Comparison of Global and Daily Ratings of Associations between Anxiety and Depressive Behaviors and Impairment in Preschool-Aged Children.

Anxiety and depressive difficulties can emerge during early childhood and cause impairment in functioning. Anxiety and depressive behaviors and impairment are typically assessed with global questionnaires that require recall of children's behavior over an extended period which could reduce the accuracy of parent report of children's behavior and functioning. The current study compared parents' report of children's anxiety and depressive behaviors and impairment when evaluated with global measures versus a daily diary measure. Participants (N = 901 parents of 3-5-year-old children) completed global and daily measures of children's behavior and impairment during enrollment to the study. Global measures were completed at baseline and the 14 daily diary measures were completed consecutively for two weeks. Across most measures, daily associations between parent-reported anxiety and depressive behaviors and impairment were stronger compared to associations with global measures. These results suggest that daily measures may better capture links between young children's typical behavior and functioning compared to global measures. In addition, daily assessment might be more effective for measuring mild to moderate yet still impairing behaviors that may be missed on global reports that require longer periods of recall.

Mapping the duration and severity of preschool-aged children's depressive moods and behaviors.

BACKGROUND: Depressive moods and behaviors are developmentally normative, yet potentially impairing, in preschool-aged children. In addition to frequency, duration of behavior is an important parameter to consider when characterizing risk for worsening mood dysregulation. The goal of this study was to identify the duration and severity of depressive moods and behaviors and associations with impairment in a large community sample of preschool-aged children using an online parent-report daily diary. METHODS: Primary caregivers (N = 900) of 3-5-year-old children reported the daily duration of each instance of seven depressive moods and behaviors for 14 days. We used item response theory analyses to examine duration item characteristics. RESULTS: Moods and behaviors occurred at specific durations to be considered psychometrically severe/rare; for example, instances of sadness had to last an average total of 32 min per day or more, irritability at least 38 min, tantrums at least 30 min, and tearfulness/sensitivity at least 35 min. Longer durations of mood and behavior were associated with daily impairment, as well as older child age and less parental education. CONCLUSIONS: To our knowledge, this is the first study to delineate specific duration ranges for depressive moods and behaviors in preschool-aged children. These data, coupled with information about the frequency of mood-related behaviors, can assist child practitioners in differentiating normative patterns from less normative mood problems to evaluate which children may be at risk. Future work should identify the duration of depressive moods and behaviors in early childhood that predict clinically significant psychopathology over time.

Preschool-aged children's hair cortisol and parents' behavior, psychopathology, and stress.

Parental factors, including parenting behavior, parent mental health, and parent stress, are associated with child stress. More recently, studies have shown that these parental factors may also be associated with children's hair cortisol concentration (HCC). HCC is a novel biomarker for chronic stress. HCC indexes cumulative cortisol exposure thereby reflecting longer-term stress reactivity. Although HCC is associated with a range of problems in adults such as depression, anxiety, appraisal of stressful events, and diabetes, studies investigating HCC in children have been inconsistent, with particularly little information about parental factors and HCC. As chronic stress may have long-term physiological and emotional effects on children, and parent-based interventions can reduce these effects, it is important to identify parental factors that relate to children's HCC. The aim of this study was to examine associations between preschool-aged children's physiological stress measured via HCC and mother- and father-reported parenting behavior, psychopathology, and stress. Participants included N = 140 children ages 3-5-years-old and their mothers (n = 140) and fathers (n = 98). Mothers and fathers completed questionnaire measures on their parenting behavior, depressive and anxiety symptoms, and perceived stress. Children's HCC was assessed by processing small hair samples. HCC levels were higher in boys compared to girls, and higher in children of color compared to white children. There was a significant association between children's HCC and fathers' authoritarian parenting. Children's HCC was positively associated with physical coercion, a specific facet of fathers' authoritarian parenting, even after accounting for sex of the child, race/ethnicity of the child, stressful life events, fathers' depression, fathers' anxiety, and fathers' perceived stress. In addition, there was a significant interaction between higher levels of both mothers' and fathers' authoritarian parenting and children's HCC. Children's HCC was not significantly related to mothers' and fathers' anxiety and depression or mothers' and fathers' perceived stress. These findings contribute to the large literature that links harsh and physical parenting practices with problematic outcomes in children.

Transcriptomic Analysis of Mouse Brain After Traumatic Brain Injury Reveals That the Angiotensin Receptor Blocker Candesartan Acts Through Novel Pathways.

Traumatic brain injury (TBI) results in complex pathological reactions, where the initial lesion is followed by secondary inflammation and edema. Our laboratory and others have reported that angiotensin receptor blockers (ARBs) have efficacy in improving recovery from traumatic brain injury in mice. Treatment of mice with a subhypotensive dose of the ARB candesartan results in improved functional recovery, and reduced pathology (lesion volume, inflammation and gliosis). In order to gain a better understanding of the molecular mechanisms through which candesartan improves recovery after controlled cortical impact injury (CCI), we performed transcriptomic profiling on brain regions after injury and drug treatment. We examined RNA expression in the ipsilateral hippocampus, thalamus and hypothalamus at 3 or 29 days post injury (dpi) treated with either candesartan (0.1 mg/kg) or vehicle. RNA was isolated and analyzed by bulk mRNA-seq. Gene expression in injured and/or candesartan treated brain region was compared to that in sham vehicle treated mice in the same brain region to identify genes that were differentially expressed (DEGs) between groups. The most DEGs were expressed in the hippocampus at 3 dpi, and the number of DEGs reduced with distance and time from the lesion. Among pathways that were differentially expressed at 3 dpi after CCI, candesartan treatment altered genes involved in angiogenesis, interferon signaling, extracellular matrix regulation including integrins and chromosome maintenance and DNA replication. At 29 dpi, candesartan treatment reduced the expression of genes involved in the inflammatory response. Some changes in gene expression were confirmed in a separate cohort of animals by qPCR. Fewer DEGs were found in the thalamus, and only one in the hypothalamus at 3 dpi. Additionally, in the hippocampi of sham injured mice, 3 days of candesartan treatment led to the differential expression of 384 genes showing that candesartan in the absence of injury had a powerful impact on gene expression specifically in the hippocampus. Our results suggest that candesartan has broad actions in the brain after injury and affects different processes at acute and chronic times after injury. These data should assist in elucidating the beneficial effect of candesartan on recovery from TBI.

Comparison of the effects of osmotic pump implantation with subcutaneous injection for administration of drugs after total body irradiation in mice.

The increasing potential for radiation exposure from nuclear accidents or terrorist activities has intensified the need to develop pharmacologic countermeasures against injury from total body irradiation (TBI). Many initial experiments to develop and test these countermeasures utilize murine irradiation models. Yet, the route of drug administration can alter the response to irradiation injury. Studies have demonstrated that cutaneous injuries can exacerbate damage from radiation, and thus surgical implantation of osmotic pumps for drug delivery could adversely affect the survival of mice following TBI. However, daily handling and injections to administer drugs could also have negative consequences. This study compared the effects of subcutaneous needlesticks with surgical implantation of osmotic pumps on morbidity and mortality in a murine model of hematopoietic acute radiation syndrome (H-ARS). C57BL/6 mice were sham irradiated or exposed to a single dose of 7.7 Gy 60Co TBI. Mice were implanted with osmotic pumps containing sterile saline seven days prior to irradiation or received needlesticks for 14 days following irradiation or received no treatment. All irradiated groups exhibited weight loss. Fewer mice with osmotic pumps survived to 30 days post irradiation (37.5%) than mice receiving needlesticks or no treatment (70% and 80%, respectively), although this difference was not statistically significant. However, mice implanted with the pump lost significantly more weight than mice that received needlesticks or no treatment. These data suggest that surgical implantation of a drug-delivery device can adversely affect the outcome in a murine model of H-ARS.