or disagreed with statements about psilocybin and psychedelics on a five-point Likert scale. The statements aimed to assess knowledge and exposure to psilocybin including opinions on research and legalization, safety and addiction potential, medical use, and potential benefits and usages. Forty-nine responses were recorded. Eighty-two percent of participants reported having "some knowledge" of psilocybin. Eighty-six percent believed psilocybin should be researched for medicinal value, and 71% would prescribe psilocybin if it were proven beneficial for their patient's illness. Fifty-seven percent believed it should be considered a first-line treatment for certain conditions, while 73% believed it should be used only after exhausting all other treatment modalities. The study had an overall 10.5% response rate, potentially limiting the generalizability of the findings. Louisiana psychiatrists in our sample appear open to integrating psilocybin into their practice if there is strong regulatory support. Psilocybin research is rapidly expanding and will soon reach Louisiana and other states with a limited history of psychedelic clinical research. These findings warrant the development of an educational program on psychedelics to arm psychiatrists and patients with the knowledge to make the most informed decisions.

Cue-induced craving is a core driver of addiction and relapse, and its significant heterogeneity represents a major barrier to precision intervention. Currently, there remains a lack of objective, quantifiable, and individualized neurobiological biomarkers. Here, we employed task-based electroencephalography (EEG) to capture the dynamic neural signatures underlying cue-induced craving in patients with heroin use disorder (HUD) and developed an individualized functional connectivity (FC)-based prediction model. We identified &#x3b2;-band power envelope connectivity (PEC) as a reliable biomarker capable of estimating subjective craving severity at the individual level. Notably, even after FC reconfiguration induced by intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (L-DLPFC) or precuneus (PCu), the PEC-based framework's prediction of immediate craving levels following these perturbed states remained effective. Crucially, baseline &#x3b2;-band PEC demonstrated strong prognostic value for improvements in craving scores (L-DLPFC-iTBS: r&#x2009;=&#x2009;0.856, P <&#x2009;0.001; PCu-iTBS: r = 0.675, P&#x2009;=&#x2009;0.008). This individualized predictive model was further validated in an independent dot-probe task dataset, demonstrating its generalizability across distinct cue-induced craving paradigms. Together, our study demonstrates that EEG FC features predict individual cue-induced craving levels and intervention outcomes, facilitating the advancement of digital biomarker-driven precision medicine.

Preclinical evidence indicates a link between the endocannabinoid system (ECS) and addiction by modulating reward and stress processes. Rodent and recent human studies reported ECS alterations in cannabis use disorder. However, little is known about cannabis abstinence effects on the ECS in humans. We performed a secondary data analysis from a prospective study comparing changes in plasma endocannabinoids anandamide (AEA) and 1-arachidonoylglycerol (1-AG) from baseline (L1) to 2-3 weeks later (L2) between four groups: individuals with ad libitum cannabis and nicotine use at L1 who 1) abstained from cannabis for three days and nicotine for at least 15h prior to L2 (n&#x2009;=&#x2009;30; Abstain), or 2) sustained ad libitum cannabis-only use but abstained from nicotine for at least 15h prior to L2 (n&#x2009;=&#x2009;18; Can-only); 3) individuals with ad libitum nicotine-only use at L1, who abstained from nicotine for at least 15h prior to L2 (n&#x2009;=&#x2009;17; Nic-only); and 4) healthy controls (n&#x2009;=&#x2009;13) who were drug-na&#xef;ve at L1 and L2. We found a significant increase of AEA from L1 to L2 but no differences of 1-AG, within the Abstain group (p&#x2009;=&#x2009;.004). In contrast, AEA levels decreased significantly within the Can-only group at L2 (p&#x2009;=&#x2009;.011). Controls and the Nic-only group showed stable AEA and 1-AG levels over time. Our findings indicate alterations of the ECS related to cannabis abstinence. While AEA decreased in the Can-only group, AEA increased in the Abstain group, which might indicate a compensatory response of the ECS during cannabis abstinence after chronic excitatory activation of the ECS.

Alcohol use disorder (AUD) is a complex, chronic medical disease wherein patients have traditionally benefited from a multidisciplinary and comprehensive therapeutic approach, including a comprehensive treatment plan that addresses the psychological, behavioral, and social dimensions of the individual. Holistic health is a nontraditional system of wellness that focuses on well-being through body, mind, and spirit and aims to restore balance through combined physical, mental, and emotional care. This approach may incorporate nonpharmacological and alternative treatments alongside allopathic medicine. In recent years, there has been a growing interest in integrating holistic health strategies into addiction treatment. The primary objective of this scoping review is to identify and characterize holistic health interventions currently used in the management of people with AUD. A secondary objective is to collate the reported efficacy of these interventions. Additionally, this review will identify gaps in the literature and suggest areas for future research. This review will adhere to the Arksey and O'Malley methodological framework for scoping reviews. Published research and pilot clinical trials reporting on holistic health interventions in AUD will be included. Five databases will be searched: PubMed and MEDLINE, Embase, CINAHL, Web of Science, and Scopus. There will be no date restrictions, though only English-language articles will be included. To qualify, studies must include at least one holistic intervention (eg, meditation, homeopathy, and special diets). Excluded studies will include those that do not involve people with AUD and/or hazardous drinking or that only test pharmaceutical treatments without a holistic component. Two reviewers will independently screen and extract data with a third reviewer as a tiebreaker; discrepancies will be resolved through discussion. This scoping review began in Covidence in December 2024 and is currently funded by the National Institutes of Health Intramural Research Program. Data collection was completed in February 2026, and data analysis was completed in June 2026. Results are expected to be published in late 2026. This review will provide an overview of holistic approaches and interventions used in AUD treatment. It will highlight gaps in the literature and recommend directions for future research. Results will be submitted for publication in a peer-reviewed journal. No ethics approval is required because the review involves only publicly available literature.

Background and Objectives: Gambling disorder (GD) is a behavioral addiction associated with distress, comorbidity, and functional impairment. This exploratory cross-sectional study examined associations between DSM-5-TR symptom burden, personality dimensions, cognitive emotion regulation, quality of life, and sociodemographic variables in a Romanian clinical sample. Materials and Methods: The sample included 122 adults with psychiatrist-confirmed pathological gambling/GD recruited from "Prof. Dr. Alexandru Obregia" Clinical Hospital of Psychiatry, Bucharest. Personality was assessed with the Personality Clinical Form (PCF; 109 valid profiles), cognitive emotion regulation with the Cognitive Emotion Regulation Questionnaire, and quality of life with the Quality of Life Inventory. Symptom burden was measured using a nine-item binary DSM-5 symptom burden index. Results: The symptom burden index showed a pronounced ceiling effect: median = 9.00 (IQR = 9.00-9.00; range = 4-9), with 91.0% classified as severe and 77.9% meeting all nine criteria. In PCF analyses, symptom burden was positively associated, after Benjamini-Hochberg correction, with broad personality pathology, including maladaptive personality dimensions, personality-functioning indicators, and personality-disorder feature scales; the strongest association involved borderline features. Catastrophizing and Blaming Others were positively associated with severity, whereas Positive Reappraisal, Putting into Perspective, and Positive Refocusing were negatively associated. Quality of life was very low overall and associated with personality and coping variables, but not directly with symptom burden. Criterion-count rank distributions differed by marital status and perceived social support; occupational status showed an omnibus distributional difference, but no pairwise contrast survived correction. Conclusions: GD was characterized by severe symptom burden and restricted score variability. Findings support multidimensional assessment of personality functioning, emotion regulation, quality of life, and social-contextual vulnerability.

The misuse of opioid medications is a significant health issue in the United States. Very few studies have investigated the effect of opioids on perineuronal nets (PNNs), scaffold-like structures that surround neurons and are involved in the regulation of plasticity-dependent mechanisms such as development, learning and memory, and acquisition of addiction-like phenotypes. Regulation of PNNs in the orbitofrontal cortex (OFC) during periods of drug intoxication or withdrawal is widely unknown. In this study, male Wistar rats were injected with fentanyl (0.125 mg/kg, s.c.) or 0.9% saline twice daily for 7 days and once on day 8 (7 continuous days following by 3 days of abstinence) or twice daily for 15 days (5 continuous days followed by 2 days of abstinence for more than 3 weeks) and twice on day 16. Antinociception was evaluated using the tail immersion test immediately before and 30 min after injections. Whole-brain coronal slices were collected, and histochemistry was used to identify Wisteria Floribunda Agglutinin (WFA)-positive PNNs and parvalbumin (PV)-expressing cells. Results confirmed that repeated fentanyl injections induced tolerance to the antinociceptive effects, which normalized following acute abstinence periods. WFA intensity decreased following 8 days of injections. Analyses confirmed significant correlations between PV+ density and tail withdrawal latency following 8 days of fentanyl injections. These data confirm that repeated fentanyl injections modulate both WFA+ and PV+ expression in the rodent brain and antinociceptive tolerance in a duration-dependent manner. Overall, these data suggest that perineuronal nets may mediate opioid-induced behavioral effects, such as antinociceptive tolerance, following repeated administration and abstinence in rats.

Anorexia Nervosa (AN) is a neuropsychiatric disorder marked by compulsive weight-loss and hyperactivity, with poorly understood underlying mechanisms and limited treatment outcomes. Here we show that women with AN, at the first medical evaluation, exhibit hyperactivity and hypercortisolemia, together with a reduced immune cell count yet paradoxically showing increased levels of cell activation. One year later, only subjects considered in remission showed greater increases in cortisol and cytokine levels, along with enhanced monocyte differentiation and recruitment. Using the activity-based anorexia (ABA) rat model, we reproduced AN core features, including hypercorticosteronemia, and observed innate-skewed immune profiles, as well as persistent microglial and glucocorticoid receptor (GR) dysfunction in the ventral hippocampus. Pharmacological blockade of GR with RU486 attenuated hyperactivity and reshaped microglial phenotype in the ventral hippocampus. Our results suggest that cortisol elevation and immune cell adaptation may perpetuate disease vulnerability beyond weight normalization, challenging the notion of weight regain as an indicator of remission.

Schizophrenia, major depressive disorder (MDD), and Alzheimer's disease (AD) involve dysfunction of distributed cortical-subcortical networks that support complex cognitive processes and emotion regulation. Convergent evidence identifies the dorsolateral prefrontal cortex (dlPFC) as a critical site of molecular, cellular, and circuitry alterations in these disorders. The primate dlPFC contains recurrent, excitatory microcircuits in layer III that sustain working memory and top-down control through specialized forms of neurotransmission and intracellular signaling. Specifically, NMDA receptor and cholinergic modulation, as well as tightly regulated calcium-cAMP signaling within dendritic spines, support task-specific firing of layer III pyramidal neurons, but may also increase vulnerability to genetic risk, stress, inflammation and aging. This review integrates findings from human postmortem studies, neuroimaging, and genetics to examine how dlPFC circuitry is altered in these disease states. In schizophrenia, layer III pyramidal neurons exhibit altered synaptic and cytoskeletal signaling, lower dendritic spine density, and compensatory shifts in inhibitory inputs that likely weaken recurrent excitation and network synchrony. In MDD, dysfunction of dlPFC pathways regulating subgenual cingulate cortex contributes to impaired top-down control of emotion and motivation. In AD and frontotemporal lobar degeneration, tau pathology and neurodegeneration target association cortices, including layer III dlPFC circuits, contributing to progressive cognitive decline and impaired executive function. The review also highlights how studies in rhesus macaques and genetically engineered marmosets have provided important insight into the organization, physiology, and disease vulnerability of primate dlPFC circuits. Together, these findings inform the development of emerging therapeutic strategies aimed at strengthening prefrontal network function.