Maternal Depression Trajectories Relate to Youths' Psychosocial and Cognitive Functioning at Adolescence and Young Adulthood.

This study evaluated how patterns of mothers' depressive symptoms across their child's childhood relate to children's psychosocial adjustment at adolescence and young adulthood and to cognitive functioning at adolescence. Depressive symptoms were measured in 1,273 mothers when their children were 1, 5, 10, and 14.6 years of age. Children (53.5% male; n = 1,024) completed the Youth Self-Report at adolescence (M = 14.6y), and the Adult Self-Report in young adulthood (M = 20.5y; n = 817) to assess internalizing and externalizing symptoms. Adolescents also completed standardized cognitive tests to assess verbal and mathematical skills. Growth mixture modeling analyses identified four patterns of maternal depressive symptom trajectories: infrequent (55%), increasing at adolescence (20%), decreasing at adolescence (14%), and chronic severe (11%). Results indicated that exposure to maternal depression of any duration, severity or time period during childhood portended higher levels of externalizing and attention problems at both adolescence and adulthood and higher levels of internalizing problems at adulthood. Adolescents whose mothers had chronic severe depressive symptoms had lower language, vocabulary, reading comprehension and mathematical test scores than youth whose mothers had stable infrequent depressive symptoms. Findings illustrate the significance and long-term ramifications of mothers' depressed mood for their children's mental and psychosocial health into adulthood. Findings also demonstrate that the lower cognitive abilities among children of severely depressed mothers persist beyond childhood and pertain to a broad range of cognitive abilities.

Persistent Encopresis, Enuresis, and Anxiety in a 7-Year-Old Girl.

CASE: Sonia is a 7-year-old old girl who was referred to the Developmental-Behavioral Pediatrics Clinic by the Pediatric Urology Clinic because of persistent wetting and soiling behaviors. Since age 3 years, she has had a history of encopresis (and wetting) for which she has seen gastroenterology and urology specialists. The mother reports that Sonia has accidents almost daily, and she is not upset when sitting in her urine or feces. She dislikes going into the bathroom or sitting on the toilet by herself. She participated in a behavior modification program associated with the pediatric urology clinic, which helps children learn healthy voiding habits and achieve continence.Sonia also has anxious behaviors. She bites her nails and chews on her hair or shirt. She is afraid of small spaces such as those between the bed and the wall and needs to have stuffed animals cover them. Other instances that trigger her anxious behaviors include loud noises, having a substitute teacher, being separated from her mother, and going to certain bathrooms or new places. She also has severe tantrums, which involve throwing and breaking objects, kicking, and hitting her head against doors.A cognitive behavioral therapy program was recommended to target anxiety symptoms, in addition to timed toileting after meals and polyethylene glycol. At a clinic visit several months later, symptoms of anxiety, encopresis, and enuresis persisted. Cognitive behavior therapy was continued and sertraline 25 mg was prescribed for anxiety. In addition, she was referred to a pediatrician who specializes in relaxation techniques and hypnotherapy.Sonia showed modest improvement with these interventions. There were fewer episodes of angry outbursts and a decrease in soiling and wetting, but at times, but she continued to have intermittent periods of wetting and soiling and fear of going to the bathroom by herself persisted.(This Challenging Case extends observations reviewed in a previous Challenging Case: J Dev Behav Pediatr 2010;531:513-515; DOI: 10.1097/DBP.0b013e3181e5a464.).

Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.

Detection of low-affinity or transient interactions can be a bottleneck in our understanding of signaling networks. To address this problem, we developed an arrayed screening strategy based on protein complementation to systematically investigate protein-protein interactions in live human cells, and performed a large-scale screen for regulators of telomeres. Maintenance of vertebrate telomeres requires the concerted action of members of the Telomere Interactome, built upon the six core telomeric proteins TRF1, TRF2, RAP1, TIN2, TPP1, and POT1. Of the ∼12,000 human proteins examined, we identified over 300 proteins that associated with the six core telomeric proteins. The majority of the identified proteins have not been previously linked to telomere biology, including regulators of post-translational modifications such as protein kinases and ubiquitin E3 ligases. Results from this study shed light on the molecular niche that is fundamental to telomere regulation in humans, and provide a valuable tool to investigate signaling pathways in mammalian cells.

TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs.

In mammalian cells, the telomeric repeat binding factor (TRF) homology (TRFH) domain-containing telomeric proteins TRF1 and TRF2 associate with a collection of molecules necessary for telomere maintenance and cell-cycle progression. However, the specificity and the mechanisms by which TRF2 communicates with different signaling pathways remain largely unknown. Using oriented peptide libraries, we demonstrate that the TRFH domain of human TRF2 recognizes [Y/F]XL peptides with the consensus motif YYHKYRLSPL. Disrupting the interactions between the TRF2 TRFH domain and its targets resulted in telomeric DNA-damage responses. Furthermore, our genome-wide target analysis revealed phosphatase nuclear targeting subunit (PNUTS) and microcephalin 1 (MCPH1) as previously unreported telomere-associated proteins that directly interact with TRF2 via the [Y/F]XL motif. PNUTS and MCPH1 can regulate telomere length and the telomeric DNA-damage response, respectively. Our findings indicate that an array of TRF2 molecules functions as a protein hub and regulates telomeres by recruiting different signaling molecules via a linear sequence code.