Alcohol consumption, depression, overweight and cortisol levels as determining factors for NR3C1 gene methylation.

The NR3C1 glucocorticoid receptor (GR) gene is a component of the stress response system, which can be regulated by epigenetic mechanisms. NR3C1 methylation has been associated with trauma and mental issues, including depression, post-traumatic stress, anxiety, and personality disorders. Previous studies have reported that stressful events are involved in NR3C1 gene methylation, suggesting that its regulation under environmental effects is complex. The present study aimed to analyze associations involving stressors such as socioeconomic status, health conditions, and lifestyle in relation to NR3C1 methylation in adults. This study included 386 individual users of the Brazilian Public Unified Health System (SUS), and evaluated socioeconomic and health conditions, body mass index, cortisol levels, and lifestyle. Data were correlated with NR3C1 methylation, determined using DNA pyrosequencing. The results showed that alcohol consumption, overweight, and high cortisol levels were related to NR3C1 demethylation, while depression was related to its methylation. Habits, lifestyle, and health status may influence NR3C1 gene regulation via methylation, revealing the complexity of environmental impacts on NR3C1 methylation.

Factors Associated with Depressive Symptoms Among Rural Residents from Remote Areas.

This study aimed to investigate the risk factors for depressive symptoms among rural residents in Brazil. A representative sample of two hundred eighty-eight volunteers aged from 18 to 65 years was included and determining factors for high BDI-II score were investigated through a multivariate logistic model. Sadness, loss of pleasure, crying, worthlessness and loss of interest in sex are more likely to be observed in females, and risk factors to this high depression score among rural residents were shown to be: female gender, tobacco use, pesticide application, poor self-perceived health and presence of chronic disease. These data contribute to the knowledge of factors determining depressive symptoms among rural residents and may help to expand health policies to improve quality of rural life on these communities and others with similar characteristics.

Psychosocial stress and central adiposity: A Brazilian study with a representative sample of the public health system users.

OBJECTIVE: To assess the association between indicators of psychosocial stress and central adiposity in adult users of the Unified Health System (SUS) from Southeast of Brazil. METHODS: This cross-sectional study was conducted with 384 adults (20 to 59 years old) from the city of Alegre, Southeastern Brazil. The simple random sample represented the population using the public health system of the municipality. The prevalence of obesity was based on the Body Mass Index, and central adiposity (dependent variable) was measured by waist circumference in centimeters. The independent variables were the following indicators of psychosocial stress: food and nutrition insecurity (yes/no), serum cortisol (µg/dL), symptoms suggestive of depression using the Beck Depression Inventory-II ≥ 17 (yes/no), and altered blood pressure ≥ 130/85 mmHg (yes/no). Univariate linear regression was performed between central adiposity and each stress indicator, and later the models were adjusted for socioeconomic, health, and lifestyle variables. All analyses were made separately by rural and urban location. RESULTS: The prevalence of weight excess, by the classification of the Body Mass Index ≥ 25.0 kg/m2, was 68.3% and, by waist circumference, 71.5% of individuals presented an increased risk for metabolic complications related to central adiposity. Mean waist circumference scores for the rural and urban population were 89.3 ± 12.7 cm and 92.9 ± 14.7 cm, respectively (p = 0.012). Indicators of stress that were associated with central adiposity were: cortisol in the rural population (ß = -0.60; 95% CI = -1.09;-0.11) and altered blood pressure in the urban population (ß = 6.66; 95% CI = 2.14;11.18). This occurred both in the raw analysis and in the models adjusted for confounding factors. CONCLUSION: Central adiposity was inversely associated with cortisol in the rural population and directly associated with higher arterial blood pressure in the urban population, suggesting a local influence on how individuals react to stress.

Pesticide exposure, tobacco use, poor self-perceived health and presence of chronic disease are determinants of depressive symptoms among coffee growers from Southeast Brazil.

The lifestyle and other factors associated with the appearance of several health conditions that affect quality of life in rural zone is an issue that has been increasingly explored. Brazil is the largest coffee-producing nation in the world and has been a considerable consumer of pesticides since 2008. The aim of the present study was to investigate factors that could be contributing to the appearance of depressive symptoms in rural workers. Two hundred twenty male volunteers from nine cities in Southeast Brazil completed the Beck Depression Inventory-II (BDI-II) questionnaire about depressive symptoms and provided other information about socio-demographic characteristics and additional confounding factors. The adjusted multivariate logistic analysis demonstrated that pesticide exposure, tobacco use, poor self-perceived health and the presence of chronic disease contribute as risk factors for the appearance of depressive symptoms at a level above ups and downs considered normal in the BDI-II. This survey contributes to the search for solutions to improve quality of life and mental health in the rural living to the extent that social determinants of depression are being investigated.

Increased electroencephalographic activity in crack-cocaine users visualizing crack cues.

This study aimed to examine electrophysiologically the cerebral function under visual cue-reactivity paradigm in crack-cocaine users. This was an exploratory open trial in which young crack-cocaine-users and non-users were clinically examined. The participants' brain activity was analyzed by an event-related potentials procedure under a cue-reactivity paradigm with the random visual presentation of crack-related and neutral images. Nine young male crack-cocaine users and nine age-matched male healthy subjects from research center's neighborhood volunteered themselves to participate in this study. We demonstrated through electrophysiological tools that crack-cocaine users are more likely to show higher brain activity, notably in the frontal lobe region, when processing crack-related images. Though imaging studies have already showed increased brain activity in this paradigm, this data shows that event-related potentials can be an effective tool for brain evaluation in addiction.

Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

Cognitive related electrophysiological changes induced by non-invasive cortical electrical stimulation in crack-cocaine addiction.

Prefrontal dysfunction is a hallmark in drug addiction, yet interventions exploring modulation of prefrontal cortex function in drug addiction have not been fully investigated with regard to physiological alterations. We tested the hypothesis that non-invasive prefrontal stimulation would change neural activity in crack-cocaine addiction, investigating the effects of transcranial Direct Current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex (DLPFC) induced cortical excitability modulation on the visual P3 Event Related Potentials (ERP) component under neutral and drug cue exposition in crack-cocaine addicts. Thirteen crack-cocaine users were randomly distributed to receive five applications (once a day, every other day) of bilateral (left cathodal/right anodal) tDCS (20 min, 2 mA, 35 cm2) or sham tDCS over the DLPFC. Brain activity was measured under crack-related or neutral visual-cued ERPs. There were significant differences in P3-related parameters when comparing group of stimulation (active vs. sham tDCS) and number of sessions (single vs. repetitive tDCS). After a single session of tDCS, P3 current intensity in the left DLPFC increased during neutral cues and decreased during crack-related cues. This effect was opposite to what was observed in the sham-tDCS group. In contrast, repetitive tDCS increased current density not only in the DLPFC, but also in a wider array of prefrontal areas, including presumably the frontopolar cortex (FPC) orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), when subjects were visualizing crack-related cues. Thus, single and repetitive application of tDCS can impact cognitive processing of neutral and especially crack-related visual cues in prefrontal areas, which may be of importance for treatment of crack-cocaine addiction.

Behavioral effects of transcranial direct current stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence.

Transcranial Direct Current Stimulation (tDCS) has been shown to reduce acute substance craving in drug addicts, and improve cognition in neuropsychiatric patients. Here we aimed to explore further tDCS induced behavioral and neurophysiological modulation including assessment of relapse rate over a prolonged time course in alcoholism. We examined the effects of repeated anodal tDCS (2mA, 35 cm(2), 20min) over the left dorsolateral prefrontal cortex (DLPFC) on relapse to the use of alcohol in alcoholics from outpatient services, who received additional routine clinical treatment. Furthermore, event related potentials (ERPs), cognitive and frontal executive processes, craving, depressive and anxiety symptoms were obtained before and after treatment. From thirteen alcoholic subjects, seven were randomized to sham-tDCS and six to real tDCS treatment (once a week for five consecutive weeks). Depressive symptoms and craving were reduced to a larger extent in the tDCS group compared to the sham group (p=0.005 and p=0.015, respectively). On the other hand, active tDCS was able to block the increase in neural activation triggered by alcohol related and neutral cues in prefrontal cortex (PFC) as indexed by ERP as seen in the sham-tDCS group. Finally, there was a trend for increased change in executive function in the tDCS group compared to the sham-tDCS group (p=0.082), and, similarly, a trend for more relapses in the tDCS group compared to sham tDCS (four alcoholic subjects (66.7%) vs. one (14.3%), p=0.053).These results confirm the previous findings of tDCS effects on craving in alcoholism and also extend these findings as we showed also tDCS-related mood improvement. However, potential increase in relapse is possible; thus the clinical value of an increase in craving and improvement in depression and executive function needs to be carefully assessed in further studies; including investigation of optimal parameters of stimulation.

Clozapine and SCH 23390 prevent the spatial working memory disruption induced by Δ9-THC administration into the medial prefrontal cortex.

Marijuana (Cannabis sativa) is one of the most widely used illicit drugs in the world. Its use is associated with impairments in cognitive function. We previously reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive component of marijuana, impaired spatial working memory in the radial maze task when injected intracortically (IC) into the medial prefrontal cortex (mPFC) of rats. Here, we used this paradigm to evaluate the involvement of prefrontal dopamine receptors in working memory disruption induced by Δ(9)-THC. Intracortical pre-treatment of animals with either the D(1)- or D(2)-like dopamine receptor antagonists SCH 23390 or clozapine, respectively, significantly reduced the number of errors rats made in the radial maze following treatment with Δ(9)-THC also administered intracortically. These results were obtained in the absence of locomotor impairment, as evidenced by the time spent in each arm a rat visited. Our findings suggest that prefrontal dopamine receptors are involved in Δ(9)-THC-induced disruption of spatial working memory. This interaction between the cannabinoid system and dopamine release in the PFC contributes to new directions in research and to treatments for cognitive dysfunctions associated with drug abuse and dependence.