Prenatal alcohol use as a risk for attention-deficit/hyperactivity disorder

Pagnin, Daniel; Grecco, Maria Luiza Zamboni; Furtado, Erikson Felipe

doi:10.1007/s00406-018-0946-7

Cited by 34 publications

(26 citation statements)

References 35 publications

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“…For instance, it was shown that genetic polymorphisms in the alcohol dehydrogenase 1B (ADH1B) gene, a gene responsible for alcohol metabolism, can lead to an increase of vulnerability to FASDs 12 . Furthermore, binge drinking during pregnancy was associated with lower academic scores and behavioral disorders 13,14 , while continuous drinking throughout the pregnancy can cause fetal alcohol syndrome (FAS), which is the most severe type of FASDs and exhibits both physical and neurobehavioral problems 15 . Binge drinking is defined as a pattern of alcohol consumption that elevates blood alcohol concentration (BAC) to 80 mg/dL or above.…”

Section: Introductionmentioning

confidence: 99%

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

et al. 2020

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Maternal alcohol exposure during pregnancy can substantially impact the development of the fetus, causing a range of symptoms, known as fetal alcohol spectrum disorders (FASDs), such as cognitive dysfunction and psychiatric disorders, with the pathophysiology and mechanisms largely unknown. Recently developed human cerebral organoids from induced pluripotent stem cells are similar to fetal brains in the aspects of development and structure. These models allow more relevant in vitro systems to be developed for studying FASDs than animal models. Modeling binge drinking using human cerebral organoids, we sought to quantify the downstream toxic effects of alcohol (ethanol) on neural pathology phenotypes and signaling pathways within the organoids. The results revealed that alcohol exposure resulted in unhealthy organoids at cellular, subcellular, bioenergetic metabolism, and gene expression levels. Alcohol induced apoptosis on organoids. The apoptotic effects of alcohol on the organoids depended on the alcohol concentration and varied between cell types. Specifically, neurons were more vulnerable to alcohol-induced apoptosis than astrocytes. The alcohol-treated organoids exhibit ultrastructural changes such as disruption of mitochondria cristae, decreased intensity of mitochondrial matrix, and disorganized cytoskeleton. Alcohol exposure also resulted in mitochondrial dysfunction and metabolic stress in the organoids as evidenced by (1) decreased mitochondrial oxygen consumption rates being linked to basal respiration, ATP production, proton leak, maximal respiration and spare respiratory capacity, and (2) increase of non-mitochondrial respiration in alcohol-treated organoids compared with control groups. Furthermore, we found that alcohol treatment affected the expression of 199 genes out of 17,195 genes analyzed. Bioinformatic analyses showed the association of these dysregulated genes with 37 pathways related to clinically relevant pathologies such as psychiatric disorders, behavior, nervous system development and function, organismal injury and abnormalities, and cellular development. Notably, 187 of these genes are critically involved in neurodevelopment, and/or implicated in nervous system physiology and neurodegeneration. Furthermore, the identified genes are key regulators of multiple pathways linked in networks. This study extends for the first time animal models of binge drinking-related FASDs to a human model, allowing in-depth analyses of neurotoxicity at tissue, cellular, subcellular, metabolism, and gene levels. Hereby, we provide novel insights into alcohol-induced pathologic phenotypes, cell type-specific vulnerability, and affected signaling pathways and molecular networks, that can contribute to a better understanding of the developmental neurotoxic effects of binge drinking during pregnancy.

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Section: Introductionmentioning

confidence: 99%

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

et al. 2020

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“…To date, ample evidence has shown that parental alcohol abuse during the perinatal period may induce ADHD-like phenotypes in offspring such as hyperactivity and inattention [ 29 ]. In this study, we aimed to find out metabolic alterations in PAE-induced ADHD-like model and to investigate the recovery of phenotypes after the HX106 treatment, a nutraceutical previously developed to improve cognitive function.…”

Section: Discussionmentioning

confidence: 99%

GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice

Lee

Jeon

et al. 2020

Nutrients

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Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in children characterized by inattention and hyperactivity. Prenatal alcohol exposure (PAE) can disrupt fetal neuronal development and cause an ADHD-like hyperactive behavior in the offspring. In this study, we hypothesized that metabolic disturbance would involve in ADHD neuropathology and aimed to investigate the changes in metabolite profile in PAE-induced ADHD-like model and the effects of HX106, a nutraceutical, on ADHD-like pathophysiology and metabolite changes. To this end, we administered HX106 to the mouse offspring affected by PAE (OPAE) and assessed the hyperactivity using the open field test. We observed that HX106-treated OPAE showed less hyperactive behavior than vehicle-treated OPAE. The effects of HX106 were found to be related to the regulation of dopamine transporter and D2 dopamine receptor expression. Furthermore, using gas chromatography time-of-flight mass spectrometry-based metabolomics, we explored the metabolite changes among the experimental groups. The metabolite profile, particularly related with the amino acids, linoleic acid and amino sugar pathways, was altered by PAE and reversed by HX106 treatment partially similar to that observed in the control group. Overall, this study suggest that metabolite alteration would be involved in ADHD pathology and that HX106 can be an efficient supplement to overcome ADHD by regulating dopamine signaling-related protein expression and metabolite changes.

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“…In fact, on one hand, a positive association with BN, even after controlling for confounding factors such as offspring BMI in adulthood or variation between childhood and adult BMI, was reported (Montgomery et al 2005), but on the other hand, a negative association between mother's smoking and AN was shown, even if attenuated upon adjustment for parental education (Goodman et al 2014). Although a larger number of studies (i.e., 7) investigated the association between maternal alcohol use and EDs onset in the offspring, no significant data emerged; since this datum is not in line with other fields of psychiatry (Pagnin et al 2019), future studies are needed to clarify this issue.…”

Section: Maternal Factorsmentioning

confidence: 91%

The role of prenatal and perinatal factors in eating disorders: a systematic review

Marzola

Cavallo

Panero

et al. 2020

Arch Womens Ment Health

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Numerous studies showed that factors influencing fetal development and neonatal period could lead to lasting alterations in the brain of the offspring, in turn increasing the risk for eating disorders (EDs). This work aims to systematically and critically review the literature on the association of prenatal and perinatal factors with the onset of EDs in the offspring, updating previous findings and focusing on anorexia nervosa (AN) and bulimia nervosa (BN). A systematic literature search was performed on Pubmed, PsycINFO, and Scopus. The drafting of this systematic review was conducted following the PRISMA statement criteria and the methodological quality of each study was assessed by the MMAT 2018. A total of 37 studies were included in this review. The factors that showed a more robust association with AN were higher maternal age, preeclampsia and eclampsia, multiparity, hypoxic complications, prematurity, or being born preterm (< 32 weeks) and small for gestational age or lower birth size. BN was only associated with maternal stress during pregnancy. Many methodological flaws emerged in the considered studies, so further research is needed to clarify these inconsistencies. Altogether, data are suggestive of an association between prenatal and perinatal factors and the onset of EDs in the offspring. Nevertheless, given the methodological quality of the available literature, firm conclusions cannot be drawn and whether this vulnerability is specific to EDs or mental disorders remains to be defined. Also, a strong need for longitudinal and well-designed studies on this topic emerged.

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Prenatal alcohol use as a risk for attention-deficit/hyperactivity disorder

Cited by 34 publications

References 35 publications

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice

The role of prenatal and perinatal factors in eating disorders: a systematic review

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