Mania- and anxiety-like behavior and impaired maternal care in female diacylglycerol kinase eta and iota double knockout mice

Genome-wide association studies linked diacylglycerol kinase eta and iota to mood disorders, including bipolar disorder and schizophrenia, and both genes are expressed throughout the brain. Here, we generated and behaviorally characterized female mice lacking Dgkh alone, Dgki alone, and double Dgkh/Dgki-knockout (dKO) mice. We found that fewer than 30% of newborn pups raised by dKO females survived to weaning, while over 85% of pups survived to weaning when raised by wild-type (WT) females. Poor survival under the care of dKO mothers was unrelated to pup genotype. Moreover, pups from dKO dams survived when fostered by WT dams, suggesting the poor survival rate of dKO-raised litters was related to impaired maternal care by dKO dams. Nest building was similar between WT and dKO dams; however, some dKO females failed to retrieve any pups in a retrieval assay. Pups raised by dKO dams had smaller or absent milk spots and reduced weight, indicative of impaired nursing. Unlike WT females, postpartum dKO females showed erratic, panicked responses to cage disturbances. Virgin dKO females showed behavioral signs of anxiety and mania, which were not seen in mice lacking either Dgkh or Dgki alone. Our research indicates that combined deletion of Dgkh and Dgki impairs maternal behavior in the early postpartum period, and suggests female dKO mice model symptoms of mania and anxiety

TPH1A218C polymorphism and temperament in major depression

BACKGROUND: In major depression, one of the candidate genes possibly affecting the risk and severity of symptoms has been found to be tryptophan hydroxylase (TPH1). Variation in treatment response to antidepressive agents according to TPH1 genotype has also been found in several studies. However, the relationship between temperament and TPH1 genotype in major depression is poorly understood, as only one study has been published so far. There are no earlier studies on the interaction between temperament traits, antidepressive medication response and TPH1 genotype. This interaction was studied in 97 subjects with major depression treated for six weeks with selective serotonine reuptake inhibitors. METHODS: Temperament dimensions Harm Avoidance (HA), Novelty Seeking (NS), Reward Dependence (RD) and Persistence (P) scores at baseline (1) and endpoint (2) were rated with the Temperament and Character Inventory (TCI) and compared between TPH1 A218C genotypes. Multivariate analysis of co-variance (MANCOVA) was used to analyze the interaction between the TPH1 genotype, treatment response and the different temperament dimensions at baseline and endpoint. In the analysis model, treatment response was used as a covariate and TPH1 genotype as a factor. A post hoc analysis for an interaction between remission status and TPH1 A218C genotype at endpoint HA level was also performed. RESULTS: The number of TPH1 A-alleles was associated with increasing levels in NS1 and NS2 scores and decreasing levels in HA1 and HA2 scores between TPH1 A218C genotypes. In the MANCOVA model, TPH1 genotype and treatment response had an interactive effect on both HA1 and HA2 scores, and to a lesser degree on NS2 scores. Additionally, an interaction between remission status and TPH1 A218C genotype was found to be associated with endpoint HA score, with a more marked effect of the interaction between CC genotype and remission status compared to A-allele carriers. CONCLUSIONS: Our results suggest that in acute depression TPH1 A218C polymorphism and specifically the CC genotype together with the information on remission or treatment response differentiates between different temperament profiles and their changes

Evidence for an Association Between Hearing Impairment and Disrupted Sleep: Scoping Review

Purpose: Hearing impairment (HI) is the most common sensory impairment and may negatively impact sleep through reduced auditory input. Factors associated with HI, such as anxiety regarding communication in daily life, may also adversely impact an individual’s sleep. Here, research on the relationship between HI and sleep disruption was catalogued using scoping review methodology. Methods: A systematic strategy was employed to search various electronic databases. This review is reported according to Preferred Reporting Items for Systematic Review and Meta-analysis Scoping Review Extension (PRISMA-ScR). Results: Sixteen records met inclusion criteria. Studies have investigated sleep in HI as a primary aim in noise exposed workers or large surveys in older participants. Experimental and quasi-experimental studies report alterations to sleep architecture of potential neuroplastic origins. Studies reporting sleep as a secondary aim generally report poorer in sleep in HI participants. Conclusions: This scoping review has catalogued evidence that altered or negatively impacted sleep may be associated with HI. Potential confounding factors, mechanisms, and considerations for future research are discussed