Chronic maternal depression is associated with reduced weight gain in latino infants from birth to 2 years of age

Background

Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories.

Objectives

To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants.

Methods

We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression.

Results

We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94—0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92).

Conclusions

Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention.     

GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder that affects ~5% of school-aged children; however, the mechanisms underlying ADHD remain largely unclear. Here we report a previously unidentified association between G protein-coupled receptor kinase-interacting protein-1 (GIT1) and ADHD in humans. An intronic single-nucleotide polymorphism in GIT1, the minor allele of which causes reduced GIT1 expression, shows a strong association with ADHD susceptibility in humans. Git1-deficient mice show ADHD-like phenotypes, with traits including hyperactivity, enhanced electroencephalogram theta rhythms and impaired learning and memory. Hyperactivity in Git1(-/-) mice is reversed by amphetamine and methylphenidate, psychostimulants commonly used to treat ADHD. In addition, amphetamine normalizes enhanced theta rhythms and impaired memory. GIT1 deficiency in mice leads to decreases in ras-related C3 botulinum toxin substrate-1 (RAC1) signaling and inhibitory presynaptic input; furthermore, it shifts the neuronal excitation-inhibition balance in postsynaptic neurons toward excitation. Our study identifies a previously unknown involvement of GIT1 in human ADHD and shows that GIT1 deficiency in mice causes psychostimulant-responsive ADHD-like phenotypes.     

Polymorphism in maternal LRP8 gene is associated with fetal growth

Fetal growth restriction (FGR) affects >200,000 pregnancies in the United States annually and is associated with increased perinatal mortality and morbidity, as well as poorer long-term health for infants with FGR compared with infants without FGR. FGR appears to be a complex trait, but the role of genetic factors in the development of FGR is largely unknown. We conducted a candidate-gene association study of birth weight and FGR in two independent study samples obtained at the Boston Medical Center. We first investigated the association between maternal genotypes of 68 single-nucleotide polymorphisms (SNPs) from 41 candidate genes and fetal growth in a sample of 204 black women selected for a previous study of preeclampsia, 92 of whom had preeclampsia (characterized by high blood pressure and the presence of protein in the urine). We found significant association between SNP rs2297660 in the LRP8 gene and birth weight. Subsequently, we replicated the association in a larger independent sample of 1,094 black women; similar association between LRP8 and FGR was observed in this sample. The "A" allele at rs2297660 was associated with a higher standardized birth weight and a lower risk of FGR. Under the additive genetic model, each additional copy of the "A" allele reduced the risk of FGR by 33% (P<.05). In conclusion, results from the two independent samples of black women provide consistent evidence that SNP rs2297660 in LRP8 is associated with fetal growth.     

Lung function is associated with arterial stiffness in children

Background

In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life.

Objective

To determine the relationship between lung function and carotid augmentation index (AIx), a measure of vascular stiffness, in 8-year old children.

Methods

Data on brachial blood pressure, lung function (FEV₁, FVC, FEV₁/FVC, obtained by spirometry) and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry) was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS) exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention) as covariates.

Results

In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = −0.17,b = −6.72, partial R² = .02, p = 0.03), FVC (standardised β = −0.29, b = −9.31, partial R² = 0.04, p<0.001) and FEV1/FVC (standardised β = .13, b = 18.4, partial R² = 0.02, p = 0.04).

Conclusion

Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems.     

Sleep microstructure is not altered in children with attention-deficit/hyperactivity disorder (ADHD)

The high rate of occurrence of sleep disturbances in children with attention-deficit/hyperactivity disorder (ADHD) prompted the idea that structural and neurotransmitter changes might give rise to specific sleep pattern abnormalities. The aim of this study was to evaluate the microstructure of sleep in children with ADHD who had no polysomnographically diagnosed sleep disorder, had never been treated for ADHD, and were free from any psychiatric comorbidity. Participants were 14 patients with ADHD (12 boys and 2 girls aged 7-12 years, mean age 9.6+/-1.6). ADHD was diagnosed according to DSM-IV criteria (Diagnostic and statistical manual of mental disorders). Psychiatric comorbidities were ruled out by detailed psychiatric examination. The patients underwent two consecutive overnight video-polysomnographic (PSG) recordings, with the sleep microstructure (cyclic alternating pattern - CAP) scoring during the second night. The data were compared with age- and sex-matched controls. Sleep microstructure analysis using CAP revealed no significant differences between the ADHD group and the controls in any of the parameters under study. In conclusions, no ADHD-specific alterations were found in the sleep microstructure.     

Human maternal behaviour is associated with arginine vasopressin receptor 1A gene

Parenting is one of the main influences on children's early development, and yet its underlying genetic mechanisms have only recently begun to be explored, with many studies neglecting to control for possible child effects. This study focuses on maternal behaviour and on an allele at the RS3 promoter region of the arginine vasopressin receptor 1A (AVPR1A) gene, previously associated with autism and with higher amygdala activation in a face-matching task. Mothers were observed during a free-play session with each of their 3.5-year-old twins. Multilevel regression analyses revealed that mothers who are carriers of the AVPR1A RS3 allele tend to show less structuring and support throughout the interaction independent of the child's sex and RS3 genotype. This finding advances our understanding of the genetic influences on human maternal behaviour.     

Heart rate variability and methylphenidate in children with ADHD

Although an extensive number of studies support the efficacy and tolerability of stimulants in the treatment of attention deficit/hyperactivity disorder (ADHD), in recent years, increasing concerns have been raised about their cardiovascular safety. We investigated whether a time domain analysis of heart rate variability (HRV) recordings in 24-h ECG under medication with stimulants yielded new information about therapy control in ADHD. We analysed the HRV parameter standard deviation of all normal sinus RR intervals over 24 h (SDNN), percentage of successive normal sinus RR intervals > 50 ms (pNN50) and root-mean-square of the successive normal sinus RR interval difference (rMSSD) from 23 children diagnosed by ADHD (19 boys and 4 girls), aged 10.5 ± 2.2 years, who were consecutively referred to our outpatient clinic for paediatric cardiology. Eleven children received medication with methylphenidate (MPH), while twelve children were initially examined without medication. Of these, eight probands were re-examined after therapy with MPH was established. Controls comprised 19 children (10 boys, 9 girls) from our Holter ECG data base without any cardiac or circulatory disease. Compared to healthy controls, the ADHD children with and without MPH treatment showed significantly higher mean heart rates (ADHD without MPH: 94.3 ± 2.2; ADHD with MPH: 90.5 ± 1.8, controls: 84.7 ± 1.8). pNN50 (ADHD without MPH: 6.5 ± 2.7; ADHD with MPH: 14.2 ± 6.9, controls: 21.5 ± 9.0) and rMSSD (ADHD without MPH: 26.1 ± 4.1; ADHD with MPH: 36.7 ± 8.3, controls: 44.5 ± 10.1) were lowest in ADHD children without MPH, middle in ADHD children with MPH and highest in controls. SDNN values were not significantly different. The hourly analysis shows highly significant reduced pNN50 and rMSSD values in untreated ADHD children between 5:00 pm and 6:00 am while the pattern approaches to levels of controls during MPH treatment. Data of this pilot study indicate a decreased vagal tone with significantly diminished HRV and higher heart rates in unmedicated ADHD children. These parameters of autonomic activation are ameliorated by MPH treatment. No evidence for negative impact of MPH on HRV was detected. Further studies will clarify a potential cardio-protective effect of MPH in ADHD.     

Alkyllysophospholipid influenced melanoma cell morphology is associated with decreased attachment to basement membrane.

The alkyllysophospholipid analog 1-0-octadecyl-2-0-methyl-3-phosphorylcholine (ET-18-OCH3) was examined for possible anti attachment effects on B16-F10 murine melanoma cells in vitro. At sub-lethal lipid concentrations B16-F10 cells were inhibited from attaching to reconstituted basement membrane (Matrigel) during a 45 min assay. This type of inhibition was also imparted by the isoprenoid farnesol but not by egg lysophosphatidylcholine (LPC) at concentrations up to 10 micrograms/ml. Both lipids were toxic to B16-F10 cells in the absence of bovine serum albumin (BSA), BSA (0.1%) completely protected the cells from lysis except when both lipids were combined as a mixture. Light and electron microscopy, as well as electronic sizing of cells, gave evidence of alkyllysophospholipid induced reduction in cell size which correlated well with attachment inhibition. The results suggest that alkyllysophospholipid induced reduction of cell surface area leads to inhibition of cell attachment to basement membrane which 8 with our experimental conditions, was not permanent since cells eventually attach within 24 h after treatment. The enhanced lytic effect the lysophospholipid imparts on the alkyl compound, in conjunction with the anti-attachment properties should be important areas for future research.     

Placental size is associated with mental health in children and adolescents

Background

The role of the placenta in fetal programming has been recognized as a highly significant, yet often neglected area of study. We investigated placental size in relation to psychopathology, in particular attention deficit hyperactivity disorder (ADHD) symptoms, in children at 8 years of age, and later as adolescents at 16 years.

Methodology/Principal Findings

Prospective data were obtained from The Northern Finland Birth Cohort (NFBC) 1986. Placental weight, surface area and birth weight were measured according to standard procedures, within 30 minutes after birth. ADHD symptoms, probable psychiatric disturbance, antisocial disorder and neurotic disorder were assessed at 8 years (n = 8101), and ADHD symptoms were assessed again at 16 years (n = 6607), by teachers and parents respectively. We used logistic regression analyses to investigate the association between placental size and mental health outcomes, and controlled for gestational age, birth weight, socio-demographic factors and medical factors, during gestation. There were significant positive associations between placental size (weight, surface area and placental-to-birth-weight ratio) and mental health problems in boys at 8 and 16 years of age. Increased placental weight was linked with overall probable psychiatric disturbance (at 8y, OR  = 1.14 [95% CI  = 1.04–1.25]), antisocial behavior (at 8 y, OR  = 1.14 [95% CI  = 1.03–1.27]) and ADHD symptoms (inattention-hyperactivity at 16y, OR  = 1.19 [95% CI  = 1.02–1.38]). No significant associations were detected among girls.

Conclusions/Significance

Compensatory placental growth may occur in response to prenatal insults. Such overgrowth may affect fetal development, including brain development, and ultimately contribute to psychopathology.     

Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition

Among other factors, fetal growth requires maternal supply of cholesterol. Cellular cholesterol uptake is mainly mediated by the LDL receptor (LDL-R) and the scavenger receptor family. We hypothesized that expression levels of key receptors of these families were regulated differently in placentas from IUGR pregnancies with varying degrees of severity. Third-trimester placentas from IUGR pregnancies with (IUGR-S) and without (IUGR-M) fetal hemodynamic changes and from control (AGA) pregnancies were studied. LDL-R, LDL-R-related protein (LRP-1), and scavenger receptor class B type I (SR-BI) mRNA and protein levels were measured. Cholesterol concentration and composition of lipoproteins were analyzed enzymatically and by lipid electrophoresis, respectively, in maternal and umbilical cord blood. LDL-R mRNA levels in IUGR-M were similar to AGA but lower (P < 0.05) in IUGR-S. In contrast, LDL-R protein was twofold (IUGR-M) and 1.8-fold (IUGR-S) higher (P < 0.05) than in the AGA group. LRP-1 mRNA and protein levels were not altered in the IUGR cases. SR-BI mRNA was unchanged in IUGR, but protein levels were lower (P < 0.05) in IUGR-S than in the other groups. Maternal plasma concentrations of LDL cholesterol were higher (P < 0.05) in the AGA group (188.5 +/- 23.6 mg/dl) than in the IUGR-S group (154.2 +/- 26.1). Electrophoretic mobility of the LDL fraction in maternal plasma demonstrated significant changes in migration toward higher values (AGA 0.95 +/- 0.06, IUGR-M 1.12 +/- 0.11, P < 0.001; IUGR-S 1.28 +/- 0.20, P = 0.002). We conclude that LDL-R and SR-BI levels are altered in IUGR pregnancies. These differences were associated with changes in LDL, but not HDL, mobility and cholesterol concentration in maternal circulation.     

Physical fatty acid deficiency signs in children with ADHD symptoms

Fatty acid deficiency symptoms (FADS) of dry hair and skin, frequent thirst and urination have been observed to be higher in children with attention deficit hyperactivity disorder (ADHD). Two studies investigated FADS in 7-12-year-old children; Study 1 in a general population (N=347) and Study 2 in children with ADHD symptoms (N=104). Correlations between FADS and ADHD-related symptoms were found at baseline in Study 1 but not Study 2. FADS did not improve after supplementation with omega-3 and omega-6 polyunsaturated fatty acids (PUFA) versus placebo after 15 weeks in Study 2, and were not related to improvements in ADHD symptoms in the PUFA groups. However, FADS did improve in all groups, possibly attributable to the linoleic acid present in both the PUFA and placebo (palm oil) supplements. FADS are not a reliable selection criterion for children with ADHD who might benefit from omega-3 PUFA supplementation.     

Plasmid segregation into minicells is associated with membrane attachment and independent of plasmid replication.

The role of plasmid replication in the segregation of plasmids into Escherichia coli minicells was investigated with temperature-sensitive replication mutants derived from E. coli plasmids ColE1 and pSC101. For as long as six generations of growth, at permissive or nonpermissive temperatures (when greater than 80% of plasmid replication was inhibited), the same amount of previously 3H-labeled plasmid DNA segregated into minicells. Density gradient separations of wild-type and temperature-sensitive plasmid DNA from both replicons segregated into the minicells showed that about 20 to 25% was stably associated with the minicell membrane at both temperatures. Electron microscopy showed this DNA to consist of circular plasmid molecules attached to the minicell membrane. These combined findings suggest that segregation of plasmids into minicells and their association with the minicell membrane are interrelated and independent of plasmid replication.     

Reduced LINE-1 methylation is associated with arsenic-induced genotoxic stress in children

Early life exposure to arsenic has profound effect towards development of arsenic induced toxic outcomes. Some districts in the state of West Bengal, India are highly affected by arsenic, mainly through ground water. In children, not much of the toxic outcomes like dermatological lesions are observed but it is thought that the exposure leads to transient alteration in their biological processes that leads to various deleterious health effects later on. We evaluated the global methylation status by analyzing the LINE-1 methylation profile in children from arsenic exposed region between the age group 5–15 years along with the cytogenetic stress induced by arsenic as measured by lymphocyte micronucleus (MN) frequency. A total of 52 arsenic exposed and 32 unexposed children were analyzed. Whole blood DNA was used to measure the LINE-1 methylation by qRT-MSP. We found a significant association of MN-frequency in exposed individuals with highly depleted LINE-1 methylation compared to the exposed individuals with near baseline (which was comparable to unexposed control) methylation index as well as with those with the hypermethylated LINE-1 promoters. From our results, we interpret that LINE-1 methylation index may serve as a potent global epigenetic mark to detect the degree of arsenic genotoxicity at a very early age. We propose that this may be utilized to determine the extent of toxic influence exerted by arsenic, from a very early age.     

Protopathic stimulant use among children with symptoms of ADHD

The purpose of the current study was to examine protopathic stimulant use among children with the symptoms of ADHD but do not have a diagnosis of ADHD. Protopathic or prodromal stimulant use refers to the use of stimulants by children with the symptoms of ADHD prior to a diagnosis of ADHD. In the current study, we examined children with the symptoms of ADHD who received stimulant treatment across time and with respect to several background variables. Our results indicate that these children who receive stimulant treatment without a diagnosis of ADHD are significantly more like to be eventually diagnosed with ADHD than not. Results also indicate that these children who receive stimulant treatment but do not yet have a diagnosis of ADHD are significantly more likely to have insurance that does not pay for diagnostic procedures. These results are discussed in view of treatment.     

Ethical concerns associated with childhood depression

Children always merit special ethical concern in mental health research and treatment. But children with depression are a particularly vulnerable population because of developmental considerations and the severity of the illness. This article reviews ethical concerns regarding assessment of depression, clinical care, and research with children.     

Genetic variant of AMD1 is associated with obesity in urban Indian children

Background

Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI). We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children.

Methodology/Principal Findings

We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW) and 463 over-weight/obese (OW/OB) children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB) in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [OR = 1.41, P = 1.5×10^-4] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [OR = 1.28, P = 4.2×10^-3] and meta-analysis [OR = 1.35, P = 1.9×10^-6]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis.

Conclusions/Significance

Our study provides first evidence for the association of AMD1 variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken.