Identifying the role of (dis)inhibition in the vicious cycle of substance use through ecological momentary assessment and resting-state fMRI.

Functional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral integrity. Whereas treatment is challenged by a multitude of substances that patients often use, no study has yet unraveled if inhibition and related cerebral integrity could prevent relapse from multiples substances, that is, one's primary drug of choice and secondary ones. Individuals with primary alcohol, cannabis, or tobacco use disorders completed intensive Ecological Momentary Assessment (EMA) coupled with resting-state functional MRI (rs-fMRI) to characterize the extent to which inhibition and cerebral substrates interact with craving and use of primary and any substances. Participants were 64 patients with SUD and 35 healthy controls who completed one week EMA using Smartphones to report 5 times daily their craving intensity and substance use and to complete Stroop inhibition testing twice daily. Subsamples of 40 patients with SUD and 34 control individuals underwent rs-fMRI. Mixed Model Analysis revealed that reported use of any substance by SUD individuals predicted later use of any and primary substance, whereas use of the primary substance only predicted higher use of that same substances. Craving and inhibition level independently predicted later use but did not significantly interact. Preserved inhibition performance additionally influenced use indirectly by mediating the link between subsequent uses and by being linked to rs-fMRI connectivity strength in fronto-frontal and cerebello-occipital connections. As hypothesized, preserved inhibition performance, reinforced by the integrity of inhibitory neurofunctional substrates, may partake in breaking an unhealthy substance use pattern for a primary substance but may not generalize to non-target substances or to craving management.

Corticostriatal responses to social reward are linked to trait reward sensitivity and subclinical substance use in young adults.

Aberrant levels of reward sensitivity have been linked to substance use disorder and are characterized by alterations in reward processing in the ventral striatum (VS). Less is known about how reward sensitivity and subclinical substance use relate to striatal function during social rewards (e.g. positive peer feedback). Testing this relation is critical for predicting risk for development of substance use disorder. In this pre-registered study, participants (N = 44) underwent fMRI while completing well-matched tasks that assess neural response to reward in social and monetary domains. Contrary to our hypotheses, aberrant reward sensitivity blunted the relationship between substance use and striatal activation during receipt of rewards, regardless of domain. Moreover, exploratory whole-brain analyses showed unique relations between substance use and social rewards in temporoparietal junction. Psychophysiological interactions demonstrated that aberrant reward sensitivity is associated with increased connectivity between the VS and ventromedial prefrontal cortex during social rewards. Finally, we found that substance use was associated with decreased connectivity between the VS and dorsomedial prefrontal cortex for social rewards, independent of reward sensitivity. These findings demonstrate nuanced relations between reward sensitivity and substance use, even among those without substance use disorder, and suggest altered reward-related engagement of cortico-VS responses as potential predictors of developing disordered behavior.

Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Refining the circuits of drug addiction: The ventral pallidum.

The ventral pallidum is a prominent structure within the basal ganglia, regulating reward and motivational processes. Positioned at the interface between motor and limbic structures, its function is crucial to the development and maintenance of substance use disorders. Chronic drug use induces neuroplastic events in this structure, leading to long-term changes in VP neuronal activity and synaptic communication. Moreover, different neuronal populations within the VP drive drug-seeking behavior in opposite directions. This review explores the role of the VP as a hub for reward, motivation, and aversion, establishing it as an important contributor to the pathophysiology of substance use disorders.

Substance use disorders are characterised by increased voxel-wise intrinsic measures in sensorimotor cortices: An ALE meta-analysis.

Substance use disorders (SUDs) are severe psychiatric illnesses. Seed region and independent component analyses are currently the dominant connectivity measures but carry the risk of false negatives due to selection. They can be complemented by a data-driven and whole-brain usage of voxel-wise intrinsic measures (VIMs). We meta-analytically integrated VIMs, namely regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), voxel-mirrored homotopy connectivity (VMHC) and degree centrality (DC) across different SUDs using the Activation Likelihood Estimation (ALE) algorithm, functionally decoded emerging clusters, and analysed their connectivity profiles. Our systematic search identified 51 studies including 1439 SUD participants. Although no overall convergent pattern of alterations across VIMs in SUDs was found, sensitivity analyses demonstrated two ALE-derived clusters of increased ReHo and ALFF in SUDs, which peaked in the left pre- and postcentral cortices. Subsequent analyses showed their involvement in action execution, somesthesis, finger tapping and vibrotactile monitoring/discrimination. Their numerous clinical correlates across included studies highlight the under-discussed role of sensorimotor cortices in SUD, urging a more attentive exploration of their clinical significance.

Differential effects of high-definition transcranial direct current stimulation (HD-tDCS) on attentional guidance by working memory in males with substance use disorder according to memory modality.

Information stored in working memory can guide perception selection, and this process is modulated by cognitive control. Although previous studies have demonstrated that neurostimulation over the left dorsolateral prefrontal cortex (lDLPFC) contributes to restore cognitive control among individuals with substance use disorder (SUD), there remains an open question about the potential stimulation effects on memory-driven attention. To address this issue, the present study adopted a combined working memory/attention paradigm while employing high-definition transcranial direct current stimulation (HD-tDCS) to stimulate the lDLPFC. Observers were asked to maintain visual or audiovisual information in memory while executing a search task, while the validity of the memory contents for the subsequent search task could be either invalid or neutral. The results showed a faint memory-driven attentional suppression effect in sham stimulation only under the audiovisual condition. Moreover, anodal HD-tDCS facilitated attentional suppression effect in both the strength and temporal dynamics under the visual-only condition, whereas the effect was impaired or unchanged under the audiovisual condition. Surprisingly, cathodal HD-tDCS selectively improved temporal dynamics of the attentional suppression effect under the audiovisual condition. The present study revealed the differential enhancement of HD-tDCS on cognitive control over visual and audiovisual memory-driven attention among individuals with SUD.

Electrophysiological biomarkers in dual pathology.

INTRODUCTION: The co-occurrence of substance use disorder with at least one other mental disorder is called dual pathology, which in turn is characterised by heterogeneous symptoms that are difficult to diagnose and have a poor response to treatment. For this reason, the identification and validation of biomarkers is necessary. Within this group, possible electroencephalographic biomarkers have been reported to be useful in diagnosis, treatment and follow-up, both in neuropsychiatric conditions and in substance use disorders. This article aims to review the existing literature on electroencephalographic biomarkers in dual pathology. METHODS: A narrative review of the literature. A bibliographic search was performed on the PubMed, Science Direct, OVID, BIREME and Scielo databases, with the keywords: electrophysiological biomarker and substance use disorder, electrophysiological biomarker and mental disorders, biomarker and dual pathology, biomarker and substance use disorder, electroencephalography, and substance use disorder or comorbid mental disorder. RESULTS: Given the greater amount of literature found in relation to electroencephalography as a biomarker of mental illness and substance use disorders, and the few articles found on dual pathology, the evidence is organised as a biomarker in psychiatry for the diagnosis and prediction of risk and as a biomarker for dual pathology. CONCLUSIONS: Although the evidence is not conclusive, it suggests the existence of a subset of sites and mechanisms where the effects of psychoactive substances and the neurobiology of some mental disorders could overlap or interact.

Neuroendocrine mechanisms in the links between early life stress, affect, and youth substance use: A conceptual model for the study of sex and gender differences.

Early life stress (ELS) is defined as an acute or chronic stressor that negatively impacts a child's development. ELS is associated with substance use and mental health problems. This narrative literature review focuses on sex and gender differences in the effects of ELS on 1) adolescent neuroendocrine development; 2) pubertal brain maturation; and 3) development of internalizing symptoms and subsequent substance use. We posit that ELS may generate larger hormonal dysregulation in females than males during puberty, increasing internalizing symptoms and substance use. Future research should consider sex and gender differences in neuroendocrine developmental processes when studying the link between ELS and negative health outcomes.

Effects of ambient temperature on locomotor activity and place conditioning elicited by abused psychostimulants in mice: Role of 3,4-methylenedioxy moiety.

BACKGROUND: Humans often administer psychostimulants in party or music festival settings characterized by warm ambient temperatures, which may impact drug effects; however, preclinical studies rarely investigate drug effects at multiple ambient temperatures. Work with 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) suggests that the presence of a 3,4-methylenedioxy ring moiety may influence ambient temperature-dependent effects. METHODS: Locomotor activity and conditioned place preference dose-response curves were generated at 20±2°C for two amphetamine analogues (MDMA and methamphetamine [METH]) and two cathinone analogues (MDPV and α-pyrrolidinopentiophenone [αPVP]) in mice. Effects were then redetermined at 29±2°C for each drug and assay. RESULTS: All four drugs elicited dose-dependent locomotor stimulation at the cool ambient temperature. At the warm ambient temperature, MDMA and MDPV produced sensitization to stereotypy, whereas METH and αPVP produced sensitization to locomotor activity. Regarding place conditioning, the warm ambient environment potentiated place preference elicited by doses of METH and αPVP that were sub-threshold in the cool ambient environment, but attenuated the effects of analogous doses of MDMA and MDPV. CONCLUSIONS: These studies suggest that warmer ambient temperatures may potentiate typical stimulant effects for the drugs lacking the 3,4-methylenedioxy ring, but may potentiate the behaviorally toxic/adverse effects for the drugs containing a 3,4-methylenedioxy ring. Thus, preclinical abuse liability studies conducted at standard laboratory temperatures may not fully capture the effects of psychostimulants and highlight the need to model the environments in which drugs are typically used by humans.

Can internet use become addictive?

Problematic internet use parallels drug addiction, but the mechanisms are not yet clear.

Comparison of Pain in Male Drug Rehabilitees with and without Human Immunodeficiency Virus in Yunnan Province, China.

BACKGROUND The purpose of this study was to compare pain symptoms in drug rehabilitees with or without human immunodeficiency virus (HIV) in Yunnan Province, China. MATERIAL AND METHODS This was a retrospective single-center cohort study. A total of 120 male substance users, including 65 with HIV, were enrolled after admission to the Fifth Drug Rehabilitation Center in Yunnan Province. Individuals who were >18 years of age and who had illicit drugs detected in their urine, despite not having used drugs for at least 2 months, were included. The patients evaluated their average pain intensity for the previous 4 weeks using a visual analog scale. PainDETECT questionnaire scores were used to classify pain into nociceptive and mixed component subgroups. Sleep quality was also evaluated using the Pittsburgh Sleep Quality Index scale. RESULTS The prevalence and intensity of the pain symptoms were higher for the drug rehabilitees with HIV than for those without HIV. Moreover, the rehabilitees with HIV were more likely to experience neuropathic and nociceptive pain, whereas those without HIV reported only nociceptive pain. The sleep quality of the rehabilitees with HIV was also lower, regardless of the pain symptoms. CONCLUSIONS Our results showed that the drug rehabilitees with HIV in Yunnan Province, China, experienced more frequent and stronger pain (both nociceptive and neuropathic) than those without HIV. They also experienced poorer sleep quality, although it was unrelated to pain. Our results provide data to support clinical diagnosis and treatment.

Personal attributes and attitudes to substance use disorder: A study among Jordanian undergraduate medical majors students.

BACKGROUND: Emerging health professionals in undergraduate programs should be equipped to provide care to people with substance use disorder (SUD). The students' personal attributes may impact their attitude toward those with SUD. This study aims to evaluate the impact of personal attributes of Jordanian undergraduate health students on their attitudes toward SUD and examine the relationship between the personal attributes and their devaluation and discriminatory (stigmatory) behaviour toward those with SUD. METHOD: A cross-sectional descriptive design was used to examine the attitudes and stigmatory behaviours. The data were collected between May to October 2017 with a structured questionnaire that consisted of three parts: 1) a data sheet to collect the socio-demographic characteristics of the participants, 2) the Acute Mental Health Scale (ATAMHS), and 3) the Devaluation-Discrimination Scale (DDS). FINDINGS: Younger and females demonstrated a positive attitude toward those with SUD compared to older or male students. Age, gender, and previous experience with SUD are significant factors that affect their attitude. CONCLUSION: Identifying the attitude to people with SUD and personal attributes of emerging health professionals in Jordan will help identify the need to educate them prior to their entry into practice.

Closing the brain-heart loop: Towards more holistic models of addiction and addiction recovery.

Much research seeks to articulate the brain structures and pathways implicated in addiction and addiction recovery. Prominent neurobiological models emphasize the interplay between cortical and limbic brain regions as a main driver of addictive processes, but largely do not take into consideration sensory and visceral information streams that link context and state to the brain and behavior. Yet these brain-body information streams would seem to be necessary elements of a comprehensive model of addiction. As a starting point, we describe the overlap between one current model of addiction circuitry and the neural network that not only regulates cardiovascular system activity but also receives feedback from peripheral cardiovascular processes through the baroreflex loop. We highlight the need for neurobiological, molecular, and behavioral studies of neural and peripheral cardiovascular signal integration during the experience of internal states and environmental contexts that drive alcohol and other drug use behaviors. We end with a call for systematic, mechanistic research on the promising, yet largely unexamined benefits to addiction treatment of neuroscience-informed, adjunctive interventions that target the malleability of the cardiovascular system to alter brain processes.

Effects of substance misuse on inhibitory control in patients with attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) are often diagnosed with comorbid substance misuse (SM), which is associated with poor treatment efficacy. Although literature indicates similar inhibitory control deficits in both conditions, it is unclear whether SM in ADHD exaggerates pre-existing deficits, with additive or distinct impairments in patients. Our aim was to examine SM effects on inhibitory control in ADHD. Behavioural and functional magnetic resonance imaging (fMRI) data from a stop-signal task were compared across ADHD patients with and without SM (ADHD + SM and ADHD-only, respectively) and controls (n = 33/group; 79 males, mean age 18.02 ± 2.45). To limit substance use disorder (SUD) trait effects, groups were matched for parental SUD. Overall, we found worse performance for ADHD-only and/or ADHD + SM compared with controls but no difference between the ADHD groups. Moreover, the ADHD groups showed decreased frontostriatal and frontoparietal activity during successful and failed stop trials. There were no differences between the ADHD groups in superior frontal nodes, but there was more decreased activation in temporal/parietal nodes in ADHD-only compared with ADHD + SM. During go-trials, ADHD + SM showed decreased activation in inferior frontal nodes compared with ADHD-only and controls. Findings during response inhibition showed deficits in inhibition and attentional processes for ADHD patients with and without SM. Despite no evidence for SM effects during response inhibition, results during go-trials suggest distinct effects on nodes that are associated with several executive functions. Future studies should investigate whether distinct deficits in ADHD + SM relate to poor treatment results and can direct development of distinct ADHD treatment strategies for these patients.

Association of prenatal substance use disorders with pregnancy and birth outcomes following bariatric surgery.

BACKGROUND/OBJECTIVES: While an increased risk for substance use disorders (SUD) and also for several adverse pregnancy and birth outcomes in patients who have undergone bariatric surgery have been well documented when considered separately, an association between these important risk factors has not been investigated. This study explored the potential dependence of these two bariatric surgery-related risks. SUBJECTS/METHODS: This study was a retrospective cohort study with adult women (18-45) who underwent bariatric surgery between 1996 and 2016 and who gave birth after surgery between 1996 and 2018. The study population consisted of 1849 post-bariatric surgery women with 3010 reported post-surgical births. Subjects with post-surgical, prenatal SUD were identified based on diagnosis codes extracted within the 10 months prior to delivery. Using random-effects logistic regression with retrospective cohort data, preterm birth, low birth weight, macrosomia, Caesarian delivery, congenital anomalies, and neonatal intensive care unit admission were considered as outcomes. RESULTS: About 10% (n = 289) of women had an SUD diagnosis within 10 months prior to child delivery. Women with SUD during pregnancy had significantly more pregnancy and birth complications compared to women without SUD: preterm birth (OR = 2.08, p = 0.03, 95% CI: 1.07-4.03), low birth weight (OR = 3.41, p < 0.01, 95% CI: 1.99-5.84), Caesarian delivery (OR = 9.71, p < 0.01, 95% CI: 2.69-35.05), and neonatal intensive care unit admission (OR = 3.87, p < 0.01, 95% CI: 2.04-7.34). Women with SUD had lower risk for macrosomia than women without SUD (OR = 0.07, p = 0.02, 95% CI: 0.01-0.70). CONCLUSION: Results from this study demonstrated that post-bariatric surgery women who had SUD during pregnancy had significantly more pregnancy- and birth-related complications than post-surgery pregnant women without SUD, despite the reduction in macrosomia. Where possible, greater prenatal surveillance of post-surgery women with SUD should be considered.

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders.

Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

Barreiras para a prática de atividades físicas entre usuários de substâncias psicoativas / Barreras para la actividad física en consumidores de sustancias psicoactivas / Barriers to physical activity among users of psychoactive substances

Objetivo: Verificar as barreiras que influenciam a não realização de atividade física no tempo livre entre usuários de substâncias psicoativas.Método: 144 indivíduos com média de idade de 44.3±12.6 anos foram entrevistados respondendo um questionário que verifica as barreiras para a prática de atividades físicas. Foi aplicado o teste Qui-quadrado de independência aceitando um p<0.05 como significativo.Resultados: Os dados mostraram que há associação entre as sentenças do questionário e o padrão de resposta dos indivíduos [x2(13)=193.88; p≤0.001]. Foi encontrada significância como barreira para prática de atividade física o cansaço físico, falta de companhia, falta de incentivo familiar e acometimento de dores leves ou mal-estar. Por outro lado, a falta de tempo, fator climático, não disponibilidade no ambiente, não disponibilidade de equipamento e falta de habilidade física foram apontados, significativamente, como não serem barreiras para a prática de atividade física em usuários de substâncias psicoativas.Conclusão: A partir destes dados será possível estabelecer estratégias mais efetivas para a promoção da prática de atividade física nesta população. (AU)

Objetivo: Verificar las barreras que influyen en los usuarios de sustancias psicoactivas para no utilizar su tiempo libre para practicar actividad física.Método: 144 personas, con edad de 44.3 ± 12.6 años, respondieron a un cuestionario sobre las barreras para la practica de actividad física. Se aplicó el test de independencia de chi-cuadrado, aceptando como significativa um valor de p<0.05.Resultados: Los datos muestran que existe asociación entre las sentencias del cuestionario y el patrón de respuesta de los individuos [x2(13)=193.88; p≤0.001]. Se consideró significativa la existencia de barreras para la práctica de actividad física como el cansancio físico, la falta de un compañero y motivación familiar, padecimiento de dolores o malestar ligeros. Por otro lado, la falta de tiempo, el factor climático, la indisponibilidad en el medio ambiente, la falta de equipos y de entrenamiento físico no fueron señalados de manera significativa como barreras para la práctica de actividad física en usuarios de sustancias psicoactivas.Conclusión: En base a estos datos, será posible establecer estrategias más efectivas para promover la práctica de actividad física en esta población. (AU)

Objective: To verify the barriers that influence the non-performance of physical activity in free time among users of psychoactive substances.Methods: 144 individuals with a mean age of 44.3±12.6 years were interviewed by answering a questionnaire that checks the barriers to physical activity. The Chi-square test of independence was applied accepting a p<0.05 as significant.Results: The data showed that there is an association between the sentences of the questionnaire and the response pattern of individuals [x2(13)=193.88; p≤0.001]. Significance was found as a barrier to physical activity the physical tiredness, lack of company, lack of family incentive and involvement of mild pain or discomfort. On the other hand, lack of time, climatic factor, non-availability in the environment, non-availability of equipment, and lack of physical ability were significantly pointed out as not being barriers to the practice of physical activity in users of psychoactive substances.Conclusion: From these data it will be possible to establish more effective strategies for the promotion of physical activity in this population. (AU)

Effects of adolescent substance use disorders on central cholinergic function.

Adolescence is a transitional period between childhood and adulthood, in which the individual undergoes significant cognitive, behavioral, physical, emotional, and social developmental changes. During this period, adolescents engage in experimentation and risky behaviors such as licit and illicit drug use. Adolescents' high vulnerability to abuse drugs and natural reinforcers leads to greater risk for developing substance use disorders (SUDs) during adulthood. Accumulating evidence indicates that the use and abuse of licit and illicit drugs during adolescence and emerging adulthood can disrupt the cholinergic system and its processes. This review will focus on the effects of peri-adolescent nicotine and/or alcohol use, or exposure, on the cholinergic system during adulthood from preclinical and clinical studies. This review further explores potential cholinergic agents and pharmacological manipulations to counteract peri-adolescent nicotine and/or alcohol abuse.