Mothering from the Inside Out (MIO) is a mentalization-based parenting intervention developed to address challenges common among mothers experiencing substance use disorders (SUDs) and previously deemed effective when delivered by research clinicians. This randomized clinical trial was designed to test the efficacy of MIO when delivered by community-based addiction counselors in Connecticut, USA. Ninety-four mothers [M(SD)age = 31.01(4.01) years; 75.53% White] caring for a child 11-60 months of age were randomly assigned to participate in 12 sessions of either MIO or psychoeducation. Caregiving, psychiatric, and substance use outcomes were assessed repeatedly from baseline through 12-week follow-up. Mothers who participated in MIO showed decreased certainty about their childs mental states, and decreased depression; their children demonstrated increased clarity of cues. Participation in MIO was not associated with the same degree of improvement that was observed in prior trials where MIO was delivered by research clinicians. However, when delivered by community-based clinicians, MIO may be protective against a deterioration in caregiving over time often seen in mothers with addictions. The drop in efficacy of MIO in this trial raises questions about intervention-intervenor fit. Research should examine factors influencing MIO effectiveness to close the science-to-service gap common in the dissemination of empirically validated interventions.

In this study, we replicated a rigorous test of the proposed mechanisms of change associated with Mothering from the Inside out (MIO), an evidence-based parenting therapy that aims to enhance maternal reflective functioning and mental representations of caregiving in mothers enrolled in addiction treatment and caring for young children. First, using data from 84 mothers who enrolled in our second randomized controlled trial, we examined whether therapist fidelity to core MIO treatment components predicted improvement in maternal reflective functioning and mental representations of caregiving, even after taking fidelity to non-MIO components into account. Next, we examined whether improvement in directly targeted outcomes (e.g., maternal mentalizing and mental representations of caregiving) led to improvements in the indirectly targeted outcome of maternal caregiving sensitivity, even after controlling for other plausible competing mechanisms (e.g., improvement in maternal psychiatric distress and substance use). Third, we examined whether improvement in targeted parenting outcomes (e.g., maternal mentalizing, mental representations of caregiving and caregiving sensitivity) was associated in improvement in child attachment status, even after controlling for competing mechanisms (e.g., improvement in maternal psychiatric distress and substance use). Finally, we examined whether improvement in maternal mentalizing and caregiving representations was associated with a reduction in relapse to substance use. Support was found for the first three tests of mechanisms but not the fourth. Implications for future research and intervention development are discussed.

Mothers with histories of alcohol and drug addiction have shown greater difficulty parenting young children than mothers with no history of substance misuse. This study was the second randomized clinical trial testing the efficacy of Mothering From the Inside Out (MIO), a 12-week mentalization-based individual therapy designed to address psychological deficits commonly associated with chronic substance use that also interfere with the capacity to parent young children. Eighty-seven mothers caring for a child between 11 and 60 months of age were randomly assigned to receive 12 sessions of MIO versus 12 sessions of parent education (PE), a psychoeducation active control comparison. Maternal reflective functioning, representations of caregiving, mother-child interaction quality, and child attachment were evaluated at baseline and posttreatment and 3-month follow-up. Mother-child interaction quality was assessed again at 12-month follow-up. In comparison with PE mothers, MIO mothers demonstrated a higher capacity for reflective functioning and representational coherence at posttreatment and 3-month follow-up. At 12-month follow-up, compared to PE cohorts, MIO mothers demonstrated greater sensitivity, their children showed greater involvement, and MIO dyads showed greater reciprocity. As addiction severity increased, MIO also appeared to serve as a protective factor for maternal reflective functioning, quality of mother-child interactions, and child attachment status. Results demonstrate the promise of mentalization-based interventions provided concomitant with addiction treatment for mothers and their young children.

Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene (BHLHE41) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin, also known as hypocretin (Hcrt), gene expression is increased in the mouse model expressing the mutant hDEC2 transgene (hDEC2-P384R). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal. In cell culture, DEC2 suppressed prepro-orexin promoter-luc (ore-luc) expression through cis-acting E-box elements. The mutant DEC2 has less repressor activity than WT-DEC2, resulting in increased orexin expression. DEC2-binding affinity for the prepro-orexin gene promoter is decreased by the P384R mutation, likely due to weakened interaction with other transcription factors. In vivo, the decreased immobility time of the mutant transgenic mice is attenuated by an orexin receptor antagonist. Our results suggested that DEC2 regulates sleep/wake duration, at least in part, by modulating the neuropeptide hormone orexin.

Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene (BHLHE41) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin, also known as hypocretin (Hcrt), gene expression is increased in the mouse model expressing the mutant hDEC2 transgene (hDEC2-P384R). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal. In cell culture, DEC2 suppressed prepro-orexin promoter-luc (ore-luc) expression through cis-acting E-box elements. The mutant DEC2 has less repressor activity than WT-DEC2, resulting in increased orexin expression. DEC2-binding affinity for the prepro-orexin gene promoter is decreased by the P384R mutation, likely due to weakened interaction with other transcription factors. In vivo, the decreased immobility time of the mutant transgenic mice is attenuated by an orexin receptor antagonist. Our results suggested that DEC2 regulates sleep/wake duration, at least in part, by modulating the neuropeptide hormone orexin.

Although numerous studies have demonstrated that poor sleep increases the development of AD, direct evidence elucidating the benefits of good sleep on the AD pathogenesis is lacking. Familial Natural Short Sleepers (FNSS) are genetically wired to have lifelong reduction in nightly sleep duration without evident consequence on cognitive demise, implying that they may have better sleep quality. Here we investigated two FNSS mutations, DEC2-P384R and Npsr1-Y206H, on the development of tau and amyloid pathology in AD-like mouse models. We found that the development of tau pathology is attenuated in the hippocampus of tau mice carrying FNSS mutations. We also found that DEC2-P384R;5XFAD and female Npsr1-Y206H;5XFAD mice exhibit significantly less amyloid plaques than control mice at 6 months of age. Together, these results reveal that these two FNSS alleles are strong genetic modifiers of AD pathology and may confer resilience to the progression of tau pathology and amyloid plaque formation in neurodegeneration.

Sleep deprivation can generate inflammatory responses in the central nervous system. In turn, this inflammation increases sleep drive, leading to a rebound in sleep duration. Microglia, the innate immune cells found exclusively in the CNS, have previously been found to release inflammatory signals and exhibit altered characteristics in response to sleep deprivation. Together, this suggests that microglia may be partially responsible for the brain's response to sleep deprivation through their inflammatory activity. In this study, we ablated microglia from the mouse brain and assessed resulting sleep, circadian, and sleep deprivation phenotypes. We find that microglia are dispensable for both homeostatic sleep and circadian function and the sleep rebound response to sleep deprivation. However, we uncover a phenomenon by which microglia appear to be essential for the protection of fear-conditioning memories formed during the recovery sleep period following a period of sleep deprivation. This phenomenon occurs potentially through the upregulation of synaptic-homeostasis related genes to protect nascent dendritic spines that may be otherwise removed or downscaled during recovery sleep. These findings further expand the list of known functions for microglia in synaptic modulation.

Familial Advanced Sleep Phase (FASP) is a heritable human sleep phenotype characterized by very early sleep and wake times. We identified a missense mutation in the human Cryptochrome 2 (CRY2) gene that co-segregates with FASP in one family. The mutation leads to replacement of an alanine residue at position 260 with a threonine (A260T). In mice, the CRY2 mutation causes a shortened circadian period and reduced phase-shift to early-night light pulse associated with phase-advanced behavioral rhythms in the light-dark cycle. The A260T mutation is located in the phosphate loop of the flavin adenine dinucleotide (FAD) binding domain of CRY2. The mutation alters the conformation of CRY2, increasing its accessibility and affinity for FBXL3 (an E3 ubiquitin ligase), thus promoting its degradation. These results demonstrate that CRY2 stability controlled by FBXL3 plays a key role in the regulation of human sleep wake behavior.

Sleep is a crucial physiological process for our survival and cognitive performance, yet the factors controlling human sleep regulation remain poorly understood. Here, we identified a missense mutation in a G protein-coupled neuropeptide S receptor 1 (NPSR1) that is associated with a natural short sleep phenotype in humans. Mice carrying the homologous mutation exhibited less sleep time despite increased sleep pressure. These animals were also resistant to contextual memory deficits associated with sleep deprivation. In vivo, the mutant receptors showed increased sensitivity to neuropeptide S exogenous activation. These results suggest that the NPS/NPSR1 pathway might play a critical role in regulating human sleep duration and in the link between sleep homeostasis and memory consolidation.

Ground-based measurement of the spatial distribution of soil moisture can be difficult because sampling is essentially made at a point and the choice of both sample depth and sample spacing affects the interpretation of the measurements. Hydrological interest has generally been in soil moisture of the root zone. Microwave Remote Sensing methods are now available that allow the interpretation of spatial distributions of soil moisture, however, their signals respond to moisture in the upper few centimetres of soil. These instruments are still being developed, but one of the questions surrounding their application is how to interpret the surface moisture in a hydrological context. In this study we compare measurements of soil moisture in 0-30 cm of soil with those in 0-6 cm to examine how representative this surface measure is with regard to the root zone. Detailed spatial measurements of soil moisture were conducted at three pasture sites in the 50 km2 Mahurangi River catchment of northern New Zealand as part of a comprehensive hydrology project; MARVEX (MAhurangi River Variability EXperiment). In three field sites, on each of three occasions, field measurements were made using both 30 and 6 cm dielectric-based instruments. Spatial grids of several hundred moisture measurements were collected over 0-30 cm and compared with those collected simultaneously over 0-6 cm. Results indicate that temporal and spatial issues interfere with correlation of the two sets of series. Rapid wetting of 0-6 cm compared with 0-30 cm is seen following storm activity. Some evidence of the decoupling of moisture content response is also evident when sites are measured on days following a storm. Rapid, but not unrealistic, response to intense rainfall was also observed. Implications are that detailed and accurate knowledge of local soil conditions and a sound model of soil water redistribution are required before surface soil moisture measurements can be used to infer root zone behaviour. Such knowledge was not available in this study, from either published data or field observation. In this study, without suitable a priori knowledge, soil property information was found via calibration. © 2003 Elsevier Science B.V. All rights reserved.