Hippocampal Gene Expression Analysis Highlights Ly6a/Sca-1 as Candidate Gene for Previously Mapped Novelty Induced Behaviors in Mice

In this study, we show that the covariance between behavior and gene expression in the brain can help further unravel the determinants of neurobehavioral traits. Previously, a QTL for novelty induced motor activity levels was identified on murine chromosome 15 using consomic strains. With the goal of narrowing down the linked region and possibly identifying the gene underlying the quantitative trait, gene expression data from this F2-population was collected and used for expression QTL analysis. While genetic variation in these mice was limited to chromosome 15, eQTL analysis of gene expression showed strong cis-effects as well as trans-effects elsewhere in the genome. Using weighted gene co-expression network analysis, we were able to identify modules of co-expressed genes related to novelty induced motor activity levels. In eQTL analyses, the expression of Ly6a (a.k.a. Sca-1) was found to be cis-regulated by chromosome 15. Ly6a also surfaced in a group of genes resulting from the network analysis that was correlated with behavior. Behavioral analysis of Ly6a knock-out mice revealed reduced novelty induced motor activity levels when compared to wild type controls, confirming functional importance of Ly6a in this behavior, possibly through regulating other genes in a pathway. This study shows that gene expression profiling can be used to narrow down a previously identified behavioral QTL in mice, providing support for Ly6a as a candidate gene for functional involvement in novelty responsiveness

Many-body calculations of plasmon and phonon satellites in angle-resolved photoelectron spectra using the cumulant expansion approach

The interaction of electrons with crystal lattice vibrations (phonons) and collective charge-density fluctuations (plasmons) influences profoundly the spectral properties of solids revealed by photoemission spectroscopy experiments. Photoemission satellites, for instance, are a prototypical example of quantum emergent behavior that may result from the strong coupling of electronic states to plasmons and phonons. The existence of these spectral features has been verified over energy scales spanning several orders of magnitude (from 50 meV to 15-20 eV) and for a broad class of compounds such as simple metals, semiconductors, and highly-doped oxides. During the past few years the cumulant expansion approach, alongside with the GW approximation and the theory of electron-phonon and electron-plasmon coupling in solids, has evolved into a predictive and quantitatively accurate approach for the description of the spectral signatures of electron-boson coupling entirely from first principles, and it has thus become the state-of-the-art theoretical tool for the description of these phenomena. In this chapter we introduce the fundamental concepts needed to interpret plasmon and phonon satellites in photoelectron spectra, and we review recent progress on first-principles calculations of these features using the cumulant expansion method

Pathways to child and adolescent psychiatric clinics: a multilevel study of the significance of ethnicity and neighbourhood social characteristics on source of referral

<p>Abstract</p> <p>Background</p> <p>In the Swedish society, as in many other societies, many children and adolescents with mental health problems do not receive the help they need. As the Swedish society becomes increasingly multicultural, and as ethnic and economic residential segregation become more pronounced, this study utilises ethnicity and neighbourhood context to examine referral pathways to child and adolescent psychiatric (CAP) clinics.</p> <p>Methods</p> <p>The analysis examines four different sources of referrals: family referrals, social/legal agency referrals, school referrals and health/mental health referrals. The referrals of 2054 children aged 11-19 from the Stockholm Child-Psychiatric Database were studied using multilevel logistic regression analyses.</p> <p>Results</p> <p>Results indicate that ethnicity played an important role in how children and adolescents were referred to CAP-clinics. Family referrals were more common among children and adolescents with a Swedish background than among those with an immigrant background. Referrals by social/legal agencies were more common among children and adolescents with African and Asian backgrounds. Children with Asian or South American backgrounds were more likely to have been referred by schools or by the health/mental health care sector. A significant neighbourhood effect was found in relation to family referrals. Children and adolescents from neighbourhoods with low levels of socioeconomic deprivation were more likely to be referred to CAP-clinics by their families in comparison to children from other neighbourhoods. Such differences were not found in relation in relation to the other sources of referral.</p> <p>Conclusions</p> <p>This article reports findings that can be an important first step toward increasing knowledge on reasons behind differential referral rates and uptake of psychiatric care in an ethnically diverse Swedish sample. These findings have implications for the design and evaluation of community mental health outreach programs and should be considered when developing measures and strategies intended to reach and help children with mental health problems. This might involve providing information about the availability and accessibility of health care for children and adolescents with mental health problems to families in certain neighbourhoods and with different ethnic backgrounds.</p

Reciprocal relationships between trajectories of depressive symptoms and screen media use during adolescence

Adolescents are constantly connected with each other and the digital landscape through a myriad of screen media devices. Unprecedented access to the wider world and hence a variety of activities, particularly since the introduction of mobile technology, has given rise to questions regarding the impact of this changing media environment on the mental health of young people. Depressive symptoms are one of the most common disabling health issues in adolescence and although research has examined associations between screen use and symptoms of depression, longitudinal investigations are rare and fewer still consider trajectories of change in symptoms. Given the plethora of devices and normalisation of their use, understanding potential longitudinal associations with mental health is crucial. A sample of 1,749 (47% female) adolescents (10-17 years) participated in six waves of data collection over two years. Symptoms of depression, time spent on screens, and on separate screen activities (social networking, gaming, web browsing, TV/passive) were self-reported. Latent growth curve modelling revealed three trajectories of depressive symptoms (Low-Stable, High-Decreasing, and Low-Increasing) and there were important differences across these groups on screen use. Some small, positive associations were evident between depressive symptoms and later screen use, and between screen use and later depressive symptoms. However, a Random Intercept Cross Lagged Panel Model revealed no consistent support for a longitudinal association. The study highlights the importance of considering differential trajectories of depressive symptoms and specific forms of screen activity to understand these relationships

Unexpected differential metabolic responses of Campylobacter jejuni to the abundant presence of glutamate and fucose

Introduction: Campylobacter jejuni is the leading cause of foodborne bacterial enteritis in humans, and yet little is known in regard to how genetic diversity and metabolic capabilities among isolates affect their metabolic phenotype and pathogenicity. Objectives: For instance, the C. jejuni 11168 strain can utilize both l-fucose and l-glutamate as a carbon source, which provides the strain with a competitive advantage in some environments and in this study we set out to assess the metabolic response of C. jejuni 11168 to the presence of l-fucose and l-glutamate in the growth medium. Methods: To achieve this, untargeted hydrophilic liquid chromatography coupled to mass spectrometry was used to obtain metabolite profiles of supernatant extracts obtained at three different time points up to 24 h. Results: This study identified both the depletion and the production and subsequent release of a multitude of expected and unexpected metabolites during the growth of C. jejuni 11168 under three different conditions. A large set of standards allowed identification of a number of metabolites. Further mass spectrometry fragmentation analysis allowed the additional annotation of substrate-specific metabolites. The results show that C. jejuni 11168 upon l-fucose addition indeed produces degradation products of the fucose pathway. Furthermore, methionine was faster depleted from the medium, consistent with previously-observed methionine auxotrophy. Conclusions: Moreover, a multitude of not previously annotated metabolites in C. jejuni were found to be increased specifically upon l-fucose addition. These metabolites may well play a role in the pathogenicity of this C. jejuni strain.</p

Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models

The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar–Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism

Abstract: Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition? In this study we investigated if a genetic predisposition for autism is associated with childhood trauma using polygenic scores (PGS) and genetic correlations in the UK Biobank (105,222 < N < 105,638), and tested potential mediators and moderators of the association between autism, childhood trauma and SSBI. Autism PGS were significantly associated with childhood trauma (max R2 = 0.096%, P < 2 × 10−16), self-harm ideation (max R2 = 0.108%, P < 2 × 10−16), and self-harm (max R2 = 0.13%, P < 2 × 10−16). Supporting this, we identified significant genetic correlations between autism and childhood trauma (rg = 0.36 ± 0.05, P = 8.13 × 10−11), self-harm ideation (rg = 0.49 ± 0.05, P = 4.17 × 10−21) and self-harm (rg = 0.48 ± 0.05, P = 4.58 × 10−21), and an over-transmission of PGS for the two SSBI phenotypes from parents to autistic probands. Male sex negatively moderated the effect of autism PGS on childhood trauma (β = −0.023 ± 0.005, P = 6.74 × 10−5). Further, childhood trauma positively moderated the effect of autism PGS on self-harm score (β = 8.37 × 10−3 ± 2.76 × 10−3, P = 2.42 × 10−3) and self-harm ideation (β = 7.47 × 10−3 ± 2.76 × 10−3, P = 6.71 × 10−3). Finally, depressive symptoms, quality and frequency of social interactions, and educational attainment were significant mediators of the effect of autism PGS on SSBI, with the proportion of effect mediated ranging from 0.23 (95% CI: 0.09–0.32) for depression to 0.008 (95% CI: 0.004–0.01) for educational attainment. Our findings identify that a genetic predisposition for autism is associated with adverse life-time outcomes, which represent complex gene-environment interactions, and prioritizes potential mediators and moderators of this shared biology. It is important to identify sources of trauma for autistic individuals in order to reduce their occurrence and impact

Protective Mechanisms for Depression among Racial/Ethnic Minority Youth: Empirical Findings, Issues, and Recommendations

We (1) review empirical studies that report findings regarding putative protective mechanisms when exposed to risk of depression in African American and Hispanic adolescents; (2) identify key protective mechanisms for different risk contexts that garner empirical support; (3) synthesize the mechanisms identified as protective against depression among racial/ethnic minority adolescents; and (4) discuss improved methods for advancing understanding of resilience against depression in minority youth. The studies were selected from PsycINFO searches that met the following inclusion criteria: participants between 12 and 21&nbsp;years of age, inclusions of racial/ethnic minority members, examining protection through an interaction with a risk factor, and outcome measures of depression, depressed mood, or depressive symptomatology. We found 39 eligible studies; 13 of which included multiple racial/ethnic groups. The following were supported as protective mechanisms, at least preliminarily, for at least one racial/ethnic group and in at least one risk context: employment, extracurricular activities, father–adolescent closeness, familism, maternal support, attending predominately minority schools, neighborhood composition, non-parent support, parental inductive reasoning, religiosity, self-esteem, social activities, and positive early teacher relationships. To investigate protective mechanisms more comprehensively and accurately across individual, social, and community levels of influence, we recommend incorporating multilevel modeling or multilevel growth curve analyses and large diverse samples