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1.
Life Sci ; 251: 117597, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32243926

RESUMO

Stress during pregnancy adversely affects foetal development and leads to later behavioural outcomes in offspring. Preclinical studies have reported conflicting effects of prenatal stress on depression-related symptoms in rodent offspring. This study aimed to study the combined effect of strain and sex on prenatal stress outcomes in a single study. To this end, male and female offspring from outbred Wistar and inbred Lewis rats, and outbred NMRI and inbred C57BL6 mice were compared. As outcomes we focussed on depression-related behaviour and related molecular and neurochemical parameters. Prenatally stressed and non-stressed offspring were subjected to the sucrose preference, novelty-suppressed feeding, tail suspension, and forced swim tests. We measured basal and stress-induced corticosterone levels in the serum, and brain-derived-neurotrophic-factor (BDNF), interleukin-1ß, tumor necrosis factor-α, glutamate and serotonin in the brain to determine changes in hypothalamic-pituitary-adrenal-(HPA)-axis function, neuroplasticity, neuroinflammation, and neurotransmission. Our findings revealed that prenatal stress increases depression-like behaviour, HPA-axis (re) activity, pro-inflammatory cytokines and glutamate levels, and decreases BDNF and serotonin levels in a strain and sex-dependent manner in rodent offspring. Overall, male and female Lewis rats, female Wistar rats, male NMRI mice and female C57BL6 mice were found to be most responsive to prenatal stress. Based on these results, we conclude that genetic background and sex contribute to the great diversity in the effects of prenatal maternal stress in rodents.


Assuntos
Depressão/psicologia , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estresse Psicológico/psicologia , Animais , Encéfalo/metabolismo , Corticosterona/sangue , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Fatores Sexuais , Especificidade da Espécie
2.
Pediatrics ; 144(6)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31744890

RESUMO

BACKGROUND AND OBJECTIVES: Fetal alcohol spectrum disorders (FASD) comprise the continuum of disabilities associated with prenatal alcohol exposure. Although infancy remains the most effective time for initiation of intervention services, current diagnostic schemes demonstrate the greatest confidence, accuracy, and reliability in school-aged children. Our aims for the current study were to identify growth, dysmorphology, and neurodevelopmental features in infants that were most predictive of FASD at age 5, thereby improving the timeliness of diagnoses. METHODS: A cohort of pregnant South African women attending primary health care clinics or giving birth in provincial hospitals was enrolled in the project. Children were followed longitudinally from birth to 60 months to determine their physical and developmental trajectories (N = 155). Standardized protocols were used to assess growth, dysmorphology, and development at 6 weeks and at 9, 18, 42, and 60 months. A structured maternal interview, including estimation of prenatal alcohol intake, was administered at 42 or 60 months. RESULTS: Growth restriction and total dysmorphology scores differentiated among children with and without FASD as early as 9 months (area under the receiver operating characteristic curve = 0.777; P < .001; 95% confidence interval: 0.705-0.849), although children who were severely affected could be identified earlier. Assessment of developmental milestones revealed significant developmental differences emerging among children with and without FASD between 18 and 42 months. Mothers of children with FASD were significantly smaller, with lower BMIs and higher alcohol intake during pregnancy, than mothers of children without FASD. CONCLUSIONS: Assessment of a combination of growth, dysmorphology, and neurobehavioral characteristics allows for accurate identification of most children with FASD as early as 9 to 18 months.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/psicologia , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Transtornos do Espectro Alcoólico Fetal/psicologia , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/psicologia , Consumo de Bebidas Alcoólicas/epidemiologia , Pré-Escolar , Estudos de Coortes , Feminino , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de Risco , África do Sul/epidemiologia
3.
Klin Padiatr ; 231(5): 262-268, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31505693

RESUMO

OBJECTIVE: The consumption of illegal substances during pregnancy is an increasing social and medical issue. Main substances of prenatal drug exposure are beside tehtrahydrocannabinol (THC), opioids and methamphetamine. The effect of these substances on the long-term development of children remains uncertain. METHODS: Since 2012 newborn infants born at the university hospital of children at Leipzig which were prenatal exposed to drugs were followed long-term at the out-patient clinic for child protection. For 42 children with prenatal opioid or methamphetamine exposure the developmentent was analysed using the Bayley Scales (BSID III) at the age of 2-3 years. The children were compared with 84 unexposed control children. One case matched to 2 controls, adapted by age, gender, gestational age and birth weight. RESULTS: Motoric development between prenatal methylamphetamine, opioid exposed children and the control group showed no significant difference. Methylamphetamine exposed children (n=23) At 2 exposure show significantly lower scores in cognition and language (79,1 compared 95,9 of the control group), opioid exposed children have a slight cognitive deficits with a medium score of 91,7 (n=19). 56% of the methamphetamine group were developmentally retarded at the measurement date. Additionally, children had significant lower Bayley Scores which had single parent and/ or low educational and professional qualifications of their caregiver. Both substances increased the risk of postnatal complications to 46-53% despite of similar gestational ages in all groups. CONCLUSION: Children with prenatal methamphetamine or opioid exposure seem to have cognition and language deficits at 2 and 3 years of age. Methamphetamine might have a higher negative effect than opioids. The psychosocial risk factors associated with parental drug abuse are important for achieving age-appropriate development.


Assuntos
Analgésicos Opioides/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Metanfetamina/toxicidade , Atividade Motora/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Comportamento do Lactente/efeitos dos fármacos , Comportamento do Lactente/psicologia , Recém-Nascido , Idioma , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia
4.
Environ Pollut ; 254(Pt B): 113081, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473391

RESUMO

Due to the lack of substantial and reliable evidence on the relationship between prenatal cadmium (Cd) exposure and cognitive development of offspring, we conducted the present systematic review. Leading electronic databases-including Pubmed, Embase, Web of Science, the Cochrane Library, PsycINFO, PsycARTICLES, and the Psychology and Behavioral Sciences Collection-were searched on February 14, 2019. There was no date, study design or language limit imposed in our search. All of the included studies satisfied our predetermined study population (pregnant mothers and their offspring), exposure (prenatal Cd exposure), and outcome measurements (adverse effects on cognitive development). The quality assessment for the included studies was conducted with the Newcastle-Ottawa Scale (NOS). Nine prospective cohort studies met the inclusion criteria, and six of them were assessed to be of high quality based on the NOS (NOS score ≥ 7). The prenatal Cd exposure was tested in maternal blood samples (4/9), umbilical cord blood samples (4/9), or maternal urinary samples (3/9). Among the nine studies included, six reported at least one inverse association between prenatal Cd exposure and the cognitive development of offspring, mainly in terms of language development (4/8), performance ability development (3/5), and general cognitive development (3/8). Furthermore, among six studies with high methodological quality (NOS score ≥ 7), prenatal Cd exposure was reported to be associated with language development in three studies (3/5), performance ability development in three studies (3/4), and general cognitive development in three studies (3/5). This systematic review provides convincing evidence that prenatal exposure to Cd is inversely associated with neurodevelopment of offspring. Larger prospective studies using standardized criteria and assessments of cognitive development are needed to confirm the dose-response effect and gender difference of prenatal Cd exposure on cognitive development of offspring.


Assuntos
Cádmio/toxicidade , Cognição/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/psicologia , Cádmio/sangue , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos Prospectivos
5.
Pediatrics ; 144(2)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31320466

RESUMO

The developmental impact of opioid use during pregnancy is a subject of ongoing debate. Short-term neonatal outcomes, such as lower birth weight and neonatal abstinence syndrome, are the most well-recognized outcomes. However, knowledge gaps exist regarding longer-term neurocognitive and mental health outcomes. In this article, we summarize an expert panel discussion that was held in April 2018 by the Substance Abuse and Mental Health Services Administration and attended by national experts in the field of perinatal opioid exposure and its impact on child development. Despite the challenges with research in this area, there is emerging literature revealing an association between neonates exposed to opioids in utero and longer-term adverse neurocognitive, behavioral, and developmental outcomes. Although adverse sequalae may not be apparent in the neonatal period, they may become more salient as children develop and reach preschool and school age. Multiple variables (genetic, environmental, and biological) result in a highly complex picture. The next steps and strategies to support families impacted by opioid use disorder are explored. Model programs are also considered, including integrated care for the child and mother, parenting supports, and augmentations to home visiting.


Assuntos
Analgésicos Opioides/efeitos adversos , Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Criança , Comportamento Infantil/fisiologia , Comportamento Infantil/psicologia , Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Congressos como Assunto , Feminino , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/psicologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estados Unidos/epidemiologia , United States Substance Abuse and Mental Health Services Administration/tendências
6.
Dev Neuropsychol ; 44(5): 429-442, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31353953

RESUMO

Prenatal cocaine exposure (PCE) has ramifications for feedback processing. Measuring neural oscillatory dynamics (during electroencephalography) provides insight into the time signatures and neural processes of feedback processing in adolescents with PCE. We measured spectral power in alpha and theta frequency bands while 49 adolescents with PCE and 34 non-drug exposed (NDE) performed a task with win/no-win feedback. Compared to NDE individuals, those with PCE showed reduced alpha power and increased theta power in response to no-win feedback. These findings suggest altered reactivity in PCE adolescents.


Assuntos
Ritmo alfa , Ritmo beta , Cocaína/efeitos adversos , Retroalimentação Psicológica/fisiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Adolescente , Eletroencefalografia , Feminino , Humanos , Masculino , Gravidez
7.
Soc Psychiatry Psychiatr Epidemiol ; 54(11): 1299-1309, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31324962

RESUMO

PURPOSE: Exposure to prenatal stress has been reported to affect the risk of adverse neurodevelopmental outcomes in the offspring; however, there is currently no clear consensus. The aim of this systematic review and meta-analysis was to examine the existing literature on the association between prenatal stress and autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) in the offspring. METHODS: Based on a registered protocol, we searched several electronic databases for articles in accordance with a detailed search strategy. We performed this study following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RESULTS: Prenatal stress was significantly associated with an increased risk of both ASD (pooled OR 1.64 [95% CI 1.15-2.34]; I2 = 90%; 15 articles) and ADHD (pooled OR 1.72 [95% CI 1.27-2.34]; I2 = 85%; 12 articles). CONCLUSIONS: This study suggests that prenatal stress may be associated with ASD and ADHD; however, several limitations in the reviewed literature should be noted including significant heterogeneity and there is a need for carefully controlled future studies in this area.


Assuntos
Exposição Materna/efeitos adversos , Transtornos do Neurodesenvolvimento/psicologia , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estresse Psicológico/complicações , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Espectro Autista/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez
8.
Psychopharmacology (Berl) ; 236(12): 3429-3437, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31236644

RESUMO

RATIONALE: Although the influence of gestational cocaine exposure on offspring has been the focus of a sustained research effort, the effect of preconception cocaine self-administration by dams on progeny has received far less attention. METHOD: In the current study, adult female rats were allowed to self-administer cocaine 2 h a day for 60 days and then after a 10-day wash out period, bred to naïve males. Maternal behavior was measured in dams until weaning. When male and female progeny reached adulthood, anxiety-like behavior, memory, and cocaine self-administration were assessed in separate cohorts of rats. RESULTS: Despite a total of at least 30 days of cocaine abstinence, the quality of maternal behaviors was negatively affected by previous cocaine exposure as reflected by less time spent with pups as well as an excess of other maladaptive maternal behaviors. Measures of anxiety-like behavior and memory were not affected by maternal cocaine intake in either male or female offspring. In contrast, male, but not female, the progeny of dams exposed to cocaine showed increased reinforcing efficacy of cocaine as measured by cocaine self-administration under a progressive ratio schedule. The fact that cocaine self-administration was influenced only in the male offspring of cocaine-exposed dams argues against this phenotype being linked to altered maternal behavior, although this possibility cannot be ruled out completely. CONCLUSIONS: Collectively, these results indicate that preconception cocaine self-administration by dams results in the relatively selective enhancement of cocaine addiction-like behavior in male offspring.


Assuntos
Comportamento Aditivo/psicologia , Cocaína/administração & dosagem , Comportamento Materno/psicologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Animais , Comportamento Aditivo/induzido quimicamente , Cocaína/efeitos adversos , Feminino , Masculino , Comportamento Materno/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Autoadministração
9.
Biol Psychol ; 146: 107716, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31176750

RESUMO

We set out to examine the relations between prenatal exposure to the natural disaster Superstorm Sandy, maternal depression, and offspring electrodermal activity (EDA). EDA was measured via skin conductance response (SCR) magnitude in 198 children (M = 42.54 months, SD = 12.76) during a startle paradigm. In keeping with prior research, we expected prenatal depression to be associated with hyporeactive EDA and prenatal stress to be associated with hyperreactive EDA. SCR magnitude was lower in children prenatally exposed to depression alone, when compared to Superstorm Sandy, and controls. SCR magnitude of children prenatally exposed to both maternal depression and the storm was lower than that of all other groups. Our results emphasize the influence of maternal prenatal mental health, support targeted risk assessment for children who experienced an adverse prenatal environment, and highlight the need for a deeper understanding of the interactions between maternal mood and stress on the developing child.


Assuntos
Tempestades Ciclônicas/história , Depressão/fisiopatologia , Desastres/história , Exposição Materna/efeitos adversos , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Pré-Escolar , Depressão/psicologia , Feminino , Resposta Galvânica da Pele , História do Século XXI , Humanos , Masculino , Exposição Materna/história , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Reflexo de Sobressalto , Medição de Risco , Estados Unidos
10.
PLoS One ; 14(6): e0217830, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170221

RESUMO

Many women experience anxiety or sleep disorders during pregnancy and require pharmacological treatment with benzodiazepines (BZDs) or z-hypnotics. Limited information is currently available on how prenatal exposure to these medications affects behavioral problems in children over the long term. Therefore, from a public health perspective, this issue is highly important. The present study aimed to determine whether prenatal exposure to BZDs and z-hypnotics affected externalizing and internalizing behavior problems in children at age 5 years. This study was based on The Norwegian Mother and Child Cohort Study and The Medical Birth Registry of Norway. The final study population included data for 36 401 children, from questionnaires completed by the mothers throughout the 5-year follow up. Children's behaviors were measured at age 5, based on parental responses to The Child Behavior Checklist. Children T-scores of 63 or above were considered to indicate clinically relevant behavior problems. We applied inverse probability of treatment weighting (IPTW) and log-binomial regression models to estimate risk ratios (RRs) and bootstrapped 95% confidence intervals (CIs) with censoring weights to account for loss during follow-up. Several sensitivity analyses were performed to assess the robustness of the main results. The final sample included 273 (0.75%) children that were exposed to BZDs and/or z-hypnotics during pregnancy. The main, IPTW and censoring weighted analyses showed that prenatal exposure to BZD and/or z-hypnotics increased the risks of internalizing behavioral problems (RR: 1.35, 95% CI: 0.73-2.49) and externalizing behavioral problems (RR: 1.51, 95% CI: 0.86-2.64). However, based on sensitivity analyses, we concluded that the risks of displaying externalizing and internalizing problems at 5 years of age did not significantly increase after prenatal exposure to BZDs and/or z-hypnotics. Instead, the sensitivity analyses suggested that residual confounding and selection bias might explain the increased risks observed in the main analyses.


Assuntos
Benzodiazepinas/efeitos adversos , Transtornos do Comportamento Infantil/etiologia , Transtornos do Comportamento Infantil/psicologia , Hipnóticos e Sedativos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/psicologia , Criança , Comportamento Infantil , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Noruega , Gravidez , Probabilidade , Fatores de Risco
11.
Int J Dev Neurosci ; 76: 65-71, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229525

RESUMO

OBJECTIVES: Tangshan earthquake which had a magnitude of 7.8 killed approximately 250,000 people in China in 1976. In the present study, we sought to determine the prevalence and risks of mental disorders in adults who experienced earthquake as an infant or in the prenatal period. METHODS: This cross-sectional cohort study recruited participants based on the urban resident registry of Tangshan, Hebei province, 2013 using a multistage stratified cluster sampling method with selection probabilities proportional to size. We recruited subjects who were born between July 29, 1975 and April 28, 1978 that was one year before and 1.9 years after the occurrence of Tangshan Earthquake, respectively. Current psychiatric diagnoses and lifetime psychiatric diagnoses were obtained through the Structured Clinical Interview for DSM-IV Axis I Disorders Patient Research Version. Unconditional logistic regression analysis was performed to analyze risk factors of mental disorders. RESULTS: Totally1380 subjects were included with 392 subjects exposed to the earthquake in the fetal period, 399 subjects who experienced the earthquake during their infancy, and 589 subjects who had no exposure to the earthquake. Twenty-one (2.7%; current 1.9%) subjects exposed to earthquake were diagnosed with major depressive disorderversus 2.3% (current 1.5%) in the non-exposure group. Five (0.6%; current 0.6%) subjects with exposure to earthquake had bipolar disorder versus 0.9% in the non-exposure group.Thirteen (1.6%; current 1.6%) subjects with exposure to earthquake had schizophreniaversus 0.2% in the non-exposure group (P=0.006). Furthermore, 5.2% (current 3.7%) subjects with exposure to earthquake had anxiety disorders versus 5.7% (current 3.9%) in the non-exposure group. Moreover, 8.1% (current 7.0%)subjects with exposure to earthquake had alcohol use disorders versus 7.1% (current 5.3%) in the non-exposure group. Furthermore, the prevalence of schizophrenia of the prenatal exposure group (2.3%) was significantly higher than the other two groups (χ2 = 10.273, P = 0.006); however, no statistically significant difference was found in the current and lifetime prevalence of other DSM-IV axis I disorders among the three groups (P > 0.05). Our multivariate regression analysis showed that prenatal earthquake stress exposure was not a significant risk of any of the lifetime or current DSD-IV axis I disorders. CONCLUSION: Adults who were exposed to earthquake in the prenatal period had a significantly higher rate of schizophrenia than those who were not exposed or who experienced earthquake in their infancy. No statistically significant difference was found in the current and lifetime prevalence of other DSM-IV axis I disorders between those exposed and those not exposed to earthquake. Furthermore, prenatal earthquake stress exposure was not a significant risk of any of the lifetime or current DSD-IV axis I disorders.


Assuntos
Terremotos , Transtornos Mentais/epidemiologia , Adulto , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Prevalência , Sistema de Registros , Fatores de Risco , Esquizofrenia/epidemiologia , Fatores Socioeconômicos , Estresse Psicológico , Inquéritos e Questionários
12.
Drug Alcohol Depend ; 200: 50-58, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31085378

RESUMO

BACKGROUND: Prenatal cocaine exposure (PCE) is associated with arousal dysregulation, but interactions between exposure and age are rarely investigated directly with longitudinal study designs. Our previous study had examined task-elicited emotional arousal and noted persistently high amygdala activations in the development of adolescents with PCE. However, while externally imposed emotional arousal could be considered a "state" effect depending on specific task stimuli, it is still unclear whether similar developmental alterations extend to intrinsic functional connectivity (FC), reflecting more of a "trait" effect. METHODS: We used a longitudinal design and analyzed resting-state functional magnetic resonance imaging data acquired twice from 25 adolescents with PCE and 16 non-exposed controls. Both groups were each scanned first at the mean age of 14.3 and then again at 16.6 years. Seeding in bilateral amygdalae and comparing the 2nd scan with the 1st, we examined the interaction effect between PCE and age on FCs in the emotional network. RESULTS: Compared with the younger age, we observed a generally decreased FC in the emotional network of the control group at the older age, but these FCs were generally increased at the older age in this same network of the PCE group. Additionally, this interaction effect of exposure by age in the right fusiform was positively correlated with the emotional interference imposed by external task stimuli. CONCLUSIONS: These results provided additional data directly characterizing developmental changes in the emotional network of adolescents with PCE, complementing and extending the notion of a PCE-associated long-term teratogenic effect on arousal regulation.


Assuntos
Tonsila do Cerebelo/diagnóstico por imagem , Nível de Alerta/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Cocaína/efeitos adversos , Rede Nervosa/diagnóstico por imagem , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Adolescente , Adulto , Tonsila do Cerebelo/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/psicologia , Emoções/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Masculino , Rede Nervosa/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/psicologia
13.
Int J Dev Neurosci ; 76: 6-16, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128204

RESUMO

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosis by two main behavioral phenotypes i.e. social-communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. Valproic acid (VPA), a teratogen is known to induce characteristic features related to ASD in rodents. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR-γ, pioglitazone in prenatal VPA induced experimental ASD symptomatology in Wistar rats. The prenatal administration of VPA has induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, prenatal VPA-treated rats have shown higher levels of oxidative stress (increased in thiobarbituric acid reactive species, and decreased in reduced glutathione level) and inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. Treatment with pioglitazone significantly attenuated the prenatal VPA-induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the prenatal VPA-induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, it may be concluded that pioglitazone may provide neurobehavioral and biochemical benefits in prenatal VPA-induced autistic phenotypes in rats.


Assuntos
Anticonvulsivantes/toxicidade , Transtorno do Espectro Autista/prevenção & controle , Transtorno do Espectro Autista/psicologia , Hipoglicemiantes/farmacologia , Pioglitazona/farmacologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ácido Valproico/antagonistas & inibidores , Ácido Valproico/toxicidade , Animais , Ansiedade/induzido quimicamente , Ansiedade/psicologia , Transtorno do Espectro Autista/induzido quimicamente , Química Encefálica/efeitos dos fármacos , Citocinas/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Comportamento Social
14.
Nord J Psychiatry ; 73(4-5): 257-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31070508

RESUMO

Background: Prenatal maternal stress increases the risk of offspring developmental and psychological difficulties. The biological mechanisms behind these associations are mostly unknown. One explanation suggests that exposure of the fetus to maternal stress may influence DNA methylation. However, this hypothesis is largely based on animal studies, and human studies of candidate genes from single timepoints. Aim: The aim of this study was to investigate if prenatal maternal stress, in the form of maternal depressive symptoms, was associated with variation in genome-wide DNA methylation at two timepoints. Methods: One-hundred and eighty-four mother-child dyads were selected from a population of pregnant women in the Little-in-Norway study. The Edinburgh Postnatal Depression Scale (EPDS) measured maternal depressive symptoms. It was completed by the pregnant mothers between weeks 17 and 32 of gestation. DNA was obtained from infant saliva cells at two timepoints (age 6 weeks and 12 months). DNA methylation was measured in 274 samples from 6 weeks (n = 146) and 12 months (n = 128) using the Illumina Infinium HumanMethylation 450 BeadChip. Linear regression analyses of prenatal maternal depressive symptoms and infant methylation were performed at 6 weeks and 12 months separately, and for both timepoints together using a mixed model. Results: The analyses revealed no significant genome-wide association between maternal depressive symptoms and infant DNA methylation in the separate analyses and for both timepoints together. Conclusions: This sample of pregnant women and their infants living in Norway did not reveal associations between maternal depressive symptoms and infant DNA methylation.


Assuntos
Metilação de DNA/fisiologia , Depressão/psicologia , Epigenômica/métodos , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Adulto , Animais , Depressão/epidemiologia , Depressão/genética , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Recém-Nascido , Estudos Longitudinais , Mães/psicologia , Noruega/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/genética , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Adulto Jovem
15.
Ecotoxicol Environ Saf ; 180: 123-129, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31082575

RESUMO

1-Nitropyrene (1-NP), a typical nitrated polycyclic aromatic hydrocarbon, is widely distributed in the environment and is well known for its mutagenic effects. Recently, we found that gestational 1-NP exposure induced fetal growth restriction. In this study, we further evaluated the effect of in utero 1-NP exposure on postnatal growth and neurobehavioral development in the offspring. Pregnant mice were administered with 1-NP (10 µg/kg) by gavage daily in late pregnancy (GD13-GD17). The body weight of each offspring was measured from PND1 to 12 weeks postpartum. Exploration and anxiety related activities were detected by open-field test at 6 weeks postpartum. Learning and memory were assessed by Morris Water Maze at 7 weeks postpartum. And depressive-like behaviors were estimated by sucrose preference test at 10 weeks postpartum. Significant body weight reduction was observed in 1-NP-exposed female offspring at PND1, PND14 and PND21 while the lower body weight was only found at PND1 for 1-NP-exposed male offspring. Exploration and anxiety activities at puberty, and depressive-like behavior in adulthood were not disturbed in offspring prenatally exposed to 1-NP. Interestingly, spatial learning and memory ability at puberty was impaired in females but not in males prenatally exposed to 1-NP. These findings suggest that gestational 1-NP exposure delays postnatal growth and impaired neurobehavioral development in a gender-dependent manner.


Assuntos
Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Mutagênicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Pirenos/toxicidade , Animais , Feminino , Masculino , Memória/efeitos dos fármacos , Camundongos Endogâmicos ICR , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Fatores Sexuais , Aprendizagem Espacial/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos
16.
Int J Dev Neurosci ; 75: 27-35, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30954504

RESUMO

BACKGROUND: Maternal infection during pregnancy is known to adversely affect foetal development, but previous studies have rarely investigated the impact of gynaecological diseases during pregnancy on offspring during adulthood. Vaginitis is one of the most prevalent gynaecological diseases during pregnancy. METHODS: The effect of maternal vaginal inflammation on offspring was simulated by inducing maternal vaginal infection. We performed a transvaginal injection of lipopolysaccharide (LPS) in pregnant mice to induce vaginitis and investigated their offspring by means of behavioural tests and molecular and cellular measurements. RESULTS: Behavioural tests revealed that the offspring of mothers transvaginally injected with LPS exhibited sex-dependent differences. Male offspring showed increased anxiety-related behaviours, including reduced time exploring the open arm in the elevated plus maze test and light chamber in the light-dark box test. Serum levels of corticosterone were increased in LPS male offspring, indicating activation of the hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing hormone (CRH) protein expression and c-Fos positive cells were increased in the hypothalamic paraventricular nucleus (PVN) in LPS male offspring, which presented with an increased number of microglia. CONCLUSION: This study suggests that prenatal vaginal infection increases anxiety-like behaviour in male offspring, possibly via activation of the HPA axis.


Assuntos
Ansiedade/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Inflamação/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Vagina/fisiopatologia , Animais , Ansiedade/psicologia , Comportamento Animal/fisiologia , Feminino , Inflamação/induzido quimicamente , Inflamação/psicologia , Lipopolissacarídeos , Masculino , Camundongos , Atividade Motora/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia
17.
Med Sci (Paris) ; 35(3): 236-243, 2019 Mar.
Artigo em Francês | MEDLINE | ID: mdl-30931908

RESUMO

Autism is a neuro-developmental pathology affecting 1 out of 100 children worldwide. The trauma and social consequences induced by autism are a real public health issue. Clinically, autism is characterized primarily by communications and social interactions deficits associated with repetitive behaviors and restricted interests. The term of autism spectrum disorders (ASD) is used to account for the diversity of symptoms that characterize this pathology. Based on observations made in humans, a rodent (rats and mice) model of autism was obtained and validated by prenatal exposure to sodium valproate. Using this model, mechanisms that concern both the functioning of neural networks and the properties of neurons have been proposed to account for some disorders that characterize autism. This model is also widely used in pre-clinical studies to evaluate new therapies against ASD.


Assuntos
Transtorno Autístico/induzido quimicamente , Transtorno Autístico/patologia , Modelos Animais de Doenças , Ácido Valproico , Animais , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/patologia , Feminino , Humanos , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos
18.
Clin Rheumatol ; 38(9): 2529-2539, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31020474

RESUMO

INTRODUCTION: Research describes higher incidence of neurodevelopmental disorders and learning disabilities in offspring of women affected by lupus. Factors implied are pregnancy and delivery adversities and exposure to maternal antibodies and cytokines. Little is known about the offspring immunological condition or the relation between offspring and maternal condition. OBJECTIVES: This study was conducted in order to analyze immunological configuration, psychopathology, and neuropsychological performance of young offspring of women with lupus, in comparison with healthy controls and in relation to maternal psychophysical condition. METHODS: Twenty-one offspring aged 8-17 of 17 women with lupus and 34 controls were recruited. Pregnancy conditions, stress factors, and immunological, psychopathological, and neuropsychological characteristics were compared. Immunological tests included standard lupus screening, lupus-related autoantibodies, antibodies against GluN2 subunit of the N-methyl-D-aspartate receptor (NMDAR) (anti-DWEYS Ab), and levels of ten cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GMCSF, IFN-γ, TNF-α). RESULTS: Offspring had lower leukocyte count (p = 0.001) and higher levels of anti-dsDNA Ab (p = 0.022), anti-DWEYS-GluN2 Ab (p < 0.001), and eight cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α-all p < 0.001-and IFN-γ, p = 0.026) than controls. Their cytokine levels did not differ from their mothers'; 23.9% of offspring met the criteria for a clinical psychiatric diagnosis. No differences were found in intelligence measures. Various neuropsychological scores correlated inversely with maternal psychophysical health. CONCLUSIONS: Offspring's profile suggests proinflammatory and autoimmune activation. Their rate of psychiatric diagnosis appears higher than in the general population, and their cognitive performance is related to maternal psychophysical health. Longitudinal research might investigate whether immunological and psychosocial conditions influence psychopathology and cognition. Graphical abstract The hypothesized sequence for physical and neuropsychological development for the SLE offspring.


Assuntos
Autoanticorpos/sangue , Filho de Pais Incapacitados , Transtornos Cognitivos/diagnóstico , Citocinas/sangue , Lúpus Eritematoso Sistêmico , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Adolescente , Criança , Transtornos Cognitivos/sangue , Feminino , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/psicologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-30823531

RESUMO

This study examines pre-pregnancy Body Mass Index (BMI) and gestational weight gain (GWG) in relation to early childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and related executive self-regulation behaviors. The analyses sample (n = 331) included a subsample of participants from a birth cohort recruited from prenatal clinics and hospital facilities from April 2005 to June 2011 in Durham, North Carolina. Pre-pregnancy BMI was calculated from weight at the last menstrual period and height was extracted from medical records. Gestational weight gain was calculated from pre-pregnancy weight and weight measured at the time of delivery. ADHD symptoms and executive self-regulation behaviors were assessed by maternal report (mean age = 3 years). Multivariable regression methods with inverse probability weighting (IPW) were used to evaluate associations accounting for sample selection bias and confounding. Pre-pregnancy BMI at levels ≥35 was positively associated with higher ADHD symptoms and worse executive self-regulation behaviors (inhibitory control and attention). Compared to adequate GWG, less than adequate GWG was related to more ADHD hyperactive-impulsive symptoms, whereas greater than adequate GWG was related to more problematic behaviors related to working memory and planning. The findings support a link between maternal weight and child neurodevelopment. Continued research that help identify biological mechanisms are needed.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Índice de Massa Corporal , Função Executiva , Ganho de Peso na Gestação , Efeitos Tardios da Exposição Pré-Natal/etiologia , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , North Carolina , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Análise de Regressão , Fatores de Risco
20.
Infant Behav Dev ; 55: 1-9, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30818136

RESUMO

BACKGROUND: People in war zones are exposed to heavy metal contamination deriving from new-generation weapons, in addition to exposure to psychologically traumatizing war events. Pregnant women and their children-to-be are particularly vulnerable to both biological and psychological war effects. OBJECTIVE: The aim of the current study was to analyse the impact of maternal prenatal heavy metal contamination on infant emotional development and to examine the potential moderating role of maternal symptoms of post-traumatic stress disorder (PTSD) in the association between heavy metal load and infant emotional development. METHODS: The participants were 502 Palestinian mothers, pregnant in their first trimester during the 2014 War on Gaza. The mothers were recruited at their delivery (T1) and followed at the infants' age of 6-7 months (T2; N = 392). The load of five weapon-related heavy metals (chromium, mercury, vanadium, strontium, and uranium) was analysed by Inductively Coupled Plasma Mass Spectrometry (ICP/MS) from mothers' hair samples at childbirth (T1). Assessment of maternal PTSD symptoms was based on the Harvard Trauma Questionnaire (HTQ) and infant emotional development on the Infant Behavior Questionnaire (IBQ), both reported by mothers (T2). RESULTS: Two of the analysed metals, chromium and uranium, adversely predicted children's early emotional development, indicated by decreased positive affectivity, increased negative emotionality, and problems in early orientation and regulation. Mother's PTSD did not moderate the impact of heavy metal contamination on children's emotional development. CONCLUSIONS: Adverse impact of war is not limited to those who experience it directly, but is passed on to future generations through multiple mechanisms. International organizations are obliged to protect parents and infants from the modern weaponry in wars.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Emoções/efeitos dos fármacos , Metais Pesados/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/psicologia , Exposição à Guerra/efeitos adversos , Adulto , Criança , Desenvolvimento Infantil/fisiologia , Emoções/fisiologia , Feminino , Cabelo/química , Cabelo/efeitos dos fármacos , Humanos , Lactente , Comportamento do Lactente/efeitos dos fármacos , Comportamento do Lactente/fisiologia , Comportamento do Lactente/psicologia , Masculino , Oriente Médio/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Inquéritos e Questionários
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