Exposure to Gestational Diabetes Mellitus and Low Socioeconomic Status

Nomura, Yoko; Marks, David J.; Grossman, Bella; Yoon, Michelle; Loudon, Holly; Stone, Joanne; Halperin, Jeffrey M.

doi:10.1001/archpediatrics.2011.784

Cited by 158 publications

(67 citation statements)

References 59 publications

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“…In 2000, the WHO estimated that 2.2% of the total global population was diabetic and predicted a two-fold increase to 4.4% by 2030 (Wild et al, 2004). Notably, a key aspect of type 2 diabetes is its comorbidity with neuropsychiatric disorders including depression, schizophrenia, anxiety, and drug addiction (Niswender et al, 2011), as well as gestational diabetes contributing to offspring risk of neurodevelopmental disorders including autism and attention deficit hyperactivity disorder (Krakowiak et al, 2012; Lyall et al, 2012; Nomura et al, 2012). These brain disorders have been linked, at least in part, with dysregulated 5-HT neurocircuitry (Daws et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor function

Saunders

Siuta

Robertson

et al. 2014

Neurochemistry International

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The serotonergic system regulates a wide range of behavior, including mood and impulsivity, and its dysregulation has been associated with mood disorders, autism spectrum disorder, and addiction. Diabetes is a risk factor for these conditions. Insulin resistance in the brain is specifically associated with susceptibility to psychostimulant abuse. Here, we examined whether phosphorylation of Akt, a key regulator of the insulin signaling pathway, controls serotonin (5-HT) signaling. To explore how impairment in Akt function regulates 5-HT homeostasis, we used a brain-specific rictor knockout (KO) mouse model of impaired neuronal phosphorylation of Akt at Ser473. Cortical 5-HT1A and 5-HT2A receptor binding was significantly elevated in rictor KO mice. Concomitant with this elevated receptor expression, the 5-HT1A receptor agonist 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) led to an increased hypothermic response in rictor KO mice. The increased cortical 5-HT1A receptor density was associated with higher 5-HT1A receptor levels on the cortical cell surface. In contrast, rictor KO mice displayed significantly reduced head-twitch response (HTR) to the 5-HT2A/C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI), with evidence of impaired 5-HT2A/C receptor signaling. In vitro, pharmacological inhibition of Akt significantly increased 5-HT1A receptor expression and attenuated DOI-induced 5-HT2A receptor signaling, thereby lending credence to the observed in vivo cross-talk between neuronal Akt signaling and 5-HT receptor regulation. These data reveal that defective central Akt function alters 5-HT signaling as well as 5-HT-associated behaviors, demonstrating a novel role for Akt in maintaining neuronal 5-HT receptor function.

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Section: Discussionmentioning

confidence: 99%

Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor function

Saunders

Siuta

Robertson

et al. 2014

Neurochemistry International

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“…For instance, maternal use of tobacco, alcohol, caffeine, and certain psychotropic medication during pregnancy may increase risk of ADHD in offspring [16,30]. Poor maternal nutrition (e.g., obesity, low iron, and fatty acids) [31,32], maternal stress during pregnancy [33], maternal gestational diabetes [34], and exposure to chemicals and heavy metals have also been implicated [16,30]. As only some children with these exposures go on to develop ADHD, it is possible that genes influence sensitivity to at least some adverse prenatal environmental factors.…”

Section: Prenatal Environmentmentioning

confidence: 99%

Preventive Interventions for ADHD: A Neurodevelopmental Perspective

2012

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It is proposed that the time is ripe for the development of secondary preventive interventions for attentiondeficit/hyperactivity disorder (ADHD). By targeting preschool children, a developmental stage during which ADHD symptoms first become evident in most children with the disorder, many of the adverse long-term consequences that typify the trajectory of ADHD may be avoided. A dynamic/ interactive model of the biological and environmental factors that contribute to the emergence and persistence of ADHD throughout the lifespan is proposed. Based on this model, it is argued that environmental influences and physical exercise can be used to enhance neural growth and development, which in turn should have an enduring and long-term impact on the trajectory of ADHD. Central to this notion are 2 hypotheses: 1) environmental influences can facilitate structural and functional brain development, and 2) changes in brain structure and function are directly related to ADHD severity over the course of development and the degree to which the disorder persists or remits with time. We present experimental and correlational data supporting the first hypothesis and longitudinal data in individuals with ADHD supporting the second. The case is made for initiating such an intervention during the preschool years, when the brain is likely to be more "plastic" and perhaps susceptible to lasting modifications, and before complicating factors, such as comorbid psychiatric disorders, academic failure, and poor social and family relationships emerge, making successful treatment more difficult. Finally, we review recent studies in young children with ADHD that might fall under the umbrella of secondary prevention.Keywords ADHD . prevention . environmental enrichment . development . early intervention . preschool.Attention-deficit/hyperactivity disorder (ADHD) is an early emerging neurodevelopmental disorder that persists into adolescence and early adulthood for a substantial portion of afflicted individuals [1]. In addition to the "core symptoms" of inattention, impulsiveness, and hyperactivity that define the disorder, a substantial portion of individuals diagnosed with ADHD present with an array of neurocognitive deficits, psychiatric comorbidities, and social and emotional difficulties [2,3]. As a result of persisting impairments across an array of behavioral domains, long-term outcome for many, if not most, children with ADHD is far from optimal [4].There are several evidence-based pharmacological and psychosocial interventions that are effective for treating the core symptoms and, to a lesser extent, the associated features in youth with ADHD. Both stimulant [5] and nonstimulant [6] medications reduce the severity of core ADHD symptoms, as well as associated oppositional defiant behaviors. Similarly, parent-and school-based behavioral interventions have

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“…1 Attention-deficit/ hyperactivity disorder is a costly health condition rivaling traditional medical diseases in its effect on social, financial, and quality-of-life issues. Clinicians held a conviction in the early and mid-20th century that children with ADHD had minimal brain damage or minimal brain dysfunction.…”

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confidence: 99%

“…Direct studies of epigenetic change in the human brain remain impossible during a person’s lifetime, and it remains unclear to what extent epigenetic effects in the brain will eventually be able to be detected in peripheral tissues. However, studies of epigenetic effects in the placenta can be a powerful tool for understanding influences during fetal development 1 that predict later changes in brain or behavior. Overall, both animal and human studies will be needed to explore the epigenetic consequences of the key exposures associated with ADHD, as well as other mental disorders, and to seek convergence of effects.…”

mentioning

confidence: 99%

Environment, Developmental Origins, and Attention-Deficit/Hyperactivity Disorder

Nigg¹

2012

Arch Pediatr Adolesc Med

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Exposure to Gestational Diabetes Mellitus and Low Socioeconomic Status

Cited by 158 publications

References 59 publications

Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor function

Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor function

Preventive Interventions for ADHD: A Neurodevelopmental Perspective

Environment, Developmental Origins, and Attention-Deficit/Hyperactivity Disorder

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