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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.

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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.

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Objetivo: descrever o caso de um lactente exposto à cocaína e as repercussões clínicas da sua ingestão por meio do leite materno. Relato do caso: lactente, com um mês e três dias de vida e peso de 3.920g vem à emergência, por quadro de hipoatividade, rebaixamento de sensório, choro e sangramento nasal. Afebril, irritada, chorosa, sem sinais de esforço ventilatório ou sangramentos ativos. Exames mostraram leucocitose 13490/uL, acidose metabólica discreta, aumento de transglutaminase oxalacética e provas de coagulação alargadas. Demais exames laboratoriais sem alterações e culturas negativas. Screening toxicológico revelou cocaína no plasma da lactente. O Centro de Informações Toxicológicas, recomendou monitorização e suporte clínico. A paciente recebeu alta da unidade de terapia intensiva para enfermaria cinco dias após admissão, com melhora do sensório, seguindo acompanhamento com a equipes especializadas. Conclusão: o pronto reconhecimento da síndrome de abstinência neonatal permite o melhor manejo da mesma em benefício dos pacientes. O diagnóstico diferencial com quadro séptico pode ser de grande importância em quadros como este.

Objective: describing a case of an infant exposed to cocaine through breast milk and its clinical repercussions. Case report: infant, one month and three days old, weighing 3,920g, came to the emergency room due to hypoactivity, sensory impairment and nose bleeding. Afebrile, irritated, tearful, no signs of ventilatory effort or active bleeding. Tests showed leukocytosis 13490/uL, mild metabolic acidosis, increased serum glutamic-oxaloacetic transaminase and enlarged coagulation tests. Other laboratory tests were normal. Toxicological screening revealed cocaine in the infant's plasma. Toxicological Information Center, recommended monitorization, and clinical support. The patient was discharged from the intensive care unit to the ward five days after admission, with sensorium improvement and a follow-up with specialized teams. Conclusions: prompt recognition of the neonatal abstinence syndrome allows for better management of it and high chances of recovery for patients. The differential diagnosis with septic condition can be of great importance in conditions like this one.

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White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.

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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.

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