The industrial solvent trichloroethylene induces LRRK2 kinase activity and dopaminergic neurodegeneration in a rat model of Parkinson's disease.

Gene-environment interaction is implicated in the majority of idiopathic Parkinson's disease (PD) risk, and some of the most widespread environmental contaminants are selectively toxic to dopaminergic neurons. Pesticides have long been connected to PD incidence, however, it has become increasingly apparent that other industrial byproducts likely influence neurodegeneration. For example, organic solvents, which are used in chemical, machining, and dry-cleaning industries, are of growing concern, as decades of solvent use and their effluence into the environment has contaminated much of the world's groundwater and soil. Like some pesticides, certain organic solvents, such as the chlorinated halocarbon trichloroethylene (TCE), are mitochondrial toxicants, which are collectively implicated in the pathogenesis of dopaminergic neurodegeneration. Recently, we hypothesized a possible gene-environment interaction may occur between environmental mitochondrial toxicants and the protein kinase LRRK2, mutations of which are the most common genetic cause of familial and sporadic PD. In addition, emerging data suggests that elevated wildtype LRRK2 kinase activity also contributes to the pathogenesis of idiopathic PD. To this end, we investigated whether chronic, systemic TCE exposure (200 mg/kg) in aged rats produced wildtype LRRK2 activation and caused nigrostriatal dopaminergic dysfunction. Interestingly, we found that TCE not only induced LRRK2 kinase activity in the brain, but produced a significant dopaminergic lesion in the nigrostriatal tract, elevated oxidative stress, and caused endolysosomal dysfunction and α-synuclein accumulation. Together, these data suggest that TCE-induced LRRK2 kinase activity contributed to the selective toxicity of dopaminergic neurons. We conclude that gene-environment interactions between certain industrial contaminants and LRRK2 likely influence PD risk.

Arabidopsis mRNA decay landscape arises from specialized RNA decay substrates, decapping-mediated feedback, and redundancy.

The decay of mRNA plays a vital role in modulating mRNA abundance, which, in turn, influences cellular and organismal processes. In plants and metazoans, three distinct pathways carry out the decay of most cytoplasmic mRNAs: The mRNA decapping complex, which requires the scaffold protein VARICOSE (VCS), removes a protective 5' cap, allowing for 5' to 3' decay via EXORIBONUCLEASE4 (XRN4, XRN1 in metazoans and yeast), and both the exosome and SUPPRESSOR OF VCS (SOV)/DIS3L2 degrade RNAs in the 3' to 5' direction. However, the unique biological contributions of these three pathways, and whether they degrade specialized sets of transcripts, are unknown. In Arabidopsis, the participation of SOV in RNA homeostasis is also unclear, because Arabidopsis sov mutants have a normal phenotype. We carried out mRNA decay analyses in wild-type, sov, vcs, and vcs sov seedlings, and used a mathematical modeling approach to determine decay rates and quantify gene-specific contributions of VCS and SOV to decay. This analysis revealed that VCS (decapping) contributes to decay of 68% of the transcriptome, and, while it initiates degradation of mRNAs with a wide range of decay rates, it especially contributes to decay of short-lived RNAs. Only a few RNAs were clear SOV substrates in that they decayed more slowly in sov mutants. However, 4,506 RNAs showed VCS-dependent feedback in sov that modulated decay rates, and, by inference, transcription, to maintain RNA abundances, suggesting that these RNAs might also be SOV substrates. This feedback was shown to be independent of siRNA activity.

School-age social behavior and pragmatic language ability in children with prenatal serotonin reuptake inhibitor exposure.

Studies examining associations between fetal serotonin reuptake inhibitor (SRI) exposure and child autism spectrum disorder (ASD) diagnoses or delayed language remain mixed and rarely prospectively follow children or employ gold-standard assessments. We prospectively followed a cohort of mother-child dyads from pregnancy through early elementary school (N = 178), and obtained maternal and alternate-caregiver ratings of behaviors related to ASD (N = 137), as well as direct, gold-standard assessments of child ASD symptoms and pragmatic language among dyads who experienced prenatal depression and either took SRIs or were medication free during pregnancy (N = 44). Prenatal SRI exposure was related to maternal ratings of ASD-related behaviors (ß = 0.24 95% confidence interval; CI [0.07, 0.48]), and, among boys, alternative caregiver ratings (males-only ß = 0.28 95% CI [0.02, 0.55], females-only ß = -0.21 95% CI [-0.63, 0.08]). However, results of our direct assessments suggest an association between SRI exposure and reduced pragmatic language scores (ß = -0.27, 95% CI [-0.53, -0.01], but not ASD (Autism Diagnostic Observation Schedule ß = 0.14 95% CI [-0.15, 0.41]; Social Responsiveness Scale ß = 0.08 95% CI [-0.25, 0.40]). These discrepancies point to issues regarding how ASD is assessed, and the possibility that SRIs may be more strongly associated with language or other broader behaviors that coincide with ASD. Larger prospective studies that incorporate thorough, gold-standard assessments of ASD, language, and other ASD-related behaviors are needed.

Maternal early-life trauma and affective parenting style: the mediating role of HPA-axis function.

A history of childhood trauma is associated with increased risk for psychopathology and interpersonal difficulties in adulthood and, for those who have children, impairments in parenting and increased risk of negative outcomes in offspring. Physiological and behavioral mechanisms are poorly understood. In the current study, maternal history of childhood trauma was hypothesized to predict differences in maternal affect and HPA axis functioning. Mother-infant dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped during a 3-min naturalistic interaction, and their behavior was coded for positive, neutral, and negative affect. Maternal salivary cortisol was measured six times across the study visit, which also included an infant stressor paradigm. Results showed that childhood trauma history predicted increased neutral affect and decreased mean cortisol in the mothers and that cortisol mediated the association between trauma history and maternal affect. Maternal depression was not associated with affective measures or cortisol. Results suggest that early childhood trauma may disrupt the development of the HPA axis, which in turn impairs affective expression during mother-infant interactions in postpartum women. Interventions aimed at treating psychiatric illness in postpartum women may benefit from specific components to assess and treat trauma-related symptoms and prevent secondary effects on parenting.

Social stress and the oxytocin receptor gene interact to predict antisocial behavior in an at-risk cohort.

Polymorphisms in the oxytocin receptor gene are commonly associated with prosocial behaviors in the extant literature, yet their role in antisocial behaviors has rarely been explored, particularly during the transition from adolescence to early adulthood. We examined a prospective cohort (N = 404), collecting youth, mother, and clinician reports of conduct-disordered and antisocial behavior at ages 15 and 20. The oxytocin receptor gene rs53576 polymorphism was hypothesized to interact with social stress to predict antisocial outcomes. Structural equation modeling results revealed a significant main effect at age 15 (p = .025); those with the G allele exhibited higher levels of conduct problems. Structural equation modeling revealed a significant Gene × Environment interaction at age 20 (p = .029); those with the G allele who experienced high social stress exhibited higher levels of antisocial behavior. Heterozygous (AG) grouping models were compared, and parameter estimations supported G dominant groupings. These novel findings suggest that rs53576 polymorphisms may influence social salience and contribute to risk for antisocial outcomes, particularly under conditions of high social stress.

Physiological regulation in infants of women with a mood disorder: examining associations with maternal symptoms and stress.

BACKGROUND: The offspring of mothers with mood disorders may evidence increased behavioral problems as early as preschool; however, no study to date has examined psychophysiological characteristics during infancy, particularly among offspring of mothers diagnosed with bipolar disorder. Elucidating psychobiological mechanisms of risk early in development is critical to inform prevention and early intervention efforts. METHOD: This study compared physiological and behavioral responsivity in 6-month-old infants (N = 329) of mothers with lifetime histories of bipolar disorder (BD, n = 44), major depressive disorder (MDD, n = 244), or no history of Axis I disorders (CTL, n = 41). Infant respiratory sinus arrhythmia (RSA) was measured in a laboratory stressor paradigm. Measures of infant affect and behavior during mother-infant interaction, current maternal depressive symptoms, and exposure to stressful life events were examined with respect to diagnostic group and RSA. RESULTS: Groups did not differ in baseline RSA or infant affect measures. However, during the stressor task, infants of mothers with BD evidenced increases in RSA, while infants of MDD and CTL mothers evidenced decreases in RSA. Though levels of postnatal stress and current levels of maternal depressive symptoms differed among groups, neither of these factors predicted infant psychophysiological responses. CONCLUSIONS: At 6 months of age, infants of mothers with BD show differences in psychophysiological regulation. These differences cannot be accounted for by perinatal outcome, current maternal depressive symptoms, or exposure to stressful life events, and thus may reflect endophenotypic markers of psychopathological risk.

Feeding preferences and the effect of temperature on feeding rates of the graceful kelp crab, Pugettia gracilis.

Graceful kelp crabs (Pugettia gracilis) are abundant consumers in shallow subtidal ecosystems of the Salish Sea. These dynamic habitats are currently experiencing multiple changes including invasion by non-native seaweeds and ocean warming. However, little is known about P. gracilis' foraging ecology, therefore we investigated their feeding preferences between native and invasive food sources, as well as feeding rates at elevated temperatures to better assess their role in changing coastal food webs. To quantify crab feeding preferences, we collected P. gracilis from San Juan Island, WA and conducted no-choice and choice experiments with two food sources: the native kelp, Nereocystis luetkeana, and the invasive seaweed, Sargassum muticum. In no-choice experiments, P. gracilis ate equal amounts of N. luetkeana and S. muticum. However, in choice experiments, P. gracilis preferred N. luetkeana over S. muticum. To test effects of temperature on these feeding rates, we exposed P. gracilis to ambient (11.5 ± 1.3 °C) or elevated (19.5 ± 1.8 °C) temperature treatments and measured consumption of the preferred food type, N. luetkeana. Crabs exposed to elevated temperatures ate significantly more than those in the ambient treatment. Our study demonstrates the diet flexibility of P. gracilis, suggesting they may be able to exploit increasing populations of invasive S. muticum in the Salish Sea. Warming ocean temperatures may also prompt P. gracilis to increase feeding, exacerbating harmful impacts on N. luetkeana, which is already vulnerable to warming and invasive competitors.

Smoking in pregnancy and parenting stress: maternal psychological symptoms and socioeconomic status as potential mediating variables.

INTRODUCTION: The purpose of this study was to examine the impact of smoking in pregnancy on parenting stress. Maternal psychological symptoms and socioeconomic status (SES) were evaluated as potential mediating factors between prenatal cigarette use and later parenting stress. METHOD: The sample included 218 mothers who were recruited at the hospital after birth and completed a 6-month visit with their infants at a university laboratory. Based on the mothers' responses to interviews at the hospital on tobacco use during pregnancy, the sample included 77 nonsmokers and 141 smokers. Information on sociodemographic variables, prenatal care, and other substance use during pregnancy was collected at the hospital interview. At the 6-month visit, the mothers completed measures of parenting stress and psychological symptoms. Cotinine levels were assessed at both timepoints. RESULTS: Regression analysis showed that maternal smoking during pregnancy predicted parenting stress in infancy. Maternal symptoms of psychological distress and SES were evaluated simultaneously to determine whether they functioned as mediating variables between smoking in pregnancy and parenting stress. A multiple mediation analysis (Preacher & Hayes, 2008a) showed that maternal psychological symptoms functioned as a mediating variable but that SES did not. CONCLUSIONS: Results suggest that mothers who smoke in pregnancy are likely to experience higher levels of psychological symptoms, which, in turn, predict higher levels of parenting stress. Smoking in pregnancy may be a marker for symptoms of psychological distress in mothers.

Memory and brain volume in adults prenatally exposed to alcohol.

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.

Verbal and nonverbal memory in adults prenatally exposed to alcohol.

BACKGROUND: Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains. METHODS: In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope. RESULTS: Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. CONCLUSION: These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

Does a continuous measure of handedness predict reading processes and reading-related skills across the lifespan?

The purpose of this research was to investigate the relationship between handedness, reading skills, and reading-related cognitive processes. Although lateralised differences in brain functioning are well known, research regarding handedness, specific reading skills, and reading-related cognitive processes is ambiguous at best because handedness is often measured as a dichotomous variable rather than a continuous variable. This methodological difference contributes to the diverse research findings, therefore the present investigation addressed these methodological limitations. A large normative sample of up to 1383 participants who ranged in age from 4 to 80 completed the Woodcock Johnson Psycho-Educational Battery-Revised (Woodcock & Johnson, 1989a, 1989b) or the Woodcock Johnson Psycho-Educational Battery-Third Edition (Woodcock, McGrew, & Mather, 2001) in combination with the Dean Woodcock Sensory Motor Battery (Dean & Woodcock, 2003) lateral preference scale, a continuous measure of handedness. Polynomial multiple regression analyses indicated curvilinear relationships between handedness and reading skills, along with handedness and auditory working memory. Individuals towards the extremes of the handedness continuum performed less well on the reading-related tasks. Therefore, just knowing a general classification of right, left, or mixed handed will not provide significant knowledge regarding lateralisation or potential cognitive and academic consequences but rather knowledge of an individual's hand preference on a continuum may well be useful for evaluative purposes.

Maternal depression and anxiety effects on the human fetus: Preliminary findings and clinical implications.

Newborns of depressed and anxious mothers show biobehavioral abnormalities suggesting that maternal psychological distress has negative effects on the fetus. Two studies examined the fetuses of depressed and nondepressed mothers: (a) a cross-sectional investigation of fetal activity during the second and third trimesters and (b) an examination of behavioral and heart rate response to vibratory stimulation in late-gestation fetuses. Fetuses of depressed mothers were more active during the fifth, sixth, and seventh gestational months. Assessment of late-term fetuses consisted of a baseline, trials of vibratory stimulation directed towards measuring habituation, and a poststimulation period. During baseline, the fetuses of depressed mothers exhibited a lower heart rate. During stimulation trials, they showed less total movement and appeared to habituate more often. Approximately 35% of the variance in fetal behavior was accounted for by the mothers' depression and anxiety symptoms. Maternal depression may be linked to greater fetal activity during the second and third trimesters and decreased behavioral responsivity during late gestation. The response of late-term fetuses of depressed mothers to vibratory stimulation may reflect "receptor adaptation/effector fatigue" and not true habitation. Future studies should examine the value of clinical interventions provided to the pregnant mother.

The pH-dependent conformational transition of beta-lactoglobulin modulates the binding of protoporphyrin IX.

We have investigated the interaction between PPIX and beta-lactoglobulin (beta-lg) as a function of the pH of the solution. beta-lg is a small globular protein (MW approximately 18 kDa) with a very well characterized structure that reveals several possible binding sites for ligands. The interaction with beta-lg affects the photophysical properties of PPIX. The shift of PPIX emission maximum, excitation maximum and the increase of the fluorescence intensity is an indicator that binding between the porphyrin and beta-lg occurs. The binding constant appears to be modulated by the pH of the solution. Spectroscopic measurements do not reveal any significant energy transfer between the Trp residues of beta-lg and PPIX, however, fluorescence anisotropy decay measurements confirm the binding and the modulation introduced by the pH of the solution. Since beta-lg has been shown to be stable within the range of pH adopted in our experiments (5.0-9.0), the results suggest that PPIX binds a site affected by the pH of the solution. Because of the crystallographic evidence an obvious site is near the aperture of the interior beta-barrel however an alternative (or concurrent) binding site may still be present.

Maternal Prenatal Psychological Distress and Preschool Cognitive Functioning: the Protective Role of Positive Parental Engagement.

Considerable animal research and available human studies suggest that psychological distress experienced by mothers during gestation is associated with later neurodevelopmental deficits in offspring; however, little research has examined potential protective factors that might mitigate this risk. The current study examined the impact of maternal prenatal psychological distress during pregnancy on cognitive outcomes in preschoolers (ages 2.5-5 years) and positive parenting as a potential protective factor. Mother-child dyads (N = 162, mean child age = 44 months, 49 % female) were recruited from a longitudinal cohort of women who had previously participated in a study of maternal mood disorders during pregnancy. Maternal prenatal distress was assessed with multiple measures collected throughout pregnancy. During a follow-up visit, mothers were interviewed about their psychological symptoms since the birth of the child, parenting behaviors were recorded during a parent-child interaction, and children's cognitive abilities were measured using the Differential Ability Scales, 2nd Edition. Maternal prenatal distress significantly predicted lower general cognitive abilities; however, this relationship was strongest for children whose mothers exhibited low levels of positive engagement and not significant when mothers exhibited high levels of positive engagement. Results suggest that positive parental engagement can protect against the detrimental effects of maternal prenatal distress on preschoolers' cognitive abilities.

Clinical predictors and timing of New York Heart Association class improvement with cardiac resynchronization therapy in patients with advanced chronic heart failure: results from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) trials.

BACKGROUND: Based on current patient selection criteria, a significant proportion of recipients of cardiac resynchronization therapy (CRT) do not respond to treatment. The purpose of this analysis is to identify predictors and characterize the timing of response to CRT in patients with advanced heart failure. METHODS: Patients randomized to receive CRT in the MIRACLE and MIRACLE-ICD trials, designed to assess the benefit of CRT compared with standard medical therapy in patients with advanced heart failure, left ventricular ejection fraction <0.35, and QRS > or =130 milliseconds, were included for this analysis. Patients with an improvement of > or =1 New York Heart Association (NYHA) class from baseline to the 6-month follow-up were considered responders and those who had no change or worse NYHA class or died were classified as nonresponders. Responders were subdivided into early (within 1-3 months) and late (6 months). RESULTS: One hundred forty-three (64%) of 224 and 190 (61%) of 313 patients in the MIRACLE and MIRACLE-ICD trials, respectively, responded to therapy, with 81 (57%) of 143 and 100 (53%) of 190 responding early. Several but differing factors predicted CRT response and timing in the two trials with a high sensitivity (89%-90%) but, owing to a low specificity (31%-49%), a modest predictive accuracy (66%-75%). CONCLUSIONS: Based on improvement of > or =1 NYHA class, less than two thirds of patients enrolled in the MIRACLE or MIRACLE-ICD trials responded to CRT, with just more than half responding within the first month. Several factors predicted CRT response and timing, but given their modest predictive accuracy, comparable for both studies, additional methods for selecting candidates most likely to benefit from CRT are needed.

Preschool outcomes following prenatal serotonin reuptake inhibitor exposure: differences in language and behavior, but not cognitive function.

OBJECTIVE: To test the hypothesis that prenatal exposure to serotonin reuptake inhibitors (SRIs) is associated with language and behavioral outcomes in preschool-aged children, while accounting for confounds such as concomitant exposures and maternal mental illness. METHOD: An observational, prospective, longitudinal study of mental illness in pregnancy was conducted at a university-based women's mental health clinic (April 2010-November 2012). A sample of 178 mother-child dyads participated in a laboratory visit at preschool age (2.5-5.5 years). The majority of women (87%) received psychotropic medication during pregnancy. Psychiatric status (based on DSM-IV), other medication use, and substance use were serially assessed and tested as confounds. Primary outcome measures included standardized measures of expressive language and cognitive function and mother and alternate caregiver ratings of child behavior problems, including the Pervasive Developmental Disorders (PDD) subscale of the Child Behavior Checklist. RESULTS: Linear regression analyses revealed that, after controlling for relevant covariates, expressive language scores from the Test of Early Language Development, 3rd edition, were negatively associated with prenatal SRI exposure (ß = -0.15, t = -2.41), while the PDD behavioral problems subscales completed by alternate caregivers and mothers were positively associated with prenatal SRI exposure (ß = 0.17, t = 2.01; ß = 0.16, t = 2.00, respectively). Cognitive function, measured using the Differential Ability Scales, 2nd edition, was not associated with any medication exposures. CONCLUSIONS: The current data suggest a small but significant association between prenatal SRI exposure and preschool outcomes, including expressive language and behavior problems. These data corroborate data from recent, population-based studies, although overall, published findings are mixed. Replication and identification of moderating risk factors are needed to understand potential clinical implications.

Decreased sleep duration is associated with increased fMRI responses to emotional faces in children.

In adults and children, sleep loss is associated with affective dysregulation and increased responsivity to negative stimuli. Adult functional neuroimaging (fMRI) studies have demonstrated associations between restricted sleep and neural alterations in the amygdala and reward circuitry when viewing emotional picture and face stimuli. Despite this, few studies have examined the associations between short sleep duration and emotional responsivity in typically developing children, and no studies have investigated this relationship using fMRI. The current study examined the relationship between sleep duration and fMRI activation to emotional facial expressions in 15 male children (ages 7-11 years). During fMRI scanning, subjects viewed and made perceptual judgments regarding negative, neutral, and positive emotional faces. Maternal reported child sleep duration was negatively associated with (a) activation in the bilateral amygdala, left insula, and left temporal pole activation when viewing negative (i.e., fearful, disgust) vs. neutral faces, (b) right orbitofrontal and bilateral prefrontal activation when viewing disgust vs. neutral faces, and (c) bilateral orbitofrontal, right anterior cingulate, and left amygdala activation when viewing happy vs. neutral faces. Consistent with our prediction, we also noted that emotion-dependent functional connectivity between the bilateral amygdala and prefrontal cortex, cingulate, fusiform, and occipital cortex was positively associated with sleep duration. Paralleling similar studies in adults, these findings collectively suggest that decreased sleep duration in school-aged children may contribute to enhanced reactivity of brain regions involved in emotion and reward processing, as well as decreased emotion-dependent functional connectivity between the amygdala and brain regions associated with emotion regulation.

Prospective associations between chronic youth sleep problems and young adult health.

OBJECTIVES: The current study investigated prospective associations between youth sleep problems across childhood and adolescence, as well as the relationship between chronic youth sleep problems and young adult health. Exploratory analyses investigated this sleep-health relationship in the context of several established risk factors, including youth depression and environmental stress. DESIGN: This project is an extension of the Mater-University Study of Pregnancy, a longitudinal study that followed more than 7000 children across early development. SETTING: Brisbane, Australia. PARTICIPANTS: Seven hundred ten mother-child dyads assessed from birth to age 20. MEASUREMENTS: We used maternal report measures to assess the persistence of youth sleep problems. We used structural equation modeling to explore the relationship between chronic maternal-reported youth sleep problems and subjective reports of young adult health quality and to assess whether associations remained when other potential health risks were included in the model. RESULTS: Path analyses revealed that sleep problems in early childhood predicted sleep problems in middle adolescence, which predicted sleep problems at age 20. Structural equation models showed that chronic youth sleep problems predicted youth health quality at age 20 (ß = .263, P < .001) over and above the effects of early adversity, chronic childhood illness, maternal depression, lifetime youth depression, and chronic youth stress. CONCLUSIONS: Chronic sleep problems can emerge in childhood and may contribute to negative health outcomes in young adulthood. Chronic youth sleep problems remain a significant predictor of poor health when tested against other known health risk factors, suggesting that sleep may be an important health intervention target.

Coronary sinus lead placement via the internal jugular vein in patients with advanced heart failure: a simplified percutaneous approach.

BACKGROUND: Placement of coronary sinus (CS) leads is usually achieved via the left cephalic-axillary-subclavian (CAS) venous system. In some cases, however, such as lack of venous access a right side approach is required. Cannulation of the CS via the right CAS vein is often technically difficult, leaving the right IJ vein as a suitable alternative. OBJECTIVE: The feasibility of IJ vein as a conduit for transvenous left ventricular (LV) pacing in patients with heart failure (HF) has not been reported. METHODS AND RESULTS: Between July 2002 and April 2004, we implanted 339 biventricular devices in patients with moderate-to-severe HF. In 15 patients with similar clinical characteristics, in whom the left CAS vein could not be used, the CS leads were placed via the right CAS venous system (n = 5) or the IJ vein (n = 10). The ten patients (6 men and 4 women; age 66 +/- 15 years; LV ejection fraction .19 +/- .07; QRS duration 183 +/- 35 ms) who required IJ CS lead placement had no procedure related complications and all retained appropriate LV pacing and showed significant improvement in HF symptoms after a median follow-up of 12 months (6 to 22 months). CONCLUSIONS: Thus, in patients with HF for whom the traditional CAS venous approach cannot be used (left side) or is technically difficult (right side), CS leads can be deployed safely via the right IJ vein. In these situations, it seems appropriate to consider this approach prior to the more invasive epicardial approaches.

Prenatal antipsychotic exposure and neuromotor performance during infancy.

CONTEXT: Despite the expanding clinical utility of antipsychotics beyond psychotic disorders to include depressive, bipolar, and anxiety disorders, reproductive safety data regarding the neurodevelopmental sequelae of fetal antipsychotic exposure are scarce. OBJECTIVE: To examine whether intrauterine antipsychotic exposure is associated with deficits in neuromotor performance and habituation in 6-month-old infants. DESIGN, SETTING, AND PARTICIPANTS: A prospective controlled study was conducted from December 1999 through June 2008 at the Infant Development Laboratory of the Emory Psychological Center examining maternal-infant dyads (N=309) at 6 months postpartum with pregnancy exposure to antipsychotics (n=22), antidepressants (n=202), or no psychotropic agents (n=85). Examiners masked to maternal-infant exposure status administered a standardized neuromotor examination (Infant Neurological International Battery [INFANIB]) that tests posture, tone, reflexes, and motor skills and a visual habituation paradigm using a neutral female face. MAIN OUTCOME MEASURES: The INFANIB composite score; number of trials required to achieve a 50% decrease in infant fixation during a visual habituation task; and mean time looking at the stimulus across 10 trials. RESULTS: Infants prenatally exposed to antipsychotics (mean=64.71) showed significantly lower INFANIB scores than those with antidepressant (mean=68.57) or no psychotropic (mean=71.19) exposure, after controlling for significant covariates (F(2,281)=4.51; P=.01; partial η(2)=0.033). The INFANIB scores were also significantly associated with maternal psychiatric history, including depression, psychosis, and overall severity/chronicity (P's.05) and maternal depression during pregnancy was associated with less efficient habituation (r(245)=0.16; P.02). There were no significant differences regarding habituation between medication exposure groups. CONCLUSIONS: Among 6-month-old infants, a history of intrauterine antipsychotic exposure, compared with antidepressant or no psychotropic exposure, was associated with significantly lower scores on a standard test of neuromotor performance, highlighting the need for further scrutiny of the reproductive safety and neurodevelopmental sequelae of fetal antipsychotic exposure. Disentangling medication effects from maternal illness effects, which also contributed, remains a critical challenge.