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1.  Is the Measure the Message: The BSID and Nutritional Interventions 
Pediatrics  2012;129(6):1166-1167.
PMCID: PMC3362912  PMID: 22641756
2.  Long Chain Polyunsaturated Fatty Acid Supplementation in Infancy Reduces Heart Rate and Positively Affects Distribution of Attention 
Pediatric research  2011;70(4):406-410.
A double-blind, randomized, controlled, parallel-group prospective trial was conducted to determine whether a dose-response existed for four different levels of docosahexaenoic acid (DHA) supplementation on the cognitive performance of infants. A total of 122 term infants were fed one of four different formulas varying in their DHA composition (0.00%, 0.32%, 0.64% and 0.96% of total fatty acids as DHA) from birth to 12 months. The three DHA-supplemented formulas also contained 0.64% of total fatty acids as arachidonic acid (ARA, 20:4n-6). Infants were tested at 4, 6, and 9 months of age on a visual habituation protocol that yielded both behavioral and psychophysiological indices of attention. Infants in all DHA+ARA-supplemented conditions had lower heart rates than those in the unsupplemented condition; there was no dose-response for this effect. The distribution of time that infants spent in different phases of attention (a cognitive index derived from the convergence of behavioral and cardiac responses) varied as a function of dosage. Infants supplemented at the two lower DHA doses spent proportionately more time engaged in active stimulus processing than infants fed the unsupplemented formula, while infants fed the highest dose were intermediate and did not differ from any other group.
PMCID: PMC3172991  PMID: 21705959
3.  Cognition 
PMCID: PMC4285386  PMID: 24457567
The current report provides a brief background introducing 30 years of research on LCPUFA and infant development, but focuses mainly on challenges for future studies. Infants fed formulas containing only vegetable fats were found to have lower docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) status than infants fed human milk. Studies soon focused on efforts to improve LCPUFA status and evaluate functions suggested by early primate studies of DHA deficiency. Despite evidence for the importance of these fatty acids for development, particularly DHA, several recent meta-analyses conclude dietary supplementation does not enhance development. Future studies should employ 1) more finely grained measures of brain development as opposed to global measures; and 2) tests that evaluate development later in childhood when children are able to be tested on more complex behaviors (if found effective these would also be evidence of early brain programming). 3) Studies are needed to understand the cause of high variability in transfer of DHA to the fetus. Finally 4) the role of single nucleotide polymorphisms (SNPs) of the fatty acid desaturase genes (FADS1/2) of mother and infant needs study to determine how they affect requirements for these fatty acids by the fetus/infant.
PMCID: PMC4188474  PMID: 24107504
5.  Maternal DHA levels and Toddler Free-Play Attention 
Developmental neuropsychology  2009;34(2):159-174.
We investigated the relationship between maternal docosahexaenoic acid (DHA) levels at birth and toddler free-play attention in the second year. Toddler free-play attention was assessed at 12 and 18 months, and maternal erythrocyte (red-blood cell; RBC) phospholipid DHA (percentage of total fatty acids) was measured from mothers at delivery. Overall, higher maternal DHA status at birth was associated with enhanced attentional functioning during the second year. Toddlers whose mothers had high DHA at birth exhibited more total looking and fewer episodes of inattention during free-play than did toddlers whose mothers had low DHA at birth. Analyses also provided further information on changes in attention during toddlerhood. These findings are consistent with evidence suggesting a link between DHA and cognitive development in infancy and early childhood.
PMCID: PMC3752039  PMID: 19267293
6.  Docosahexaenoic acid and cognitive function: Is the link mediated by the autonomic nervous system? 
Docosahexaenoic acid is a long-chain polyunsaturated fatty acid that is found in large quantity in the brain and which has repeatedly been observed to be related in positive ways to both cognitive function and cardiovascular health. The mechanisms through which docosahexaenoic acid affects cognition are not well understood, but in this article, we propose a hypothesis that integrates the positive effects of docosahexaenoic acid in the cognitive and cardiovascular realms through the autonomic nervous system. The autonomic nervous system is known to regulate vital functions such as heart rate and respiration, and has also been linked to basic cognitive components related to arousal and attention. We review the literature from this perspective, and delineate the predictions generated by the hypothesis. In addition, we provide new data showing a link between docosahexaenoic acid and fetal heart rate that is consistent with the hypothesis.
PMCID: PMC3751406  PMID: 18930644
7.  On the Existence of Constant Accrual Rates in Clinical Trials and Direction for Future Research 
Many clinical trials fall short of their accrual goals. This can be avoided with accurate accrual prediction tools. Past researchers provide important methodological alternative models for predicting accrual in clinical trials. One model allows for slow accrual at the start of the study, which eventually reaches a threshold. A simpler model assumes a constant rate of accrual. A comparison has been attempted but we wish to point out some important considerations when comparing these two models. In fact, we can examine the reasonableness of a constant accrual assumption (simpler model) which had data 239 days into a three-year study. We can now update that and report accumulated from the full three years of accrual data and we can demonstrate that constant accrual rate assumption was met in this particular study. We will use this report to frame future research in the area of accrual prediction.
PMCID: PMC3712523  PMID: 23869201
prior elicitation; exponential; inverse gamma; Bayesian; sample size
8.  Beta-Cell Injury in Ncb5or-null Mice is Exacerbated by Consumption of a High-Fat Diet 
NADH-cytochrome b5 oxidoreductase (Ncb5or) in endoplasmic reticulum (ER) is involved in fatty acid metabolism, and Ncb5or−/− mice fed standard chow (SC) are insulin-sensitive but weigh less than wild type (WT) littermates. Ncb5or−/− mice develop hyperglycemia at about age 7 weeks due to β-cell dysfunction and loss associated with saturated fatty acid accumulation and manifestations of ER and oxidative stress. Here we report that when Ncb5or−/− mice born to heterozygous mothers fed a high fat (HF) diet continue to ingest HF, they weigh as much as SC-fed WT at age 5 weeks. By age 7 weeks, diabetes mellitus develops in all HF-fed vs. 68% of SC-fed Ncb5or−/− mice. Islet β-cell content in age 5-week Ncb5or−/− mice fed HF for 7 days is lower (53%) than for those fed SC (63%), and both are lower than for WT (75%, SC, vs. 69%, HF). Islet transcript levels for markers of mitochondrial biogenesis (PGC-1α) and ER stress (ATF6α) are higher in Ncb5or−/− than WT mice but not significantly affected by diet. Consuming a HF diet exacerbates Ncb5or−/− β-cell accumulation of intracellular saturated fatty acids and increases the frequency of ER distention from 11% (SC) to 47% (HF), thus accelerates β-cell injury in Ncb5or−/− mice.
PMCID: PMC3348618  PMID: 22582025
diabetes; beta-cells; lipotoxicity; high-fat diet; ER stress
Psychoneuroendocrinology  2008;33(9):1279-1292.
Decreased tissue levels of docosahexaenoic acid (DHA; 22:6n-3) are implicated in the etiologies of non-puerperal and postpartum depression. With the aim of determining neurobiological sequelae of decreased brain DHA content, this study examined the effects of a loss of brain DHA content and concurrent reproductive status in adult female Long-Evans rats. An α-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 23–26% lower than virgin and parous rats fed a control diet containing adequate α-linolenic acid. Parous dams were tested/euthanized at weaning (postnatal day 20) of the second litter; virgin females, during diestrus. Decreased brain DHA was associated with decreased hippocampal BDNF gene expression and increased relative corticosterone response to an intense stressor, regardless of reproductive status. In virgin females with decreased brain DHA, serotonin content and turnover in frontal cortex were decreased compared to virgin females with normal brain DHA. In parous dams with decreased brain DHA, the density of 5-HT1A receptors in the hippocampus was increased, corticosterone response to an intense stressor was increased, and the latency to immobility in the forced swim test was decreased compared to parous dams with normal DHA. These findings demonstrate neurobiological alterations attributable to decreased brain DHA or an interaction of parous status and brain DHA level. Furthermore, the data are consistent with findings in depressed humans, and thus support a role for DHA as a factor in the etiologies of depressive illnesses, particularly postpartum depression.
PMCID: PMC2582014  PMID: 18707812
omega-3 polyunsaturated fatty acid; brain-derived neurotrophic factor; serotonin 1A receptor; forced swim; postpartum; corticosterone
10.  Dopamine receptor alterations in female rats with diet-induced decreased brain docosahexaenoic acid (DHA): interactions with reproductive status 
Nutritional Neuroscience  2010;13(4):161-169.
Decreased tissue levels of n-3 (omega-3) fatty acids, particularly docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and postpartum depression. This study examined the effects of a diet-induced loss of brain DHA content and concurrent reproductive status on dopaminergic parameters in adult female Long–Evans rats. An α-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 20–22% lower than those fed a control diet containing adequate α-linolenic acid. Decreased brain DHA produced a significant main effect of decreased density of ventral striatal D2-like receptors. Virgin females with decreased DHA also exhibited higher density of D1-like receptors in the caudate nucleus than virgin females with normal DHA. These receptor alterations are similar to those found in several rodent models of depression, and are consistent with the proposed hypodopaminergic basis for anhedonia and motivational deficits in depression.
PMCID: PMC2955509  PMID: 20670471
omega-3; polyunsaturated fatty acid; dopamine receptor; postpartum; docosahexaenoic acid; rat

Results 1-10 (10)