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Research suggests that genetic variants linked to hypothalamic-pituitary-adrenal (HPA)-axis functioning moderate the association between environmental stressors and depression, but examining gene–environment interactions with single polymorphisms limits power. The current study used a multilocus genetic profile score (MGPS) approach to measuring HPA-axis–related genetic variation and examined interactions with acute stress, chronic stress, and childhood adversity (assessed using contextual threat interview methods) with depressive symptoms as outcomes in an adolescent sample (ages 14–17, N = 241; White subsample n = 192). Additive MGPSs were calculated using 10 single nucleotide polymorphisms within HPA-axis genes (CRHR1, NR3C2, NR3C1, FKBP5). Higher MGPS directly correlated with adolescent depressive symptoms. Moreover, MGPS predicted stronger associations between acute and chronic stress and adolescent depressive symptoms and also moderated the effect of interpersonal, but not noninterpersonal, childhood adversity. Gene–environment interactions individually accounted for 5%–8% of depressive symptom variation. All results were retained following multiple test correction and stratification by race. Results suggest that using MGPSs provides substantial power to examine gene–environmental interactions linked to affective outcomes among adolescents.
Childhood adversity (CA) is known to predict sensitization to proximal stressors. Researchers have suggested that disruptions in hypothalamus–pituitary–adrenal axis functioning may be a biological mechanism. If so, CA may predict altered associations between proximal life stress and markers of cortisol secretion. We examined whether CA moderates associations between recent episodic stress and (a) the cortisol awakening response (CAR), and (b) depressive symptoms, in 241 adolescents aged 14–17 years (cortisol n = 196). Salivary cortisol was sampled at 0, 30, and 60 min postawakening for 2 days. The CAR was calculated as the area under the curve with respect to increase and waking cortisol. CA and episodic stress were assessed using contextual-threat-method-coded objective interviews. CA significantly interacted with episodic stress to predict both the CAR and depression. Among those with low CA, episodic stress predicted increased CAR but did not predict depression. For adolescents with high CA, episodic stress predicted lower CAR and higher depression. These interactions were found only for independent (uncontrollable, fateful) events, and not for dependent (self-generated) stress. Increased allostatic load resulting from CA exposure may interfere with adolescents' ability to optimally regulate their CAR in relation to recent stress, contributing to increased depression risk.
The Caltech imaging γ-ray telescope was launched by balloon from Alice Springs, NT, Australia and performed observations of the galactic center during the period 12.62 to 13.00 April 1988 UT. The first coded-aperture images of the galactic center region at energies above 30 keV show a single strong γ-ray source which is located 0.7±0.1° from the galactic nucleus and is tentatively identified as 1E1740.7-2942. If the source is at the distance of the galactic center, it is one of the most luminous objects in the galaxy at energies from 35 to 200 keV.
Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR) and examined contributory roles of chronic stress and family discord. Three hundred eighty-one youth participated at ages 15 and 20. The results indicated that 5-HTTLPR moderated the association between age 15 romantic involvement and age 20 depressive symptoms, with strongest effects for short homozygotes. Conditional process analysis revealed that chronic stress functioned as a moderated mediator of this association, fully accounting for the romantic involvement–depression link among short/short genotypes. Also, romantic involvement predicted later depressive symptoms most strongly among short-allele carriers with high family discord. The results have important implications for understanding the romantic involvement–depression link and the behavioral and emotional correlates of the 5-HTTLPR genotype.
Previous research supports gene–environment interactions for polymorphisms in the corticotropin hormone receptor 1 gene (CRHR1) and the serotonin transporter gene linked polymorphic region (5-HTTLPR) in predicting depression, but it has rarely considered genetic influences on stress sensitization processes, whereby early adversities (EA) increase depressive reactivity to proximal stressors later in life. The current study tested a gene–environment–environment interaction (G × E × E; specifically, gene–EA–proximal stress interaction) model of depression in a 20-year longitudinal study. Participants were assessed prospectively for EA up to age 5 and recent chronic stress and depressive symptoms at age 20 and genotyped for CRHR1 single nucleotide polymorphism rs110402 and 5-HTTLPR. EA predicted stronger associations between recent chronic stress and depression, and the effect was moderated by genes. CRHR1 A alleles and 5-HTTLPR short alleles were associated with greater stress sensitization (i.e., greater depressive reactivity to chronic stress for those also exposed to high levels of EA). The results are consistent with the notion that EA exposure results in neurobiological and cognitive–emotional consequences (e.g., altered hypothalamic–pituitary–adrenal axis functioning), leading to emotional distress in the face of recent stressors among those with certain genetic characteristics, although further research is needed to explore explanatory mechanisms.
Protein deficiency impairs local and systemic immune responses to Heligmosomoides bakeri infection but little is known about their individual and interactive impacts on tissue architecture of maternal lymphoid (thymus, spleen) and visceral (small intestine, kidney, liver, pancreas) organs during the demanding period of lactation. Using a 2×2 factorial design, pregnant CD1 mice were fed a 24% protein sufficient (PS) or a 6% protein deficient (PD) isoenergetic diet beginning on day 14 of pregnancy and were infected with 100 H. bakeri larvae four times or exposed to four sham infections. On day 20 of lactation, maternal organs were examined histologically and serum analytes were assayed as indicators of organ function. The absence of villus atrophy in response to infection was associated with increased crypt depth and infiltration of mast cells and eosinophils but only in lactating dams fed adequate protein. Infection-induced lobular liver inflammation was reduced in PD dams, however, abnormalities in the kidney caused by protein deficiency were absent in infected dams. Bilirubin and creatinine were highest in PD infected mice. Infection-induced splenomegaly was not due to an increase in the lymphoid compartment of the spleen. During lactation, infection and protein deficiency have interactive effects on extra-intestinal pathologies.
We describe the current, 9-spacecraft Interplanetary Network (IPN). The IPN detects about
325 gamma-ray bursts per year, of which about 100 are not localized by any other missions.
We give some examples of how the data, which are public, can be utilized.
Numerous studies have supported an association between maternal depression and child psychiatric outcomes, but few have controlled for the confounding effects of both maternal and offspring co-morbidity. Thus, it remains unclear whether the correspondence between maternal and offspring depressive and anxiety disorders is better explained by associations between shared features of maternal and offspring internalizing disorders or by specific effects exerted by unique aspects of individual disorders.
Pairs of mothers and offspring overselected for maternal depression (n = 815) were assessed at offspring age 15 years for anxiety and depressive disorders; 705 completed a follow-up at offspring age 20 years. For both mothers and offspring, structural equation modeling was used to distinguish transdiagnostic internalizing pathology – representing the overlap among all depressive and anxiety disorders – from diagnosis-specific forms of pathology. To discriminate between general versus specific pathways of intergenerational transmission of psychopathology, we examined (a) the general association between the maternal and offspring internalizing factors and (b) the correlations between maternal and offspring diagnosis-specific pathology for each disorder.
For mothers and offspring, a unidimensional latent variable model provided the best fit to the correlations among depressive and anxiety disorders. The maternal transdiagnostic internalizing factor strongly predicted the corresponding factor among offspring. In addition, the unique component of post-traumatic stress disorder among offspring was significantly related to the analogous unique component among mothers, but specific components of other maternal disorders, including depression, did not predict corresponding offspring pathology.
Results suggest that intergenerational transmission of internalizing disorders is largely non-specific.
The etiology of postconcussive symptoms is not clearly understood. Development of etiological models of those symptoms will be helpful for accurate diagnosis and for planning effective treatment. Such a model should characterize the role of subject characteristics (education, premorbid intelligence), social psychological factors and symptom validity. Toward that end, the present study examined the association of postconcussive complaints and cognitive performance with symptom attribution and level of effort on testing. In a sample of 155 veterans, attribution to concussion was associated with endorsement of more severe postconcussive complaints, after controlling for the effects of other factors such as subject characteristics. Similarly, effort was associated with cognitive performance after controlling for the effects of these other factors. The present findings are consistent with previous reports that illness perception and effort on testing are associated with postconcussive complaints. This supports previous recommendations to routinely educate all concussion patients immediately after injury to reduce distorted perceptions and related persistent complaints. Finally, these findings highlight a need for routine assessment of patients’ perception of their injury to identify cases that may require psychotherapy to address any misattributions that develop. (JINS, 2013, 19, 1–8)
We present simulation results of the effect of nanoscopic and micron-sized fillers on the structure, dynamics and mechanical properties of polymer melts and blends. At the smallest length scales, we use molecular dynamics simulations to study the effect of a single nano-filler on the structure and dynamics of the surrounding melt. We find a tendency for polymer chains to be elongated and flattened near the filler surface. Additionally, the simulations show that the dynamics of the polymers can be dramatically altered by the choice of polymer-filler interactions. We use time-dependent Ginzburg-Landau simulations to model the mesoscale phase-separation of an ultra-thin blend film in the presence of an immobilized filler particle. These simulations show the influence of filler particles on the mesoscale blend structure when one component of the blend preferentially wets the filler. Finally, we present some preliminary finite element calculations used to predict the effect of mesoscale structure on macroscopic ultrathin film mechanical properties.
Symptoms of anxiety and depression are common in older people, but the relative importance of factors operating in early and later life in influencing risk is unclear, particularly in the case of anxiety.
We used data from five cohorts in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme: the Aberdeen Birth Cohort 1936, the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study and the Lothian Birth Cohort 1921. We used logistic regression to examine the relationship between factors from early and later life and risk of anxiety or depression, defined as scores of 8 or more on the subscales of the Hospital Anxiety and Depression Scale, and meta-analysis to obtain an overall estimate of the effect of each.
Greater neuroticism, poorer cognitive or physical function, greater disability and taking more medications were associated in cross-sectional analyses with an increased overall likelihood of anxiety or depression. Associations between lower social class, either in childhood or currently, history of heart disease, stroke or diabetes and increased risk of anxiety or depression were attenuated and no longer statistically significant after adjustment for potential confounding or mediating variables. There was no association between birth weight and anxiety or depression in later life.
Anxiety and depression in later life are both strongly linked to personality, cognitive and physical function, disability and state of health, measured concurrently. Possible mechanisms that might underlie these associations are discussed.
Following the evolving microstructure of composites through all stages of chemical vapor infiltration (CVI) is a key to improved understanding and control of the process. X-ray Tomographic Microscopy (XTM), i.e., very high resolution computed tomography, allows the microstructure of macroscopic volumes of a composite to be imaged nondestructively with resolution approaching one micrometer. Results obtained with XTM on dense SiC/SiC composites and on woven SiC fiber preforms illustrate how details of the densification process can be followed using this technique during interruptions in processing. Ways in which the three-dimensional microstructural information may be used to improve modeling are also indicated.
Background: The Hospital Anxiety and Depression Scale (HADS) is widely used but evaluation of its psychometric properties has produced equivocal results. Little is known about its structure in non-clinical samples of older people.
Methods: We used data from four cohorts in the HALCyon collaborative research program into healthy aging: the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study, and the Lothian Birth Cohort 1921. We used exploratory factor analysis and confirmatory factor analysis with multi-group comparisons to establish the structure of the HADS and test for factorial invariance between samples.
Results: Exploratory factor analysis showed a bi-dimensional structure (anxiety and depression) of the scale in men and women in each cohort. We tested a hypothesized three-factor model but high correlations between two of the factors made a two-factor model more psychologically plausible. Multi-group confirmatory factor analysis revealed that the sizes of the respective item loadings on the two factors were effectively identical in men and women from the same cohort. There was more variation between cohorts, particularly those from different parts of the U.K. and in whom the HADS was administered differently. Differences in social-class distribution accounted for part of this variation.
Conclusions: Scoring the HADS as two subscales of anxiety and depression is appropriate in non-clinical populations of older men and women. However, there were differences between cohorts in the way that individual items were linked with the constructs of anxiety and depression, perhaps due to differences in sociocultural factors and/or in the administration of the scale.
Background. The National Adult Reading Test (NART) is widely used in research and clinical practice as an estimate of pre-morbid or prior ability. However, most of the evidence on the NART's validity as a measure of prior intellectual ability is based on concurrent administration of the NART and an IQ measure.
Method. We followed up 179 individuals who had taken an IQ test (the Moray House Test) at age 11 and administered the NART and the Mini-Mental State Examination (MMSE) at age 77. A subset (N=97) were also re-administered the original IQ test.
Results. The correlation between NART performance at age 77 and IQ age 11 was high and statistically significant (r=0·73; P<0·001). This correlation was comparable to the correlation between NART and current IQ, and childhood IQ and current IQ, despite the shared influences on the latter variable pairings. The NART had a significant correlation with the MMSE but this correlation fell to near zero (r=0·02) after partialling out the influence of childhood IQ.
Discussion. The pattern of results provides strong support for the claim that the NART primarily indexes prior (rather than current) intellectual ability.
Factors influencing the rate, form, and severity of phenotypic expression among relatives of
autistic probands are examined. Family history data on 3095 first- and second-degree
relatives and cousins from 149 families with a child with autism and 36 families with a child
with Down syndrome are studied. The results provide further evidence of an increased risk
among autism relatives for the broadly defined autism phenotype. Of proband characteristics,
severity of autism and obstetric optimality were confirmed as being related to
familial loading for probands with speech. There was little variation in loading among
probands lacking speech. The type of phenotypic profile reported in relatives appeared little
influenced by characteristics of the relative or the proband, except for variation by degree of
relative, parental status of relative, and perhaps proband's birth optimality score. Phenotypic
rates among parents suggested reduced fitness for the severest and more communication-related forms of expression but not for the more mild and social forms of expression.
Patterns of expression within the families did not support a simple X-linked nor an imprinted
X-linked mode of inheritance. The basis for sex differences in rates of expression is discussed.
Reports have suggested that isoniazid treatment may be associated with poor concentration
and subtle reduction in memory. This study examines attentional function and processing speed
in a group of 25 adolescents who received isoniazid prophylaxis for at least 6 months. As
adolescents often face major educational assessment milestones, such cognitive side effects may
have important implications. Participants were assessed before treatment, 1 month into
treatment and at least 1 week after treatment cessation. Measures included the Paced Auditory
Serial Addition Test and subtests of the appropriate Wechsler scale sensitive to attention and
speed of information processing. Isoniazid does not appear to cause significant adverse effects
on attentional function in adolescents.
The repeatability of energy-expenditure measurements were studied in five children and four adults without disabilities using the Cosmed K4 (high technology). The ability to detect change in measurements was compared between this instrument and the Physiological Cost Index (PCI; low technology). The results of repeatability (95% range) for oxygen cost were 13.1% in children and 13% in adults. In contrast, the SD of PCI was 6 to 72% of the mean in adults and wider in children (91%; 95% range). The validity of PCI as an outcome measure was questioned. In addition, 177 children with motor disability were prospectively studied using the Cosmed K4. Previous experience with the Cosmed K2 (intermediate technology) helped to develop a practical and repeatable protocol for testing children with disability using the Cosmed K4. The protocol commenced with 5 minutes of rest to achieve baseline values of heart rate and oxygen consumption, followed by 10 minutes of continuous walking at a self-selected speed on a 10-metre level oval walking track. The test concluded with 5 minutes of rest to monitor the return to baseline values. Ninety-one percent of the children with disability quickly reached a steady-state of oxygen consumption and carbon-dioxide production. The carbon-dioxide sensor in the Cosmed K4 has enabled a new group of severely involved children with cerebral palsy (9%) to be defined. These children have been termed ‘physiologically marginal ambulators’.