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Biology of Sex Differences Jul 2023Biological factors are known to influence disease trajectories and treatment effectiveness in alcohol addiction and preclinical and clinical evidence suggests that sex...
BACKGROUND
Biological factors are known to influence disease trajectories and treatment effectiveness in alcohol addiction and preclinical and clinical evidence suggests that sex is an important factor influencing disease dynamics in alcohol dependence. Another critical factor is age at first intoxicating drink, which has been identified as a risk factor for later alcohol binging. Preclinical research allows prospective monitoring of rodents throughout the lifespan, providing very detailed information that cannot be acquired in humans. Lifetime monitoring in rodents can be conducted under highly controlled conditions, during which one can systematically introduce multiple biological and environmental factors that impact behaviors of interest.
METHODS
Here, we used the alcohol deprivation effect (ADE) rat model of alcohol addiction in a computerized drinkometer system, acquiring high-resolution data to study changes over the course of addictive behavior as well as compulsive-like drinking in cohorts of adolescent vs. adult as well as male vs. female rats.
RESULTS
Female rats drank more alcohol than male rats during the whole experiment, drinking much more weak alcohol (5%) and similar amounts of stronger alcohol solutions (10%, 20%); female rats also consumed more alcohol than male rats during quinine taste adulteration. Increased consumption in females compared to males was driven by larger access sizes of alcohol. Differences in circadian patterns of movement were observed between groups. Early age of onset of drinking (postnatal day 40) in male rats had surprisingly little impact on the development of drinking behavior and compulsivity (quinine taste adulteration) when compared to rats that started drinking during early adulthood (postnatal day 72).
CONCLUSIONS
Our results suggest that there are sex-specific drinking patterns, not only in terms of total amount consumed, but specifically in terms of solution preference and access size. These findings provide a better understanding of sex and age factors involved in the development of drinking behavior, and can inform the preclinical development of models of addiction, drug development and exploration of options for new treatments.
Topics: Humans; Rats; Male; Female; Animals; Adolescent; Adult; Alcoholism; Alcohol Drinking; Quinine; Prospective Studies; Behavior, Addictive; Ethanol; Age Factors
PubMed: 37420305
DOI: 10.1186/s13293-023-00529-4 -
Nature Communications Nov 2023The faster a drug enters the brain, the greater its addictive potential, yet the brain circuits underlying the rate dependency to drug reward remain unresolved. With...
The faster a drug enters the brain, the greater its addictive potential, yet the brain circuits underlying the rate dependency to drug reward remain unresolved. With simultaneous PET-fMRI we linked dynamics of dopamine signaling, brain activity/connectivity, and self-reported 'high' in 20 adults receiving methylphenidate orally (results in slow delivery) and intravenously (results in fast delivery) (trial NCT03326245). We estimated speed of striatal dopamine increases to oral and IV methylphenidate and then tested where brain activity was associated with slow and fast dopamine dynamics (primary endpoint). We then tested whether these brain circuits were temporally associated with individual 'high' ratings to methylphenidate (secondary endpoint). A corticostriatal circuit comprising the dorsal anterior cingulate cortex and insula and their connections with dorsal caudate was activated by fast (but not slow) dopamine increases and paralleled 'high' ratings. These data provide evidence in humans for a link between dACC/insula activation and fast but not slow dopamine increases and document a critical role of the salience network in drug reward.
Topics: Adult; Humans; Behavior, Addictive; Brain; Dopamine; Methylphenidate; Reward; Clinical Trials as Topic
PubMed: 37938560
DOI: 10.1038/s41467-023-41972-6 -
International Journal of Environmental... Oct 2023Mental health problems, broadly understood, are highly prevalent [...].
Mental health problems, broadly understood, are highly prevalent [...].
Topics: Humans; Mental Health; Social Stigma; Behavior, Addictive; Causality; Mental Disorders
PubMed: 37887653
DOI: 10.3390/ijerph20206915 -
Nature Communications Sep 2023The M muscarinic acetylcholine receptor (M mAChR) has emerged as a drug target of high therapeutic interest due to its expression in regions of the brain involved in the...
The M muscarinic acetylcholine receptor (M mAChR) has emerged as a drug target of high therapeutic interest due to its expression in regions of the brain involved in the regulation of psychosis, cognition, and addiction. The mAChR agonist, xanomeline, has provided significant improvement in the Positive and Negative Symptom Scale (PANSS) scores in a Phase II clinical trial for the treatment of patients suffering from schizophrenia. Here we report the active state cryo-EM structure of xanomeline bound to the human M mAChR in complex with the heterotrimeric G transducer protein. Unexpectedly, two molecules of xanomeline were found to concomitantly bind to the monomeric M mAChR, with one molecule bound in the orthosteric (acetylcholine-binding) site and a second molecule in an extracellular vestibular allosteric site. Molecular dynamic simulations supports the structural findings, and pharmacological validation confirmed that xanomeline acts as a dual orthosteric and allosteric ligand at the human M mAChR. These findings provide a basis for further understanding xanomeline's complex pharmacology and highlight the myriad of ways through which clinically relevant ligands can bind to and regulate GPCRs.
Topics: Humans; Allosteric Site; Behavior, Addictive; Brain; Cognition
PubMed: 37673901
DOI: 10.1038/s41467-023-41199-5 -
Frontiers in Psychology 2024We all experience occasional self-control failures (SCFs) in our daily lives, where we enact behaviors that stand in conflict with our superordinate or long-term goals....
INTRODUCTION
We all experience occasional self-control failures (SCFs) in our daily lives, where we enact behaviors that stand in conflict with our superordinate or long-term goals. Based on the assumption that SCFs share common underlying mechanisms with addictive disorders, we tested the hypothesis that a generally higher susceptibility to daily SCFs predicts more addictive behavior, or vice versa.
METHODS
At baseline, 338 individuals (19-27 years, 59% female) from a community sample participated in multi-component assessments. These included among others (1) a clinical interview on addictive behaviors (quantity of use, frequency of use, DSM-5 criteria; = 338) and (2) ecological momentary assessment of SCFs ( = 329, 97%). At the 3-year and 6 year follow-up, participation rates for both assessment parts were 71% ( = 240) and 50% ( = 170), respectively.
RESULTS
Controlling for age, gender, IQ, and baseline addiction level, random-intercept cross-lagged panel models revealed that participants who reported more SCFs also showed pronounced addictive behavior at the between-person level, but we found no evidence of a predictive relationship at the within-person level over time.
DISCUSSION
A higher rate of SCFs is associated with more addictive behavior, while there is no evidence of an intraindividual predictive relationship. Novel hypotheses suggested by additional exploratory results are that (1) only addiction-related SCFs in daily life are early markers of an escalation of use and thus for addictive disorders and that (2) an explicit monitoring of SCFs increases self-reflection and thereby promotes the mobilization of cognitive control in response to goal-desire conflicts.
PubMed: 38751764
DOI: 10.3389/fpsyg.2024.1382483 -
Scientific Reports Oct 2023The surge in social network services (SNS) usage has ignited concerns about potential addictive behaviors stemming from excessive engagement. This research focuses on...
The surge in social network services (SNS) usage has ignited concerns about potential addictive behaviors stemming from excessive engagement. This research focuses on pinpointing the primary determinants of SNS addiction by introducing a theoretical framework centered on flow, perceived enjoyment, and habit. A sample of 282 SNS users from South Korea was surveyed, and the gathered data was assessed through partial least squares structural equation modeling (PLS-SEM). The evaluation revealed that positive affect closely relates to flow and perceived enjoyment, whereas negative affect amplifies flow but diminishes perceived enjoyment. Additionally, the research underscored that social influence significantly shapes habits and affects perceived enjoyment. Notably, flow demonstrated a strong connection to addiction, and perceived enjoyment influenced both flow and habit significantly. Habit was directly linked to addiction. These insights pave the way for more in-depth studies on SNS addiction patterns and offer a foundation for devising effective strategies to mitigate its adverse effects.
Topics: Humans; Social Media; Social Networking; Behavior, Addictive; Pleasure; Happiness
PubMed: 37794135
DOI: 10.1038/s41598-023-43796-2 -
Biological Psychiatry Sep 2023A large body of evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the TaqIA polymorphism is...
BACKGROUND
A large body of evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the TaqIA polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the ankyrin repeat and kinase domain containing 1 kinase (Ankk1) near the dopamine D receptor (D2R) gene. Homozygous expression of the A1 allele correlates with a 30% to 40% reduction of striatal D2R, a typical feature of addiction, overeating, and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior are unknown.
METHODS
Here, we used transgenic and viral-mediated strategies to reveal the role of Ankk1 in the regulation of activity and functions of the striatum.
RESULTS
We found that Ankk1 is preferentially enriched in striatal D2R-expressing neurons and that Ankk1 loss of function in the dorsal and ventral striatum leads to alteration in learning, impulsivity, and flexibility resembling endophenotypes described in A1 carriers. We also observed an unsuspected role of Ankk1 in striatal D2R-expressing neurons of the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with or without the A1 allele.
CONCLUSIONS
Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for Ankk1 in the regulation of body metabolism.
Topics: Humans; Dopamine; Receptors, Dopamine D2; Behavior, Addictive; Neurons; Reward
PubMed: 36805080
DOI: 10.1016/j.biopsych.2023.02.010 -
Scientific Reports Aug 2023The alteration in circadian typology and insomnia were prevalent among both Individuals with IGD and those with attention deficit hyperactivity disorder (ADHD), the most...
The alteration in circadian typology and insomnia were prevalent among both Individuals with IGD and those with attention deficit hyperactivity disorder (ADHD), the most comorbid psychiatric disorder of IGD. This study aimed to evaluate the relationships between circadian typologies, insomnia, and internet gaming disorder (IGD) and how ADHD affects this relationship. We recruited three groups of 69 young adults: an IGD group, a control group comprising age- and sex-matched nongamers, and a group of gamers without IGD through diagnostic interviews. The participants with IGD exhibited lower composite scale of morningness (CSM) scores and thus a higher eveningness preference In addition, the score of Pittsburgh insomnia rating scale-20-item version (PIRS_20) was significantly higher among those with IGD. The participants with IGD and ADHD exhibited lower CSM scores but higher PRIS_20 scores than the participants with IGD but without ADHD. The present findings indicate that participants with IGD exhibited a tendency of eveningness preference and experienced more severe insomnia. ADHD exacerbated the eveningness preference and insomnia of individuals with IGD. Close attention should be paid to sleep problems in individuals with IGD, particularly to those with ADHD.
Topics: Young Adult; Humans; Attention Deficit Disorder with Hyperactivity; Sleep Initiation and Maintenance Disorders; Internet Addiction Disorder; Comorbidity; Internet; Video Games; Behavior, Addictive
PubMed: 37550315
DOI: 10.1038/s41598-023-39462-2 -
Molecular Psychiatry Aug 2023Treatment outcomes for individuals with substance use disorders (SUDs) are variable and more individualized approaches may be needed. Cross-validated, machine-learning...
Treatment outcomes for individuals with substance use disorders (SUDs) are variable and more individualized approaches may be needed. Cross-validated, machine-learning methods are well-suited for probing neural mechanisms of treatment outcomes. Our prior work applied one such approach, connectome-based predictive modeling (CPM), to identify dissociable and substance-specific neural networks of cocaine and opioid abstinence. In Study 1, we aimed to replicate and extend prior work by testing the predictive ability of the cocaine network in an independent sample of 43 participants from a trial of cognitive-behavioral therapy for SUD, and evaluating its ability to predict cannabis abstinence. In Study 2, CPM was applied to identify an independent cannabis abstinence network. Additional participants were identified for a combined sample of 33 with cannabis-use disorder. Participants underwent fMRI scanning before and after treatment. Additional samples of 53 individuals with co-occurring cocaine and opioid-use disorders and 38 comparison subjects were used to assess substance specificity and network strength relative to participants without SUDs. Results demonstrated a second external replication of the cocaine network predicting future cocaine abstinence, however it did not generalize to cannabis abstinence. An independent CPM identified a novel cannabis abstinence network, which was (i) anatomically distinct from the cocaine network, (ii) specific for predicting cannabis abstinence, and for which (iii) network strength was significantly stronger in treatment responders relative to control particpants. Results provide further evidence for substance specificity of neural predictors of abstinence and provide insight into neural mechanisms of successful cannabis treatment, thereby identifying novel treatment targets. Clinical trials registation: "Computer-based training in cognitive-behavioral therapy web-based (Man VS Machine)", registration number: NCT01442597 . "Maximizing the Efficacy of Cognitive Behavior Therapy and Contingency Management", registration number: NCT00350649 . "Computer-Based Training in Cognitive Behavior Therapy (CBT4CBT)", registration number: NCT01406899 .
Topics: Male; Humans; Cannabis; Cocaine; Cognitive Behavioral Therapy; Substance-Related Disorders; Treatment Outcome; Opioid-Related Disorders; Cocaine-Related Disorders
PubMed: 37308679
DOI: 10.1038/s41380-023-02120-0 -
Neuropsychopharmacology : Official... Mar 2024While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated.... (Meta-Analysis)
Meta-Analysis
While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.
Topics: Humans; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation; Substance-Related Disorders; Behavior, Addictive; Craving; Prefrontal Cortex
PubMed: 38086901
DOI: 10.1038/s41386-023-01776-0