Developmental Windows for Effects of Choline and Folate on Excitatory and Inhibitory Neurotransmission During Human Gestation.

Choline and folate are critical nutrients for fetal brain development, but the timing of their influence during gestation has not been previously characterized. At different periods during gestation, choline stimulation of α7-nicotinic receptors facilitates conversion of γ-aminobutyric acid (GABA) receptors from excitatory to inhibitory and recruitment of GluR1-R2 receptors for faster excitatory responses to glutamate. The outcome of the fetal development of inhibition and excitation was assessed in 159 newborns by P50 cerebral auditory-evoked responses.

Maternal Plasma Choline during Gestation and Small for Gestational Age Infants.

Objective: Small for gestational age (SGA) infants are at increased risk for neonatal morbidity and developmental problems in childhood. No current interventions during human pregnancy address this problem. This study investigated the possible relationship between maternal choline concentration during pregnancy and SGA infants.

Maternal corticosteroids and depression during gestation and decreased fetal heart rate variability.

Objective: Maternal depression during gestation is an adverse factor in fetal brain development that manifests in later childhood behavioral problems. Fetal heart rate variability (FHRV) mediated by parasympathetic input is a marker of gestational nervous system development. Biological mediators of adverse effects of maternal depression may involve the mother's corticosteroids; however, links between depression, corticosteroids, and early nervous system development remain inconclusive.

Maternal prenatal choline and inflammation effects on 4-year-olds' performance on the Wechsler Preschool and Primary Scale of Intelligence-IV.

Maternal gestational inflammation from infection, obesity, depression, and adverse childhood experiences negatively affects offspring cognitive development. Choline is a key nutrient in fetal brain development. We investigated whether higher maternal plasma choline concentrations have a positive association with offspring cognition, specifically processing speed, in the presence of inflammation.

Maternal nutrients and effects of gestational COVID-19 infection on fetal brain development.

Background & Aims: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders.

Targeting Treatments to Health Disparities.

These initial data suggest that with prenatal vitamins and choline supplements, we might decrease one risk factor associated with poorer health outcomes disproportionally affecting Black families, ie, preterm birth. Dissemination of this research fulfills the principle of Justice in the Belmont Report, to ensure that participants from different racial, ethnic and socioeconomic groups receive benefits from research directed to their specific problems.

Choline, folic acid, Vitamin D, and fetal brain development in the psychosis spectrum.

Choline, folic acid, and Vitamin D are essential for fetal brain development that may be the first steps in the pathogenesis of the psychotic spectrum. Micronutrient deficiencies have been associated with changes in fetal brain development, manifest as early problems in childhood behavior, and cognition, and later as increased incidence of psychotic and autism spectrum disorders. Micronutrient supplements may not only prevent deficiency, but they may also positively affect brain development in the context of other maternal risk factors, including maternal infection, stress, inflammation, and substance abuse.

Prenatal choline, cannabis, and infection, and their association with offspring development of attention and social problems through 4 years of age.

Background: Prenatal choline is a key nutrient, like folic acid and vitamin D, for fetal brain development and subsequent mental function. We sought to determine whether effects of higher maternal plasma choline concentrations on childhood attention and social problems, found in an initial clinical trial of choline supplementation, are observed in a second cohort.

Methods: Of 183 mothers enrolled from an urban safety net hospital clinic, 162 complied with gestational assessments and brought their newborns for study at 1 month of age; 83 continued assessments through 4 years of age.

Black American Maternal Prenatal Choline, Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness.

Black Americans have increased risk for schizophrenia and other mental illnesses with prenatal origins. Prenatal choline promotes infant brain development and behavioral outcomes, but choline has not been specifically assessed in Black Americans. Pregnant women (N = 183, N = 25 Black Americans) enrolled in a study of prenatal stressors and interactions with prenatal choline.

Maternal Prenatal Depression in Pregnancies With Female and Male Fetuses and Developmental Associations With C-reactive Protein and Cortisol.

Background: Prenatal depression has lasting effects on development in offspring, including later mental illness risk. Maternal responses to depression include inflammation and hypothalamic-pituitary-adrenal axis stimulation. Effects on development of cerebral inhibitory neurocircuits may differ for female and male fetuses.

Prospects for improving future mental health of children through prenatal maternal micronutrient supplementation in China.

Prenatal micronutrients in pregnant women's diets, including supplements, have an essential role in fetal brain development and may reduce the risk of mental disorders in offspring. Folic acid, vitamin D, omega-3 fatty acids, and choline have been investigated for this purpose. Folic acid supplementation throughout pregnancy has well-established positive effects.

Maternal choline and respiratory coronavirus effects on fetal brain development.

Prenatal COVID-19 infection is anticipated by the U.S. Centers for Disease Control to affect fetal development similarly to other common respiratory coronaviruses through effects of the maternal inflammatory response on the fetus and placenta.

P50 inhibitory sensory gating in schizophrenia: analysis of recent studies.

Introduction: Inhibitory sensory gating of the P50 cerebral evoked potential to paired auditory stimuli (S1, S2) is a widely used paradigm for the study of schizophrenia and related conditions. Its use to measure genetic, treatment, and developmental effects requires a metric with more stable properties than the simple ratio of the paired responses.

Methods: This study assessed the ratio P50μV/P50μV and P50μV co-varied for P50μV in all 27 independent published studies that compared schizophrenia patients with healthy controls from 2000 to 2019.

Double blind, two dose, randomized, placebo-controlled, cross-over clinical trial of the positive allosteric modulator at the alpha7 nicotinic cholinergic receptor AVL-3288 in schizophrenia patients.

Despite their theoretical rationale, nicotinic alpha-7 acetylcholine (nα) receptor agonists, have largely failed to demonstrate efficacy in placebo-controlled trials in schizophrenia. AVL-3288 is a nα positive allosteric modulator (PAM), which is only active in the presence of the endogenous ligand (acetylcholine), and thus theoretically less likely to cause receptor desensitization. We evaluated the efficacy of AVL-3288 in a Phase 1b, randomized, double-blind, placebo-controlled, triple cross-over study.

Male fetus susceptibility to maternal inflammation: C-reactive protein and brain development.

Background: Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown.

Methods: Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline.

A VNTR Regulates miR-137 Expression Through Novel Alternative Splicing and Contributes to Risk for Schizophrenia.

The MIR137HG gene encoding microRNA-137 (miR-137) is genome-wide associated with schizophrenia (SZ), however, the underlying molecular mechanisms remain unknown. Through cloning and sequencing of individual transcripts from fetal and adult human brain tissues we describe novel pri-miR-137 splice variants which exclude the mature miR-137 sequence termed 'del-miR-137' that would function to down-regulate miR-137 expression. Sequencing results demonstrate a significant positive association between del-miR-137 transcripts and the length of a proximal variable number tandem repeat (VNTR) element.

Interaction of maternal choline levels and prenatal Marijuana's effects on the offspring.

Background: This study investigated whether higher maternal choline levels mitigate effects of marijuana on fetal brain development. Choline transported into the amniotic fluid from the mother activates α7-nicotinic acetylcholine receptors on fetal cerebro-cortical inhibitory neurons, whose development is impeded by cannabis blockade of their cannabinoid-1(CB1) receptors.

Methods: Marijuana use was assessed during pregnancy from women who later brought their newborns for study.

Transcription of PIK3CD in human brain and schizophrenia: regulation by proinflammatory cytokines.

PIK3CD encodes the phosphoinositide 3-kinase (PI3K) catalytic subunit, p110δ, a lipid kinase linked to neurodevelopmental disorders, including schizophrenia (SZ). PIK3CD is regulated at the transcript level through alternate use of 5' untranslated exons (UTRs), promoters, and proinflammatory cytokines. Increases in global PIK3CD expression and downregulation by neuroleptics are observed in SZ, and preclinical efficacy of a p110δ-selective inhibitor is seen in rodent models of risk.