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1.
Neuron ; 103(4): 563-581, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437453

RESUMO

Spike-timing-dependent synaptic plasticity (STDP) is a leading cellular model for behavioral learning and memory with rich computational properties. However, the relationship between the millisecond-precision spike timing required for STDP and the much slower timescales of behavioral learning is not well understood. Neuromodulation offers an attractive mechanism to connect these different timescales, and there is now strong experimental evidence that STDP is under neuromodulatory control by acetylcholine, monoamines, and other signaling molecules. Here, we review neuromodulation of STDP, the underlying mechanisms, functional implications, and possible involvement in brain disorders.


Assuntos
Plasticidade Neuronal/fisiologia , Neurotransmissores/fisiologia , Potenciais de Ação , Animais , Astrócitos/fisiologia , Comportamento/fisiologia , Encefalopatias/tratamento farmacológico , Encefalopatias/fisiopatologia , Mapeamento Encefálico , Humanos , Aprendizagem/fisiologia , Consolidação da Memória/fisiologia , Modelos Neurológicos , Terapia de Alvo Molecular , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/fisiopatologia , Neurônios/fisiologia , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/fisiopatologia , Terminações Pré-Sinápticas/fisiologia , Receptores de Neurotransmissores/fisiologia , Reforço (Psicologia) , Transdução de Sinais/fisiologia , Especificidade da Espécie , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Fatores de Tempo
2.
Einstein (Sao Paulo) ; 17(3): eAO4607, 2019 Jun 13.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31215590

RESUMO

OBJECTIVE: To determine associations between sex and neurodevelopmental outcomes in human milk-fed very preterm infants, adjusted to early measured nutrient intakes and other neonatal cofactors. METHODS: Consecutive inborn human milk-fed infants, with gestational age <33 weeks, were eligible. In-hospital energy and protein intakes have relied on measured human milk composition. The Bayley Scales of Infant Development II mental and psychomotor developmental indexes were used to assess neurodevelopment at 20 months' corrected age. After univariate analysis, some covariables were used for linear multiple regression. RESULTS: Thirty-two infants were included, with a mean (standard deviation) gestational age of 29.8 (1.8) weeks, and a median birth weight of 1168g (interquartile range 990-1419g). Minimum recommended intakes were achieved in 63.6% and 15.2% of infants for protein and energy, respectively. The mental and psychomotor developmental indexes were within normal limits in 93.8% of infants. The mean mental and psychomotor developmental indexes were significantly lower in males. Only male sex negatively and significantly affected the mental and psychomotor developmental indexes (B=-9.44; 95%CI: -17.64- -1.23; adjusted r2=0.17; p=0.026), adjusted to gestational age and measured energy intake. CONCLUSION: In human milk-fed very preterm infants, males had a significantly lower mental and psychomotor developmental indexes score at 20 months' corrected age, adjusted for gestational age and measured energy intake.


Assuntos
Doenças do Prematuro/etiologia , Recém-Nascido Prematuro , Leite Humano , Transtornos do Neurodesenvolvimento/etiologia , Fatores Etários , Peso ao Nascer/fisiologia , Estudos de Coortes , Ingestão de Energia/fisiologia , Feminino , Idade Gestacional , Humanos , Doenças do Prematuro/fisiopatologia , Masculino , Transtornos do Neurodesenvolvimento/fisiopatologia , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia , Fatores de Risco , Fatores Sexuais , Estatísticas não Paramétricas , Fatores de Tempo
3.
J Autism Dev Disord ; 49(8): 3328-3350, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31102194

RESUMO

This review was performed to investigate the characteristics of vestibular dysfunctions in children with neurodevelopmental disorders (NDDs). The majority of the included studies reported central and/or peripheral vestibular aberrations in a subset of these children. These alterations may result in symptoms of distorted motor coordination or postural instability, and might explain some of the balance problems observed in this population. However, high-quality studies with an extensive vestibular test battery are required to further characterize the vestibular function in NDDs since current findings are ambiguous and mainly based on evaluation of the horizontal semicircular canals alone. Importantly, since vestibular dysfunctions may result in comparable characteristics as found in NDDs, clinicians should be aware of these similarities when establishing the NDD diagnosis.


Assuntos
Transtornos do Neurodesenvolvimento/fisiopatologia , Equilíbrio Postural , Vestíbulo do Labirinto/fisiopatologia , Criança , Feminino , Humanos
4.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071949

RESUMO

Individuals born preterm have higher rates of neurodevelopmental disorders such as schizophrenia, autistic spectrum, and attention deficit/hyperactivity disorders. These conditions are often sexually dimorphic and with different developmental trajectories. The etiology is likely multifactorial, however, infections both during pregnancy and in childhood have emerged as important risk factors. The association between sex- and age-dependent vulnerability to neuropsychiatric disorders has been suggested to relate to immune activation in the brain, including complex interactions between sex hormones, brain transcriptome, activation of glia cells, and cytokine production. Here, we will review sex-dependent effects on brain development, including glia cells, both under normal physiological conditions and following perinatal inflammation. Emphasis will be given to sex-dependent effects on brain regions which play a role in neuropsychiatric disorders and inflammatory reactions that may underlie early-life programming of neurobehavioral disturbances later in life.


Assuntos
Encéfalo/crescimento & desenvolvimento , Inflamação/fisiopatologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Neuroglia/patologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Humanos , Inflamação/diagnóstico por imagem , Nascimento Prematuro/fisiopatologia , Esquizofrenia/fisiopatologia , Caracteres Sexuais
5.
Nutrients ; 11(4)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30986970

RESUMO

Cognitive impairment is strongly associated with functional outcomes in psychiatric patients. Involvement of n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), in particular docosahexaenoic acid (DHA), in brain functions is largely documented. DHA is incorporated into membrane phospholipids as structural component, especially in the central nervous system where it also has important functional effects. The aim of this review is to investigate the relationship between DHA and cognitive function in relation to mental disorders. Results from few randomized controlled trials (RCTs) on the effects of DHA (alone or in combination) in psychotic, mood and neurodevelopmental disorders, respectively, suggest that no conclusive remarks can be drawn.


Assuntos
Encéfalo/efeitos dos fármacos , Fármacos do Sistema Nervoso Central/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Afeto/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Ácidos Docosa-Hexaenoicos/metabolismo , Humanos , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/metabolismo , Transtornos do Humor/fisiopatologia , Transtornos do Humor/psicologia , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/psicologia
6.
Nat Commun ; 10(1): 928, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30804331

RESUMO

Dosage of key regulators impinge on developmental disorders such as FOXG1 syndrome. Since neither knock-out nor knock-down strategy assures flexible and precise protein abundance control, to study hypomorphic or haploinsufficiency expression remains challenging. We develop a system in human pluripotent stem cells (hPSCs) using CRISPR/Cas9 and SMASh technology, with which we can target endogenous proteins for precise dosage control in hPSCs and at multiple stages of neural differentiation. We also reveal FOXG1 dose-dependently affect the cellular constitution of human brain, with 60% mildly affect GABAergic interneuron development while 30% thresholds the production of MGE derived neurons. Abnormal interneuron differentiation accounts for various neurological defects such as epilepsy or seizures, which stimulates future innovative cures of FOXG1 syndrome. By means of its robustness and easiness, dosage-control of proteins in hPSCs and their derivatives will update the understanding and treatment of additional diseases caused by abnormal protein dosage.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transtornos do Neurodesenvolvimento/metabolismo , Células-Tronco Pluripotentes/metabolismo , Animais , Diferenciação Celular , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Humanos , Interneurônios/citologia , Interneurônios/metabolismo , Masculino , Camundongos , Camundongos SCID , Proteínas do Tecido Nervoso/genética , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/fisiopatologia , Células-Tronco Pluripotentes/citologia , Ácido gama-Aminobutírico/metabolismo
7.
Scand J Clin Lab Invest ; 79(1-2): 99-107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30616423

RESUMO

Thyroid function in pregnant women is of clinical importance considering the crucial role of thyroid hormones during fetal brain development, but the current level of evidence is insufficient to recommend for or against the routine testing of thyroid function in pregnant women. As part of this debate, it is important to evaluate the frequency of undiagnosed and untreated thyroid function abnormalities in pregnant women and to address challenges related to the biochemical assessment of maternal thyroid function in early pregnancy. A hypothesis of fetal programming by maternal thyroid disease has been proposed, but more evidence in humans is needed to extend the hypothesis and to evaluate child neurodevelopmental outcomes after in utero exposure to different abnormalities in maternal thyroid function. The nationwide registers in the Nordic countries provide unique opportunities within reproductive epidemiology to study the impact of various in utero exposures, and stored blood samples from pregnant women in nationwide birth cohorts provide a valuable source for the establishment of pregnancy specific reference ranges. This review addresses the frequency and outcomes of thyroid function abnormalities in pregnant women mainly focusing on observational studies that combine data from the Danish nationwide registers and biological specimens from the Danish National Birth Cohort. Dynamic changes in the reference range of maternal TSH and free T4 during the first trimester of pregnancy are described and discussed. A high frequency of unidentified maternal thyroid function abnormalities is illustrated, and outcomes of child neurodevelopment are evaluated according to subtypes and severity of maternal thyroid dysfunction.


Assuntos
Hipertireoidismo/diagnóstico , Hipotireoidismo/diagnóstico , Transtornos do Neurodesenvolvimento/diagnóstico , Sistema de Registros , Glândula Tireoide/metabolismo , Adulto , Biomarcadores/sangue , Dinamarca , Feminino , Desenvolvimento Fetal , Feto , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/complicações , Hipertireoidismo/fisiopatologia , Hipotireoidismo/sangue , Hipotireoidismo/complicações , Hipotireoidismo/fisiopatologia , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Estudos Observacionais como Assunto , Gravidez , Primeiro Trimestre da Gravidez , Índice de Gravidade de Doença , Glândula Tireoide/fisiopatologia , Tireotropina/sangue , Tiroxina/sangue
8.
J Hum Genet ; 64(4): 313-322, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30655572

RESUMO

Casein kinase 2 (CK2) is a serine threonine kinase ubiquitously expressed in eukaryotic cells and involved in various cellular processes. In recent studies, de novo variants in CSNK2A1 and CSNK2B, which encode the subunits of CK2, have been identified in individuals with intellectual disability syndrome. In this study, we describe four patients with neurodevelopmental disorders possessing de novo variants in CSNK2A1 or CSNK2B. Using whole-exome sequencing, we detected two de novo variants in CSNK2A1 in two unrelated Japanese patients, a novel variant c.571C>T, p.(Arg191*) and a recurrent variant c.593A>G, p.(Lys198Arg), and two novel de novo variants in CSNK2B in Japanese and Malaysian patients, c.494A>G, p.(His165Arg) and c.533_534insGT, p.(Pro179Tyrfs*49), respectively. All four patients showed mild to profound intellectual disabilities, developmental delays, and various types of seizures. This and previous studies have found a total of 20 CSNK2A1 variants in 28 individuals with syndromic intellectual disability. The hotspot variant c.593A>G, p.(Lys198Arg) was found in eight of 28 patients. Meanwhile, only five CSNK2B variants were identified in five individuals with neurodevelopmental disorders. We reviewed the previous literature to verify the phenotypic spectrum of CSNK2A1- and CSNK2B-related syndromes.


Assuntos
Caseína Quinase II/genética , Deficiências do Desenvolvimento/genética , Convulsões/genética , Adolescente , Criança , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Humanos , Lactente , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Masculino , Mutação , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/fisiopatologia , Linhagem , Convulsões/complicações , Convulsões/fisiopatologia , Sequenciamento Completo do Exoma
9.
Brain ; 142(1): 80-92, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30544257

RESUMO

Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders.


Assuntos
Epilepsia/genética , Transtornos do Neurodesenvolvimento/genética , Receptores de N-Metil-D-Aspartato/genética , Adolescente , Adulto , Idoso , Animais , Células Cultivadas , Córtex Cerebelar/metabolismo , Criança , Pré-Escolar , Epilepsia/fisiopatologia , Feminino , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos do Neurodesenvolvimento/fisiopatologia , Fenótipo , Ratos , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/fisiologia , Adulto Jovem
10.
Congenit Anom (Kyoto) ; 59(3): 81-87, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30592100

RESUMO

The rapid rise in the prevalence of autism spectrum disorders (ASD) and other psychiatric disorders displaying similar traits has increased the need to elucidate their molecular mechanisms. Epidemiological studies have shown that maternal infection during mid-pregnancy is associated with increased risk of neurodevelopmental disorders such as ASD in offspring. Using maternal infection models, researchers have gathered evidence relevant to such disorders. A comprehensive summary of the changes in the brain structure, function, and behavior in offspring induced by maternal immune activation (MIA) has been reported. However, the molecular mechanisms underlying the association between MIA and improper brain development, which ultimately lead to neurodevelopmental disorders, have not been fully reviewed. This paper summarizes the currently known molecular mechanisms associated with the MIA model, with a special focus on the role of the placenta in fetal brain development.


Assuntos
Infecções Bacterianas/genética , Encéfalo/imunologia , Interleucina-6/genética , Transtornos do Neurodesenvolvimento/genética , Complicações Infecciosas na Gravidez/genética , Viroses/genética , Animais , Infecções Bacterianas/complicações , Infecções Bacterianas/imunologia , Infecções Bacterianas/fisiopatologia , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Feminino , Feto , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Imunidade Inata/efeitos dos fármacos , Interleucina-6/imunologia , Lipopolissacarídeos/farmacologia , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/imunologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Placenta , Poli I-C/farmacologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/fisiopatologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Viroses/complicações , Viroses/imunologia , Viroses/fisiopatologia
12.
Res Dev Disabil ; 85: 217-228, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30580152

RESUMO

Most research does not address the overlap between neurodevelopmental disorders when investigating concomitant mental health problems. The purpose of the present study was to examine the association of intellectual disability (ID), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) with the presence of behavioural and emotional problems after controlling for other well-known correlates and risk factors. The sample included 4- to 18-year-old children who attended neuropaediatric clinics (N = 331). After controlling for adversity, age, gender, other developmental/neurological disorders, parental emotional problems, and parenting strategies, the presence of ADHD but not ASD or ID was uniquely associated with behaviour problems. Neither ADHD nor ASD nor ID was significantly associated with emotional problems after controlling for other risk factors. However, ADHD, ASD and behavioural/emotional disorders but not ID were significantly associated with functional impairment in everyday activities after controlling for other risk factors. Because children with neurodevelopmental disorders have complex needs, a holistic approach to diagnosis and interventions is highly warranted, including the assessment and treatment of behavioural and emotional disorders.


Assuntos
Atividades Cotidianas , Transtornos de Ansiedade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Transtorno da Conduta/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Deficiência Intelectual/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adolescente , Transtornos de Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/fisiopatologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Transtorno do Espectro Autista/psicologia , Criança , Pré-Escolar , Transtorno da Conduta/psicologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Deficiência Intelectual/psicologia , Masculino , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/psicologia , Razão de Chances , Poder Familiar , Pais/psicologia , Classe Social , Transtornos de Estresse Pós-Traumáticos/psicologia
13.
J Neurodev Disord ; 10(1): 38, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30541449

RESUMO

BACKGROUND: Despite advances in antenatal and neonatal care, preterm birth remains a leading cause of neurological disabilities in children. Infants born prematurely, particularly those delivered at the earliest gestational ages, commonly demonstrate increased rates of impairment across multiple neurodevelopmental domains. Indeed, the current literature establishes that preterm birth is a leading risk factor for cerebral palsy, is associated with executive function deficits, increases risk for impaired receptive and expressive language skills, and is linked with higher rates of co-occurring attention deficit hyperactivity disorder, anxiety, and autism spectrum disorders. These same infants also demonstrate elevated rates of aberrant cerebral structural and functional connectivity, with persistent changes evident across advanced magnetic resonance imaging modalities as early as the neonatal period. Emerging findings from cross-sectional and longitudinal investigations increasingly suggest that aberrant connectivity within key functional networks and white matter tracts may underlie the neurodevelopmental impairments common in this population. MAIN BODY: This review begins by highlighting the elevated rates of neurodevelopmental disorders across domains in this clinical population, describes the patterns of aberrant structural and functional connectivity common in prematurely-born infants and children, and then reviews the increasingly established body of literature delineating the relationship between these brain abnormalities and adverse neurodevelopmental outcomes. We also detail important, typically understudied, clinical, and social variables that may influence these relationships among preterm children, including heritability and psychosocial risks. CONCLUSION: Future work in this domain should continue to leverage longitudinal evaluations of preterm infants which include both neuroimaging and detailed serial neurodevelopmental assessments to further characterize relationships between imaging measures and impairment, information necessary for advancing our understanding of modifiable risk factors underlying these disorders and best practices for improving neurodevelopmental trajectories in this high-risk clinical population.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Recém-Nascido Prematuro/fisiologia , Transtornos do Neurodesenvolvimento/patologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Mapeamento Encefálico , Humanos , Recém-Nascido , Recém-Nascido Prematuro/psicologia , Imagem por Ressonância Magnética , Vias Neurais/patologia , Vias Neurais/fisiopatologia
14.
Dev Psychopathol ; 30(3): 743-762, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30068407

RESUMO

The prenatal period is increasingly considered as a crucial target for the primary prevention of neurodevelopmental and psychiatric disorders. Understanding their pathophysiological mechanisms remains a great challenge. Our review reveals new insights from prenatal brain development research, involving (epi)genetic research, neuroscience, recent imaging techniques, physical modeling, and computational simulation studies. Studies examining the effect of prenatal exposure to maternal distress on offspring brain development, using brain imaging techniques, reveal effects at birth and up into adulthood. Structural and functional changes are observed in several brain regions including the prefrontal, parietal, and temporal lobes, as well as the cerebellum, hippocampus, and amygdala. Furthermore, alterations are seen in functional connectivity of amygdalar-thalamus networks and in intrinsic brain networks, including default mode and attentional networks. The observed changes underlie offspring behavioral, cognitive, emotional development, and susceptibility to neurodevelopmental and psychiatric disorders. It is concluded that used brain measures have not yet been validated with regard to sensitivity, specificity, accuracy, or robustness in predicting neurodevelopmental and psychiatric disorders. Therefore, more prospective long-term longitudinal follow-up studies starting early in pregnancy should be carried out, in order to examine brain developmental measures as mediators in mediating the link between prenatal stress and offspring behavioral, cognitive, and emotional problems and susceptibility for disorders.


Assuntos
Encéfalo/embriologia , Encéfalo/fisiopatologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estresse Psicológico/complicações , Tonsila do Cerebelo/embriologia , Tonsila do Cerebelo/fisiopatologia , Cerebelo/embriologia , Cerebelo/fisiopatologia , Feminino , Hipocampo/embriologia , Hipocampo/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Rede Nervosa/embriologia , Rede Nervosa/fisiopatologia , Transtornos do Neurodesenvolvimento/psicologia , Lobo Parietal/embriologia , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/embriologia , Córtex Pré-Frontal/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estudos Prospectivos , Fatores de Risco , Lobo Temporal/embriologia , Lobo Temporal/fisiopatologia
15.
Dev Psychopathol ; 30(3): 725-742, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30068420

RESUMO

This article extends the research focusing on the early origins of psychopathology into the prenatal period, by exploring the association between maternal prenatal depression and offspring (fetal and infant) neurobehavior. The sample is recruited from a rural population in South India where women in the third trimester of pregnancy were assessed for depression and the heart rate responses of their fetuses to extrinsically applied vibroacoustic stimuli were studied. At 2 months postbirth, infant temperament and cortisol responsivity to immunization were assessed. The association between maternal prenatal depression and fetal responsivity to vibroacoustic stimulation, and infant responsivity to immunization, was U shaped with higher levels of responsivity noted in the offspring of mothers with very high and very low depression scores, and lower levels noted in the offspring of mothers with moderate depression scores. Maternal prenatal depression was not associated with infant temperament. The findings highlight the importance of environmental influences in the developmental origins of neurobehavior, suggesting that such differences, not evident at baseline, may emerge upon exposure to stressors. The study also emphasizes the need for further investigation in low- and middle-income contexts by providing preliminary evidence of the differing patterns of association observed between high- and low-income populations.


Assuntos
Transtorno Depressivo/fisiopatologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Complicações na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Temperamento/fisiologia , Populações Vulneráveis , Adulto , Estudos de Coortes , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Humanos , Hidrocortisona/sangue , Índia , Lactente , Recém-Nascido , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/psicologia , Pobreza/psicologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , População Rural , Populações Vulneráveis/psicologia
16.
Dev Psychopathol ; 30(3): 1063-1086, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30068419

RESUMO

Accumulating evidence indicates that the fetal environment plays an important role in brain development and sets the brain on a trajectory across the life span. An abnormal fetal environment results when factors that should be present during a critical period of development are absent or when factors that should not be in the developing brain are present. While these factors may acutely disrupt brain function, the real cost to society resides in the long-term effects, which include important mental health issues. We review the effects of three factors, fetal alcohol exposure, teratogen exposure, and nutrient deficiencies, on the developing brain and the consequent risk for developmental psychopathology. Each is reviewed with respect to the evidence found in epidemiological and clinical studies in humans as well as preclinical molecular and cellular studies that explicate mechanisms of action.


Assuntos
Encéfalo/fisiopatologia , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Desenvolvimento Fetal/fisiologia , Desnutrição/fisiopatologia , Transtornos Mentais/diagnóstico , Transtornos do Neurodesenvolvimento/diagnóstico , Feminino , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Transtornos do Espectro Alcoólico Fetal/psicologia , Humanos , Desnutrição/psicologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/psicologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Teratogênios/toxicidade
17.
Nutrients ; 10(6)2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29857555

RESUMO

This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks' gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother's own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.


Assuntos
Nutrição Enteral , Medicina Baseada em Evidências , Fenômenos Fisiológicos da Nutrição do Lactente , Doenças do Prematuro/prevenção & controle , Leite Humano , Nascimento Prematuro/dietoterapia , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/fisiopatologia , Enterocolite Necrosante/prevenção & controle , Humanos , Lactente , Fórmulas Infantis , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/etiologia , Doenças do Prematuro/fisiopatologia , Recém-Nascido de muito Baixo Peso , Sepse Neonatal/etiologia , Sepse Neonatal/fisiopatologia , Sepse Neonatal/prevenção & controle , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Nascimento Prematuro/fisiopatologia , Índice de Gravidade de Doença
18.
EBioMedicine ; 31: 143-149, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29709497

RESUMO

BACKGROUND: Children exposed to gestational diabetes mellitus (GDM) in utero are at increased risk of neurodevelopmental difficulties, including autism and impaired motor control. However, the underlying neurophysiology is unknown. METHODS: Using transcranial magnetic stimulation, we assessed cortical excitability, long-term depression (LTD)-like neuroplasticity in 45 GDM-exposed and 12 control children aged 11-13 years. Data were analysed against salivary cortisol and maternal diabetes severity and treatment (insulin [N = 22] or metformin [N = 23]) during pregnancy. FINDINGS: GDM-exposed children had reduced cortical excitability (p = .003), LTD-like neuroplasticity (p = .005), and salivary cortisol (p < .001) when compared with control children. Higher maternal insulin resistance (IR) before and during GDM treatment was associated with a blunted neuroplastic response in children (p = .014) and this was not accounted for by maternal BMI. Additional maternal and neonatal measures, including fasting plasma glucose and inflammatory markers, predicted neurophysiological outcomes. The metformin and insulin treatment groups had similar outcomes. INTERPRETATION: These results suggest that GDM can contribute to subtle differences in child neurophysiology, and possibly cortisol secretion, persisting into early adolescence. Importantly, these effects appear to occur during second trimester, before pharmacologic treatment typically commences, and can be predicted by maternal insulin resistance. Therefore, earlier detection and treatment of GDM may be warranted. Metformin appears to be safe for these aspects of neurodevelopment.


Assuntos
Transtorno Autístico , Córtex Cerebral/fisiopatologia , Diabetes Gestacional , Hidrocortisona/metabolismo , Plasticidade Neuronal , Saliva/metabolismo , Estimulação Magnética Transcraniana , Adolescente , Transtorno Autístico/etiologia , Transtorno Autístico/metabolismo , Transtorno Autístico/fisiopatologia , Transtorno Autístico/terapia , Criança , Feminino , Humanos , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/terapia , Gravidez
20.
Dev Med Child Neurol ; 60(10): 1052-1058, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29572821

RESUMO

AIM: To assess the impact of perioperative neonatal brain injury and brain volumes on neurodevelopment throughout school-age children with critical congenital heart disease (CHD). METHOD: Thirty-four survivors of neonatal cardiac surgery (seven females, 27 males) were included. Neonatal preoperative and postoperative cerebral magnetic resonance imaging was performed and neurodevelopment was assessed at 24 months (SD 0.7, n=32, using Bayley Score of Infant and Toddler Development, Child Behavior Checklist) and 6 years (mean age 5y 11mo; SD 0.3, n=30, using Movement Assessment Battery for Children, Wechsler Preschool and Primary Scale of Intelligence, Child Behavior Checklist, Teacher Report Form). Brain injury, brain volumes, and cortical measures were related to outcome with adjustment for maternal educational level. RESULTS: Two-year cognitive score and 6-year Full-scale IQ were poorer in children with neonatal white matter injury (n=21, all p<0.05), with higher teacher-reported attention problems (p=0.03). Five of six children with involvement of the posterior limb of the internal capsule showed motor problems (p=0.03). Children with a below-average Fulll-scale IQ (<85, n=9) showed smaller volumes of basal ganglia thalami (-8%, p=0.03) and brain stem (-7%, p=0.03). INTERPRETATION: Our findings provide evidence of unfavourable outcome in school-age children with critical CHD who acquire perioperative neonatal brain injury. WHAT THIS PAPER ADDS: This paper extends knowledge about neonatal brain injury and long-term outcome in congenital heart disease. Children with white matter injury show lower IQ and more attention problems at school age. Injury of the posterior limb of the internal capsule increases the risk of motor problems. This study provides evidence for worse outcomes in neonates acquiring brain injury around cardiac surgery.


Assuntos
Lesões Encefálicas/fisiopatologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Desenvolvimento Infantil/fisiologia , Cardiopatias Congênitas/cirurgia , Inteligência/fisiologia , Cápsula Interna/patologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Testes Neuropsicológicos , Escalas de Wechsler
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