Internet gaming disorder (IGD) is a behavioural addiction characterized by substantial clinical heterogeneity. The present study aimed to investigate this heterogeneity by analysing the deviation patterns of interindividual brain functional connectivity. Resting-state functional magnetic resonance imaging (fMRI) data from 87 patients with IGD and 56 healthy controls (HCs) were included. First, functional connectivity matrices were constructed, and the interindividual deviation of functional connectivity (IDFC) of each patient with IGD relative to the HC group was quantified at the network level. K-means clustering was then applied to identify IGD subtypes. Edge-wise functional connectivity analysis with network contingency analysis (NCA) was used to characterize subtype-specific patterns of altered connections. Finally, support vector regression (SVR) based on network-level IDFC features was used to predict Internet Addiction Test (IAT) scores in the overall IGD cohort. Two distinct IGD subtypes were identified based on IDFC patterns. Compared with HCs, Subgroup 1 showed a widespread hypoconnectivity pattern, whereas Subgroup 2 showed a relative hyperconnectivity pattern. Network-level IDFC features also predicted IAT scores in the overall IGD cohort using SVR (r = 0.391, one-tailed permutation p = 0.038). Patients with IGD exhibit substantial interindividual variability in brain functional connectivity. Subtyping IGD based on these connectivity deviation patterns may improve the understanding of its neurobiological heterogeneity and facilitate the development of more precise individualized interventions.
Methamphetamine (METH) is a globally prevalent, highly addictive synthetic psychostimulant, for which no FDA-approved pharmacotherapy is currently available for METH use disorder (MUD). The microbiota-gut-brain axis has been well established as a key regulatory pathway in substance use disorders, yet its specific mechanistic basis and translational potential in METH addiction remain to be systematically elucidated. This review synthesizes current preclinical and clinical evidence demonstrating that METH exposure induces profound gut microbiota dysbiosis, characterized by the depletion of beneficial genera such as Faecalibacterium and Lactobacillus, enrichment of proinflammatory phylum Proteobacteria and concurrent dysregulation of microbial metabolites including short-chain fatty acids (SCFAs), tryptophan derivatives and bile acids. These microbial signals mediate bidirectional gut-CNS crosstalk through neuroimmune, neuroendocrine (hypothalamic-pituitary-adrenal (HPA) axis) and vagal pathways, thereby exacerbating the core central pathologies of METH addiction: neurotransmitter system imbalance, neuroinflammation and oxidative stress and dysfunction of addiction-related neural circuits. We further elaborate that gut microbiota-driven epigenetic modifications and transgenerational effects reinforce the persistence and heritability of addictive phenotypes. Importantly, microbiota-targeted interventions, including probiotics, prebiotics, faecal microbiota transplantation (FMT) and dietary modulation, can alleviate METH-induced affective disturbances (anxiety/depression-like behaviours), multiorgan damage (neurotoxicity, reproductive impairment) and relapse risk, via restoring gut microbial homeostasis, repairing intestinal barrier integrity and normalizing gut-brain axis signalling. Collectively, this review positions the gut microbiota as a critical peripheral regulatory node in METH addiction, providing a robust preclinical foundation for the development of gut-brain axis-targeted combination therapies for MUD.
Craving is one of the most robust proximal predictors of both treatment dropout and relapse during early recovery for alcohol use disorder (AUD). Craving can onset rapidly, and the ability to accurately detect or modulate cravings varies significantly within- and between-persons. Because of this, craving management is a central feature of most current AUD treatment models. However, impaired interoceptive awareness, which is common in early AUD recovery, can stymie individuals' capacity to implement craving management strategies. Measurement and detection of craving through passive biosensor monitoring could support novel just-in-time adaptive interventions that can mitigate this vulnerability. This study sought to characterize the biosignatures of craving through the measurement of heart rate variability (HRV) using a combination of ambulatory electrocardiogram (ECG) monitoring and ecological momentary assessment (EMA) in individuals in the first year of a current AUD recovery attempt (N = 40, observations = 400). A multilevel negative binomial regression analysis was conducted to estimate correlations between craving and HRV. Results demonstrated that, at the within-person level, high-frequency HRV (HF-HRV; IRR = 1.01, p = 0.013) and SD1 (IRR = 0.97, p = 0.020) were associated with craving at the same moment. Findings highlight HRV as a viable target for passive monitoring in interventions aimed at supporting craving mitigation in early AUD recovery, particularly at the momentary level.
Betel quid (BQ) is classified as a Group 1 carcinogen, underscoring a significant public health challenge. Neuroimaging evidence demonstrated that betel quid dependence (BQD) was linked to alterations in reward-related brain regions. However, resting-state functional connectivity (FC) in the reward circuit and their neural correlates with pathophysiological characteristics of BQD remain largely unexplored. We recruited 53 male BQD chewers and 53 male healthy controls (HCs) to participate in this study. Eleven reward circuit seeds, such as ventral striatum (VS), ventromedial prefrontal cortex (VMPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and others, were selected. Resting-state functional magnetic resonance imaging (rs-fMRI) data were analysed to evaluate FC between predefined seed regions and the whole brain. Association between aberrant FC and clinical features was further investigated. Relative to HCs, individuals with BQD exhibited altered FC in the reward circuit, mainly in VS, VMPFC, ACC, PCC and thalamus (Th). Correlation analysis indicated that FC between right Th and PCC was negatively correlated with BQD scales and dosage of BQ use in BQD subjects. Our findings provided the first empirical evidence that individuals with BQD showed aberrant resting-state FC in the reward circuit. Additionally, decreased connectivity between right Th and PCC was negatively associated with dependence degree and dosage of BQ use. These results highlighted the importance of the reward circuit in the pathophysiology of BQD and suggested that reward circuit dysfunction could serve as a potential circuit-level biomarker.
Objective Prenatal substance use is associated with negative outcomes for both the pregnant person and child. Entering substance use treatment during pregnancy is associated with improved outcomes but there are many barriers to treatment such as stigma. To improve prevention and treatment outcomes, it is critical to understand the relationship between risk/protective factors for substance use during pregnancy and to look for temporal changes in these relationships.Method Pregnant people (N = 32) with substance use disorder and a history of trauma exposure were included in this secondary analysis. Participants completed ecological momentary assessment (EMA), three times per day for 28 days. We used time-varying effects models (TVEMs) to examine the effects of craving on substance use, PTSD symptoms on craving, prenatal bonding on craving, and PTSD symptoms on prenatal bonding.Results Craving predicted substance use from gestational weeks 19.58 to 26.96. The relationship decreased over time and was not significant after week 27. PTSD symptoms predicted cravings at three times (weeks: 19.96-20.30, 23.36-31.68, 36.22-36.79). Maternal-fetal quality of attachment predicted craving from weeks 19.58-25.63. Maternal-fetal intensity of preoccupation predicted craving from weeks 19.58-22.42 and 31.31-31.87. PTSD symptoms predicted maternal fetal quality of attachment between weeks 25.06-26.20. There was no relationship between PTSD symptoms and maternal-fetal intensity of preoccupation over time.Conclusions These findings support prior research on the relationship between risk/protective factors for substance use during pregnancy. However, these relationships appear to fluctuate over time indicating that other factors might impact substance use during pregnancy.
