Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation.

BACKGROUND: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles. METHODS: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. RESULTS: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1ß, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. CONCLUSION: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

Cocaine use disorder effects on blood oxytocin levels and OXTR DNA methylation.

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. The Addiction Severity Index was used to assess clinical characteristics. We found higher oxytocin levels in men with CUD (56.5 pg/mL; 95% CI: 48.2-64.7) than in control men (33.6 pg/mL; 95% CI: 20.7-46.5), while no differences between women with and without CUD were detected. With a moderate effect size, the interaction effect between group and sex remained significant when controlling for height, weight and age data. A positive correlation in the CUD sample was found between oxytocin levels and days of psychological suffering prior to treatment enrollment. No group differences were observed regarding DNA methylation data. This suggests that CUD is associated with higher peripheral oxytocin levels in men during acute abstinence. This finding may be considered in future studies that aim at using exogenous oxytocin as a potential treatment for cocaine addiction.

Decision-making under risk and theory of mind in adolescent offenders in provisional deprivation of liberty.

INTRODUCTION: Delinquent behaviors are risky behaviors that increase during puberty and reach their highest peak in late adolescence. It has been proposed that poor decision-making and theory of mind (ToM) are key cognitive processes implicated with delinquency during adolescence, affecting evaluation of risks and impairing appreciation of social norms. Nevertheless, it is not yet clear whether adolescent offenders who are subjected to provisional deprivation of liberty due to conflict with the law (adolescents in conflict with the law [ACL]) might, in fact, present a specific profile with regard to these cognitive processes. OBJECTIVES: To assess deliberative decision-making and ToM among adolescents in conflict with the law and adolescents not in conflict with the law. METHODS: The sample comprised 62 participants: ACL (n = 29) and a control group (CG) (n = 33). ToM was assessed with the Reading the Mind in the Eyes Test (RMET) and decision-making was assessed with the Columbia Card Task (CCT). Substance use, callous-unemotional traits, childhood maltreatment, and intelligence quotient (IQ) were also assessed. RESULTS: ACL had more ToM errors for negative mental states in comparison to CG, but not for error rates concerning neutral and positive mental states. With regards to decision-making, our results suggest that ACL group members did not vary their behavior based on the available information and that the risk information had an opposite effect on the number of cards chosen (risk-taking behavior) when compared to CG. CONCLUSION: These findings have important implications for development of interventions for these adolescents, suggesting that they tend to learn little from negative outcomes and have reduced capacity to process negative emotions.

Gender differences in progression to crack-cocaine use and the role of sexual and physical violence.

OBJECTIVE: This study aimed to evaluate whether progression from first drug use to crack-cocaine use differs according to gender, and whether the report of sexual or physical violence impacts the time of progression. METHODS: We interviewed 896 crack-cocaine users (548 men; 348 women) from addiction treatment units. Cox regression models evaluated the time of progression from first drug use to crack use. We analyzed gender differences according to the absence or presence of sexual or physical violence, also considering whether violence, when present, had occurred before or after the onset of crack use. RESULTS: Women presented a faster progression to crack use regardless of exposure to sexual or physical violence (p < 0.05). Compared to unexposed men, there was a similar progression for men exposed to sexual or physical violence before the first use of crack (p = 0.167 and p = 0.393, respectively). In both genders, we observed a faster progression among individuals exposed to these types of violence after the onset of crack use (p < 0.01). CONCLUSIONS: We found a faster progression to crack use among women and among individuals exposed to sexual and physical violence after the onset of crack use. These results encourage differentiated treatment strategies, focused on gender and individual characteristics.

Gender differences in progression to crack-cocaine use and the role of sexual and physical violence

Objective: This study aimed to evaluate whether progression from first drug use to crack-cocaine use differs according to gender, and whether the report of sexual or physical violence impacts the time of progression. Methods: We interviewed 896 crack-cocaine users (548 men; 348 women) from addiction treatment units. Cox regression models evaluated the time of progression from first drug use to crack use. We analyzed gender differences according to the absence or presence of sexual or physical violence, also considering whether violence, when present, had occurred before or after the onset of crack use. Results: Women presented a faster progression to crack use regardless of exposure to sexual or physical violence (p < 0.05). Compared to unexposed men, there was a similar progression for men exposed to sexual or physical violence before the first use of crack (p = 0.167 and p = 0.393, respectively). In both genders, we observed a faster progression among individuals exposed to these types of violence after the onset of crack use (p < 0.01). Conclusions: We found a faster progression to crack use among women and among individuals exposed to sexual and physical violence after the onset of crack use. These results encourage differentiated treatment strategies, focused on gender and individual characteristics.

Sex differences in brain regional homogeneity during acute abstinence in cocaine use disorder.

There are significant sex differences in the clinical characteristics of cocaine use disorder (CUD). As this is a brain disorder that involves changes in functional connectivity, we investigated the existence of sex differences among people with CUD and controls. We used a data-driven method comparing males (n = 20, CK-M) and females with CUD (n = 20, CK-F) and healthy controls (20 males, HC-M and 20 females, HC-F). The participants undertook a resting-state functional magnetic resonance imaging exam. Regional homogeneity (ReHo) was performed to identify group and sex differences. Persons with CUD of both sexes presented lower ReHo parameters than controls, especially within the parietal lobule. Males with CUD showed higher ReHo than females in three right-side brain areas: postcentral gyrus, putamen and fusiform gyrus. It was found that abstinence symptoms severity was associated with lower ReHo values in the right postcentral gyrus and the right fusiform gyrus. Participants with CUD exhibited altered ReHo parameters compared to controls, similar to what is found in ageing-related disorders. Our data also indicate that cocaine has sex-specific effects on brain functioning when analysing ReHo.

Decision-making under risk and theory of mind in adolescent offenders in provisional deprivation of liberty

Abstract Introduction Delinquent behaviors are risky behaviors that increase during puberty and reach their highest peak in late adolescence. It has been proposed that poor decision-making and theory of mind (ToM) are key cognitive processes implicated with delinquency during adolescence, affecting evaluation of risks and impairing appreciation of social norms. Nevertheless, it is not yet clear whether adolescent offenders who are subjected to provisional deprivation of liberty due to conflict with the law (adolescents in conflict with the law [ACL]) might, in fact, present a specific profile with regard to these cognitive processes. Objectives To assess deliberative decision-making and ToM among adolescents in conflict with the law and adolescents not in conflict with the law. Methods The sample comprised 62 participants: ACL (n = 29) and a control group (CG) (n = 33). ToM was assessed with the Reading the Mind in the Eyes Test (RMET) and decision-making was assessed with the Columbia Card Task (CCT). Substance use, callous-unemotional traits, childhood maltreatment, and intelligence quotient (IQ) were also assessed. Results ACL had more ToM errors for negative mental states in comparison to CG, but not for error rates concerning neutral and positive mental states. With regards to decision-making, our results suggest that ACL group members did not vary their behavior based on the available information and that the risk information had an opposite effect on the number of cards chosen (risk-taking behavior) when compared to CG. Conclusion These findings have important implications for development of interventions for these adolescents, suggesting that they tend to learn little from negative outcomes and have reduced capacity to process negative emotions.

Cortical thickness and subcortical volume abnormalities in male crack-cocaine users.

Crack-cocaine offers a higher risk of abuse than intranasal and intravenous use of cocaine. Yet, current treatments remain disappointing and our understanding of the mechanism of crack-cocaine neurotoxicity is still incomplete. Magnetic resonance images studies on brain changes of crack-cocaine addicts show divergent data. The present study investigated gray matter (GM) abnormalities in crack-cocaine dependents (n = 18) compared to healthy controls (n = 17). MRI data was analysed using FreeSurfer and voxel-based morphometry (VBM). FreeSurfer analysis showed that CD had decreased cortical thickness (CT) in the left inferior temporal cortex (lTC), left orbitofrontal cortex (lOFC) and left rostro frontal cortex (lRFC), enlargement in left inferior lateral ventricle, and smaller GM volume in right hippocampus and right ventral diencephalon. VBM analysis showed that CD had significantly decreased GM volume in left Putamen and left nucleus accumbens. Furthermore, we found a negative correlation between duration of crack-cocaine use and lTC CT. These results provide compelling evidence for GM abnormalities in CD and also suggest that duration of crack-cocaine use may be associated with CT alterations.

Prediction of attempted suicide in men and women with crack-cocaine use disorder in Brazil.

BACKGROUND: Suicide is a severe health problem, with high rates in individuals with addiction. Considering the lack of studies exploring suicide predictors in this population, we aimed to investigate factors associated with attempted suicide in inpatients diagnosed with cocaine use disorder using two analytical approaches. METHODS: This is a cross-sectional study using a secondary database with 247 men and 442 women hospitalized for cocaine use disorder. Clinical assessment included the Addiction Severity Index, the Childhood Trauma Questionnaire, and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, totalling 58 variables. Descriptive Poisson regression and predictive Random Forest algorithm were used complementarily to estimate prevalence ratios and to build prediction models, respectively. All analyses were stratified by gender. RESULTS: The prevalence of attempted suicide was 34% for men and 50% for women. In both genders, depression (PRM = 1.56, PRW = 1.27) and hallucinations (PRM = 1.80, PRW = 1.39) were factors associated with attempted suicide. Other specific factors were found for men and women, such as childhood trauma, aggression, and drug use severity. The men's predictive model had prediction statistics of AUC = 0.68, Acc. = 0.66, Sens. = 0.82, Spec. = 0.50, PPV = 0.47 and NPV = 0.84. This model identified several variables as important predictors, mainly related to drug use severity. The women's model had higher predictive power (AUC = 0.73 and all other statistics were equal to 0.71) and was parsimonious. CONCLUSIONS: Our findings indicate that attempted suicide is associated with depression, hallucinations and childhood trauma in both genders. Also, it suggests that severity of drug use may be a moderator between predictors and suicide among men, while psychiatric issues shown to be more important for women.

Instruments for measuring perceived and experienced mental illness Stigma: a systematic review / Instrumentos de avaliação do estigma percebido e estigma experienciado na doença mental: uma revisão sistemática / Instrumentos de evaluación del estigma percibido y el estigma experimentado en enfermedades mentales: una revisión sistemática

In order to investigate which instruments are most utilized when measuring perceived and experienced mental illness stigma (MIS) in adults, and some of the variables that may moderate or interfere in measured outcomes, 101 published empirical and peer-reviewed studies were systematically extracted from electronic databases (PubMed, Scopus, EBSCO, Web of Science, and PsycINFO). The results revealed that MIS is commonly evaluated by five scales. When considering the most tested and reported associative effects, age, and symptoms’ severity were identified as potentially intervening variables. Other variables, such as sex, diagnostic, and treatment regimen (inpatient/outpatient) were evaluated by a few studies and presented inconsistent results. These findings suggest that future studies should use well-established instruments in the literature to assess MIS, as well as to aim for the cross-cultural adaptation of instruments that evaluate MIS since no instruments presented in this review are validated to the Brazilian population.

Objetivando investigar quais instrumentos são mais utilizados na mensuração do estigma da doença mental (EDM) percebido e experienciado por adultos, e quais variáveis podem moderar ou interferir nos resultados da mensuração, 101 artigos foram sistematicamente selecionados nas bases de dados eletrônicas (MEDLINE/PubMed, Scopus, EBSCO, Web of Science e PsycINFO). Os resultados revelaram que existem cinco instrumentos comumente utilizados para medir o EDM. Ao considerar os efeitos associativos mais testados e reportados sobre o estigma, a idade e a severidade dos sintomas foram apontadas como variáveis potencialmente intervenientes. Outras variáveis, como sexo, diagnóstico e regime de tratamento (internamento/ambulatório) foram avaliadas por poucos estudos e apresentaram resultados inconsistentes. Essas descobertas sugerem que trabalhos futuros devem utilizar instrumentos bem estabelecidos na literatura para avaliar o EDM, assim como visar à adaptação transcultural de instrumentos que avaliem o EDM, uma vez que nenhum dos instrumentos apresentados nesta revisão é validado para a população brasileira.

Con el objetivo de investigar qué instrumentos son más utilizados en la medición del estigma de la enfermedad mental (EEM) percibido y experimentado en adultos, así como las variables que pueden moderar o interferir en los resultados de la evaluación, 101 artículos fueron sistemáticamente extraídos en las bases de datos electrónicas (MEDLINE/PubMed, Scopus, EBSCO, Web of Science y PsycINFO). Los resultados revelaron que existen cinco instrumentos comúnmente utilizados para medir el EEM. Al considerar los efectos asociativos más comprobados y reportados sobre el estigma, la edad y la severidad de los síntomas fueron identificadas como variables potencialmente intervinientes. Otras variables, como el sexo, diagnóstico y condición de tratamiento (internación/ambulatorio) fueron evaluadas en pocos estudios y presentaron resultados inconsistentes. Estos hallazgos sugieren que trabajos futuros deben utilizar instrumentos consolidados en la literatura para evaluar el EEM, así como para la adaptación transcultural de instrumentos que evalúen el EEM, ya que ninguno de los instrumentos presentados en esta revisión ha sido validado para la población brasileña.

Association of CHRNA5 Gene Variants with Crack Cocaine Addiction.

Genome-wide studies provide increasing evidence of association of genetic variants with different behaviors. However, there is a growing need for replication and subsequent characterization of specific findings. In this sense, the CHRNA5 gene has been associated with nicotine (with genome-wide significance), alcohol and cocaine addictions. So far, this gene has not been evaluated in smoked (crack) cocaine. We aimed to analyze the influence of CHRNA5 variants in crack addiction susceptibility and severity. The sample includes 300 crack-addicted patients and 769 non-addicted individuals. The CHRNA5 SNPs evaluated were rs588765, rs16969968, and rs514743. Homozygosity for rs16969968 and rs588765 major alleles was nominally associated with a risk to crack addiction (GG, P = 0.032; CC, P = 0.036, respectively). Haplotype analyses reveal significant associations (rs588765|rs16969968|rs514743 pglobal-corrected = 7.66 × 10-5) and suggest a substantial role for rs16969968. These findings corroborate previous reports in cocaine addiction-in line with the expected effects of cocaine in the cholinergic system-and in the opposite direction of significant GWAS findings for nicotine addiction susceptibility. These results are strengthened by the first report of an association of rs588765 with crack addiction and by the haplotype findings. In summary, our study highlights the relevance of the α5 subunit on crack cocaine addiction, replicating previous results relating CHRNA5 with the genetics and pathophysiology of addiction of different drugs.

Association Between Recent Cannabis Consumption and Withdrawal-Related Symptoms During Early Abstinence Among Females With Smoked Cocaine Use Disorder.

BACKGROUND: The effects of cannabis on clinical outcomes of treatment services for other drug use disorders remains unclear. The primary aim of the current study was to investigate the effects of recent cannabis consumption on the severity of cocaine withdrawal and depressive symptoms during a 3-week inpatient treatment program for women with cocaine use disorder. The second goal of this study was to test the effect of recent alcohol or tobacco use on the aforementioned outcomes. METHODS: This was a longitudinal study with 2 assessment time points: at enrollment and upon discharge from a medically managed intensive inpatient unit. The sample was composed of 214 early abstinence females with cocaine use disorder. Cocaine withdrawal and depressive symptoms were measured using the Cocaine Selective Severity Assessment (CSSA) and the Beck Depressive Inventory (BDI-II). Recent substance use was evaluated using the Addiction Severity Index (ASI-6). RESULTS: Patients with cocaine use disorder and with frequent recent cannabis use reported higher severity of cocaine withdrawal and depressive symptoms after 3 weeks of inpatient treatment. Neither recent alcohol nor tobacco use was associated with increased CSSA or BDI outcomes, suggesting these substances play a minor role compared to recent cannabis use in affecting withdrawal-related symptoms. CONCLUSIONS: The assessment of recent cannabis use may help identify patients in need of additional treatment to manage severe cocaine withdrawal symptoms and depressive symptoms during early abstinence.

An fMRI study of inhibitory control and the effects of exposure to violence in Latin-American early adolescents: alterations in frontoparietal activation and performance.

We used functional magnetic resonance to investigate the effects of exposure to violence on early adolescent brain function in an inhibitory control task. We investigated the association among scores on self-reported exposure to violence, performance and brain activation. Thirty-seven early adolescents (ages 10-14) from a Latin-American urban region participated in the study. Results showed that recent and chronic exposure to violence was associated with less activation of a network of frontal regions, including the anterior cingulate gyrus and the superior frontal cortex; recent exposure to violence was also associated with less activation of the superior parietal lobe. Results also showed that less activation correlated with more prominent deterioration in the performance in the inhibitory control task (increased latency with time). The findings suggest that early adolescence exposure to violence is associated with differences in activation of a neural network commonly associated with executive function and control. The results underscore the urgency of addressing exposure to violence in adolescence, a period of high susceptibility to the environment, and are discussed in the light of the evidence of the effects of violence on adolescent brain function. Executive function training may be a candidate for targeted cognitive interventions aimed at mitigating these effects.

Cocaine Use Disorder Is Associated With Changes in Th1/Th2/Th17 Cytokines and Lymphocytes Subsets.

Background: Cocaine is a psychostimulant drug with high addictive proprieties. Evidence suggests that cocaine use leads to critical changes in the immune system, with significant effects on T, B, and natural killer (NK) cells and influencing peripheral levels of cytokines. The presence of abstinence-related symptoms during detoxification treatment is known to influence the prognosis. Here, our aim was to investigate immune profiles in women with cocaine use disorder (CUD) according to withdrawal symptoms severity. Methods: Blood samples and clinical data were collected at onset of detoxification treatment of 50 women with CUD. The patients were stratified according to Cocaine Selective Severity Assessment (CSSA) scores in low withdrawal (L-W) and high withdrawal (H-W) categories. In addition, we also included a control group with 19 healthy women as reference to immune parameters. Peripheral blood was collected and lymphocyte subsets were phenotyped by multi-color flow cytometry (B cells, CD4+ T, CD8+ T, NK cells, and different stages of T-cell differentiation). PBMCs from patients and healthy controls were stimulated in vitro with phytohemagglutinin (1%) for 72 h to assess the production of Th1/Th2/Th17 cytokines. Results: Following stimulation, lymphocytes from women with CUD produced increased levels of Th1/Th2/Th17 cytokines. However, higher levels of IL-2 and IL-17 were observed only in the L-W group, while higher levels of IL-6 were detected in the H-W group compared to controls. H-W group showed lower percentage of early-differentiated Th cells (CD4+CD27+CD28+), elevated percentage of Th cells (CD3+CD4+), intermediate-differentiated Th cells (CD4+CD27-CD28+), and B cells (CD3-CD19+). Both CUD groups showed decreased percentages of naïve T cells (CD3+CD4+CD45RA+ and CD3+CD8+CD45RA+). Conclusion: Our data demonstrated that CUD can lead to increased production of Th1/Th2/Th17 cytokines and lymphocyte changes.

Association between cognitive performance and SYT1-rs2251214 among women with cocaine use disorder.

The SNP rs2251214 of the SYT1 gene was recently associated with externalizing phenotypes, including ADHD and cocaine use disorder (CUD). Here, we investigated whether SYT1-rs2251214 could also be implicated with cognitive performance variations among women with CUD. Results showed that G homozygous (n = 146) have lower cognitive performance in the Stroop, Trail Making and Matrix Reasoning tests compared with A-allele carriers (n = 64), suggesting that rs2251214 may influence the severity of cognitive impairments in CUD.

Cocaine use disorder in females is associated with altered social decision-making: a study with the prisoner's dilemma and the ultimatum game.

BACKGROUND: Chronic cocaine use is associated with cognitive deficits, including poor performance on neuropsychological tasks of memory, executive functions, theory of mind and decision-making. However, the relationship between cocaine use disorder and social decision-making remains unclear. This is particularly relevant given the fact that many cocaine abusers present impairments in social functioning. In this sense, game theory paradigms have been helping to comprehend the behavior of psychiatric patients when they directly engage in social situations, which may better approximate many of their real-life choices. METHODS: The present study investigated social decision-making in individuals with or without cocaine use disorder, examining their behavior in the Prisoner's Dilemma and in the Ultimatum Game. Thus, 129 females diagnosed with cocaine use disorder and 55 females with no history of substance abuse were recruited and performed both social decision-making tasks. Additional assessments included information about demographics, patterns of substance consumption and executive function performance. RESULTS: Females with cocaine use disorder opted more often to not defect in the Prisoner's Dilemma, while in the Ultimatum Game they frequently chose to accept the first and unfair offer as responders. These effects were more pronounced within females with long-term history of cocaine use. Associations between cocaine use disorder and altered social decision-making were independent from demographic and executive function variables. CONCLUSIONS: The influence of cocaine use disorder on social decision-making was detected in both game paradigms, resulting in more cooperative behavior in the Prisoner's Dilemma and higher acceptance rate of unfair offers in the Ultimatum Game. Further studies should focus on investigating these associations to shed light on the putative biopsychosocial factors underlying the observed effects.

Sex-based differences in multidimensional clinical assessments of early-abstinence crack cocaine users.

Crack cocaine use disorder (CUD) has been related to sex differences. This work aimed to compare the severity of drug use and the severity of other negative related outcomes in males and females with CUD. A total of 1344 inpatients (798 males and 546 females) with crack cocaine use disorder (CUD) were evaluated by a detailed multidimensional clinical assessment, including addiction severity and trauma exposure. Linear regression predicted higher drug use severity (ß = 0.273, p < 0.001) and more problems in domains related to childcare issues (ß = 0.321), criminal involvement (ß = 0.108), work-related problems (ß = 0.281) and social support impairments (ß = 0.142) for females, all with p < 0.001. Alcohol problems were predicted to be higher in males (ß = -0.206, P < 0.001). Females had higher rates of other mental disorders, particularly trauma and stress-related disorders (OR: 3.206, CI: 2.22, 4.61). Important sex differences also emerged in trauma history and HIV infection prevalence. CUD has a more severe clinical presentation among females facing early abstinence. Sex differences in the CUD course indicate the need for consideration of sex-specific interventions and research.

The association between SYT1-rs2251214 and cocaine use disorder further supports its role in psychiatry.

Synaptotagmin-1 is an essential regulator of synaptic vesicle exocytosis, and its encoding gene (SYT1) is a genome and transcriptome-wide association hit in cognitive performance, personality and cocaine use disorder (CUD) studies. Additionally, in candidate gene studies the specific variant rs2251214 has been associated with attention-deficit/hyperactivity disorder (ADHD), antisocial personality disorder and other externalizing phenotypes in adults with ADHD, as well as with response to methylphenidate (MPH) treatment. In this context, we sought to evaluate, in an independent sample, the association of this variant with CUD, a phenotype that shares common biological underpinnings with the previously associated traits. We tested the association between SYT1-rs2251214 and CUD susceptibility and severity (addiction severity index) in a sample composed by 315 patients addicted to smoked cocaine and 769 non-addicted volunteers. SYT1-rs2251214 was significantly associated with susceptibility to CUD, where the G allele presented increased risk for the disorder in the genetic models tested (P = 0.0021, OR = 1.44, allelic; P = 0.0012, OR = 1.48, additive; P = 0.0127, OR = 1.41, dominant). This is the same allele that was associated with increased risk for ADHD and other externalizing behaviors, as well as poor response to MPH treatment in previous studies. These findings suggest that the neurotransmitter exocytosis pathway might play a critical role in the liability for psychiatric disorders, especially externalizing behaviors and CUD.

Peripheral blood microRNA levels in females with cocaine use disorder.

BACKGROUND: There is growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of addictive disorders. MicroRNAs (miRNAs) are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level. However, the role of miRNAs as potential biomarkers for addiction is still underexplored. Based on translational and clinical findings, we compared the expression levels of microRNA-124 (miR-124), microRNA-181 (miR-181), and microRNA-212 (miR-212) between a group of females with cocaine use disorder (CUD; n = 30) and a group of healthy female controls (HC; n = 20). METHODS: Blood expression levels of miR-124, miR-181, and miR-212 in the HC and CUD group were determined by qPCR, using two miRNAs as endogenous controls (miR-24 and miR-126). Substance use behavior was assessed by self-report using the Addiction Severity Index (ASI-6) and depressive symptoms severity was measured using the Beck Depressive Inventory (BDI-II). Urine screen test was performed to detect cocaine metabolites. RESULTS: Mir-124 and miR-181 were upregulated in the CUD group (p > 0.01). Furthermore, increased cognitive/affective depression symptoms were identified among a CUD subgroup with the higher miR-181 expression levels (p > 0.05). No significant difference in expression levels was found for miR-212. CONCLUSIONS: MiR-124 and miR-181 show promise as biomarkers for CUD when assessed in the peripheral blood. Further investigation is needed to elucidate the molecular mechanisms underlying these associations and to validate target genes regulated by these miRNAs.