Disinhibited attachment behavior among infants of mothers with borderline personality disorder, depression, and no diagnosis.

Disinhibited attachment behavior is related to early institutional rearing and to later social maladaptation. It is also seen among infants reared at home whose mothers have histories of child maltreatment or psychiatric hospitalization. However, little is known about the maternal psychiatric diagnoses that might be associated with disinhibited behavior or the mechanisms through which maternal diagnosis might influence infant behavior. In the current study (N = 59), 2 maternal diagnoses, borderline personality disorder (BPD; n = 13) and depression (n = 15), were compared with a no diagnosis group (n = 31) on extent of infant disinhibited behavior. Disinhibited infant behavior was assessed at infant age of 12-18 months using the validated Rating of Infant-Stranger Engagement. Mother-infant interaction was coded using the Atypical Maternal Behavior Instrument for Assessment and Classification. Results indicated that infants of mothers with BPD were significantly more likely to be rated as disinhibited in their behavior toward the stranger compared with infants of mothers with depression and with no diagnosis. Disinhibited behavior was further related to the quality of mother-infant interaction, and maternal frightened/disoriented interaction partially mediated the effect of maternal BPD on infant disinhibited behavior. Disinhibited behavior among previously institutionally reared infants is relatively resistant to intervention after toddlerhood and is associated with maladaptation into adolescence. Therefore, high priority should be placed on understanding the developmental trajectories of home-reared infants with disinhibited behavior and on providing early assessment and early parenting support to mothers with BPD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Correction: Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes.

[This corrects the article DOI: 10.1371/journal.pone.0184164.].

Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes.

Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) agonist, CDDO-Me(bardoxolone methyl), reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10) secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl) also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA). Hence, our findings with CDDO-Me(bardoxolone methyl) and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.

Knockdown of leptin A expression dramatically alters zebrafish development.

Using morpholino antisense oligonucleotide (MO) technology, we blocked leptin A or leptin receptor expression in embryonic zebrafish, and analyzed consequences of leptin A knock-down on fish development. Embryos injected with leptin A or leptin receptor MOs (leptin A or leptin receptor morphants) had smaller bodies and eyes, undeveloped inner ear, enlarged pericardial cavity, curved body and/or tail and larger yolk compared to control embryos of the same stages. The defects persisted in 6-9 days old larvae. We found that blocking leptin A function had little effect on the development of early brain (1 day old), but differentiation of both the morphant dorsal brain and retinal cells was severely disrupted in older (2 days old) embryos. Despite the enlarged pericardial cavity, differentiation of cardiac cells appeared to be similar to control embryos. Formation of the morphants' inner ear is also severely disrupted, which corroborates existing reports of leptin receptor expression in inner ear of both zebrafish and mammals. Co-injection of leptin A MO and recombinant leptin results in partial rescue of the wild-type phenotype. Our results suggest that leptin A plays distinct roles in zebrafish development.

Socially indiscriminate attachment behavior in the Strange Situation: convergent and discriminant validity in relation to caregiving risk, later behavior problems, and attachment insecurity.

Socially indiscriminate attachment behavior has been repeatedly observed among institutionally reared children. Socially indiscriminate behavior has also been associated with aggression and hyperactivity. However, available data rely heavily on caregiver report of indiscriminate behavior. In addition, few studies have been conducted with samples of home-reared infants exposed to inadequate care. The current study aimed to develop a reliable laboratory measure of socially indiscriminate forms of attachment behavior based on direct observation and to validate the measure against assessments of early care and later behavior problems among home-reared infants. Strange Situation episodes of 75 socially at-risk mother-infant dyads were coded for infant indiscriminate attachment behavior on the newly developed Rating for Infant-Stranger Engagement. After controlling for infant insecure-organized and disorganized behavior in all analyses, extent of infant-stranger engagement at 18 months was significantly related to serious caregiving risk (maltreatment or maternal psychiatric hospitalization), observed quality of disrupted maternal affective communication, and aggressive and hyperactive behavior problems at age 5. Results are discussed in relation to the convergent and discriminant validity of the new measure and to the potential utility of a standardized observational measure of indiscriminate attachment behavior. Further validation is needed in relation to caregiver report measures of indiscriminate behavior.