Do Maternal Folate and Homocysteine Levels Play a Role in Neurodevelopmental Processes That Increase Risk for Schizophrenia?

Picker, Jonathan; Coyle, Joseph T.

doi:10.1080/10673220500243372

Cited by 65 publications

(42 citation statements)

References 113 publications

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“…Patients diagnosed with Scz had significantly lower plasma folate concentrations after adjustment for homocysteine (Hcy) levels, and elevated red blood cell folate levels compared to controls. In a recent review of the literature, Picker and Coyle (2005) find substantial support for the hypothesis that maternal low folate and high homocysteine levels increase risk for developing Scz.…”

Section: Ntdmentioning

confidence: 91%

Genetic liability to schizophrenia in Oceanic Palau: a search in the affected and maternal generation

et al. 2007

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While liability to schizophrenia (Scz) is due to genetic and environmental factors, specific factors are largely unknown. We postulate a two-hit model for Scz, in which initial liability is generated during fetal brain development: this "hit" is precipitated by environmental stressors biologically interacting with maternal genetic vulnerability to the stress. Additional liability to Scz is generated by individual genetic vulnerability. To evaluate these putative levels of vulnerability, we search in the genome of both affected individuals and their mothers for variation that differs, statistically, from that in the general population. For parental analyses, mothers were treated as "affected," rather than their offspring, and the fathers were treated as "controls". We used a sample from the Palauan population: 175 individuals diagnosed with Scz, broadly defined; 87 mothers and 45 fathers of affected individuals. Pedigree and diagnostic data were available on 2,953 living and deceased subjects. DNA from 553 individuals was genotyped for short tandem repeats (STR) spaced approximately every 10 cM across the genome. We tested for association between affection status and STR alleles; such an approach was reasonable, despite the widely spaced markers, because this population has far-ranging linkage disequilibrium (LD). Results for the truly affected individuals were modest, whereas results from the maternal generation were promising. For a recessive model and a test for excess allele matching across mothers, significant findings occurred for D20S481, D10S1221, D6S1021, D13S317, and D18S976. Regions in which at least two adjacent markers produced substantial association statistics include 2p12-11.2, 2q24.1-32.1, 6q12-14.1, 10q23.2-24.21, 12q23.2-24.21 and 17q23.2-23.3.

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Section: Ntdmentioning

confidence: 91%

Genetic liability to schizophrenia in Oceanic Palau: a search in the affected and maternal generation

et al. 2007

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“…5,6 It is possible that maternal folate levels influence risk of schizophrenia in offspring, and genotypes in pathways related to folate or homocysteine metabolism may modify such influences. 8,9 However, there may be an additional mechanism. Prenatal folate deficiency may lead to vulnerability to de novo mutation, either germline or somatic in the developing fetus.…”

Section: Famine and Schizophreniamentioning

confidence: 96%

Maternal Famine, De Novo Mutations, and Schizophrenia

McClellan¹,

Süsser²,

King³

2006

JAMA

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“…Vitamin B12 and folate are important cofactors involved in homocysteine metabolism (Girelli et al, 1998). The high serum or plasma levels of total homocysteine (tHcy) has been received considerable interest because it has been associated with high risk for renal disease, neurodevelopmental processes and cardiovascular disease (Anderson et al, 2004;Fowler, 2005;Picker and Coyle, 2005;Verhoef and de Groot, 2005). Therefore, the effect of chronic hyperhomocysteine may hamper to the health of both young and adults population, supporting the idea that early detection of vitamins deficiencies with specific vitamin supplementation offers the opportunity to prevent most of these inadvertent complications (Graham and O'Callaghan, 2000;Minet et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Folate, vitamin B12 and total homocysteine levels in neonates from Brazil

Couto

Moreira²,

Santos

et al. 2006

Eur J Clin Nutr

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Objective: To determine folates, vitamin B12 and total homocysteine levels among neonates from mothers of low or high socioeconomic status. Design: We carried out a cross-sectional transversal study comprising 143 neonates from two maternity hospitals in the city of Salvador, Northeast of Brazil. Cord blood samples were obtained at the time of delivery from newborns from low (group 1, n ¼ 77) or high (group 2, n ¼ 66) socioeconomic status. The vitamin B12 and folates were analyzed by electrochemiluminescence immunoassay and by a competitive test using a natural folate-binding protein (FBP), respectively. Total homocyteine levels were measured by fluorescence polarization immunoassay. Maternal environmental risk factors for pregnancy complications were obtained from all mothers. Results: Only 2% of women from group 1 received prenatal care/vitamin supplementation, whereas almost all mothers from group 2 (96%) were properly followed. Anemia and/or infections pre-or during pregnancy was more prevalent among mothers of babies from group 1. Folate levels among newborns from group 1 and 2 were 7.3872.71 and 8.8374.06 ng/ml, respectively. No difference in the vitamin B12 levels was determined between groups. In addition, tHcy serum levels were higher among newborns from group 1 compared to those from group 2 (8.5474.06 vs 6.3571.33 mmol/l, respectively; P ¼ 0.005).Conclusion: These results demonstrate that unprivileged young woman has limited accesses to prenatal care, present high-risk factors that hamper both maternal and newborn health. Maternal and newborn health status could be improved by simply reinforcing the use of folate-enriched diet. The work presented illustrates the challenges that developing countries have to face in order to provide preventive adequate health care to the population at large.

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Do Maternal Folate and Homocysteine Levels Play a Role in Neurodevelopmental Processes That Increase Risk for Schizophrenia?

Cited by 65 publications

References 113 publications

Genetic liability to schizophrenia in Oceanic Palau: a search in the affected and maternal generation

Genetic liability to schizophrenia in Oceanic Palau: a search in the affected and maternal generation

Maternal Famine, De Novo Mutations, and Schizophrenia

Folate, vitamin B12 and total homocysteine levels in neonates from Brazil

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