Molecular detection of novel astroviruses in wild and laboratory mice.

Pooled fecal specimens collected from striped field mice (Apodemus agrarius), yellow-necked mice (Apodemus flavicollis), and bank voles (Myodes glareolus) and individual stool samples collected from laboratory mice were tested for the presence of picornaviruses and astroviruses. Picornavirus RNA was detected only in one striped field mouse sample pool, while astrovirus RNA was detected in two yellow-necked mouse sample pools and in six of the 121 laboratory mouse samples. In a 234-amino acid (aa) fragment of the viral RNA dependent RNA polymerase (RdRp), the wild mouse picornavirus revealed the closest homology to the canyon mouse (Peromyscus crinitus) (93 % aa) and canine kobuviruses (92 % aa) and to Aichi virus (88 % aa). The two astroviruses detected in the yellow-necked mouse samples shared 77 % aa homology with each other in the partial (125 aa) RdRp region, 61-62 % aa homology with rat astroviruses and only 54-58 % aa homology with the house mouse (Mus musculus) astrovirus strain USA/2008/M52. The six laboratory mouse astroviruses displayed 97-100 % aa homology to each other, and shared 71-77 % aa homology with the yellow-necked mouse astroviruses, 58-59 % aa homology with rat astroviruses and 55-56 % aa homology with strain USA/2008/M52. The sequence of a 3,263 bp genome segment including the partial ORF1b (RdRp), complete ORF2 (capsid precursor), and 3' NTR of a research mouse astrovirus strain (TF18LM) was determined. The full-length ORF2 showed low identities (17-34 % aa) with other members of the Mamastrovirus genus and only 17 % aa homology with the house mouse astrovirus strain USA/2008/M52, indicating that AstVs described in this study represent a novel Mamastrovirus species. The relevance of astrovirus infection and its effect on biomedical research conducted in mice needs to be investigated.

Patient-derived granulocyte/macrophage colony-stimulating factor autoantibodies reproduce pulmonary alveolar proteinosis in nonhuman primates.

RATIONALE: Granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibodies (GMAb) are strongly associated with idiopathic pulmonary alveolar proteinosis (PAP) and are believed to be important in its pathogenesis. However, levels of GMAb do not correlate with disease severity and GMAb are also present at low levels in healthy individuals. OBJECTIVES: Our primary objective was to determine whether human GMAb would reproduce PAP in healthy primates. A secondary objective was to determine the concentration of GMAb resulting in loss of GM-CSF signaling in vivo (i.e., critical threshold). METHODS: Nonhuman primates (Macaca fascicularis) were injected with highly purified, PAP patient-derived GMAb in dose-ranging (2.2-50 mg) single and multiple administration studies, and after blocking antihuman immunoglobulin immune responses, in chronic administration studies maintaining serum levels greater than 40 microg/ml for up to 11 months. MEASUREMENTS AND MAIN RESULTS: GMAb blocked GM-CSF signaling causing (1) a milky-appearing bronchoalveolar lavage fluid containing increased surfactant lipids and proteins; (2) enlarged, foamy, surfactant-filled alveolar macrophages with reduced PU.1 and PPARgamma mRNA, and reduced tumor necrosis factor-alpha secretion; (3) pulmonary leukocytosis; (4) increased serum surfactant protein-D; and (5) impaired neutrophil functions. GM-CSF signaling varied inversely with GMAb concentration below a critical threshold of 5 microg/ml, which was similar in lungs and blood and to the value observed in patients with PAP. CONCLUSIONS: GMAb reproduced the molecular, cellular, and histopathologic features of PAP in healthy primates, demonstrating that GMAb directly cause PAP. These results have implications for therapy of PAP and help define the therapeutic window for potential use of GMAb to treat other disorders.

Efficacy and moderators of a family group cognitive-behavioral preventive intervention for children of parents with depression.

OBJECTIVE: Building on an earlier study (Compas, Forehand, Thigpen, et al., 2011), tests of main effects and potential moderators of a family group cognitive-behavioral (FGCB) preventive intervention for children of parents with a history of depression are reported. METHOD: Assessed a sample of 180 families (242 children ages 9-15 years) in a randomized controlled trial assessed at 2, 6, 12, 18 and 24 months after baseline. RESULTS: Significant effects favoring the FGCB intervention over a written information comparison condition were found on measures of children's symptoms of depression, mixed anxiety/depression, internalizing problems, and externalizing problems, with multiple effects maintained at 18 and 24 months, and on incidence of child episodes of major depressive disorder over the 24 months. Effects were stronger for child self-reports than for parent reports. Minimal evidence was found for child age, child gender, parental education, parental depressive symptoms, or presence of a current parental depressive episode at baseline as moderators of the FGCB intervention. CONCLUSIONS: The findings provide support for sustained and robust effects of this preventive intervention.

Reducing major depression in children at high risk: opportunities for prevention.

OBJECTIVE: The profound negative impact of a parent's Major Depressive Disorder (MDD) on his or her children is of increasing concern to public health and mental health professionals. Children of a depressed parent have a markedly elevated risk for psychiatric illness, including a fourfold increased risk for MDD. The objective is to examine the scientific literature for ways to reduce this high risk to the offspring. First, we consider the relation between effective treatment of a parent's depression and reduced risk to the offspring, and review the effectiveness of treatments for adult M1DD. We then review emerging evidence that risk for psychopathology can be reduced in children of depressed parents by preventive intervention, including targeting two pathways hypothesized as links between parental MDD and offspring psychopathology: parenting skills and child coping. DATA SOURCES: Three 5-year PubMed searches, and a Cochrane Database search, and one Medline and two PsycLit searches (to 1970) were completed (search words in combinations included: depression, prevention, treatments, depression in families, family interaction, adolescents). STUDY SELECTION: Randomized controlled studies are included, and review studies and meta-analyses are highlighted to provide a critical overview of the considerable scientific literatures for specific steps that can be taken to reduce the high risk of depression to the offspring of parents with MDD. RESULTS: A deliberate clinical focus on better treatment of MDD in parents is clearly needed and has the potential additional benefit of reducing psychopathology in their children. Altering clinical treatment to address MDD "co-occurring" in both parent and child is supported by the scientific literature. There is also good evidence that preventive intervention with high-risk adolescents reduces the incidence of MDD. Targeting parenting skills and teaching children how to better cope with a parent's illness that they cannot control, appears to reduce MDD in the offspring.

Molecular detection of murine noroviruses in laboratory and wild mice.

Fecal specimens collected from 121 laboratory mice, 30 striped field mice (Apodemus agrarius), 70 yellow-necked mice (Apodemus flavicollis), and 3 bank voles (Myodes glareolus) were tested in sample pools for the presence of murine noroviruses (MNV). Ten of 41 laboratory mice and 2 of 3 striped field mice pooled samples were positive for MNV. All laboratory mouse MNVs were closely related to previously described MNVs. The complete ORF2 (VP1) of both striped field mouse MNVs identified in this study was 1623 nt (541 aa) long and differed at 12% nt (8% aa) positions from each other, at 22-24% nt (15-18% aa) positions from the laboratory mouse MNVs and at 20-22% nt (13-14% aa) positions from the recently described wood mouse (Apodemus sylvaticus) MNVs. This study provides further evidence for the circulation of novel, genetically diverse MNVs in wild mice.

Family group cognitive-behavioral preventive intervention for families of depressed parents: 18- and 24-month outcomes.

OBJECTIVE: In a long-term follow-up of a randomized controlled trial (Compas et al., 2009) to examine the effects at 18- and 24-month follow-ups of a family group cognitive-behavioral (FGCB) preventive intervention for mental health outcomes for children and parents from families (N = 111) of parents with a history of major depressive disorder (MDD). METHOD: Parents with a history of MDD and their 9- to 15-year-old children were randomly assigned to a FGCB intervention or a written information comparison condition. Children's internalizing, externalizing, anxiety/depression, and depressive symptoms; episodes of MDD and other psychiatric diagnoses; and parents' depressive symptoms and episodes of MDD were assessed at 18 and 24 months after randomization. RESULTS: Children in the FGCB condition were significantly lower in self-reports of anxiety/depression and internalizing symptoms at 18 months and were significantly lower in self-reports of externalizing symptoms at 18 and 24 months. Rates of MDD were significantly lower for children in the FGCB intervention over the 24-month follow-up (odds ratio = 2.91). Marginal effects were found for parents' symptoms of depression at 18 and 24 months but not for episodes of MDD. CONCLUSIONS: Support was found for a FGCB preventive intervention for children of parents with a history of MDD significantly reducing children's episodes of MDD over a period of 2 years. Significant effects for the FGCB intervention were also found on internalizing and externalizing symptoms, with stronger effects at 18- than at 24-month follow-up.

Coping and parenting: Mediators of 12-month outcomes of a family group cognitive-behavioral preventive intervention with families of depressed parents.

OBJECTIVE: In a randomized clinical trial with 111 families of parents with a history of major depressive disorder (86% mothers, 14% fathers; 86% Caucasian, 5% African-American, 3% Hispanic, 1% American Indian or Alaska Native, 4% mixed ethnicity), changes in adolescents' (mean age = 11 years; 42% female, 58% male) coping and parents' parenting skills were examined as mediators of the effects of a family group cognitive-behavioral preventive intervention on adolescents' internalizing and externalizing symptoms. METHOD: Changes in hypothesized mediators were assessed at 6 months, and changes in adolescents' symptoms were measured at a 12-month follow-up. RESULTS: Significant differences favoring the family intervention compared with a written information comparison condition were found for changes in composite measures of parent-adolescent reports of adolescents' use of secondary control coping skills and direct observations of parents' positive parenting skills. Changes in adolescents' secondary control coping and positive parenting mediated the effects of the intervention on depressive, internalizing, and externalizing symptoms, accounting for approximately half of the effect of the intervention on the outcomes. Further, reciprocal relations between children's internalizing symptoms and parenting were found from baseline to 6-month follow-up. CONCLUSION: The present study provides the first evidence for specific mediators of a family group cognitive-behavioral preventive intervention for families of parents with a history of major depressive disorder. The identification of both coping and parenting as mediators of children's mental health outcomes suggests that these variables are important active ingredients in the prevention of mental health problems in children of depressed parents.

Randomized controlled trial of a family cognitive-behavioral preventive intervention for children of depressed parents.

A family cognitive-behavioral preventive intervention for parents with a history of depression and their 9-15-year-old children was compared with a self-study written information condition in a randomized clinical trial (n = 111 families). Outcomes were assessed at postintervention (2 months), after completion of 4 monthly booster sessions (6 months), and at 12-month follow-up. Children were assessed by child reports on depressive symptoms, internalizing problems, and externalizing problems; by parent reports on internalizing and externalizing problems; and by child and parent reports on a standardized diagnostic interview. Parent depressive symptoms and parent episodes of major depression also were assessed. Evidence emerged for significant differences favoring the family group intervention on both child and parent outcomes; strongest effects for child outcomes were found at the 12-month assessment with medium effect sizes on most measures. Implications for the prevention of adverse outcomes in children of depressed parents are highlighted.

Cross-situational coping with peer and family stressors in adolescent offspring of depressed parents.

Offspring of depressed parents are faced with significant interpersonal stress both within their families and in peer relationships. The present study examined parent and self-reports of adolescents' coping in response to family and peer stressors in 73 adolescent children of parents with a history of depression. Correlational analyses indicated that adolescents were moderately consistent in the coping strategies used with peer stress and family stress. Mean levels of coping were similar across situations, as adolescents reported greater use of secondary control coping (i.e., acceptance, distraction) than primary control coping (i.e., problem solving, emotional expression) or disengagement coping (i.e., avoidance) with both types of stress. Regression analyses indicated that fewer symptoms of self-reported anxiety/depression and aggression were related to using secondary control coping strategies in response to family stress and primary control coping in response to peer stress. Implications for understanding the characteristics of effective coping with stress related to living with a depressed parent are highlighted.

Coping with the stress of parental depression II: adolescent and parent reports of coping and adjustment.

This study examined associations between adolescents' self-reports and parents' reports of adolescents' exposure to family stress, coping, and symptoms of anxiety/depression and aggression in a sample of 78 adolescent offspring of depressed parents. Significant cross-informant correlations were found between adolescents' reports of family stress, their stress responses, and their coping and parents' reports of adolescents' symptoms of anxiety/depression and aggression, but not between parents' reports of adolescents' stress and coping and adolescents' self-reported symptoms. Adolescents' reports of secondary control engagement coping and involuntary engagement stress responses mediated the relation between adolescents' reports of parental stress and parents' reports of adolescents' anxiety/depression symptoms. Moderate levels of correspondence were found in the correlations between parent and adolescent reports of adolescents' exposure to stress, coping, stress responses, and symptoms even after controlling for parents' current depressive symptoms. However, depressed parents reported higher levels of symptoms of anxiety/depression and aggression and more family stress than did their adolescent offspring. Implications for future research on coping and adjustment in offspring of depressed parents are highlighted.

Coping with the stress of parental depression: parents' reports of children's coping, emotional, and behavioral problems.

Examined children's coping and involuntary responses to the stress of living with a depressed parent in relation to their symptoms of anxiety/depression and aggression. Sixty-six clinically depressed adults rated their children's (ages 7 to 17 years old; N = 101) coping and involuntary responses to parental stressors and anxiety/depressive and aggressive behavior symptoms. Based on parent report, children of depressed parents had high rates of symptoms of anxiety/depression and aggression, were exposed to moderate levels of parental stressors (parental intrusiveness, parental withdrawal), and responded to the stress of living with a depressed parent in ways that were associated with symptoms of psychopathology. Children's use of secondary control coping (e.g., positive thinking, acceptance, distraction) was associated with fewer anxiety/depression and aggression symptoms. In contrast, involuntary engagement responses (e.g., rumination, intrusive thoughts) were associated with more anxiety/depression and aggression symptoms. Path analyses revealed that a model in which secondary control coping and involuntary engagement stress responses mediated the relation between family stressors and child symptoms provided the best fit with the data. Implications of these findings for developing interventions for children to reduce the risk of psychopathology are discussed.