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1.
Behav Brain Res ; 407: 113237, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33798820

RESUMO

Hypoxia-ischemia (HI) is a consequence of a lack of oxygen and glucose support to the developing brain, which causes several neurodevelopmental impairments. Environmental enrichment (EE) is considered an option to recover the alterations observed in rodents exposed to HI. The aim of this study was to investigate the impact of early EE on memory, hippocampal volume and brain-derived neurotrophic factor (Bbnf) and glucocorticoid receptor (Nr3c1) gene expression of mice exposed to HI. At P10, pups underwent right carotid artery permanent occlusion followed by 35 min of 8% O2 hypoxic environment. Starting at P11, animals were reared in EE or in standard cage (HI-SC or SHAM-SC) conditions until behavioral testing (P45). SHAM pups did not undergo carotid ligation and hypoxic exposure. Memory performance was assessed in the Y-maze, Novel object recognition, and Barnes maze. Animals were then sacrificed for analysis of hippocampal volume and Bdnf and Nr3c1 gene expression. We observed that animals exposed to HI performed worse in all three tests compared to SHAM animals. Furthermore, HI animals exposed to EE did not differ from SHAM animals in all tasks. Moreover, HI decreased hippocampal volume, while animals reared in early EE were not different compared to SHAM animals. Animals exposed to HI also showed upregulated hippocampal Bdnf expression compared to SHAM animals. We conclude that early EE from P11 to P45 proved to be effective in recovering memory impairments and hippocampal volume loss elicited by HI. Nevertheless, Bdnf expression was not associated with the improvements in memory performance observed in animals exposed to EE after a hypoxic-ischemic event.

2.
Psychiatry Res Neuroimaging ; 310: 111232, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33621927

RESUMO

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.

3.
PLoS One ; 16(1): e0245261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33465121

RESUMO

We investigated what degree of risk of infection with COVID-19 is necessary so that people intend to stay home, even when doing so means losing their salary. We conducted an online survey across Brazil during the initial outbreak, in which 8,345 participants answered a questionnaire designed to identify the maximum tolerated risk (k') necessary for them to disregard social distancing recommendations and guarantee their salaries. Generalized linear mixed models, path analysis structural equation, and conditional interference classification tree were performed to further understand how sociodemographic factors impact k' and to establish a predictive model for the risk behavior of leaving home during the pandemic. We found that, on average, people tolerate 38% risk of infection to leave home and earn a full salary, but this number decreased to 13% when the individual risk perception of becoming ill from severe acute respiratory syndrome coronavirus-2 is considered. Furthermore, participants who have a medium-to-high household income and who are older than 35 years are more likely to be part of the risk-taking group who leave home regardless of the potential COVID-19 infection level; while participants over 45 years old and with good financial health are more likely to be part of the risk-averse group, who stay home at the expense of any salary offered. Our findings add to the political and public debate concerning lockdown strategies by showing that, contrary to supposition, people with low socioeconomic status are not more likely to ignore social distancing recommendations due to personal economic matters.


Assuntos
/psicologia , Assunção de Riscos , Trabalho/psicologia , Adolescente , Adulto , Fatores Etários , Brasil , Comércio/estatística & dados numéricos , Emprego/estatística & dados numéricos , Feminino , Humanos , Renda/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Quarentena/psicologia , Comportamento Social , Trabalho/estatística & dados numéricos
4.
Front Behav Neurosci ; 14: 600766, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304248

RESUMO

Early life stress (ELS) is considered a risk factor for the development of psychiatric conditions, including depression and anxiety disorder. Individuals that live in adverse environments are usually exposed to multiple stressors simultaneously, such as maternal neglect, maltreatment, and limited resources. Nevertheless, most pre-clinical ELS models are designed to explore the impact of these events separately. For this reason, this study aims to investigate the effects of a combined model of ELS on anxiety-like behavior and hypothalamic-pituitary-adrenal (HPA) axis related targets. From PND 2 to PND 15 BALB/cJ mice were exposed simultaneously to maternal separation (MS; 3 h per day) and limited bedding (LB; ELS group) or left undisturbed (CT group). Maternal behavior was recorded in intercalated days, from PND 1 to PND 9. Male offspring were tested for anxiety-like behavior from PND 53 to PND 55 in the open field test (OF), elevated plus-maze (EPM), and light/dark test (LD). After behavioral testing, animals were euthanized, and glucocorticoid receptor (Nr3c1), corticotrophin-releasing hormone (Crh), and its receptor type 1 (Crhr1) gene expression in the hypothalamus were measured. Moreover, plasma corticosterone levels were analyzed. We observed that ELS dams presented altered quality of maternal care, characterized by a decrease in arched-back nursing, and an increase in passive nursing. Stressed dams also showed an increase in the number of exits from the nest when compared to CT dams. Furthermore, ELS animals showed increased anxiety-like behavior in the OF, EPM, and LD. Regarding gene expression, we identified an increase in hypothalamus Crh levels of ELS group when compared to CT animals, while no differences in Nr3c1 and Crhr1 expression were observed. Finally, stressed animals showed decreased levels of plasma corticosterone when compared to the CT group. In conclusion, we observed an alteration in maternal behavior in ELS dams. Later in life, animals exposed to the combined model of ELS showed increased levels of anxiety-like behavior. Moreover, the central and peripheral HPA measures observed could indicate a dysregulation in HPA function provoked by ELS exposure.

5.
Sci Rep ; 10(1): 19985, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33204022

RESUMO

The peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated in anxiety behaviour and regulation of the stress response. The effects of intra-BNST CRF administration were compared with those induced by the limited bedding (LB) procedure, a model that produces altered maternal behaviour. BALB/cJ dams were exposed to five infusions of CRF or saline into the BNST in the first weeks after birth while the LB dams were exposed to limited nesting material from postnatal days (P) 2-9. Maternal behaviour was recorded in intercalated days, from P1-9. Offspring anxiety-like behaviour was assessed during adulthood using the open-field, elevated plus-maze, and light/dark tests. Both intra-BNST CRF and LB exposure produced altered maternal care, represented by decreased arched-back nursing and increased frequency of exits from the nest. These changes in maternal care resulted in robust sex-based differences in the offspring's behavioural responses during adulthood. Females raised by CRF-infused dams exhibited increased anxiety-like behaviour, whereas males presented a significant decrease in anxiety. On the other hand, both males and females raised by dams exposed to LB showed higher locomotor activity. Our study demonstrates that maternal care is impaired by intra-BNST CRF administrations, and these maladaptations are similar to exposure to adverse early environments. These procedures, however, produce distinct phenotypes in mice during young adulthood and suggest sex-based differences in the susceptibility to poor maternal care.

6.
Exp Brain Res ; 238(9): 2097-2107, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32656651

RESUMO

Early life stress (ELS) exposure is a well-known risk factor for the development of psychiatric conditions, including anxiety disorder. Preclinical studies show that maternal separation (MS), a classical model of ELS, causes hypothalamic-pituitary-adrenal (HPA) axis alterations, a key contributor to the stress response modulation. Given that HPA axis activation has been shown to induce oxidative stress, it is possible to hypothesize that oxidative stress mediates the relationship between chronic ELS exposure and the development of several disorders. Here, we investigate the effects of MS in the oxidative status [plasma and brain reduced glutathione, catalase and thiobarbituric acid reactive substances (TBARS)], metabolism (glucose, triglycerides and cholesterol) and anxiety-like behaviors in adult Balb/cJ mice. In short, we found that MS increased anxiety-like behaviors in the open field, light/dark test but not in the elevated-plus maze. Animals also presented increased circulating cholesterol, increased TBARS in the plasma and decreased catalase in the hippocampus. Our findings suggest that MS induces long-term alterations in oxidative stress and increased anxiety-like behaviors.

7.
PLoS One ; 15(5): e0232242, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365094

RESUMO

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.


Assuntos
Experiências Adversas da Infância/estatística & dados numéricos , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína Crack/efeitos adversos , Depressão/epidemiologia , Alucinações/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Brasil/epidemiologia , Estudos Transversais , Feminino , Hospitalização , Humanos , Aprendizado de Máquina , Masculino , Prevalência , Medição de Risco , Tentativa de Suicídio/psicologia , Adulto Jovem
8.
Psicol. ciênc. prof ; 40: e192955, jan.-maio 2020. tab
Artigo em Português | LILACS-Express | LILACS, Index Psicologia - Periódicos técnico-científicos | ID: biblio-1143544

RESUMO

Resumo As percepções dos profissionais de saúde que atendem mulheres usuárias de crack podem auxiliar no aprimoramento dos atendimentos. Assim, este estudo objetivou compreender essas percepções. Se trata de um estudo qualitativo, com 33 participantes divididos em três grupos focais submetidos à análise temática. Estabeleceram-se dois eixos centrais: a) usuárias de crack e b) serviços de saúde. Posteriormente, identificaram-se oito temas e seis subtemas. No primeiro eixo destacaram-se: características das usuárias, ausência de rede de apoio, violência, estigma de gênero, prostituição e comorbidades clínicas. No segundo ressaltaram-se as dificuldades na articulação entre os serviços e questões a serem aprimoradas, como: prevenção na atenção básica, motivação dos profissionais, serviços específicos para mulheres, especificidades da gestação e combate ao estigma. A partir dos resultados, foram identificados e discutidos os desafios e as potencialidades que se dão nos atendimentos de mulheres usuárias de crack.


Abstract The perceptions of health professionals that serve crack-using women can help in the improvement of health care. Thus, this study verified such perceptions via a qualitative study with 33 participants, divided into three focus groups subjected to thematic analysis. Two a priori central axes were defined: 1) crack-using women, and 2) health services. Subsequently, eight themes and six subthemes were identified. Axis 1) showed: characteristics of the users, lack of support network, violence, gender stigma, prostitution and clinical comorbidities. In axis 2), there were challenges in articulating services and issues to be improved, such as prevention in primary care, motivation of professionals, specific services for women, specific aspects of gestation and stigma. The results allowed to identify and discuss the potentialities and challenges in providing healthcare services to crack-using women.


Resumen Las percepciones de los profesionales de la salud que atienden a mujeres usuarias de crack pueden auxiliar en el perfeccionamiento de las atenciones. Este estudio objetivó comprender las percepciones de profesionales de la salud sobre atenciones a las usuarias de crack. Es un estudio cualitativo, con 33 participantes, divididos en tres grupos focales sometidos al análisis temático. Dos ejes centrales se establecieron a priori: 1) mujeres usuarias de crack; y 2) servicios de salud. Posteriormente, se identificaron ocho temas y seis subtemas. En el primer eje se destacaron: las características de las usuarias, la ausencia de la red de apoyo, la violencia, el estigma de género, la prostitución y las comorbilidades clínicas. En el segundo eje, se resalta las dificultades en la articulación entre los servicios y también cuestiones a ser mejoradas, como: prevención en la atención básica, motivación de los profesionales, servicios específicos para mujeres, especificidades de la gestación y combate al estigma. A partir de los resultados fue posible identificar y discutir las potencialidades y desafíos en las atenciones de mujeres usuarias de crack.

9.
Neuromolecular Med ; 22(3): 384-390, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152934

RESUMO

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.

10.
Transl Psychiatry ; 10(1): 99, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184383

RESUMO

We aimed to identify blood gene expression patterns associated to psychopathological trajectories retrieved from a large community, focusing on the emergence and remission of general psychiatric symptoms. Hundred and three individuals from the Brazilian High-Risk Cohort Study (BHRCS) for mental disorders were classified in four groups according to Child Behavior Checklist (CBCL) total score at the baseline (w0) and after 3 years (w1): low-high (L-H) (N = 27), high-low (H-L) (N = 12), high-high (H-H) (N = 34) and low-low (L-L) groups (N = 30). Blood gene expression profile was measured using Illumina HT-12 Beadchips, and paired analyses comparing w0 and w1 were performed for each group. Results: 98 transcripts were differentially expressed comparing w0 and w1 in the L-H, 33 in the H-L, 177 in the H-H and 273 in the L-L. Of these, 66 transcripts were differentially expressed exclusively in the L-H; and 6 only in the H-L. Cross-Lagged Panel Models analyses revealed that RPRD2 gene expression at w1 might be influenced by the CBCL score at w0. Moreover, COX5B, SEC62, and NDUFA2 were validated with another technique and were also differentially regulated in postmortem brain of subjects with mental disorders, indicating that they might be important not only to specific disorders, but also to general psychopathology and symptoms trajectories. Whereas genes related to metabolic pathways seem to be associated with the emergence of psychiatric symptoms, mitochondrial inner membrane genes might be important over the course of normal development. These results suggest that changes in gene expression can be detected in blood in different psychopathological trajectories.

11.
Int J Dev Neurosci ; 80(2): 86-95, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31909492

RESUMO

The present study aimed to investigate the long-term effects of exercise before pregnancy on changes induced by prenatal stress. Female and male Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS), and exercise before the gestational period plus PNS (EX + PNS). As adult, fear/anxiety behavior, corticosterone secretion, expression of hypothalamic-pituitary-adrenal (HPA)-related genes, as well as epigenetic modifications were evaluated. Exercise before gestation did not prevent the increased fear/anxiety behavior in PNS mice. A nearly significant (p = .06) basal corticosterone increase was observed in PNS males and the exercise before pregnancy reduced the stress-induced corticosterone increase in PNS females. In addition, an increase on prefrontal cortex (PFC) CRHR1 gene expression was observed in PNS females, which was attenuated by the exercise before gestation. We have also found a glucocorticoid receptor (GR) gene expression decrease in the prefrontal cortex in PNS males, as well as a histone H3 acetylation decrease (p = .06) close to the significance level. In conclusion, pregestational exercise may attenuate developmental changes induced by prenatal stress in a sex-dependent manner.

12.
J Addict Med ; 14(4): e37-e43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31972760

RESUMO

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.

13.
Int J Dev Neurosci ; 80(1): 13-27, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31907967

RESUMO

RATIONALE: Exposure to early life stress (ELS) is known to have pronounced effects on the prefrontal cortex (PFC). However, not all individuals exposed to ELS manifest the same neurobiological and cognitive phenotypes when adults. Dopamine signaling could be a key factor in understanding the effects of stress on PFC-related cognitive function. OBJECTIVES: We aimed to investigate the differential effects of ELS on cognitive performance of adult mice and the dopaminergic receptors expression in the PFC. METHODS: BALB/c males were exposed to the maternal separation (MS) procedure and their cognitive performance on the eight-arm radial maze (8-RAM) were assessed during adulthood. For molecular-level assessments, we performed mRNA expression analyses for dopamine receptors-DRD1, DRD2, DRD3-and Hers1 expression in the medial PFC. RESULTS: While MS produced an overall impairment on 8-RAM, the stressed animals could be divided in two groups based on their performance: those with impaired cognitive performance (vulnerable to maternal separation, V-MS) and those without any impairment (resilient to maternal separation, R-MS). V-MS animals showed increased DRD1 and DRD2 expression in comparison with other groups. Errors on 8-RAM were also positively correlated with DRD1 and DRD2 mRNA expression. CONCLUSIONS: Our findings suggest a potential role of the dopaminergic system in the programming mechanisms of cognitive vulnerability and resilience related to ELS.


Assuntos
Cognição/fisiologia , Privação Materna , Aprendizagem em Labirinto/fisiologia , Córtex Pré-Frontal/metabolismo , Receptores Dopaminérgicos/metabolismo , Resiliência Psicológica , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C
14.
Stress ; 23(5): 546-555, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31701783

RESUMO

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.

15.
Soc Cogn Affect Neurosci ; 14(10): 1097-1107, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31820809

RESUMO

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.


Assuntos
Função Executiva/fisiologia , Exposição à Violência/psicologia , Lobo Frontal/fisiopatologia , Lobo Parietal/fisiopatologia , Adolescente , Encéfalo/fisiopatologia , Criança , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Violência/psicologia
16.
CNS Spectr ; : 1-7, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31845634

RESUMO

OBJECTIVE.: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence. METHODS.: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder. RESULTS.: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers. CONCLUSIONS.: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

17.
J Psychosom Res ; 127: 109864, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31706071

RESUMO

The impact of early life stress on mental health and telomere length shortening have been reported. Changes in brain default mode network (DMN) were found to be related to a myriad of psychiatric conditions in which stress may play a role. In this context, family environment and adverse childhood experiences (ACEs) are potential causes of stress. This is a hypothesis-driven study focused on testing two hypotheses: (i) there is an association between telomere length and the function of two main hubs of DMN: the posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC); (ii) this association is modulated by family environment and/or ACEs. To the best of our knowledge, this is the first study investigating these hypotheses. Resting-state functional magnetic resonance imaging data and blood sample were collected from 389 subjects (6-15 age range). We assessed DMN fractional amplitude of low-frequency fluctuations (fALFF) and leukocyte telomere length (LTL). We fitted general linear models to test the main effects of LTL on DMN hubs and the interaction effects with Family Environment Scale (FES) and ACEs. The results did not survive a strict Bonferroni correction. However, uncorrected p-values suggest that LTL was positively correlated with fALFF in PCC and a FES interaction between FES and LTL at mPFC. Although marginal, our results encourage further research on the interaction between DMN hubs, telomere length and family environment, which may play a role on the biological embedding of stress.


Assuntos
Mapeamento Encefálico/métodos , Leucócitos/metabolismo , Imagem por Ressonância Magnética/métodos , Telômero/metabolismo , Adolescente , Criança , Feminino , Humanos , Masculino
18.
Front Immunol ; 10: 2435, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749792

RESUMO

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.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/etiologia , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Citocinas/metabolismo , Suscetibilidade a Doenças , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores , Brasil , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Feminino , Humanos , Imunofenotipagem , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Masculino , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
19.
Clin Epigenetics ; 11(1): 146, 2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639064

RESUMO

BACKGROUND: Psychiatric symptomatology during late childhood and early adolescence tends to persist later in life. In the present longitudinal study, we aimed to identify changes in genome-wide DNA methylation patterns that were associated with the emergence of psychopathology in youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders. Moreover, for the differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcript levels by analyzing the gene expression levels in the blood and by correlating the variation of DNA methylation values with the variation of mRNA levels of the same individuals. Finally, we examined whether the variations in DNA methylation and mRNA levels were correlated with psychopathology measurements over time. METHODS: We selected 24 youths from the HRC who presented with an increase in dimensional psychopathology at a 3-year follow-up as measured by the Child Behavior Checklist (CBCL). The DNA methylation and gene expression data were compared in peripheral blood samples (n = 48) obtained from the 24 youths before and after developing psychopathology. We implemented a methodological framework to reduce the effect of chronological age on DNA methylation using an independent population of 140 youths and the effect of puberty using data from the literature. RESULTS: We identified 663 differentially methylated positions (DMPs) and 90 differentially methylated regions (DMRs) associated with the emergence of psychopathology. We observed that 15 DMPs were mapped to genes that were differentially expressed in the blood; among these, we found a correlation between the DNA methylation and mRNA levels of RB1CC1 and a correlation between the CBCL and mRNA levels of KMT2E. Of the DMRs, three genes were differentially expressed: ASCL2, which is involved in neurogenesis; HLA-E, which is mapped to the MHC loci; and RPS6KB1, the gene expression of which was correlated with an increase in the CBCL between the time points. CONCLUSIONS: We observed that changes in DNA methylation and, consequently, in gene expression in the peripheral blood occurred concurrently with the emergence of dimensional psychopathology in youths. Therefore, epigenomic modulations might be involved in the regulation of an individual's development of psychopathology.


Assuntos
Metilação de DNA , Epigenômica/métodos , Perfilação da Expressão Gênica/métodos , Transtornos Mentais/genética , Adolescente , Brasil , Criança , Ilhas de CpG , Epigênese Genética , Feminino , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , Masculino , Maturidade Sexual
20.
J Neural Transm (Vienna) ; 126(12): 1707-1711, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31562556

RESUMO

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.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Disfunção Cognitiva/genética , Sinaptotagmina I/genética , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Polimorfismo de Nucleotídeo Único
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