The lipidome in major depressive disorder: Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk.

BACKGROUND: The lipidome is rapidly garnering interest in the field of psychiatry. Recent studies have implicated lipidomic changes across numerous psychiatric disorders. In particular, there is growing evidence that the concentrations of several classes of lipids are altered in those diagnosed with MDD. However, for lipidomic abnormalities to be considered potential treatment targets for MDD (rather than secondary manifestations of the disease), a shared etiology between lipid concentrations and MDD should be demonstrated. METHODS: In a sample of 567 individuals from 37 extended pedigrees (average size 13.57 people, range=3-80), we used mass spectrometry lipidomic measures to evaluate the genetic overlap between twenty-three biologically distinct lipid classes and a dimensional scale of MDD. RESULTS: We found that the lipid class with the largest endophenotype ranking value (ERV, a standardized parametric measure of pleiotropy) were ether-phosphodatidylcholines (alkylphosphatidylcholine, PC(O) and alkenylphosphatidylcholine, PC(P) subclasses). Furthermore, we examined the cluster structure of the twenty-five species within the top-ranked lipid class, and the relationship of those clusters with MDD. This analysis revealed that species containing arachidonic acid generally exhibited the greatest degree of genetic overlap with MDD. CONCLUSIONS: This study is the first to demonstrate a shared genetic etiology between MDD and ether-phosphatidylcholine species containing arachidonic acid, an omega-6 fatty acid that is a precursor to inflammatory mediators, such as prostaglandins. The study highlights the potential utility of the well-characterized linoleic/arachidonic acid inflammation pathway as a diagnostic marker and/or treatment target for MDD.

Genome-Wide Analyses of Working-Memory Ability: A Review.

Working memory, a theoretical construct from the field of cognitive psychology, is crucial to everyday life. It refers to the ability to temporarily store and manipulate task-relevant information. The identification of genes for working memory might shed light on the molecular mechanisms of this important cognitive ability and-given the genetic overlap between, for example, schizophrenia risk and working-memory ability-might also reveal important candidate genes for psychiatric illness. A number of genome-wide searches for genes that influence working memory have been conducted in recent years. Interestingly, the results of those searches converge on the mediating role of neuronal excitability in working-memory performance, such that the role of each gene highlighted by genome-wide methods plays a part in ion channel formation and/or dopaminergic signaling in the brain, with either direct or indirect influence on dopamine levels in the prefrontal cortex. This result dovetails with animal models of working memory that highlight the role of dynamic network connectivity, as mediated by dopaminergic signaling, in the dorsolateral prefrontal cortex. Future work, which aims to characterize functional variants influencing working-memory ability, might choose to focus on those genes highlighted in the present review and also those networks in which the genes fall. Confirming gene associations and highlighting functional characterization of those associations might have implications for the understanding of normal variation in working-memory ability and also for the development of drugs for mental illness.

Universal screening for intimate partner violence in the emergency department: importance of patient and provider factors.

STUDY OBJECTIVE: Screening for intimate partner violence has been widely advocated in the health care setting, but efforts to assess effectiveness and ensure adequacy of universal screening are largely untested. We sought to identify barriers to screening of female emergency department patients for intimate partner violence during the first year of implementation of a screening protocol. METHODS: A retrospective, structured medical chart review of 1,638 randomly identified visits included demographic factors of age, race, marital status, employment status, insurance status, arrival mode, mechanism of presenting complaint, severity of condition, presentation time, and nurse gender. The study was conducted an an inner-city Level I trauma center with 43,000 annual ED visits and universal procedures for screening for intimate partner violence in place since February 1994. The participants were a cohort of 1,509 female patients, 18 years of age or older, who were discharged from the ED between July 1994 and June 1995. The main outcome measure was the odds of being screened as a function of patient and provider variables. Statistical analyses involved univariate and multivariate logistic regression on screening rates (Yes/No) as derived from universal screening instrument variables. RESULTS: Of 1,638 records reviewed, 483 patients (29.5%) were screened for intimate partner violence. Univariate analyses revealed that women presenting with nonpsychiatric, less acute complaints and those who presented during daylight hours were more likely to be screened than women who presented with psychiatric or more acute complaints, or during the night shift. Male and female nurse providers were equally likely to screen for intimate partner violence. Step-down multivariate analyses agreed with these findings. CONCLUSION: In this random sample of female patients, screening rates varied by severity of the patient's condition, type of presenting complaint, and presentation time.