Loneliness and psychotic-like experiences in middle-aged and older adults: the mediating role of selective attention to threat and external attribution biases.

OBJECTIVES: Loneliness has been associated with psychotic-like experiences (PLEs) in the general population, but the mechanisms underlying this association are poorly understood. Theoretical models, corroborated by empirical findings, signify the key role of biased cognition in both loneliness and psychosis. This study tested whether two cognitive biases - Selective Attention to Threat (ATB) and External Attribution Bias (EAB) - account for the association between loneliness and PLEs. METHOD: A convenience sample (n = 357) of middle-aged and older adults (aged 40+) was recruited online from the UK population. The parallel mediation model with two the aforementioned cognitive biases as mediators was tested. RESULTS: A mediation effect between loneliness and PLEs via ATB (ab1 = 0.441, 95% CI = [0.264, 0.646]) and EAB (ab2 = 0.354, 95% CI [0.124, 0.627] was established. This model remained significant after controlling for the current symptoms of anxiety and depression. CONCLUSION: Greater loneliness was associated with a higher rate of PLEs in the sample of middle-aged and older adults. This association was fully explained by ATB and EAB, independent of the current symptoms of anxiety and depression.

Manage Your Life Online: A Web-Based Randomized Controlled Trial Evaluating the Effectiveness of a Problem-Solving Intervention in a Student Sample.

BACKGROUND: Evidence for the efficacy of computer-based psychological interventions is growing. A number of such interventions have been found to be effective, especially for mild to moderate cases. They largely rely on psychoeducation and 'homework tasks', and are specific to certain diagnoses (e.g. depression). AIMS: This paper presents the results of a web-based randomized controlled trial of Manage Your Life Online (MYLO), a program that uses artificial intelligence to engage the participant in a conversation across any problem topic. METHOD: Healthy volunteers (n = 213) completed a baseline questionnaire and were randomized to the MYLO program or to an active control condition where they used the program ELIZA, which emulates a Rogerian psychotherapist. Participants completed a single session before completing post-study and 2-week follow-up measures. RESULTS: Analyses were per protocol with intent to follow-up. Both programs were associated with improvements in problem distress, anxiety and depression post-intervention, and again 2 weeks later, but MYLO was not found to be more effective than ELIZA. MYLO was rated as significantly more helpful than ELIZA, but there was no main effect of intervention on problem resolution. CONCLUSIONS: Findings are consistent with those of a previous smaller, laboratory-based trial and provide support for the acceptability and effectiveness of MYLO delivered over the internet for a non-clinical sample. The lack of a no-treatment control condition means that the effect of spontaneous recovery cannot be ruled out.

Discriminant diagnostic validity of paediatric bipolar disorder screening tests: A systematic review and meta-analysis.

INTRODUCTION: Bipolar disorders (BD) are among the most significantly impairing of childhood and adolescent psychiatric disorders. Although BD symptoms may begin in adolescence, they are frequently not diagnosed until adulthood, and accordingly BD scales could aid diagnostic assessment in paediatric populations. This review aims to synthesis the evidence for the accuracy of BD symptom index tests for discriminating BD from non-BD (other diagnoses or healthy controls) in paediatric population. Additionally, several theoretically relevant moderators of diagnostic accuracy were evaluated. METHODS: A systematic search across three databases were conducted from 1980 to 2022, augmented by grey literature database searches, citation chaining and contacting authors. Data from eligible studies were synthesized using meta-analysis. A multilevel model was fitted to account for nested effect sizes, with 31 potential moderators examined in univariate and multivariate models. RESULTS: Twenty-Eight studies were eligible, yielding 115 effect sizes for analysis. Meta-analytic modelling indicated BD symptom index tests have a high diagnostic accuracy (g = 1.300; 95% CI: 0.982 - 1.619; p < .001) in paediatric population. Accuracy was relative to the type of comparison group, index test content, index test informant and index test's scale or subscale. CONCLUSIONS: Screening tests based on mania content, caregiver report and non-healthy comparison groups have clinical utility in identifying paediatric BD. Other informant-and-content combination may not accurately identify paediatric BD. Unlike healthy controls, tests derived from studies using non-healthy comparison groups, represent BD symptom non-specificity and BD symptom overlap with other disorders, providing external validity and clinical utility.

Language use in depressed and non-depressed mothers and their adolescent offspring.

BACKGROUND: Approximately 10% of mothers experience depression each year, which increases risk for depression in offspring. Currently no research has analysed the linguistic features of depressed mothers and their adolescent offspring during dyadic interactions. We examined the extent to which linguistic features of mothers' and adolescents' speech during dyadic interactional tasks could discriminate depressed from non-depressed mothers. METHODS: Computer-assisted linguistic analysis (Linguistic Inquiry and Word Count; LIWC) was applied to transcripts of low-income mother-adolescent dyads (N = 151) performing a lab-based problem-solving interaction task. One-way multivariate analyses were conducted to determine linguistic features hypothesized to be related to maternal depressive status that significantly differed in frequency between depressed and non-depressed mothers and higher and lower risk offspring. Logistic regression analyses were performed to classify between dyads belonging to the two groups. RESULTS: The results showed that linguistic features in mothers' and their adolescent offsprings' speech during problem-solving interactions discriminated between maternal depression status. Many, but not all effects, were consistent with those identified in previous research using primarily written text, highlighting the validity and reliability of language behaviour associated with depressive symptomatology across lab-based and natural environmental contexts. LIMITATIONS: Our analyses do not enable to ascertain how mothers' language behaviour may have influenced their offspring's communication patterns. We also cannot say how or whether these findings generalize to other contexts or populations. CONCLUSION: The findings extend the existing literature on linguistic features of depression by indicating that mothers' depression is associated with linguistic behaviour during mother-adolescent interaction.

Linking childhood emotional abuse and adult depressive symptoms: The role of mentalizing incapacity.

BACKGROUND: Accumulated evidence suggests that childhood emotional abuse is particularly related to adulthood depression. However, this connection demands further explanation regarding potential intermediate factors. OBJECTIVE: This study aims to disentangle the independent effects of emotional abuse on adulthood depressive symptoms by statistically controlling for other forms of childhood maltreatment, and to examine mentalizing incapacity (i.e., hypermentalizing, hypomentalizing) as a potential mediator in this relationship. PARTICIPANTS: A general sample of 205 adults were assessed online. METHOD: Participants completed a set of self-report measures assessing childhood maltreatment history, mentalizing and depression symptoms. Hierarchical multiple regression was employed to assess the independent effect of emotional abuse on depression. Bootstrap analysis was used to test mediation models. RESULTS: Emotional abuse continued to exert a significant effect on adulthood depression after controlling for other forms of childhood maltreatment and mentalizing incapacity. A mediation effect between childhood emotional abuse and adulthood depression symptoms via mentalizing incapacity, both hypermentalizing (b = 2.02, 95 % CI [0.96, 3.25]) and hypomentalizing, (b = 1.26, 95 % CI [0.59, 1.99]), was established. CONCLUSIONS: This study provided preliminary evidence for hypermentalizing and hypomentalizing as mechanisms whereby early emotional abuse can lead to later depression. A normal to high level of mentalizing capacity might serve as a protective factor to suspend the pathway from childhood maltreatment to subsequent depression and become a promising target in psychological treatments. As cross-sectional data does not allow conclusions to be drawn on causal relationships, longitudinal data in a more representative sample is needed to capture relevant context and further examine our findings.

Interpersonal styles in major and chronic depression: A systematic review and meta-analysis.

BACKGROUND: McCullough's (2000) theory of chronic depression posits that a hostile-submissive interpersonal style distinguishes chronically depressed individuals from those with Major Depressive Disorder (MDD). This study sought to determine to what extent hostility and submissiveness feature in MDD, and whether there is evidence for a stronger effect in chronic depression. METHODS: A systematic literature search was conducted for research measuring the relationship between depression and hostility and/or submissiveness. A meta-analysis was carried out to determine the strength of the relationship. Separate analyses were conducted for the effects of hostility, submissiveness, and hostile-submissiveness. Subgroup analyses were performed comparing the effect sizes of chronic depression and MDD. RESULTS: Twelve studies met criteria for inclusion. Subgroup analyses revealed large effect sizes for submissiveness (d = 0.86) and hostile-submissiveness (d = 0.93) in chronic depression, and a medium effect for hostility (d = 0.72). MDD was associated with medium effects for hostility (d = 0.58) and hostile-submissiveness (d = 0.63), and a small effect for submissiveness (d = 0.40). LIMITATIONS: The review yielded a small number of papers, particularly in relation to chronic depression. The majority reported secondary analyses using baseline samples of intervention trials, with normative data as controls. Quality scores were generally low, and analyses revealed high heterogeneity, which may indicate differences between clinical populations studied. CONCLUSIONS: The review provides preliminary evidence that individuals with chronic depression are more hostile-submissive than those with MDD. Results highlight the limited research into interpersonal correlates of chronic depression.

RIP4 is an ankyrin repeat-containing kinase essential for keratinocyte differentiation.

The epidermis is a stratified, continually renewing epithelium dependent on a balance among cell proliferation, differentiation, and death for homeostasis. In normal epidermis, a mitotically active basal layer gives rise to terminally differentiating keratinocytes that migrate outward and are ultimately sloughed from the skin surface as enucleated squames. Although many proteins are known to function in maintaining epidermal homeostasis, the molecular coordination of these events is poorly understood. RIP4 is a novel RIP (receptor-interacting protein) family kinase with ankyrin repeats cloned from a keratinocyte cDNA library. RIP4 deficiency in mice results in perinatal lethality associated with abnormal epidermal differentiation. The phenotype of RIP4(-/-) mice in part resembles that of mice lacking IKKalpha, a component of a complex that regulates NF-kappaB. Despite the similar keratinocyte defects in RIP4- and IKKalpha-deficient mice, these kinases function in distinct pathways. RIP4 functions cell autonomously within the keratinocyte lineage. Unlike IKKalpha, RIP4-deficient skin fails to fully differentiate when grafted onto a normal host. Instead, abnormal hair follicle development and epidermal dysplasia, indicative of progression into a more pathologic state, are observed. Thus, RIP4 is a critical component of a novel pathway that controls keratinocyte differentiation.

Wellbeing, alcohol use and sexual activity in young teenagers: findings from a cross-sectional survey in school children in North West England.

BACKGROUND: Adolescent health is a growing concern. High rates of binge drinking and teenage pregnancies, documented in the UK, are two measures defining poor wellbeing. Improving wellbeing through schools is a priority but information on the impact of wellbeing on alcohol use, and on sexual activity among schoolchildren is limited. METHODS: A cross-sectional survey using self-completed questionnaires was conducted among 3,641 schoolchildren aged 11-14 years due to participate in a sex and relationships education pilot programme in 15 high schools in North West England. Bivariate and multivariate analyses were conducted to examine the relationship between wellbeing and alcohol use, and wellbeing and sexual activity. RESULTS: A third of 11 year olds, rising to two-thirds of 14 year olds, had drunk alcohol. Children with positive school wellbeing had lower odds of ever drinking alcohol, drinking often, engaging in any sexual activity, and of having sex. General wellbeing had a smaller effect. The strength of the association between alcohol use and the prevalence of sexual activity in 13-14 year olds, increased incrementally with the higher frequency of alcohol use. Children drinking once a week or more had 12-fold higher odds of any sexual activity, and 10-fold higher odds of having sex. Rare and occasional drinkers had a significantly higher odds compared with non-drinkers. CONCLUSIONS: The relationship between wellbeing and alcohol use, and wellbeing and sexual activity reinforces the importance of initiatives that enhance positive wellbeing in schoolchildren. The association between alcohol use and sexual activity highlights the need for integrated public health programmes. Policies restricting alcohol use may help reduce sexual exposure among young teenagers.

Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex.

The signaling pathway downstream of the mammalian interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) is evolutionally conserved with that mediated by the Drosophila Toll protein. Toll initiates its signal through the adapter molecule Tube and the serine-threonine kinase Pelle. Pelle is highly homologous to members of the IL-1R-associated kinase (IRAK) family in mammals. Recently, a novel Pelle-interacting protein called Pellino was identified in Drosophila. We now report a mammalian counterpart of Pellino, termed Pellino 1, which is required for NF kappa B activation and IL-8 gene expression in response to IL-1, probably through its signal-dependent interaction with IRAK4, IRAK, and the tumor necrosis factor receptor-associated factor 6 (TRAF6). The Pellino 1-IRAK-IRAK4-TRAF6 signaling complex is likely to be intermediate, located between the IL-1 receptor complex and the TAK1 complex in the IL-1 pathway.

Purification, cloning, and characterization of Nek8, a novel NIMA-related kinase, and its candidate substrate Bicd2.

We describe the isolation, cloning, and characterization of human Nek8, a new mammalian NIMA-related kinase, and its candidate substrate Bicd2. Nek8 was isolated as a beta-casein kinase activity in rabbit lung and has an N-terminal catalytic domain homologous to the Nek family of protein kinases. Nek8 also contains a central domain with homology to RCC1, a guanine nucleotide exchange factor for the GTPase Ran, and a C-terminal coiled-coil domain. Like Nek2, Nek8 prefers beta-casein over other exogenous substrates, has shared biochemical requirements for kinase activity, and is capable of autophosphorylation and oligomerization. Nek8 activity is not cell cycle regulated, but like Nek3, levels are consistently higher in G(0)-arrested cells. During the purification of Nek8 a second protein co-chromatographed with Nek8 activity. This protein, Bicd2, is a human homolog of the Drosophila protein Bicaudal D, a coiled-coil protein. Bicd2 is phosphorylated by Nek8 in vitro, and the endogenous proteins associate in vivo. Bicd2 localizes to cytoskeletal structures, and its subcellular localization is dependent on microtubule morphology. Treatment of cells with nocodazole leads to dramatic reorganization of Bicd2, and correlates with Nek8 phosphorylation. This may be indicative of a role for Nek8 and Bicd2 associated with cell cycle independent microtubule dynamics.