The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain.

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n1 = 30) and their age-paired controls (YC, n1 = 30), and compare it with octogenarian elder controls (EC, n1 = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50-year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD.

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.

Cingulate cortical thickness in cocaine use disorder: mediation effect between early life stress and cocaine consumption.

OBJECTIVE: The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD. METHODS: Participants aged 18-50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively. RESULTS: Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score. CONCLUSION: Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex.

Hair cortisol levels and mental health problems in children and adolescents exposed to victimization.

Youths who experience multiple forms of victimization are at a heightened risk for psychopathology across the lifespan. The hypothalamic-pituitary-adrenal (HPA) axis is a key target for the investigation of neurobiological changes induced by chronic stress and violence exposure. The measurement of hair cortisol concentration allows the investigation of long-term HPA activity and its association with victimization. The present study investigated the impact of exposure to polyvictimization in Latin-American children and adolescents on hair cortisol levels. We investigated association among cortisol, mental health problems and victimization. The study included 83 youths (mean age 10.84 years-old) from southern Brazil. We assessed self-reported victimization scores (Juvenile Victimization Questionnaire - JVQ-R2), mental health problems (Child Behavior Checklist - CBCL/6-18), and hair cortisol concentrations for the previous 30 days. The results showed an association between exposure to multiple forms of victimization and higher concentrations of hair cortisol; the results also showed that cortisol levels and mental health problems were associated with the severity of polyvictimization. These findings suggest that preadolescent victimization is associated with hyperactivation of HPA axis and with increased risk of mental health issues.

Consortium Profile: The Methylation, Imaging and NeuroDevelopment (MIND) Consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults. To bridge this gap, we established the Methylation, Imaging and NeuroDevelopment (MIND) Consortium, which aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies. MIND currently integrates 15 cohorts worldwide, comprising (repeated) measures of DNA methylation in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging across up to five time points over a period of up to 21 years (N pooled DNAm = 11,299; N pooled neuroimaging = 10,133; N pooled combined = 4,914). By triangulating associations across multiple developmental time points and study types, we hope to generate new insights into the dynamic relationships between peripheral DNA methylation and the brain, and how these ultimately relate to neurodevelopmental and psychiatric phenotypes.

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.

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.