Nutrient Abundance Signals the Changing of the Seasons by Phosphorylating PER2.

The circadian clock synchronizes metabolic and behavioral cycles with the rotation of the Earth by integrating environmental cues, such as light. Nutrient content also regulates the clock, though how and why this environmental signal affects the clock remains incompletely understood. Here, we elucidate a role for nutrient in regulating circadian alignment to seasonal photoperiods. High fat diet (HFD) promoted entrainment to a summer light cycle and inhibited entrainment to a winter light cycle by phosphorylating PER2 on serine 662. PER2-S662 phospho-mimetic mutant mice were incapable of entraining to a winter photoperiod, while PER2-S662 phospho-null mutant mice were incapable of entraining to a summer photoperiod, even in the presence of HFD. Multi-omic experimentation in conjunction with isocaloric hydrogenated-fat feeding, revealed a role for polyunsaturated fatty acids in nutrient-dependent seasonal entrainment. Altogether, we identify the mechanism whereby nutrient content shifts circadian rhythms to anticipate seasonal photoperiods in which that nutrient state predominates. HIGHLIGHTS: High fat diet promotes entrainment to summer but inhibits entrainment to winter.Calorie restriction promotes entrainment to winter but inhibits entrainment to summer.PER2-S662 phosphorylation is required for nutritional regulation of seasonal circadian entrainment.Dietary polyunsaturated fatty acids regulate seasonal circadian entrainment.

Seasonally increasing parasite load is associated with microbiome dysbiosis in wild bumblebees.

The microbiome is increasingly recognized for its complex relationship with host fitness. Bumblebees are host to a characteristic gut microbiome community that is derived and reinforced through social contact between individuals. The bumblebee microbiome is species-poor, and primarily composed from a small number of core taxa that are associated with the greater tribe of corbiculate bees. Experimental findings support a role for the core bumblebee microbiome in resistance to severe infections by a common trypanosomal parasite, Crithidia bombi. However, most studies have been small in scale, often considering just one or two bumblebee species, or making use of commercially-reared bees. To better understand the microbiome diversity of wild populations, we have deeply sampled field populations of ten sympatric species found throughout central and down east Maine in a three-year microbiome field survey. We have used 16S amplicon sequencing to produce microbiome community profiles, and qPCR to screen samples for infections by Crithidia bombi. The breadth of our dataset has enabled us to test for seasonal and interspecific trends in the microbiome community. Controlling for these external sources of variation, we have identified microbial factors associated with infection and parasite load that support the role of the core microbiome in resistance to severe infection.

Self-report measure of parental reflective functioning: A study of reliability and validity across three samples of varying clinical risk.

The Parental Reflective Functioning Questionnaire (PRFQ) provides an efficient way to measure a parent's capacity to recognize their child's mental states and to understand the relationship between underlying mental states and behavior. To date, limited work evaluates its psychometric properties beyond initial validation studies. Here we examined the reliability and validity of the PRFQ in three samples of varying clinical risk (e.g., community sample, previous mental health diagnosis, substance use disorder diagnosis). Across samples, the majority (e.g., 75%-78%) of mothers identified as White; all mothers were from the USA. We compared the PRFQ to task-based measures of mentalization, the Parent Development Interview (PDI), and measures of the parent-child relationship. The PRFQ was a reliable measure across samples, and it was associated in theoretically consistent ways with task-based measures of mentalization. Parental RF across the PDI and PRFQ were not highly correlated in a sample of mothers with substance use disorders. Existing RF measures may be tapping into a different component of the broader construct of parental reflective functioning (PRF). The PRFQ was further validated by demonstrating relationships with parent-report measures of the parent-child relationship. Taken together, these findings provide additional support for the reliability and validity of the PRFQ.

El Cuestionario del Funcionamiento con Reflexión del Progenitor (PRFQ) aporta una manera eficaz de medir la capacidad del progenitor para reconocer los estados mentales de su niño y comprender la relación entre los estados mentales subyacentes y el comportamiento. A la fecha, un trabajo limitado evalúa sus propiedades sicométricas más allá de los estudios de validación inicial. Aquí examinamos la confiabilidad y validez del PRFQ en tres grupos muestra de riesgo clínico variado (v.g. grupo comunitario, previa diagnosis de salud mental, diagnosis de trastorno por uso de sustancias). A través de los grupos muestra, la mayoría (v.g., 75-78%) de las madres se identifican como blancas; todas las madres eran de los Estados Unidos. Comparamos el PRFQ con medidas de mentalización basadas en tareas, la Entrevista del Desarrollo del Progenitor (PDI), y medidas de la relación progenitor-niño. El PRFQ fue una medida confiable a lo largo de los grupos muestra, y se asoció de maneras teoréticamente consistentes con las medidas de mentalización basadas en tareas. El funcionamiento con reflexión del progenitor a lo largo del PDI y PRFQ no se correlacionaron altamente en un grupo muestra de madres con trastornos de uso de sustancias. Las medidas del funcionamiento con reflexión existentes pudieran sacar provecho de un componente diferente de la más amplia edificación del funcionamiento con reflexión del progenitor. Se validó además el PRFQ por medio de demostrar las relaciones con las medidas auto reportadas por el progenitor de la relación progenitor-niño. Tomados en conjunto, estos resultados aportan un apoyo adicional para la confiabilidad y validez del PRFQ.

Le Questionnaire de Fonctionnement de Réflexion Parental (QFRP) offre une manière efficace de mesurer la capacité d'un parent à reconnaître les états mentaux de leur enfant et de comprendre la relation entre les états mentaux sous-jacents et le comportement. Jusqu'à présent peu d'études ont évalué ses propriétés psychométriques au-delà des études initiales de validation. Nous examinons ici la fiabilité et la validité du QFRP chez trois échantillons de risque clinique varié (soit un échantillon communautaire, un diagnostic de santé mentale précédent, un diagnostic de trouble lié à l'usage d'une substance). Au travers des échantillons la majorité (c'est-à-dire 75-78%) des mères se sont identifiées comme étant blanches et toutes les mères étaient américaines (des USA). Nous avons comparé le QFRP à des mesures de mentalisation faites à partir d'une tâche, à l'Entretien de Développement du Parent (en anglais Parent Development Interview, soit PDI), et à des mesures de la relation parent-enfant. Le QFRP s'est avéré être une mesure fiable au travers des échantillons et était lié de manières théoriquement cohérentes à des mesures de mentalisation (basées sur des tâches). Le FR parental au travers du PDI et le QFRP n'étaient pas fortement liés chez un échantillon de mères avec un trouble lié à l'usage d'une substance. Il est possible que les mesures FR qui existent puisent dans un composant différent de la structure plus large du fonctionnement de réflexion parental, Le QFRP a été en outre validé par la démonstration de la relation entre les mesures rapportées par les parents de la relation parent-enfant. Pris dans l'ensemble ces résultats offrent un soutien supplémentaire pour la fiabilité et la validité du QFRP.

Enhancing parental reflective functioning: A special tribute to the life and work of Nancy E. Suchman, PhD.

Nancy E. Suchman's contributions to the fields of infant mental health, maternal reflective functioning, and attachment-based intervention will have long-lasting impacts. In particular, through the development and dissemination of her intervention program, Mothering from the Inside Out (MIO), she innovated a way of working with mothers with substance use disorders that represented a paradigm shift within the field of addiction. In this introduction to the special issue, written to honor her life and work, we review Nancy's background and briefly describe her academic accomplishments. The special issue contains nine qualitative and quantitative research reports written by Nancy's colleagues and their collaborators. All nine papers pertain to the theme of understanding, measuring, and promoting parents' capacity for reflective functioning. Four provide findings that advance our understanding of parental reflective functioning. The other five highlight insights from continuing evaluations of MIO, including new adaptations of the model. To introduce the special issue, we provide an overview of the scope of the work done within these projects. Finally, the special issue concludes with two commentaries contributed by Linda Mayes and Arietta Slade, leading scholars within the field who were also Nancy's close colleagues. Both provide insight into Nancy's impact on the field.

Las contribuciones de Nancy E Suchman a los campos de la salud mental infantil, del funcionamiento materno con reflexión y de la intervención con base en la afectividad tendrá un impacto duradero. Particularmente a través del desarrollo y divulgación de su programa de intervención, Cuidados Maternales de Dentro hacia Afuera (MIO), ella es innovadora de una manera de trabajar con madres con trastornos de uso de sustancias, lo cual representa un cambio de paradigma dentro del campo de la adicción. En esta introducción al número especial, dedicado en honor a su vida y trabajo, se examina la trayectoria profesional de Nancy y brevemente se describen sus logros académicos. El número especial contiene nueve reportes de investigación cualitativa y cuantitativa, escritos por colegas y colaboradores de Nancy. Todos los nueve ensayos se refieren al tema de cómo comprender, medir y promover la capacidad de los progenitores para el funcionamiento con reflexión. Cuatro de ellos aportan resultados que profundizan nuestra comprensión del funcionamiento con reflexión del progenitor. Los otros cinco resaltan ideas de las continuas evaluaciones del MIO, incluyendo nuevas adaptaciones del modelo. Para introducir el número especial, presentamos una revisión general del alcance del trabajo llevado a cabo en estos proyectos. Finalmente, el número especial concluye con dos comentarios que son contribución de Linda Mayes y Arietta Slade, líderes investigadoras profesionales dentro del campo y quienes también fueron colegas allegadas a Nancy. Ambas aportan ideas sobre el impacto que Nancy tiene en su campo.

Les contributions de Nancy E. Suchman aux domaines de la santé mentale du nourrisson et de la petite enfance, du fonctionnement de réflexion maternel et de l'intervention basée sur l'attachement auront des impacts à long terme. Plus particulièrement, au travers du développement et de la dissémination de son programme d'intervention Mothering from the Inside Out (MOI, en français le Maternage de l'Intérieur), elle a tracé une nouvelle voix innovatrice de travail avec des mères toxicomanes, voix représentant un changement de paradigme au sein même du domaine de l'addiction. Dans cette introduction à ce numéro spécial, écrite afin d'honorer sa vie et son travail, nous passons en revue le contexte personnel de Nancy et décrivons brièvement ses réalisations académiques. Ce numéro spécial contient neuf rapports de recherches qualitatives et quantitatives écrits par les collègues de Nancy et ses collaboratrices et collaborateurs. Ces neufs articles portent sur le thème de la compréhension, la mesure et la promotion de la capacité des parents à se consacrer au fonctionnement de réflexion. Quatre de ces articles offrent des conclusions qui font avancer notre compréhension du fonctionnement de réflexion parental. Les autres cinq articles mettent en lumière le travail émanant d'évaluations en cours du MOI, y compris de nouvelles adaptations du modèle. Pour présenter ce numéro spécial nous offrons un survol de la portée du travail fait au sein de ces projets. Enfin, ce numéro spécial conclut avec deux commentaires présentés par Linda Mayes et Arietta Slade, grandes spécialistes au sein de ce domaine de recherche, qui étaient aussi les proches collègues de Nancy. Elles nous offrent toutes deux un aperçu de l'impact qu'a eu Nancy sur ce domaine de recherches.

Mothering from the Inside Out: Results of a community-based randomized efficacy trial testing a mentalization-based parenting intervention for mothers with addictions.

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 child's 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.

Cuidados Maternales desde Dentro (MIO) es una intervención de crianza con base en la mentalización desarrollada para discutir los retos que son comunes entre las madres que experimentan trastornos de uso de sustancias (SUD) y que previamente eran considerados eficaces cuando los ofrecían los investigadores clínicos. Este ensayo clínico al azar se diseñó para examinar la efectividad de MIO cuando la ofrecen consejeros en asuntos de adicción con base en la comunidad, en Connecticut, Estados Unidos. Noventa y cuatro madres [M(SD) edad = 31.01(4.01) años; 75.53% blancas] con un niño de 11 a 60 meses de edad bajo su cuidado fueron asignadas al azar para participar en 12 sesiones, ya sea de MIO o de psicoeducación. Los resultados del cuidado prestado, los siquiátricos y los de uso de sustancia se evaluaron repetidamente a partir de los datos básicos hasta el seguimiento a las 12 semanas. Las madres que participaron en MIO mostraron una disminución en la certeza acerca de los estados mentales de sus niños, y una disminución en la depresión; sus niños demostraron un aumento en la claridad de las señales. La participación en MIO no se asoció con el mismo grado de mejoramiento que se observó en ensayos previos en los que MIO fue ofrecido por investigadores clínicos. Sin embargo, cuando es ofrecido por clínicos con base comunitaria, MIO pudiera servir de protección contra el deterioro de la prestación de cuidado a lo largo del tiempo, a menudo visto en madres con adicciones. La disminución de la efectividad de MIO en este ensayo genera preguntas acerca de cuán compenetrados está el interventor con la intervención. La investigación debe examinar factores que influyan en la efectividad de MIO para cerrar el vacío entre servicio y ciencia, común en la diseminación de las intervenciones empíricamente validadas.

Le maternage de l'intérieur (abrégé ici MIO pour reprendre l'anglais Mothering from the Inside Out) est une intervention de parentage basée sur la mentalisation, développée afin de répondre aux défis courants chez les mères ayant un trouble lié à l'usage d'une substance (TUS) et préalablement considérée comme efficace lorsque faite par des chercheurs cliniques. Cette étude clinique randomisée a été conçue pour tester l'efficacité du MIO lorsque offert par des intervenants en dépendance communautaires dans l'état du Connecticut aux Etats-Unis. Quatre-vingt-dix-neuf mères [M(SD)âge = 31,01(4,01) ans; 75,53% blanches] prenant soin d'un enfant de 11-60 mois ont été réparties au hasard pour participer soit au MIO soit à une psychoéducation. Les résultats de soins, les résultats psychiatriques et les résultats de toxicomanie ont été évalués de façon répétée de la base jusqu'au suivi à 12 semaines. Les mères ayant participé au MIO ont fait preuve d'une certitude diminuée à propos des états mentaux de leur enfant, et d'une dépression diminuée; leurs enfants ont fait preuve d'une clarté des indices accrue. La participation au MIO n'était pas liée au même degré d'amélioration qui a été observé dans les études préalables quand le MIO a été utilisé par des chercheurs cliniciens. Cependant, lorsqu'administré par des cliniciens communautaires, le MIO pourrait s'avérer protecteur d'une détérioration dans les soins au fil du temps que l'on voit souvent chez les mères toxicomanes. Le déclin d'efficacité du MIO dans cette étude soulève des questions quant à l'ajustement intervention-intervenant. Les recherches devraient se pencher sur les facteurs influençant l'efficacité du MIO pour réduire l'écart de la science au service dans la dissémination d'intervention validées empiriquement.

The origin of stability and high Co2+/3+ redox utilization for FePO4-coated LiCo0.90Ti0.05PO4/MWCNT nanocomposites for 5 V class lithium ion batteries.

Highly-dispersed 10 wt% FePO4 (FP)-coated LiCo0.90Ti0.05PO4 (LCTP) was successfully synthesized within a multiwalled carbon nanotube matrix via our original ultracentrifugation process. 10 wt% FP-coated LCTP sample showed a higher discharge capacity of 116 mA h g-1 together with stable cycle performance over 99% of capacity retention at the 100th cycle in high voltage. A combination of TEM, XRD, XPS, and XAFS analyses suggests that (i) Ti4+-substitution increases the utilization of Co redox (capacity increase) in LCP crystals by suppressing the Co3O4 formation and creating the vacancies in Co sites, and (ii) the FP-coating brought about the Fe enrichment of the surface of LCTP which prevents an irreversible crystal structure change and electrolyte decomposition during cycling, resulting in the stable cycle performance.

Reflective functioning in mothers with addictions: Differential relationships involving family history of mental illness and substance use.

Parental reflective functioning (RF) is often cited as an important domain in which mothers with addictions struggle in their roles as parents, though the links between addiction and RF remain unclear. Exposure to attachment trauma associated with parental mental illness and substance use is commonly associated with both addiction and lower RF. We thus examined how family history of parental mental illness and substance use may relate to the RF of mothers with addictions. One hundred ninety-four mothers in outpatient substance use treatment completed the Parent Development Interview and provided information about whether their mothers and fathers experienced mental illness or problems with substance use. Univariate ANOVAs revealed an interaction between family history of maternal mental illness and maternal substance use. Among mothers with a history of maternal substance use, those with a history of maternal mental illness had higher RF than those who had no history of maternal mental illness. Among mothers who did not report a family history of maternal mental illness, mothers who had a family history of maternal substance use exhibited significantly lower RF than mothers with no family history of maternal substance use. Exposure to paternal mental illness or substance use was not associated with mothers' RF. These findings highlight the importance of disentangling the contributions of attachment trauma to mothers' RF and utilizing interventions that support mothers' capacity to reflect about how their early experiences of being cared for by a mother with a mental illness or addiction may impact their current caregiving behaviors.

Familial natural short sleep mutations reduce Alzheimer pathology in mice.

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.

Microglia are involved in the protection of memories formed during sleep deprivation.

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.

Mothering from the Inside Out: Addressing the Intersection of Addiction, Adversity, and Attachment with Evidence-Based Parenting Intervention.

Purpose of Review: Mothers with substance use disorders are often referred for parenting support, though commonly available programs may miss the mark for families impacted by addiction. This may be related to a lack of attention to children's emotional needs, mothers' histories of adversity, and the neurobiological differences seen in mothers with addictions. We review the implications of addiction, adversity, and attachment for parenting interventions. We then describe Mothering from the Inside Out (MIO), an evidence-based parenting intervention designed specifically for mothers with addictions. Recent Findings: Evidence from clinical trials suggests that MIO improves outcomes for two generations: both mothers with addictions and their children. Recent trials demonstrate that MIO may be delivered effectively by community-based clinicians and may be beneficial for parents with other chronic stressors. Summary: Addressing addiction, adversity, and attachment simultaneously may have a positive synergistic effect. Future research should study the implementation of MIO in real-world settings and examine the impact of MIO on maternal neurobiology.

A Mitochondrial tRNA Mutation Causes Axonal CMT in a Large Venezuelan Family.

OBJECTIVE: The objective of this study was to identify the genetic cause for progressive peripheral nerve disease in a Venezuelan family. Despite the growing list of genes associated with Charcot-Marie-Tooth disease, many patients with axonal forms lack a genetic diagnosis. METHODS: A pedigree was constructed, based on family clinical data. Next-generation sequencing of mitochondrial DNA (mtDNA) was performed for 6 affected family members. Muscle biopsies from 4 family members were used for analysis of muscle histology and ultrastructure, mtDNA sequencing, and RNA quantification. Ultrastructural studies were performed on sensory nerve biopsies from 2 affected family members. RESULTS: Electrodiagnostic testing showed a motor and sensory axonal polyneuropathy. Pedigree analysis revealed inheritance only through the maternal line, consistent with mitochondrial transmission. Sequencing of mtDNA identified a mutation in the mitochondrial tRNAVal (mt-tRNAVal ) gene, m.1661A>G, present at nearly 100% heteroplasmy, which disrupts a Watson-Crick base pair in the T-stem-loop. Muscle biopsies showed chronic denervation/reinnervation changes, whereas biochemical analysis of electron transport chain (ETC) enzyme activities showed reduction in multiple ETC complexes. Northern blots from skeletal muscle total RNA showed severe reduction in abundance of mt-tRNAVal , and mildly increased mt-tRNAPhe , in subjects compared with unrelated age- and sex-matched controls. Nerve biopsies from 2 affected family members demonstrated ultrastructural mitochondrial abnormalities (hyperplasia, hypertrophy, and crystalline arrays) consistent with a mitochondrial neuropathy. CONCLUSION: We identify a previously unreported cause of Charcot-Marie-Tooth (CMT) disease, a mutation in the mt-tRNAVal , in a Venezuelan family. This work expands the list of CMT-associated genes from protein-coding genes to a mitochondrial tRNA gene. ANN NEUROL 2020;88:830-842.

Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation.

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.

A Rare Mutation of ß1-Adrenergic Receptor Affects Sleep/Wake Behaviors.

Sleep is crucial for our survival, and many diseases are linked to long-term poor sleep quality. Before we can use sleep to enhance our health and performance and alleviate diseases associated with poor sleep, a greater understanding of sleep regulation is necessary. We have identified a mutation in the ß1-adrenergic receptor gene in humans who require fewer hours of sleep than most. In vitro, this mutation leads to decreased protein stability and dampened signaling in response to agonist treatment. In vivo, the mice carrying the same mutation demonstrated short sleep behavior. We found that this receptor is highly expressed in the dorsal pons and that these ADRB1+ neurons are active during rapid eye movement (REM) sleep and wakefulness. Activating these neurons can lead to wakefulness, and the activity of these neurons is affected by the mutation. These results highlight the important role of ß1-adrenergic receptors in sleep/wake regulation.

A randomized pilot trial of two parenting interventions for fathers in residential substance use disorder treatment.

Residential substance misuse treatment programs for men typically do not integrate treatment for intimate partner violence (IPV) or parenting despite significant overlap between substance misuse, IPV and child maltreatment. A randomized trial compared two fatherhood focused interventions in 6-month residential substance misuse treatment programs. Fathers for Change (F4C) is an integrated intervention targeting IPV and child maltreatment. Dads 'n' Kids (DNK) is a psychoeducational intervention focused on child development and behavioral parenting skills. Sixty-two fathers were randomly assigned to F4C or DNK. They received 12 weeks of individual treatment while in the residential facility and were offered 4 aftercare sessions following discharge. They were assessed prior to treatment, at the time of residential discharge, following completion of the intervention booster sessions, and 3 months following intervention. Overall, both groups showed significant reductions in affect dysregulation, anger, and IPV. F4C fathers showed significantly greater decreases in affect dysregulation problems. There were no significant differences between groups on IPV but men who received F4C may have been less likely to use substances after leaving residential treatment. Integration of fatherhood focused interventions were possible and welcomed by residents at the facilities. F4C showed some benefit over DNK in terms of affect dysregulation symptoms and substance use relapse.

TIMELESS mutation alters phase responsiveness and causes advanced sleep phase.

Many components of the circadian molecular clock are conserved from flies to mammals; however, the role of mammalian Timeless remains ambiguous. Here, we report a mutation in the human TIMELESS (hTIM) gene that causes familial advanced sleep phase (FASP). Tim CRISPR mutant mice exhibit FASP with altered photic entrainment but normal circadian period. We demonstrate that the mutation prevents TIM accumulation in the nucleus and has altered affinity for CRY2, leading to destabilization of PER/CRY complex and a shortened period in nonmature mouse embryonic fibroblasts (MEFs). We conclude that TIM, when excluded from the nucleus, can destabilize the negative regulators of the circadian clock, alter light entrainment, and cause FASP.

Does maternal reflective functioning mediate associations between representations of caregiving with maternal sensitivity in a high-risk sample?

Although it is known that mothers with substance abuse disorders struggle to provide adequate parenting to their children, little is understood about the mechanisms behind this. This cross-sectional study uses an attachment perspective to examine whether reflective functioning mediates the relationship between mental representations of caregiving and maternal sensitivity, in an ethnically diverse sample of 142 substance-abusing mothers (M [SD] = 29.83 [5.79] years of age) and their toddlers (M [SD] = 24.04 [15.15] months of age). Data were baseline measures from two randomized controlled trials. The three variables of primary interest were positively correlated. As expected, there was a significant relationship between mental representations of caregiving and maternal sensitivity that was largely explained by reflective functioning. Confounding and alternate explanations were not supported by a secondary data analyses. The findings underscore the importance of reflective functioning in positive parenting within this high-risk population of mothers, and they provide support for the development of attachment-based interventions.

DEC2 modulates orexin expression and regulates sleep.

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.

Does improvement in maternal attachment representations predict greater maternal sensitivity, child attachment security and lower rates of relapse to substance use? A second test of Mothering from the Inside Out treatment mechanisms.

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.

Novel Small-Molecule Inhibitors of Protein Kinase C Epsilon Reduce Ethanol Consumption in Mice.

BACKGROUND: Despite the high cost and widespread prevalence of alcohol use disorders, treatment options are limited, underscoring the need for new, effective medications. Previous results using protein kinase C epsilon (PKCε) knockout mice, RNA interference against PKCε, and peptide inhibitors of PKCε predict that small-molecule inhibitors of PKCε should reduce alcohol consumption in humans. METHODS: We designed a new class of PKCε inhibitors based on the Rho-associated protein kinase (ROCK) inhibitor Y-27632. In vitro kinase and binding assays were used to identify the most potent compounds. Their effects on ethanol-stimulated synaptic transmission; ethanol, sucrose, and quinine consumption; ethanol-induced loss of righting; and ethanol clearance were studied in mice. RESULTS: We identified two compounds that inhibited PKCε with Ki <20 nM, showed selectivity for PKCε over other kinases, crossed the blood-brain barrier, achieved effective concentrations in mouse brain, prevented ethanol-stimulated gamma-aminobutyric acid release in the central amygdala, and reduced ethanol consumption when administered intraperitoneally at 40 mg/kg in wild-type but not in Prkce-/- mice. One compound also reduced sucrose and saccharin consumption, while the other was selective for ethanol. Both transiently impaired locomotion through an off-target effect that did not interfere with their ability to reduce ethanol intake. One compound prolonged recovery from ethanol-induced loss of righting but this was also due to an off-target effect since it was present in Prkce-/- mice. Neither altered ethanol clearance. CONCLUSIONS: These results identify lead compounds for development of PKCε inhibitors that reduce alcohol consumption.

IMPLEMENTATION OF AN EVIDENCED-BASED PARENTING PROGRAM IN A COMMUNITY MENTAL HEALTH SETTING.

The process of mental health intervention implementation with vulnerable populations is not well-described in the literature. The authors worked as a community-partnered team to adapt and pilot an empirically supported intervention program for mothers of infants and toddlers in an outpatient mental health clinic that primarily serves a low-income community. We used qualitative ethnographic methods to document the adaption of an evidence-based intervention, Mothering from the Inside Out, and the pilot implementation in a community mental health clinic. Seventeen mothers and their identified 0- to 84-month-old children were enrolled in the study. Key lessons from this implementation include (a) the importance of formative work to build community relationships and effectively adapt the intervention to meet the needs of the therapists and their clients, (b) the importance of designing plans for training and reflective supervision that fit within the flow of the clinic and can tolerate disruptions, and (c) that use of an interdisciplinary approach is feasible with the development of a plan for communication and the support of a trained reflective clinical supervisor. These key lessons advance the scientific knowledge available to healthcare managers and researchers who are looking to adapt mental health clinical interventions previously tested in clinical trials to implementation in community settings.