Telomere length and epigenetic age acceleration in adolescents with anxiety disorders.

Evidence on the relationship between genetics and mental health are flourishing. However, few studies are evaluating early biomarkers that might link genes, environment, and psychopathology. We aimed to study telomere length (TL) and epigenetic age acceleration (AA) in a cohort of adolescents with and without anxiety disorders (N = 234). We evaluated a representative subsample of participants at baseline and after 5 years (n = 76) and categorized them according to their anxiety disorder diagnosis at both time points: (1) control group (no anxiety disorder, n = 18), (2) variable group (anxiety disorder in one evaluation, n = 38), and (3) persistent group (anxiety disorder at both time points, n = 20). We assessed relative mean TL by real-time quantitative PCR and DNA methylation by Infinium HumanMethylation450 BeadChip. We calculated AA using the Horvath age estimation algorithm and analyzed differences among groups using generalized linear mixed models. The persistent group of anxiety disorder did not change TL over time (p = 0.495). The variable group had higher baseline TL (p = 0.003) but no accelerated TL erosion in comparison to the non-anxiety control group (p = 0.053). Furthermore, there were no differences in AA among groups over time. Our findings suggest that adolescents with chronic anxiety did not change telomere length over time, which could be related to a delay in neuronal development in this period of life.

Resilience and coping strategies in cognitive behavioral group therapy for patients with panic disorder.

BACKGROUND: Although resilience and coping are important factors associated with mental health, they are rarely investigated in the treatment of patients with panic disorder (PD). OBJECTIVE: To evaluate the response to four resilience and coping strategy sessions added to the standard cognitive behavioral group therapy (CBGT) protocol for PD. DESIGN: Controlled clinical trial. METHODS: The control group (n = 50) attended 12 CBGT sessions, while the intervention group (n = 50) received four additional resilience and coping strategy sessions, i.e., 16 in total. Symptom severity, resilience, coping strategies, and quality of life were assessed at baseline and post-CBGT. RESULTS: Symptom severity and maladaptive coping strategies decreased significantly in both groups. However, the intervention group had increased resilience and improvement in the environment domain of quality of life. CONCLUSIONS: Additional sessions have potential benefits for coping skills and resilience in PD patients, but these benefits should be evaluated in further long-term studies.

Structure-based design of δ-lactones for new antifungal drug development: susceptibility, mechanism of action, and toxicity.

Dermatophytes are the etiological agents of cutaneous mycoses, including the prevalent nail infections and athlete's foot. Candida spp. are opportunistic and emerging pathogens, causing superficial to deeper infections related to high mortality rates. As a consequence of prolonged application of antifungal drugs, the treatment failures combined with multidrug-resistance have become a serious problem in clinical practice. Therefore, novel alternative antifungals are required urgently. δ-Lactones have attracted great interest owing to their wide range of biological activity. This article describes the antifungal activity of synthetic δ-lactones against yeasts of the genus Candida spp. and dermatophytes (through the broth microdilution method), discusses the pathways by which the compounds exert this action (toward the fungal cell wall and/or membrane), and evaluates the toxicity to human leukocytes and chorioallantoic membrane (by the hen's egg test-chorioallantoic membrane). Two of the compounds in the series presented broader spectrum of antifungal activity, including against resistant fungal species. The mechanism of action was related to damage in the fungal cell wall and membrane, with specific target action dependent on the type of substituent present in the δ-lactone structure. The damage in the fungal cell was corroborated by electron microscopy images, which evidenced lysed and completely altered cells after in vitro treatment with δ-lactones. Toxicity was dose dependent for the viability of human leukocytes, but none of the compounds was mutagenic, genotoxic, or membrane irritant when evaluated at higher concentrations than MIC. In this way, δ-lactones constitute a class with excellent perspectives regarding their potential applications as antifungals.

Active Brazilian crack cocaine users: nutritional, anthropometric, and drug use profiles

Objective: To evaluate the nutritional status of crack users and to analyze its correlation with drug use profiles. Methods: Cross-sectional study with 108 crack users. Anthropometric data were assessed through body mass index (BMI) and bioimpedance (BIA) measurements. A blood test to analyze hematocrit, hemoglobin, glucose, and lipid profiles was also performed. Crack use was determined through a standardized interview. Results: Based on BMI and BIA, most individuals were eutrophic (about 70%). Regarding hematological parameters, we found that hemoglobin and hematocrit levels were below normal for 32.4 and 30.6% of patients, respectively. Considering normal parameters, a large part of the sample (60.2%) had low levels of HDL cholesterol and high levels of triglycerides (38%). There were no significant correlations between drug profile and nutritional variables. Conclusion: This is a pioneering study that examines the nutritional status of crack users. Our results showed that most crack users present normal anthropometric findings and the prevalence of underweight is low. However, blood analysis showed changes and a specific type of malnutrition.

Active Brazilian crack cocaine users: nutritional, anthropometric, and drug use profiles.

OBJECTIVE: To evaluate the nutritional status of crack users and to analyze its correlation with drug use profiles. METHODS: Cross-sectional study with 108 crack users. Anthropometric data were assessed through body mass index (BMI) and bioimpedance (BIA) measurements. A blood test to analyze hematocrit, hemoglobin, glucose, and lipid profiles was also performed. Crack use was determined through a standardized interview. RESULTS: Based on BMI and BIA, most individuals were eutrophic (about 70%). Regarding hematological parameters, we found that hemoglobin and hematocrit levels were below normal for 32.4 and 30.6% of patients, respectively. Considering normal parameters, a large part of the sample (60.2%) had low levels of HDL cholesterol and high levels of triglycerides (38%). There were no significant correlations between drug profile and nutritional variables. CONCLUSION: This is a pioneering study that examines the nutritional status of crack users. Our results showed that most crack users present normal anthropometric findings and the prevalence of underweight is low. However, blood analysis showed changes and a specific type of malnutrition.

Association between the Intron 8 VNTR Polymorphism of the DAT1 Gene and Crack Cocaine Addiction.

BACKGROUND: This study aims to compare allele and genotype frequencies of a 30-bp variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene, located at intron 8, between adult crack cocaine users and nonaddicted individuals. Due to its involvement in drug addiction, this gene is a good candidate for molecular studies. METHODS: A cross-sectional sample of 239 current adult crack abusers or dependents from in- and outpatient clinics and 211 control individuals was collected in Brazil. They were evaluated using ASRS, ASI-6, WAIS-III, and MINI assessments. DNA samples extracted from whole blood were genotyped for the intron 8 VNTR in DAT1. RESULTS: Logistic regression analysis was performed and controlled for gender, age, ethnicity, educational level, and comorbidities of clinical interest (generalized anxiety disorder, suicide risk, major depressive episode, and attention deficit/hyperactivity disorder). This analysis showed that the 6R6R genotype was associated with crack cocaine addiction (OR = 1.844; CI = 1.101-3.089; p = 0.020). CONCLUSIONS: Our results are consistent with the role of DAT1 in the neurobiology of drug addiction. Nevertheless, the study of other genes, environmental factors, and their interactions is also important to gain a broader understanding of this condition.

Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment.

The aim of this study was to analyze hypotheses-driven gene-environment and gene-gene interactions in smoked (crack) cocaine addiction by evaluating childhood neglect and polymorphisms in mineralocorticoid and glucocorticoid receptor genes (NR3C2 and NR3C1, respectively). One hundred thirty-nine crack/cocaine-addicted women who completed 3 weeks of follow-up during early abstinence composed our sample. Childhood adversities were assessed using the Childhood Trauma Questionnaire (CTQ), and withdrawal symptoms were assessed using the Cocaine Selective Severity Assessment (CSSA) scale. Conditional logistic regression with counterfactuals and generalized estimating equation modeling were used to test gene-environment and gene-gene interactions. We found an interaction between the rs5522-Val allele and childhood physical neglect, which altered the risk of crack/cocaine addiction (Odds ratio = 4.0, P = 0.001). Moreover, a NR3C2-NR3C1 interaction (P = 0.002) was found modulating the severity of crack/cocaine withdrawal symptoms. In the post hoc analysis, concomitant carriers of the NR3C2 rs5522-Val and NR3C1 rs6198-G alleles showed lower overall severity scores when compared to other genotype groups (P-values ≤ 0.035). This gene-environment interaction is consistent with epidemiological and human experimental findings demonstrating a strong relationship between early life stress and the hypothalamic-pituitary-adrenal (HPA) axis dysregulation in cocaine addiction. Additionally, this study extended in crack/cocaine addiction the findings previously reported for tobacco smoking involving an interaction between NR3C2 and NR3C1 genes.

Booster Sessions after Cognitive-Behavioural Group Therapy for Panic Disorder: Impact on Resilience, Coping, and Quality of Life.

BACKGROUND: Panic disorder (PD) has a chronic nature, especially as a result of maladaptive coping strategies to deal with stressful events. AIMS: To evaluate the impact of booster sessions with cognitive techniques on coping strategies, resilience, and quality of life (QoL) in patients previously submitted to standard cognitive-behavioural group therapy (CBGT) for PD. METHOD: A controlled clinical trial with 44 patients with PD (intervention = 20; control = 24) who had previously completed a 12-week CBGT protocol. PD, anxiety, and depression severity symptoms were assessed at baseline and 1, 6, and 12 months after the booster sessions. Coping strategies, resilience, and QoL were assessed by Coping Strategies Inventory (CSI), Resilience Scale, and WHOQOL-BREF respectively. RESULTS: Over time, a significant improvement in PD and depression symptoms was observed in both groups. A significant increase in the QoL social relations domain was found in the booster group, considering a time/group interaction. Coping and other QoL domains did not change after the booster sessions. Changes in resilience were dependent on the intensity of symptoms, with negative but non-significant correlations. CONCLUSIONS: The improvement in PD and depression symptoms for both groups may be a result of the group format of the intervention. Group booster sessions after CBGT are useful to maintain the benefits obtained with CBGT.

Crack cocaine users show differences in genotype frequencies of the 3' UTR variable number of tandem repeats of the dopamine transporter gene (DAT1/SLC6A3).

BACKGROUND: Due to the mechanism of action of the dopamine transporter (DAT) in drug addiction, the DAT1 gene is a potential candidate for molecular studies. This paper aims to compare the prevalence of allele and genotype frequencies created by the 3' UTR variable number of tandem repeats (VNTR) of this gene between crack cocaine users and controls. METHODS: A cross-sectional sample of 237 current adult crack cocaine abusers or dependents (DSM-IV TR criteria) from in- and outpatient clinics in southern Brazil and 205 community controls were compared. The subjects were evaluated using the Adult ADHD Self-Report Scale, the Mini-International Neuropsychiatric Interview - short version, and the Wechsler Intelligence Scale. DNA samples were genotyped for the DAT1 3' VNTR. RESULTS: Logistic regression analysis was performed to compare the frequency of the 10.10 genotype (the putative risk genotype) to those of other genotypes. A significant difference (p = 0.04, OR = 1.758, CI = 1.026-3.012) indicating an increased frequency of the 10.10 genotype in the cases (59.9%) compared to the controls (49.3%) was verified using clinical and demographic covariates. CONCLUSIONS: This is one of the first genetic association studies on crack cocaine users in the literature. The results suggest an influence of the DAT1 gene, namely the 3' VNTR 10.10 genotype. However, more analyses will confirm and clarify its contribution as a possible risk factor for crack cocaine dependence.

Factors associated with recurrence of alcohol-related traffic violations in southern Brazil

Objective: To analyze variables associated with recurrence of blood alcohol content (BAC)-related traffic violations among drivers in southern Brazil. Method: This cross-sectional study included 12,204 driving-under-the-influence (DUI) offenders according to data provided by the Rio Grande do Sul state Transportation Department. Sociodemographic characteristics, license duration, license category, and psychological assessment results were analyzed. Drivers convicted of DUI more than once in 2009/2010 were considered recidivists. Variables were evaluated using descriptive statistical analysis and Poisson regression, adjusted by sex, age, and education level. Results: A total of 538 (4.41%) drivers were considered recidivists. The following variables showed the strongest associations with recidivism: being aged 41-50 years (prevalence ratio [PR] = 3.41), being licensed for ≥ 12 years (PR = 1.86), being licensed for motorcycles, cars and trucks (PR = 1.36), having a license with psychological restrictions (PR = 1.33), and driving a truck or a similar vehicle at the moment of notification (PR = 1.08). Conclusions: In the age group with the highest risk for recurrence, drivers showed a higher probability of having a diagnosis of alcohol dependence and other psychiatric comorbidities that hinder the control of alcohol use. Psychological assessments seem to be important in predicting repeat offenses, especially when limited aptitudes are suspected, and should therefore be better investigated. .

Perceptions of parental bonding in freebase cocaine users versus non-illicit drug users.

BACKGROUND & OBJECTIVES: Evidence has suggested that parenting styles have peculiar characteristics in families with drug-related issues. This study was undertaken to investigate the perception of crack (smoke cocaine) users and non-users about parental bonding quality regarding care and control in Brazil. METHODS: A total of 198 hospitalized crack users and 104 users of any non-illicit drug were assessed using the Parental Bonding Instrument (PBI), the sixth version of the Addiction Severity Index (ASI) and Mini International Neuropsychiatric Interview (MINI). RESULTS: Adjusted logistic regression analysis showed that crack users were more likely (ORadj=9.68; 95% CI: 2.82, 33.20) to perceive neglectful mothers, as well as more likely (ORadj=4.71, 95% CI: 2.17, 10.22) to perceive controlling and affectionless fathers in comparison with non-illicit drug users who were more likely to perceive optimal parenting. INTERPRETATION & CONCLUSIONS: Our findings indicate that the perception of neglectful mothers and affectionless controlling fathers may be associated with the tendency of the children to be less resilient when facing stressful events, leading them to a greater risk to use crack.

Factors associated with recurrence of alcohol-related traffic violations in southern Brazil.

OBJECTIVE: To analyze variables associated with recurrence of blood alcohol content (BAC)-related traffic violations among drivers in southern Brazil. METHOD: This cross-sectional study included 12,204 driving-under-the-influence (DUI) offenders according to data provided by the Rio Grande do Sul state Transportation Department. Sociodemographic characteristics, license duration, license category, and psychological assessment results were analyzed. Drivers convicted of DUI more than once in 2009/2010 were considered recidivists. Variables were evaluated using descriptive statistical analysis and Poisson regression, adjusted by sex, age, and education level. RESULTS: A total of 538 (4.41%) drivers were considered recidivists. The following variables showed the strongest associations with recidivism: being aged 41-50 years (prevalence ratio [PR] = 3.41), being licensed for ≥ 12 years (PR = 1.86), being licensed for motorcycles, cars and trucks (PR = 1.36), having a license with psychological restrictions (PR = 1.33), and driving a truck or a similar vehicle at the moment of notification (PR = 1.08). CONCLUSIONS: In the age group with the highest risk for recurrence, drivers showed a higher probability of having a diagnosis of alcohol dependence and other psychiatric comorbidities that hinder the control of alcohol use. Psychological assessments seem to be important in predicting repeat offenses, especially when limited aptitudes are suspected, and should therefore be better investigated.

Correlates of unprotected sex in a sample of young club drug users.

OBJECTIVES: To assess the demographic characteristics, psychiatric symptoms, substance use patterns, and sexual risk behaviors in a sample of club drug users to identify factors associated with unprotected sex during the 12 months prior to the interview. METHODS: This cross-sectional study employed the targeted sampling and ethnographic mapping approaches via face-to-face interviews conducted at bars and electronic music festivals using an adapted, semi-structured version of the Global Appraisal of Individual Needs questionnaire. The sample comprised 240 male and female young adults who had used ecstasy and/or LSD in the 90 days prior to the interview and who were not receiving treatment for alcohol or drug abuse. RESULTS: Of the 240 subjects selected (mean age: 22.9±4.5 years), 57.9% were men; of the male subjects, 52.5% reported having had unprotected sex in the previous 12 months. Of the total sample, 63.33% reported having had unprotected sex. Multivariate regression analysis showed that anal sex (PR = 1.26; 95% confidence interval (CI): 1.044-1.543; p = 0.017) and the use of alcohol/drugs to make sex last longer (PR = 1.430; 95% CI: 1.181-1.732; p<0.001) are associated with unprotected sex. CONCLUSIONS: The implementation of intervention strategies aimed at reducing sexually risky behaviors should take into consideration the specific characteristics of drug users and should include the development of safer sex negotiation skills.

Correlates of unprotected sex in a sample of young club drug users

OBJECTIVES: To assess the demographic characteristics, psychiatric symptoms, substance use patterns, and sexual risk behaviors in a sample of club drug users to identify factors associated with unprotected sex during the 12 months prior to the interview. METHODS: This cross-sectional study employed the targeted sampling and ethnographic mapping approaches via face-to-face interviews conducted at bars and electronic music festivals using an adapted, semi-structured version of the Global Appraisal of Individual Needs questionnaire. The sample comprised 240 male and female young adults who had used ecstasy and/or LSD in the 90 days prior to the interview and who were not receiving treatment for alcohol or drug abuse. RESULTS: Of the 240 subjects selected (mean age: 22.9±4.5 years), 57.9% were men; of the male subjects, 52.5% reported having had unprotected sex in the previous 12 months. Of the total sample, 63.33% reported having had unprotected sex. Multivariate regression analysis showed that anal sex (PR = 1.26; 95% confidence interval (CI): 1.044-1.543; p = 0.017) and the use of alcohol/drugs to make sex last longer (PR = 1.430; 95% CI: 1.181-1.732; p<0.001) are associated with unprotected sex. CONCLUSIONS: The implementation of intervention strategies aimed at reducing sexually risky behaviors should take into consideration the specific characteristics of drug users and should include the development of safer sex negotiation skills. .

Effect of aging, education, reading and writing, semantic processing and depression symptoms on verbal fluency / Efeito da idade, escolaridade, hábitos de leitura e escrita, processamento semântico e sintomas de depressão na fluência verbal

Verbal fluency tasks are widely used in (clinical) neuropsychology to evaluate components of executive functioning and lexical-semantic processing (linguistic and semantic memory). Performance in those tasks may be affected by several variables, such as age, education and diseases. This study investigated whether aging, education, reading and writing frequency, performance in semantic judgment tasks and depression symptoms predict the performance in unconstrained, phonemic and semantic fluency tasks. This study sample comprised 260 healthy adults aged 19 to 75 years old. The Pearson correlation coefficient and multiple regression models were used for data analysis. The variables under analysis were associated in different ways and had different levels of contribution according to the type of verbal fluency task. Education had the greatest effect on verbal fluency tasks. There was a greater effect of age on semantic fluency than on phonemic tasks. The semantic judgment tasks predicted the verbal fluency performance alone or in combination with other variables. These findings corroborate the importance of education in cognition supporting the hypothesis of a cognitive reserve and confirming the contribution of lexical-semantic processing to verbal fluency.(AU)

As tarefas de fluência verbal são amplamente empregadas na clínica neuropsicológica para avaliar os componentes de funções executivas e processamento léxico-semântico (linguagem e memória semântica). O desempenho nessas tarefas pode ser influenciado por diferentes variáveis, como idade, escolaridade e diferentes patologias. Este estudo investigou se a idade, escolaridade, frequência dos hábitos de leitura e escrita, o desempenho em tarefas de julgamento semântico e sintomas de depressão predizem os desempenhos em tarefas de fluência verbal de critério livre, fonêmico-ortográfico e semântico. Participaram desse estudo 260 adultos saudáveis entre 19 e 75 anos. Foi utilizada a correlação de Pearson e da análise de regressão múltipla. As variáveis analisadas foram associadas em diferentes modelos combinatórios e apresentaram distintos níveis de explicação de acordo com o tipo de fluência verbal. A escolaridade foi a variáveis que melhor contribuiu para a explicação do desempenho nas tarefas de fluência verbal, seguida pela idade, principalmente na tarefa fonêmico-ortográfica. O desempenho nas tarefas de julgamento semântico predisse a performance da fluência verbal isoladamente ou em combinação com as demais variáveis. Esses resultados corroboram a importância da escolaridade na cognição, sustentando a hipótese da reserva cognitiva e confirmam a implicação do processamento léxico-semântico na fluência verbal.(AU)

Effect of aging, education, reading and writing, semantic processing and depression symptoms on verbal fluency / Efeito da idade, escolaridade, hábitos de leitura e escrita, processamento semântico e sintomas de depressão na fluência verbal

Verbal fluency tasks are widely used in (clinical) neuropsychology to evaluate components of executive functioning and lexical-semantic processing (linguistic and semantic memory). Performance in those tasks may be affected by several variables, such as age, education and diseases. This study investigated whether aging, education, reading and writing frequency, performance in semantic judgment tasks and depression symptoms predict the performance in unconstrained, phonemic and semantic fluency tasks. This study sample comprised 260 healthy adults aged 19 to 75 years old. The Pearson correlation coefficient and multiple regression models were used for data analysis. The variables under analysis were associated in different ways and had different levels of contribution according to the type of verbal fluency task. Education had the greatest effect on verbal fluency tasks. There was a greater effect of age on semantic fluency than on phonemic tasks. The semantic judgment tasks predicted the verbal fluency performance alone or in combination with other variables. These findings corroborate the importance of education in cognition supporting the hypothesis of a cognitive reserve and confirming the contribution of lexical-semantic processing to verbal fluency...

As tarefas de fluência verbal são amplamente empregadas na clínica neuropsicológica para avaliar os componentes de funções executivas e processamento léxico-semântico (linguagem e memória semântica). O desempenho nessas tarefas pode ser influenciado por diferentes variáveis, como idade, escolaridade e diferentes patologias. Este estudo investigou se a idade, escolaridade, frequência dos hábitos de leitura e escrita, o desempenho em tarefas de julgamento semântico e sintomas de depressão predizem os desempenhos em tarefas de fluência verbal de critério livre, fonêmico-ortográfico e semântico. Participaram desse estudo 260 adultos saudáveis entre 19 e 75 anos. Foi utilizada a correlação de Pearson e da análise de regressão múltipla. As variáveis analisadas foram associadas em diferentes modelos combinatórios e apresentaram distintos níveis de explicação de acordo com o tipo de fluência verbal. A escolaridade foi a variáveis que melhor contribuiu para a explicação do desempenho nas tarefas de fluência verbal, seguida pela idade, principalmente na tarefa fonêmico-ortográfica. O desempenho nas tarefas de julgamento semântico predisse a performance da fluência verbal isoladamente ou em combinação com as demais variáveis. Esses resultados corroboram a importância da escolaridade na cognição, sustentando a hipótese da reserva cognitiva e confirmam a implicação do processamento léxico-semântico na fluência verbal...