Salivary C-reactive protein exhibits a diurnal pattern and relates to biobehavioral health in military men.

C-reactive protein is a systemic inflammatory biomarker that is positively associated with the development of disease. Salivary C-reactive protein (sCRP) has previously been reported to have a diurnal rhythm with higher levels upon awakening and lower levels thereafter. The aims of this study were to evaluate the stability of sCRP across two days, characterize the daily sCRP pattern, compute morning sCRP parameters, and evaluate associations with biobehavioral health in US Navy Explosive Ordnance Disposal (EOD) technicians. Seventy male EOD technicians (age = 34.9 ± 6.5 years) participated in this study, which included a tablet-based survey, measures of health and fitness, and saliva collection. In a free-living setting, participants self-collected saliva on 2 consecutive days at WAKE, WAKE+30, WAKE+60, 4p.m., and 9p.m., for a total of 10 samples. Parameters (e.g., area under the curve) were computed to characterize the morning sCRP magnitude and pattern. Pearson product-moment correlation analyses were used to assess the stability of sCRP samples and parameters across the study period and to examine associations with biobehavioral health. Average sCRP concentrations for the 2-day period were evaluated using an analysis of variance with repeated measures. The stabilities between corresponding time points on Days 1 and 2 were very high (rs = 0.87-.94, all ps ≤ 0.001). sCRP concentrations were highest at WAKE, decreased by 73.6 % at WAKE+30, and then plateaued for the rest of the day. Parameter stabilities were good to excellent (rs = 0.77-.98, all ps ≤ 0.001). We also observed associations between sCRP parameters, self-reported health behaviors, and objective measures of health and fitness. In this study of a military population, we characterized sCRP as diurnal with robust stability across 2 consecutive days, which demonstrates the feasibility of sCRP as a biomarker. These results have significant implications for study methodology and for using sCRP as a marker of dysfunction or disease.

The Link Between Positive and Negative Parenting Behaviors and Child Inflammation: A Systematic Review.

Children's inflammation may be an important link between parenting behaviors and health outcomes. The aims of this systematic review were to: (1) describe associations between parenting behaviors and child inflammatory markers, and (2) evaluate the relevance of existing literature to the review question. Database searches identified 19 studies that included a measure of positive or negative parenting behaviors and a marker of child inflammation, 53% of which measured parental responsiveness/warmth. Greater parental responsiveness/warmth was associated with lower levels of child pro-inflammatory markers in 60% of studies. Across studies, the association between parenting and child inflammation varied as a function of parenting construct, inflammatory measure, and sample characteristics. Studies were highly relevant, with 42% rated 5 + out of 6 for study's ability to address links between parenting behavior and child inflammation. If future research uncovers causal effects of parenting behaviors on inflammation, parenting interventions could be employed as a preventative tool.

Replication and reproducibility issues in the relationship between C-reactive protein and depression: A systematic review and focused meta-analysis.

One of the most common inflammatory markers examined in depression is C-reactive protein (CRP). However, the magnitude of the association between CRP and depression when controlling for potentially confounding factors such as age, sex, socio-economic status, body mass index, medication and other substance use, and medical illness, is unclear. Inconsistencies in other methodological practices, such as sample collection, assaying, and data cleaning and transformation, may contribute to variations in results. We aggregate studies that examined the association between CRP and depression in two ways. First, a systematic review summarizes how studies of CRP and depression have reported on methodological issues. Second, a tiered meta-analysis aggregates studies that have adhered to various levels of methodological rigor. Findings from the systematic review indicate a lack of protocol detail provided. The effect between depression and CRP was small, but highly significant across all stages of the meta-analysis (p < 0.01). The effect size in the most methodologically rigorous stage of the meta-analysis, which included studies controlling for age, sex, obesity, medical conditions and substance, medication, or psychosocial factors, was small (r = 0.05). There were also only 26 articles in this stage (13% of studies from the systematic review), suggesting that more studies that consistently account for these confounding factors are needed. Additionally, an a priori quality score of methodological rigor was a significant moderator in this stage of the meta-analysis. The effect size was strikingly attenuated (r = 0.005) and non-significant in studies with higher quality scores. We describe a set of recommended guidelines for future research to consider, including sample collection and assaying procedures, data cleaning and statistical methods, and control variables to assess.

Professional Values Competency Evaluation: Comparing Student Written Assignments to Literature Findings.

Nurse educators have had no clear evidence-based method to evaluate student competency related to professional values. This article describes a comparative analysis in which the list of professional values identified in a research study of undergraduate prelicensure nursing student assignments was compared with a list identified in an integrative review of nursing literature. Comparative analysis allowed for a categorization of professional values that were either congruent between student assignments and literature, exclusively evident in literature, or exclusively evident in student assignments. Findings may contribute to curricular process improvements promoting professional values development in undergraduate nursing students.

Cortico-amygdalar maturational coupling is associated with depressive symptom trajectories during adolescence.

BACKGROUND: Adolescence is characterized by increasing prevalence of depressive symptomatology, along with significant structural brain development. While much research has examined focal abnormalities in gray matter structure underlying depression, we employed a structural coupling approach to examine whether longitudinal associations between amygdala and cortical development (referred to as maturational coupling) was related to concurrent changes in depressive symptomatology during adolescence. METHOD: 166 participants underwent up to three MRI scans (367 scans) between 11 and 20 years of age. Depressive symptoms were measured at three coinciding time points using the Center for Epidemiological Studies-Depression scale. Linear mixed models were employed to identify whether change in amygdala volume was related to development of cortical thickness, and if maturational coupling of these regions was related to changes in depressive symptomatology. RESULTS: Positive maturational coupling was identified between the right amygdala and (predominantly anterior) prefrontal cortex, as well as parts of the temporal cortices. Greater positive coupling of these regions was associated with reductions in depressive symptoms over time. CONCLUSIONS: Findings highlight significant associations between cortico-amygdalar maturational coupling and the emergence of depressive symptoms during adolescence, suggesting that synchronous development of these regions might support more adaptive affect regulation and functioning.

Mutations in folate transporter genes and risk for human myelomeningocele.

The molecular mechanisms linking folate deficiency and neural tube defect (NTD) risk in offspring remain unclear. Folate transporters (SLC19A1, SLC46A1, SLC25A32, and FOLH1) and folate receptors (FOLR1, FOLR2, and FOLR3) are suggested to play essential roles in transporting folate from maternal intestinal lumen to the developing embryo. Loss of function variants in these genes may affect folate availability and contribute to NTD risk. This study examines whether variants within the folate transporter and receptor genes are associated with an increased risk for myelomeningocele (MM). Exons and their flanking intron sequences of 348 MM subjects were sequenced using the Sanger sequencing method and/or next generation sequencing to identify variants. Frequencies of alleles of single nucleotide polymorphisms (SNPs) in MM subjects were compared to those from ethnically matched reference populations to evaluate alleles' associated risk for MM. We identified eight novel variants in SLC19A1 and twelve novel variants in FOLR1, FOLR2, and FOLR3. Pathogenic variants include c.1265delG in SLC19A1 resulting in an early stop codon, four large insertion deletion variants in FOLR3, and a stop_gain variant in FOLR3. No new variants were identified in SLC46A1, SLC25A32, or FOLH1. In SLC19A1, c.80A>G (rs1051266) was not associated with our MM cohort; we did observe a variant allele G frequency of 61.7%, higher than previously reported in other NTD populations. In conclusion, we discovered novel loss of function variants in genes involved in folate transport in MM subjects. Our results support the growing evidence of associations between genes involved in folate transport and susceptibility to NTDs.

Sleep Duration and Sleep Quality: Associations With Depressive Symptoms Across Adolescence.

This study explored whether short sleep duration and sleep quality mediate the relationship between age and depressive symptoms. For comparison, we also explored whether depressive symptoms mediate the relationship between age and short sleep duration and sleep quality. The sample comprised 741 adolescents (63.5% female, mean age 15.78 years, range 11.92-19.67 years) in grades 7-12 from 11 secondary schools in metropolitan Melbourne, Australia. Students completed the Pittsburgh Sleep Quality Index (PSQI) and Center for Epidemiologic Studies Depression Scale (CES-D). Path analyses suggested that short sleep duration significantly mediated the relationship between age and depressive symptoms. Poor sleep quality also significantly mediated this relationship when sleep quality was defined by subjective judgement, but not sleep disturbance, sleep efficiency, or sleep onset latency. Depressive symptoms significantly mediated the relationship between age and short sleep duration and sleep quality (subjective judgement, sleep disturbance, sleep efficiency, and sleep onset latency). These findings suggest that the population-wide increase in depressive symptoms across adolescence is partially mediated by sleep-related developmental changes. They also highlight the importance of examining specific sleep problems when investigating the relationship between sleep and mood in this age group.

Longitudinal Trajectories of Depression Symptoms in Adolescence: Psychosocial Risk Factors and Outcomes.

Variations in symptom trajectories within a population may represent distinct groups with different etiologies and outcomes. This study aimed to identify subgroups of depression symptom trajectories in a sample of adolescents, and to describe psychosocial attributes of the different groups. In a longitudinal study, 243 adolescents (121 males and 122 females), were assessed using a battery of measures of temperament, psychopathology, and psychological and behavioral functioning. Four phases of data collection over 7 years spanned average ages of the participants from 12 to 18 years old. Depressive symptoms from each phase were used to model latent class growth trajectories. A 4-group solution was selected as the best-fitting model: (1) ongoing stable low levels of depression; (2) very high depressive symptoms initially, but a steep decrease in symptoms over time; (3) moderately high depressive symptoms initially, but symptoms decreased over time; and (4) initially low levels of symptoms that increased over time. Trajectory group membership was associated with a range of psychosocial variables including temperament, childhood maltreatment, and young adult quality of life. Characterising these subgroups allows for a better understanding of how the interaction of risk factors increases the likelihood of depression and other poor outcomes, and highlights the importance of early interventions to prevent and treat adolescent depression.

Longitudinal Bi-directional Effects of Disordered Eating, Depression and Anxiety.

OBJECTIVE: The present study aims to explore the potentially longitudinal bi-directional effects of disordered eating (DE) symptoms with depression and anxiety. METHOD: Participants were 189 (49.5% male) adolescents from Melbourne, Australia. DE, depressive and anxiety symptoms were assessed at approximately 15, 16.5 and 18.5 years of age. RESULTS: Analysis of longitudinal bi-directional effects assessed via cross-lagged models indicated that DE symptoms of eating and shape/weight concerns were risk factors for anxiety. Results also showed that depression was a risk factor for eating concerns. CONCLUSION: Our findings provide preliminary evidence that preventative measures designed to target concerns about eating and shape/weight might be most efficacious in reducing the transmission of effects between symptoms of DE, depression and anxiety. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

The Role of Brain Structure and Function in the Association Between Inflammation and Depressive Symptoms: A Systematic Review.

OBJECTIVE: Major depressive disorder and related symptoms have been shown to be associated with inflammation, and this association is likely to be mediated through changes in brain structure and function. This article provides a systematic review of studies that have used brain imaging techniques to identify neural mechanisms linking inflammation and depressive symptoms. METHODS: A systematic search of online databases identified 26 studies that fulfilled the inclusion and exclusion criteria. RESULTS: In general, increased peripheral inflammation was associated with differences in function in several subcortical regions, as well as medial and ventral prefrontal regions-both at rest (7 studies) and during exposure to emotional stimuli (14 studies). Also, increased activation in some of these regions was associated with depression (18 studies). Too few studies have measured neuroinflammation markers (three) or brain structure (three), so generalizations about these mechanisms cannot yet be made. CONCLUSIONS: This review supports the view that peripheral inflammation is an etiological process that may influence depression via effects on brain function. Several methodological inconsistencies in the extant literature need to be addressed, most notably a lack of formal mediational testing in longitudinal designs and inconsistencies across imaging methods and inflammation induction and measurement techniques. Further work is also required to establish the mechanisms by which basal inflammation levels influence brain function and depressive symptoms in both healthy and clinical samples.

Nocturnal indicators of increased cardiovascular risk in depressed adolescent girls.

Depression is an independent risk factor for cardiovascular disease in adults, and recent literature suggests preclinical signs of cardiovascular risk are also present in depressed adolescents. No study has examined the effect of clinical depression on cardiovascular factors during sleep. This study examined the relationship between clinical depression and nocturnal indicators of cardiovascular risk in depressed adolescent girls from the general community (13-18 years old; 11 clinically depressed, eight healthy control). Continuous beat-to-beat finger arterial blood pressure and heart rate were monitored via Portapres and electrocardiogram, respectively. Cardiovascular data were averaged over each hour for the first 6 h of sleep, as well as in 2-min epochs of stable sleep that were then averaged within sleep stages. Data were also averaged across 2-min epochs of pre-sleep wakefulness and the first 5 min of continuous non-rapid eye movement sleep to investigate the blood pressure dipping response over the sleep-onset period. Compared with controls, depressed adolescents displayed a similar but significantly elevated blood pressure profile across sleep. Depressed adolescents had significantly higher systolic and diastolic blood pressure and mean arterial pressures across the entire night (P < 0.01), as well as during all sleep stages (P < 0.001). Depressed adolescents also had higher blood pressure across the sleep-onset period, but the groups did not differ in the rate of decline across the period. Higher blood pressure during sleep in depressed adolescent females suggests that depression has a significant association with cardiovascular functioning during sleep in adolescent females, which may increase risk for future cardiovascular pathology.

Impaired Maturation of Cognitive Control in Adolescents Who Develop Major Depressive Disorder.

This study examined whether development of two forms of cognitive control (proactive and reactive) between early and midadolescence was associated with the onset of major depressive disorder (MDD) during the same period and if it prospectively predicted MDD onset between mid- and late adolescence. Adolescents (N = 165) completed 3 waves of assessments, at 12 (T1), 16 (T2), and 18 (T3) years of age. Diagnostic interviews were conducted at each time point to identify three groups of adolescents: "early MDD," those who developed MDD between early (T1) and mid- (T2) adolescence (n = 23); "late MDD," those who developed MDD between mid- (T2) and late (T3) adolescence (n = 20); and "controls," those who did not develop MDD (n = 122). A modified Stroop task was completed at T1 and T2 to examine development of proactive and reactive cognitive control. Adolescents with early MDD exhibited significant declines in reactive control, as well as a trend level decline for proactive control, during this period compared to controls. No significant differences in reactive or proactive control were identified in adolescents with late MDD compared to controls, but they did exhibit significant improvements in proactive control compared to those with early MDD. These findings suggest that normative maturation of reactive, and possibly proactive, cognitive control abilities are impaired in adolescents who develop MDD between early and midadolescence. This has implications for understanding the mechanisms underlying certain forms of behavioral dysregulation that are commonly seen in MDD.

CNE Certification Drive and Exam Results.

The Certified Nurse Educator (CNE) is the only credential recognizing the advanced practice role of the academic nurse educator. This article provides information regarding a CNE Certification Drive for faculty in one school of nursing. Descriptive findings include pass rates and content-specific averages. An analysis of the relationship between the variables is offered for role (faculty vs. recent graduate), years of teaching, and differences in test scores. Results indicate no significant relationship between role and test results, χ(1) = 1.11, p = .29, and between years of teaching for those who passed (M = 10.38, SD = 9.81) versus those who failed (M = 4.75, SD = 6.36, t(18) = 1.56, p = .14). Additional research is needed to provide further understanding of variables linked with the CNE exam in multiple schools of nursing.

Trait positive affect is associated with hippocampal volume and change in caudate volume across adolescence.

Trait positive affect (PA) in childhood confers both risk and resilience to psychological and behavioral difficulties in adolescence, although explanations for this association are lacking. Neurodevelopment in key areas associated with positive affect is ongoing throughout adolescence, and is likely to be related to the increased incidence of disorders of positive affect during this period of development. The aim of this study was to prospectively explore the relationship between trait indices of PA and brain development in subcortical reward regions during early to mid-adolescence in a community sample of adolescents. A total of 89 (46 male, 43 female) adolescents participated in magnetic resonance imaging assessments during both early and mid-adolescence (mean age at baseline = 12.6 years, SD = 0.45; mean follow-up period = 3.78 years, SD = 0.21) and also completed self-report measures of trait positive and negative affect (at baseline). To examine the specificity of these effects, the relation between negative affect and brain development was also examined. The degree of volume reduction in the right caudate over time was predicted by PA. Independent of time, larger hippocampal volumes were associated with higher PA, and negative affect was associated with smaller left amygdala volume. The moderating effect of negative affect on the development of the left caudate varied as a function of lifetime psychiatric history. These findings suggest that early to mid-adolescence is an important period whereby neurodevelopmental processes may underlie key phenotypes conferring both risk and resilience for emotional and behavioral difficulties later in life.

Dual-axis hormonal covariation in adolescence and the moderating influence of prior trauma and aversive maternal parenting.

Adversity early in life can disrupt the functioning of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes and increase risk for negative health outcomes. The interplay between these axes and the environment is complex, and understanding needs to be advanced by the investigation of the multiple hormonal relationships underlying these processes. The current study examined basal hormonal associations between morning levels of cortisol, testosterone, and dehydroepiandrosterone in a cohort of adolescents (mean age 15.56 years). The moderating influence of childhood adversity was also examined, as indexed by self-reported trauma (at mean age 14.91), and observed maternal aggressive parenting (at mean age 12.41). Between-person regressions revealed significant associations between hormones that were moderated by both measures of adversity. In females, all hormones positively covaried, but also interacted with adversity, such that positive covariation was typically only present when levels of trauma and/or aggressive parenting were low. In males, hormonal associations and interactions were less evident; however, interactions were detected for cortisol-testosterone - positively covarying at high levels of aggressive parenting but negatively covarying at low levels - and DHEA-cortisol - similarly positively covarying at high levels of parental aggression. These results demonstrate associations between adrenal and gonadal hormones and the moderating role of adversity, which is likely driven by feedback mechanisms, or cross-talk, between the axes. These findings suggest that hormonal changes may be the pathway through which early life adversity alters physiology and increases health risks, but does so differentially in the sexes; however further study is necessary to establish causation.

Adolescent-Onset Depression: Are Obesity and Inflammation Developmental Mechanisms or Outcomes?

Depression often has its first onset during adolescence and is associated with obesity. Furthermore, inflammatory processes have been implicated in both depression and obesity, although research amongst adolescents is limited. This review explores associations between depression and obesity, depression and inflammation, and obesity and inflammation from a developmental perspective. The temporal relations between these factors are examined to explore whether obesity and elevated inflammation act as either risk factors for, or outcomes of, adolescent-onset depression. Sex differences in these processes are also summarized. We propose a model whereby increases in sex hormones during puberty increase risk for depression for females, which can lead to obesity, which in turn increases levels of inflammation. Importantly, this model suggests that inflammation and obesity are outcomes of adolescent depression, rather than initial contributing causes. Further research on biological and psychosocial effects of sex hormones is needed, as is longitudinal research with children and adolescents.