Perspective: the evolution of hormones and person perception-a quantitative genetic framework.

Evolutionary biology provides a unifying theory for testing hypotheses about the relationship between hormones and person perception. Person perception usually receives attention from the perspective of sexual selection. However, because person perception is one trait in a suite regulated by hormones, univariate approaches are insufficient. In this Perspectives article, quantitative genetics is presented as an important but underutilized framework for testing evolutionary hypotheses within this literature. We note tacit assumptions within the current literature on psychiatric genetics, which imperil the interpretation of findings thus far. As regulators of a diverse manifold of traits, hormones mediate tradeoffs among an array of functions. Hormonal pleiotropy also provides the basis of correlational selection, a process whereby selection on one trait in a hormone-mediated suite generates selection on the others. This architecture provides the basis for conflicts between sexual and natural selection within hormone-mediated suites. Due to its role in person perception, psychiatric disorders, and reproductive physiology, the sex hormone estrogen is highlighted as an exemplar here. The implications of this framework for the evolution of person perception are discussed. Empirical quantification of selection on traits within hormone-mediated suites remains an important gap in this literature with great potential to illuminate the fundamental nature of psychiatric disorders.

Dynamic Changes in Begging Signal Short-Term Information on Hunger and Need.

AbstractDynamic signals can convey distinct information to a receiver on different timescales, making assessment of how quickly signal strength changes important for understanding signal function. Here, we combine repeated measures of offspring begging behavior of western bluebirds with assessments of fitness as well as quantitative genetic analyses of cross-fostered offspring to investigate whether variation in begging behavior conveys information about hunger, need, or quality or has no signaling function. Begging intensity increased with food deprivation, supporting the signal-of-hunger hypothesis. However, after controlling for this variation, multiple lines of evidence showed that begging also signaled need but not quality. Specifically, begging intensity was repeatable only on short timescales, and nestlings that begged more intensely were in poorer condition. Moreover, variation in mean begging intensity was not strongly related to measures of fitness. In general, we found that begging behavior is a highly flexible trait that appears to be unconstrained by both genetic and early developmental influences, as indicated by the cross-fostering experiment that confirmed that the nest environment, not genetic relatedness, explained variation in begging behavior. Together, these results support the idea that begging dynamically signals shorter-term information: hunger and need. More generally, they show the importance of assessing the timescale of signal change to understand its function.

The role of lithium treatment on comorbid anxiety symptoms in patients with bipolar depression.

BACKGROUND: Comorbid anxiety is pervasive and carries an immense psychosocial burden for patients with bipolar disorder. Despite this, trials reporting anxiety-related outcomes in this population are uncommon, particularly with regards to monotherapies. METHODS: Patients (n = 31) with both bipolar I or II disorder in current depressive episodes were enrolled in a six-week, open-label, single-center trial assessing the efficacy of lithium monotherapy in treating symptoms depression and comorbid anxiety. Patients were mostly medication-free and lithium-naïve at baseline. RESULTS: Significant improvements in depression (HAMD) and anxiety (HAM-A) were observed at the six-week endpoint, with remission and response rates greater than 50%. There was a positive correlation between endpoint HAM-A scores and HAM-D scores, r = 0.80, (p < 0.01). Improvements were realized at low serum lithium concentrations (0.49 ± 0.20 mEq/L). LIMITATIONS: Lack of placebo control and small sample size warrants validation in larger randomized studies. CONCLUSIONS: Taken in the context of prior evidence, lithium may have an important role in treating comorbid anxiety in bipolar disorder, both as adjunct and monotherapy. Lower doses of lithium may provide equivalent efficacy and enhance tolerability and compliance.

Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival.

Nuclear factor, erythroid 2-like 2 (NFE2L2), a transcription factor also known as NF-E2-related factor 2 (Nrf2), is a key cytoprotective gene that regulates critical antioxidant and stress-responsive genes. Nrf2 has been demonstrated to be a promising therapeutic target and useful biomarker in malignant disease. We hypothesized that NFE2L2-mediated gene expression would reflect cancer severity and progression. We conducted a meta-analysis of microarray data for 240 NFE2L2-mediated genes that were enriched in tumor tissues. We then developed a risk scoring system based on NFE2L2 gene expression profiling and designated 50 tumor-associated genes as the NFE2L2-associated molecular signature (NAMS). We tested the relationship between this gene expression signature and both recurrence-free survival and overall survival in lung cancer patients. We find that NAMS predicts clinical outcome in the training cohort and in 12 out of 20 validation cohorts. Cox proportional hazard regressions indicate that NAMS is a robust prognostic gene signature, independent of other clinical and pathological factors including patient age, gender, smoking, gene alteration, MYC level, and cancer stage. NAMS is an excellent predictor of recurrence-free survival and overall survival in human lung cancer. This gene signature represents a promising prognostic biomarker in human lung cancer.

Functional and Structural Consequence of Rare Exonic Single Nucleotide Polymorphisms: One Story, Two Tales.

Genetic variation arising from single nucleotide polymorphisms (SNPs) is ubiquitously found among human populations. While disease-causing variants are known in some cases, identifying functional or causative variants for most human diseases remains a challenging task. Rare SNPs, rather than common ones, are thought to be more important in the pathology of most human diseases. We propose that rare SNPs should be divided into two categories dependent on whether the minor alleles are derived or ancestral. Derived alleles are less likely to have been purified by evolutionary processes and may be more likely to induce deleterious effects. We therefore hypothesized that the rare SNPs with derived minor alleles would be more important for human diseases and predicted that these variants would have larger functional or structural consequences relative to the rare variants for which the minor alleles are ancestral. We systematically investigated the consequences of the exonic SNPs on protein function, mRNA structure, and translation. We found that the functional and structural consequences are more significant for the rare exonic variants for which the minor alleles are derived. However, this pattern is reversed when the minor alleles are ancestral. Thus, the rare exonic SNPs with derived minor alleles are more likely to be deleterious. Age estimation of rare SNPs confirms that these potentially deleterious SNPs are recently evolved in the human population. These results have important implications for understanding the function of genetic variations in human exonic regions and for prioritizing functional SNPs in genome-wide association studies of human diseases.

Ion channel gene expression predicts survival in glioma patients.

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients.