So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

Adipose tissue as an endocrine organ.

Depression is less prevalent among older adults than among younger adults, but it can have serious consequences. More than half of cases represent a first onset in later life. Although suicide rates in the elderly are declining, they are still higher than in younger adults and are more closely associated with depression. Depressed older adults are less likely to endorse affective symptoms and more likely to display cognitive changes, somatic symptoms, and loss of interest than are depressed younger adults. Risk factors leading to the development of late-life depression likely comprise complex interactions among genetic vulnerabilities, cognitive diathesis, age-associated neurobiological changes, and stressful events. Insomnia is an often overlooked risk factor for late-life depression. We suggest that a common pathway to depression in older adults, regardless of which predisposing risks are most prominent, may be curtailment of daily activities. Accompanying self-critical thinking may exacerbate and maintain a depressed state. Offsetting the increasing prevalence of certain risk factors in late life are age-related increases in psychological resilience. Other protective factors include higher education and socioeconomic status, engagement in valued activities, and religious or spiritual involvement. Treatments including behavioral therapy, cognitive-behavioral therapy, cognitive bibliotherapy, problem-solving therapy, brief psychodynamic therapy, and life review/reminiscence therapy are effective but are too infrequently used with older adults. Preventive interventions including education for individuals with chronic illness, behavioral activation, cognitive restructuring, problem-solving skills training, group support, and life review have also received support.

Depression in Older Adults

Depression in the elderly

Stress precipitates depression and alters its natural history Major depression and the stress response share similar phenomena, mediators and circuitries Thus, many of the features of major depression potentially reflect dysregulations of the stress response The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction) Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes Patients with atypical depression present with a syndrome that seems the antithesis of melancholia They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction

https://www.neurotransmitter.net/Gold.pdf

Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states

The role of expression and secretion of the ob gene product, leptin, for the regulation of plasma leptin levels has been investigated in vitro using abdominal subcutaneous adipose tissue of 20 obese, otherwise healthy, and 11 nonobese women. Body mass index (BMI, mean+/-SEM; kg/m2) in the two groups was 41+/-2 and 23+/-1, respectively. Fat cell volume was 815+/-55 pl in the obese and 320+/-46 pl in the nonobese group. In the obese group, plasma leptin concentrations and adipose leptin mRNA (relative to gamma actin) were increased five and two times, respectively. Moreover, adipose tissue secretion rates per gram lipid weight or per fat cell number were also increased two and seven times, respectively, in the obese group. There were strong linear correlations (r = 0.6-0.8) between plasma leptin, leptin secretion, and leptin mRNA. All of these leptin measurements correlated strongly with BMI and fat cell volume (r = 0.7- 0.9). About 60% of the variation in plasma leptin could be attributed to variations in leptin secretion rate, BMI, or fat cell volume. We conclude that elevated circulating levels of leptin in obese women above all result from accelerated secretion rates of the peptide from adipose tissue because of increased ob gene expression. However, leptin mRNA, leptin secretion, and circulating leptin levels are all more closely related to the stored amount of lipids in the fat cells of adipose tissue than they are to an arbitrary division into obese versus nonobese.

/pdf/leptin-secretion-from-adipose-tissue-in-women-relationship-6j0z9dph9n.pdf

Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression.

Background The present study aimed to investigate the relative importance of genetic and environmental influences on depressive symptoms in the elderly Method Depressive symptoms were assessed through the Center for Epidemiological Studies -Depression (CES-D) scale The CES-D scale was administered to 959 twin pairs (123 female MZs, 90 male MZs, 207 same-sex female DZs, 109 same-sex male DZs and 430 opposite-sex DZs) aged 50 years or older (mean age 72 years) A dichotomous depressed state variable was constructed based on CES-D cut-offs and self-reported use of antidepressant medication Structural equation models were fitted to the data to dissect genetic and environmental variance components Results The sex-specific heritability estimates for depressive symptoms were 14% for males and 29% for females and 23% when constrained to be equal for men and women The prevalence of clinically significant depressive symptoms was 16% for men and 24% for women Heritability estimates for the dichotomous depressed state measure were 7% for males and 49% for females in the full model and 33 % when constrained to be equal Conclusion Our results suggest that depressive symptoms in the elderly are moderately heritable, with a higher heritability for women than men, although differences in heritability estimates were not statistically significant

Gender differences in heritability of depressive symptoms in the elderly.

Here we present the first large-scale effort at genotyping using a novel sequencing method, Pyrosequencing™, as a method for genotyping of single nucleotide polymorphisms (SNPs) Pyrosequencing™ genotypes were validated through duplicate analysis of 1,022 genotypes using the PSQ96™ instrument for pyrosequencing and TaqMan® for 5′nuclease assays Identical results were obtained using both methods In a small pilot study, a pooling strategy using Pyrosequencing™ was successfully tested We conclude that Pyrosequencing™ is highly efficient and accurate in the analysis of SNPs and represents a promising solution to high-throughput genotyping of large sample populations Hum Mutat 19:395–401, 2002 © 2002 Wiley-Liss, Inc

https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.10062

Large-scale genotyping of single nucleotide polymorphisms by Pyrosequencing™ and validation against the 5′nuclease (Taqman®) assay

Genetics of affective disorders.

The aim of this study was to investigate any possible association between depressed mood in the elderly and two candidate SNPs in the serotonin system: one in the 5-HTR2A gene promotor (−1438 G/A) and one in the 5-HT transporter gene (−925 C/A). DNA from a population-based Swedish twin sample (N = 1,592; mean age = 73) was genotyped using Pryosequencing™. An association was found between the 5-HTR2A gene promotor polymorphism and depressed mood (OR: 1.5, CI: 1.1–2.1) for the A/A genotype in the total sample. When the sample was analyzed by gender, a significant association (OR: 2.4, CI: 1.4–4.4) was found for males and the A/A genotype, but not for females. The 5-HT transporter gene was not associated with depressed mood in this elderly population. These results suggest that there might be different genetic mechanisms for males and females contributing to the development of depressed mood in the elderly. © 2003 Wiley-Liss, Inc.

Mårten Jansson

Papers

Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression.

Gender differences in heritability of depressive symptoms in the elderly.

Large-scale genotyping of single nucleotide polymorphisms by Pyrosequencing™ and validation against the 5′nuclease (Taqman®) assay

Genetics of affective disorders.

Association between depressed mood in the elderly and a 5-HTR2A gene variant