Addiction Traits Research Articles

The interplay of psychological resilience and adolescent mobile phone addiction in Henan province, China: insights from latent class analysis.

The aim of this study was to classify distinct subgroups of adolescents based on the severity levels of their mobile phone addiction and to investigate how these groups differed in terms of their psychosocial characteristics. We surveyed a total of 2,230 adolescents using three different questionnaires to assess the severity of their mobile phone addiction, stress, anxiety, depression, psychological resilience, and personality. Latent class analysis was employed to identify the subgroups, and we utilized Receiver Operating Characteristic (ROC) curves and multinomial logistic regression for statistical analysis. All data analyses were conducted using SPSS 26.0 and Mplus 8.5. We classified the subjects into subgroups based on their mobile phone addiction severity, and the results revealed a clear pattern with a three-class model based on the likelihood level of mobile phone addiction (p < 0.05). We examined common trends in psychosocial traits such as age, grade at school, parental education level, anxiety levels, and resilience. ROC analysis of sensitivity versus 1-specificity for various mobile phone addiction index (MPAI) scores yielded an area under the curve (AUC) of 0.893 (95% CI, 0.879 to 0.905, p < 0.001). We also determined diagnostic value indices for potential cutoff points ranging from 8 to 40. The optimal cutoff value for MPAI was found to be >14, which corresponded to the maximum Youden index (Youden index = 0.751). The latent classification process in this research confirmed the existence of three distinct mobile phone user groups. We also examined the psychosocial characteristics that varied in relation to the severity levels of addiction. This study provides valuable insights into the categorization of adolescents based on the severity of mobile phone addiction and sheds light on the psychosocial characteristics associated with different addiction levels. These findings are expected to enhance our understanding of mobile phone addiction traits and stimulate further research in this area.

Association between alexithymia, emotional intelligence, smoking addiction, and alcohol use disorder among a sample of Lebanese adults.

Alexithymia can be associated with worse addictive traits, while emotional intelligence is associated with better addictive outcomes. In Lebanon, the prevalence of cigarette and waterpipe smoking is on the rise, although people are aware of the associated harms. Also, around 11% of Lebanese adults have experienced alcohol use disorder (AUD). This study aimed to assess the association between alexithymia, emotional intelligence, smoking (cigarette and waterpipe), and AUD among a sample of Lebanese adults. A web-based cross-sectional study carried out between February and April 2020, during the lockdown period, enrolled 408 community-dwelling adults. The survey link was shared on social media to reach participants from all Lebanese districts/governorates. Taking antidepressants (Beta = 4.37) was significantly associated with more cigarette dependence, while female gender (Beta = -1.52) and having a high vs. low monthly income (Beta = 1.02) were significantly associated with less cigarette dependence. None of the variables, including alexithymia, were significantly associated with waterpipe dependence. Female gender (Beta = -0.15) and higher emotional intelligence (Beta = -0.003) were significantly associated with less AUD, whereas higher alexithymia (Beta = 0.003) was significantly associated with more AUD. This study could demonstrate a significant association between alexithymia and cigarette smoking and alexithymia and alcohol consumption. Future research is warranted to investigate the mediating effect of emotional intelligence and how these results may be used to meet the needs of alexithymic individuals with addictions.

Factors influencing the addiction characteristics of non-suicidal self-injurious behaviors in adolescents: A case-control study.

Many studies have shown that in the context of public health emergencies, the incidence rate of adolescent non-suicidal self-injury (NSSI) patients increased dramatically. This paper aims to characterize the behavioral characteristics of adolescent NSSI and analyze the influencing factors of NSSI behavior addiction characteristics. Our research was a case-control study which included 84 adolescents with NSSI (female vs. male: 59 vs. 25) and 84 healthy controls (female vs. male: 53 vs. 31). All the participants enrolled were aged 12-18 years. The differences in the scores of the following five scales were compared between the case and control groups: Egna Minnen Barndoms Uppfostran (EMBU), Perceived Social Support Scale (PSSS), Perceived Stress Scale (PSS); Bergen Social Media Addiction Scale (BSMAS) and Video Game Dependence Scale (VDG-S). The characteristics of NSSI behavior of the study group were evaluated using the Ottawa Self Inventory Chinese Revised Edition (OSIC). And a binary logistic regression model was developed to analyze the factors that influence adolescent NSSI behavioral addiction characteristics. In the study group, the emotional warmth scores in the father's and mother's rearing style scores in the EMBU were significantly lower than the controls. The BSMAS and VDG-S scores were significantly higher than those in the control group. 38 cases of NSSI with addiction characteristics accounted for 45.24% in the study group. The risk factors for NSSI addiction traits were as follows: female, single-child, high level of VDG-S scores, high scores of excessive interferences in father's rearing style, and high scores of punishments and excessive interferences in mother's rearing style score. Female, only child, internet addiction, and negative parenting styles were predictors of NSSI behavioral addiction characteristics in adolescents. Targeted coping strategies should be developed to reduce the occurrence and development of self-injurious behavior, especially for female adolescents with Internet dependence in one-child families with negative parenting styles.

A Genome-Wide Association Study Reveals a BDNF-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures.

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33 × 10-8 calculated with the Yates-corrected χ2 test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWASs of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network, where BDNF is the most significant hub gene. This study indicates that several genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The study also reveals a central role of BDNF in the pathogenesis of AD.

Association of Predicted Expression and Multimodel Association Analysis of Substance Abuse Traits

Introduction: Genome-wide association studies (GWAS) have played a critical role in identifying many thousands of loci associated with complex phenotypes and diseases. This has led to several translations of novel disease susceptibility genes into drug targets and care. This however has not been the case for analyses where sample sizes are small, which suffer from multiple comparisons testing. The present study examined the statistical impact of combining a burden test methodology, PrediXcan, with a multimodel meta-analysis, cross phenotype association (CPASSOC). Methods: The analysis was conducted on 5 addiction traits: family alcoholism, cannabis craving, alcohol, nicotine, and cannabis dependence and 10 brain tissues: anterior cingulate cortex BA24, cerebellar hemisphere, cortex, hippocampus, nucleus accumbens basal ganglia, caudate basal ganglia, cerebellum, frontal cortex BA9, hypothalamus, and putamen basal ganglia. Our sample consisted of 1,640 participants from the University of California, San Francisco (UCSF) Family Alcoholism Study. Genotypes were obtained through low pass whole genome sequencing and the use of Thunder, a linkage disequilibrium variant caller. Results: The post-PrediXcan, gene-phenotype association without aggregation resulted in 2 significant results, HCG27 and SPPL2B. Aggregating across phenotypes resulted no significant findings. Aggregating across tissues resulted in 15 significant and 5 suggestive associations: PPIE, RPL36AL, FOXN2, MTERF4, SEPTIN2, CIAO3, RPL36AL, ZNF304, CCDC66, SSPOP, SLC7A9, LY75, MTRF1L, COA5, and RRP7A; RPS23, GNMT, ERV3-1, APIP, and HLA-B, respectively. Discussion: Given the relatively small size of the cohort, this multimodel approach was able to find over a dozen significant associations between predicted gene expression and addiction traits. Of our findings, 8 had prior associations with similar phenotypes through investigation of the GWAS Atlas. With the onset of improved transcriptome data, this approach should increase in efficacy.

Attachment, deadness, desire, and addictive buzz traps

In this article I describe those caught up in an increasingly common but worrying phenomenon, that of addictive states of mind, seen, for example, in obsessional use of video games or pornography. While the contemporary world has exacerbated the risks, addictive traits often originate in attempts to escape from an inner pain or deadness towards the false promise offered by the object of addiction. The article offers a different view of the dopaminergic system. It also looks at how the contemporary world is posing new challenges for people who have developed with such a propensity, and we will see how those prone to addictive states of mind struggle to bear certain emotional states, finding them overwhelming, and instead reach for a solution via their addiction.

The Assessment of Food Addiction and the Yale Food Addiction Scale in Bariatric Surgery Populations

AbstractFood addiction (FA) appears among bariatric weight loss surgery candidates who struggle to control the intake of hyperpalatable/refined foods have high rates of psychopathology and related health problems. Despite this, prevalence rates of FA in the bariatric sector are reported as low or variable. We investigated the prevalence of FA and the applicability of conventionally used metrics for 166 pre-surgery candidates from a weight management centre (USA) and a major metropolitan hospital (Australia). Self-report measures assessed FA (Yale Food Addiction Scale (YFAS)), body mass index (BMI), disordered eating, addictive personality, psychopathology, and diet. Consistent with prior research, standard YFAS scoring, requiring the endorsement of a distress/impairment (D/I) criterion (FA + D/I), yielded a FA prevalence rate of 12.7%, compared to 37.3% when D/I was omitted (FA − D/I). We compared profiles for those with FA using each scoring method against those ‘without’, who did not meet a minimum of three YFAS symptoms (non-FA ≤ 2). Both methods differentiated those with and without FA on addictive traits, disordered eating and hyperpalatable food consumption. Only FA + D/I differentiated markers of psychological distress or impairment, including depression, anxiety and quality of life. Results indicate a need for further FA research in bariatric settings.

The digital habitus of the unwedded emerging adults: a sociological interpretation of male-female differences in Facebook behavior

PurposeBy considering Facebook as a social context of manifesting digital habitus, this paper aims to explore the differences between men and women in the compensatory use of Facebook, their engagement in crafting and exhibiting virtual self-representation, and addictive traits associated with it. It is argued that while Facebook compensates for the negative consequences of real-world experiences by allowing users, particularly women to display an ideal self or a true virtual self and so aid in socializing, users eventually develop an addiction, which results in various social difficulties.Design/methodology/approachThe study surveyed 511 male and 413 female undergraduate students who were between 19 to 26 years of age and reported being unmarried. Psycho-Social Aspects of Facebook Use Scale was used to solicit the responses. The factors were quantified by the items selected from the scale, and confirmatory factor analysis was used to assess the construct validity and reliability of items to check the usability of the scale in cross-cultural contexts. The Independent Samples t-test was used to check whether statistical evidence exists that the related sample means of men and women vary significantly.FindingsWhile there is no difference in virtualizing the self by gender; women perceive Facebook as more compensating than men. Likewise, compared with men, women are found to be more self-presenting, more addictive and highly involved in socializing. The item-wise differences show that Facebook comparatively enhances the self-esteem of the women and women are more adventurous than men in Facebook interaction.Originality/valueThe study argues that there is a strong connection between the digital habitus and the social world. Social values and conditioning constrain people’s intention of being in the digital world and reflect their intention and decisions. Overall, the study is the most elaborative quantitative examination of how men and women differ in their Facebook behavior.

Engagement and Immersion in Digital Play: Supporting Young Children's Digital Wellbeing.

For many families, young children’s engagement with screen-based technology is an ongoing concern in terms of physical, social and cognitive development. They are uneasy with the difficulty children have disengaging from screens and concerned that this behavior is obsessive or a sign of addiction. However, technology is recognized as having a “rightful role” in early childhood contexts. This scoping paper reports on a review of literature relating to digital play for children aged birth to five years, with the aim of further understanding digital wellbeing. Csikszentmihalyi’s flow theory serves as a theoretical framework for understanding why many young children enjoy digital play and become deeply engaged, with a disconnect between how young children and adults perceive digital play. Concerns about children’s deep immersion with digital play are interrogated to understand the connections with perceived addictive traits. The review highlights the critical importance of supporting children’s agency and digital citizenship skills from a young age, including the ability to critique content, balance screen-time with non-screen time and to develop self-control and self-regulation as a means to promote long-term positive outcomes for children in their digital lifeworlds and beyond.

Digital Overuse and Addictive Traits and Their Relationship With Mental Well-Being and Socio-Demographic Factors: A National Population Survey for Wales.

Introduction: Population health concerns have been raised about negative impacts from overuse of digital technologies. We examine patterns of online activity predictive of Digital Overuse and Addictive Traits (DOAT). We explore associations between DOAT and mental well-being and analyse how both relate to self-reported changes in self-esteem, perceived isolation, and anxiety about health when individuals use the internet for health purposes.Methods: A cross-sectional nationally representative household survey of adults using stratified random sampling (compliance 75.4%, n = 1,252). DOAT was measured using self-reported questions adapted from a social media addiction scale (failure to cut down use, restlessness when not using, and impact on job/studies and home/social life in the last year), combined into a single DOAT score. Higher DOAT score was defined as >1 standard deviation above population mean. The Short Warwick-Edinburgh Mental Well-being Scale was used to measure mental well-being. Analyses were limited to those with internet access (n = 1,003).Results: Negative impacts of digital technology use on work and home/social lives were reported by 7.4% of respondents. 21.2% had tried but failed to cut down use in the past year. Higher DOAT was associated with higher social media and internet use but also independently associated with greater risks of low mental well-being. Higher DOAT was associated with both improvement and worsening of self-esteem, perceived isolation and anxiety about health when using the internet for health reasons, with no change in these outcomes most likely in those with lower DOAT. Lower mental well-being was associated with a similar bi-directional impact on perceived isolation and was also associated with worsening self-esteem.Conclusions: Substantial proportions of individuals report negative impacts on home, social and working lives from digital technology use, with many trying but failing to cut down use. Individuals with higher DOAT may experience improvements or worsening in self-esteem and other measures of mental well-being when using the internet for health purposes. From a public health perspective, a greater understanding of risk factors for digital overuse, its impacts on well-being and how to reasonably limit use of technology are critical for a successful digital revolution.

Effects of massively multiplayer online roleplaying games on psychological health and inter-personal relationships of the male youth: A cross-sectional study in sub-urban Kolkata, West Bengal, India

Gaming related experiences and addictive behaviours are emerging causes of adverse psycho-social health such as depression, anxiety, in adolescents and young adults around the world. Nonetheless, there remains a dearth of information relating to adolescents and young adults in India, a country which has millions of gamers.&#x0D; Present study examined the effects of massively multiplayer online role-playing games on the psychological health and inter-personal relationships of adolescents and young male adults of sub-urban Kolkata, West Bengal, India.&#x0D; Questionnaires were used to collect data on socio-economic and lifestyle traits, psychological health and inter-personal relationships were obtained from both gamers (n = 150) and non-gamers (n = 150). Data on gaming experiences and addiction were obtained only from gamers. MANCOVA and linear regression were performed to understand the effects of socio-economic and lifestyle traits, gaming experience and addiction traits on psychological health and inter-personal relationships of gamers.&#x0D; Study findings revealed that both gamers and non-gamers derived from a similar age group (mean age = 19.94 years) and socio-economic cluster. Disparities in psychological health in terms of depression, anxiety and stress and inter-personal relationship in terms of parent and peer attachments were present across social groups and between gamers and non-gamers. Various problematic gaming experiences and gaming related addictive behaviours resulted in poor psychological health and inter-personal relationship with parents and peers.&#x0D; Male gamers were at high risk to develop adverse psychological health and poor inter-personal relationships with parents and peers due to problematic gaming experience and gaming addiction. Proper education and counselling regarding the beneficial and detrimental sides of gaming may ensure better psycho-social health of adolescents and young adults in India.

The offspring of alcohol-exposed sires exhibit heightened ethanol intake and behavioral alterations in the elevated plus maze.

Research suggests that addictive traits are indeed heritable, but very few preclinical studies have explored transgenerational effects of paternal alcohol exposure. The present study addressed this gap in knowledge. We explored whether offspring of ethanol-exposed sires would be more likely to accept ethanol than descendants of water-exposed and control sires. We also investigated whether the second generation of ethanol-exposed descendants would accept ethanol more than controls and were more or less likely to experience anxiety-like behavior in behavioral assessments. We exposed male rats to repeated binge doses of alcohol (4g/kg/day across 8 days), water, or left them untreated and mated them with untreated females. We then bred the offspring of these rats to test transgenerational effects of paternal alcohol exposure. We tested 14-day-old offspring from the first and second filial generation for their acceptance of ethanol and water, and measured anxiety-like behavior in 38-day-old, second-generation offspring using an elevated plus maze. The results indicate that offspring of ethanol-exposed sires increase ethanol acceptance in the first generation compared to untreated controls, whereas in the second-generation increased ethanol acceptance vs. these controls is seen in descendants of both ethanol- and vehicle-treated sires. At adolescence, the second generation of rats derived from alcohol-exposed sires exhibited significantly more time spent in the open arms and significantly more arm entries than any other group. The present study suggests that parental ethanol exposure is associated with lingering effects in the infant and adolescent offspring. The second filial generation was also found to be affected, albeit similarly by grandparental ethanol exposure or by the stress of the vehicle administration.

A Genome-Wide Association Study Reveals New Genes in a Molecular Network Associated with Alcohol Dependence and Related Clinical Measures

Background: Alcohol dependence (AD) is a cluster of clinical phenomena that develop after repeated alcohol use. At least 50% of factors predisposing to AD are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in a cohort of patients with AD and eight additional clinical measures. Methods: Chi-square tests and the signal localization approach were used for the genome-wide screening of associations with AD. Likelihood ratio tests were used to evaluate associations with the additional clinical measures. Regulatory sequences in the associated linkage disequilibrium blocks were retrieved from bioinformatic databases. The resulting list of regulated genes was analyzed for possible interactions. Results: A genome-wide significant association of rs220677 with AD (p-value = 1.33×10-8) was discovered in female patients. Associations with six other single nucleotide polymorphisms listed in previous GWAS of psychiatric and addiction traits were differently replicated in female and male patients. The bioinformatic analysis showed that regulatory elements in the seven associated linkage disequilibrium blocks define the expression of 78 protein-coding genes. Nearly 68% of these and of 120 other previously published coding genes associated with alcohol phenotypes directly interact in a single network (i.e. without additional interactors added by the software). Conclusions: Results of this study suggest that molecular pathways implicated in the pathogenesis of AD are the same in both sexes, but different genes play more prominent roles in men and women. The discovered gene network may contain clues to the understanding of the pathogenesis and to the discovery of new treatment options of AD.

Cocaine alters the mouse testicular epigenome with direct impact on histone acetylation and DNA methylation marks.

Recent evidence suggests that cocaine administration in animal models can trigger non-genetic inheritance of addiction traits from father to offspring, affecting development and behaviour. Is chronic cocaine intake involved in alterations of epigenetic homeostasis in the testis? Epigenetic marks and mediators in testis and isolated germ cells of adult mice treated with cocaine (10mg/kg) or vehicle (sterile saline solution) were evaluated in an intermittent binge protocol: three intraperitoneal injections, 1h apart, one day on/off for 13 days, collecting tissue 24h after the last binge administration (day 14). It was shown that chronic cocaine intake in mice disrupts testicular epigenetic homeostasis, increasing global methylated cytosine levels in DNA from germ cells and sperm. Cocaine also increased testicular and germ cell acetylated histone 3 and 4 and decreased expression of histone deacetylases HDAC1/2. Immunolocalization studies showed that HDAC1/2 and acetylated histone 3 and 4 proteins localize to meiotic germ cells. Analysis of mRNA expression in isolated germ cells shows decreased levels of Hdac1/2/8, Dnmt3b and Tet1 and increased levels of Dnmt3a gene expression after cocaine treatment. Cocaine intake is associated with testicular toxicity and significant reproductive function impairment. The results presented here broaden the basic knowledge of the impact of addictive stimulants on testicular pathophysiology, fertility and male reproductive health and imply that altered epigenetic homeostasis by cocaine may have potential consequences on future generations.

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5× 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5× 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

Genome-Wide Expression Profiles Drive Discovery of Novel Compounds that Reduce Binge Drinking in Mice.

Transcriptome-based drug discovery has identified new treatments for some complex diseases, but has not been applied to alcohol use disorder (AUD) or other psychiatric diseases, where there is a critical need for improved pharmacotherapies. High Drinking in the Dark (HDID-1) mice are a genetic model of AUD risk that have been selectively bred (from the HS/Npt line) to achieve intoxicating blood alcohol levels (BALs) after binge-like drinking. We compared brain gene expression of HDID-1 and HS/Npt mice, to determine a molecular signature for genetic risk for high intensity, binge-like drinking. Using multiple computational methods, we queried LINCS-L1000 (Library of Integrated Network-Based Cellular Signatures), a database containing gene expression signatures of thousands of compounds, to predict candidate drugs with the greatest potential to decrease alcohol consumption. Our analyses predicted novel compounds for testing, many with anti-inflammatory properties, providing further support for a neuroimmune mechanism of excessive alcohol drinking. We validated the top 2 candidates in vivo as a proof-of-concept. Terreic acid (a Bruton's tyrosine kinase inhibitor) and pergolide (a dopamine and serotonin receptor agonist) robustly reduced alcohol intake and BALs in HDID-1 mice, providing the first evidence for transcriptome-based drug discovery to target an addiction trait. Effective drug treatments for many psychiatric diseases are lacking, and the emerging tools and approaches outlined here offer researchers studying complex diseases renewed opportunities to discover new or repurpose existing compounds and expedite treatment options.

Cancer drug addiction is relayed by an ERK2-dependent phenotype switch.

Drug addiction denotes the dependency of tumors on the same therapeutic drugs to which they have acquired resistance. Observations from cultured cells1–3, animal models4 and patients5–7 raise the possibility that cancer drug addiction can instigate a potential cancer vulnerability, which may be used therapeutically. However, for this trait to become of clinical interest, it is imperative to first define the underlying mechanism. Therefore, we performed an unbiased CRISPR-Cas9 knockout screen to functionally mine the genome of melanoma cells that are both resistant and addicted to BRAF inhibition for “addiction genes”. Here, we describe a signaling pathway comprising ERK2, JUNB and FRA1, disruption of which allows tumor cells to reverse addiction and survive upon treatment discontinuation. This occurred both in culture and mice, and was irrespective of the acquired drug resistance mechanism. In melanoma and lung cancer cells, death induced by drug withdrawal was preceded by a specific ERK2-dependent phenotype switch, alongside transcriptional reprogramming reminiscent of EMT. In melanoma, this caused shutdown of the lineage survival oncoprotein MITF, restoration of which reversed both phenotype switching and drug addiction-associated lethality. In melanoma patients who had progressed on BRAF inhibition, treatment cessation was followed by increased expression of the phenotype switch-associated receptor tyrosine kinase AXL. Drug discontinuation synergized with the melanoma chemotherapeutic dacarbazine by further suppressing MITF and its prosurvival target BCL2 while inducing DNA damage. Our results uncover a pathway driving cancer drug addiction, which may guide alternating therapeutic strategies for enhanced clinical responses of drug-resistant cancers.

A preclinical model for identifying rats at risk of alcohol use disorder

Alcohol use is one of the world’s leading causes of death and disease, although only a small proportion of individuals develop persistent alcohol use disorder (AUD). The identification of vulnerable individuals prior to their chronic intoxication remains of highest importance. We propose here to adapt current methodologies for identifying rats at risk of losing control over alcohol intake by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Factor analysis showed that these three addiction criteria loaded on one underlying construct indicating that they represent a latent construct of addiction trait. Further, not only vulnerable rats displayed higher ethanol consumption, and higher preference for ethanol over sweetened solutions, but they also exhibited pre-existing higher anxiety as compared to resilient rats. In conclusion, the present preclinical model confirms that development of an addiction trait not only requires prolonged exposure to alcohol, but also depends on endophenotype like anxiety that predispose a minority of individuals to lose control over alcohol consumption.

Insular and anterior cingulate circuits in smokers with schizophrenia

Schizophrenia (SZ) is associated with high rates of smoking. We previously found that resting state functional connectivity (rsFC) between the dorsal anterior cingulate (dACC) and striatum is independently associated with nicotine addiction and psychiatric illness. Since the insula is implicated in nicotine dependence, we hypothesized that SZ smokers will have greater dysfunction in smoking-related insular and dACC circuits than normal control smokers (NC) independent of smoking severity, consistent with an inherent disease-related weakening of smoking-related circuits. Nicotine challenge was used to demonstrate that decreased rsFC in identified circuits reflects addiction trait and is not affected by pharmacological state. Twenty-four NC smokers and 20 smokers with SZ matched on nicotine addiction severity participated in a resting state fMRI study and were scanned during two separate sessions while receiving a placebo or nicotine patch, in a randomized, cross-over design. Using individualized, anatomically defined anterior and posterior insula and dACC as regions of interest (ROI), whole brain rsFC was performed using each ROI as a seed. Significant negative correlations between smoking severity and rsFC between insula, dACC and striatum were found for both groups. Furthermore, smokers with SZ demonstrated additive reductions in circuit strength between the dACC and insula compared to NC smokers independent of smoking severity. Nicotine challenge did not significantly alter rsFC in insula–dACC–striatal circuits. Reduced rsFC strength between the insula, dACC and striatum is associated with nicotine addiction severity in both non-psychiatrically ill and in SZ smokers. Decreased insula-dACC rsFC may index overlapping circuitry associated with smoking and SZ.

P.4.b.006 Aberrant resting-state functional connectivity in panic disorder patients

Schizophrenia (SZ) is associated with high rates of smoking. We previously found that resting state functional connectivity (rsFC) between the dorsal anterior cingulate (dACC) and striatum is independently associated with nicotine addiction and psychiatric illness. Since the insula is implicated in nicotine dependence, we hypothesized that SZ smokers will have greater dysfunction in smoking-related insular and dACC circuits than normal control smokers (NC) independent of smoking severity, consistent with an inherent disease-related weakening of smoking-related circuits. Nicotine challenge was used to demonstrate that decreased rsFC in identified circuits reflects addiction trait and is not affected by pharmacological state. Twenty-four NC smokers and 20 smokers with SZ matched on nicotine addiction severity participated in a resting state fMRI study and were scanned during two separate sessions while receiving a placebo or nicotine patch, in a randomized, cross-over design. Using individualized, anatomically defined anterior and posterior insula and dACC as regions of interest (ROI), whole brain rsFC was performed using each ROI as a seed. Significant negative correlations between smoking severity and rsFC between insula, dACC and striatum were found for both groups. Furthermore, smokers with SZ demonstrated additive reductions in circuit strength between the dACC and insula compared to NC smokers independent of smoking severity. Nicotine challenge did not significantly alter rsFC in insula–dACC–striatal circuits. Reduced rsFC strength between the insula, dACC and striatum is associated with nicotine addiction severity in both non-psychiatrically ill and in SZ smokers. Decreased insula-dACC rsFC may index overlapping circuitry associated with smoking and SZ.