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Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.
Aims
We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls).
Method
Medication-free participants with MDD (n = 192: 110 female, 81 male, 1 other) and controls (n = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (−1019, −1007, −681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF.
Results
Recent stress correlated positively with blood monocyte methylation at the −681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the −1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD.
Conclusions
These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.
ch 3: This chapter puts humans in our evolutionary context, answering such “who questions” as we need to answer before investigating “how questions.” First, it explains where we fit in terms of broader patterns of primate evolution. Next, it shows how human behavior differs from that of other animals. Finally, it considers how we humans differ from one another. The most important differences among humans are cultural differences. Culture has several distinct properties for which we should expect to find evidence in the prehistoric record. Failing to find such evidence can suggest problems in our methods for investigating human evolution and prehistory.
ch 14: This chapter reviews what we think we know about how earlier humans established our global diaspora. This evidence consistently refutes the hypothesis that humans migrated before they had storable and transportable food sources, such as those arising from food production. Pleistocene humans did not migrate, they dispersed. To explain these dispersals, this chapter first compares what we can observe about differences between living humans and other animals with what we think we know about the earliest Homo sapiens populations. Next, it argues that humans relied on a suite of ancestral survival skills to overcome the obstacles they faced while dispersing. Finally, the chapter considers near, longer, and longest-term challenges to our survival and what we must do to overcome them.
ch 13: This chapter considers whether Homo sapiens is as “unstoppable” as the Titanic was “unsinkable.” Reviewing scientifically credible threats to our species’ long-term survival, this chapter shows that some threats looming large in the popular imagination are actually extremely unlikely to cause human extinction. Actual threats to long-term human survival, such as meteor impacts and large-scale volcanism, garner far less attention than they deserve and they share a similar solution.
ch 12: This chapter examines prehistoric migrations to oceanic islands. First, it considers the special difficulties of reaching such islands, and reviews claims about Pleistocene preagricultural movement to oceanic islands. Next, it focuses on the peopling of the Pacific Ocean, the fastest and most geographically extensive human population movement of all time. Though some archaeologists have speculated that these islands were colonized accidentally, the evidence shows that these were purposeful voyages by people who knew exactly where they were going and how to get there. Lowered sea levels during the LGM/MIS 2 shortened distances between some islands and possibly aided humans living in Sunda, Wallacea, and Sahul in settling Near Oceania. Movements into Remote Oceania commenced around 4 Ka, and movements into Polynesia after 1 Ka. Finally, the chapter considers future human migrations on Earth and beyond. The latter, it argues, will not be “just like Star Trek.”
ch 10: This chapter examines the peopling of the “New World” (Beringia and the Americas) between 12 and 32 Ka. Like the peopling of Sahul, population movements brought Homo sapiens from Asia to American continents and offshore islands with no prior hominin presence. Historically, archaeologists envisioned these movements as land-based, passing through an “ice-free corridor” between major continental glaciers around 13 Ka, but evidence increasingly shows that humans were already present south of the ice sheets significantly earlier than this corridor existed. Unlike in Sahul, ancestral Native Americans systematically hunted many of the megafauna that became extinct during the Pleistocene-Holocene transition. Extensive alliance networks whose most durable archaeological traces include distinctive stoneworking traditions, such as the Clovis Complex, may have played a role in these mass extinctions.
ch 11: This chapter considers the relationship between food production and migration. Before Holocene times (> 12 Ka) archaeological evidence consistently shows that human population movements were dispersals and not migrations. People moved into new habitats either as individuals or in small groups, reconfiguring their economies and social identities in their destinations. From mid-Holocene times onward (after 4–8 Ka), however, the archaeological record begins to show increasing evidence for migrations. Migrating humans took their food and their culture, their “movable feasts,” with them. This chapter argues that recent human migrations result from food production using domesticated plants and animals. It describes how food production altered some of humanity’s responses to the basic six survival problems in ways that not only encourage migrations but also make them easier for archaeologists to detect, albeit within a limited chronological “window of visibility.” A case study from sub-Saharan Africa shows that archeologists can detect prehistoric migrations, but we have to ask different questions about them than traditional “who questions.”
ch 5: This chapter examines African evidence for human origins, behavior, and population movements between 50 and 600 Ka (thousands of years ago). It compares evidence associated with Homo sapiens and H. heidelbergensis. Homo sapiens and H. heidelbergensis solved survival challenges in broadly similar ways, with humans occasionally devoting more time and energy to technology (“technological intensification”). The African evidence is entirely consistent with dispersal, showing not even a hint of migration. This and other evidence suggest humans replaced earlier H. heidelbergensis not by an abrupt evolutionary event originating in one place and radiating outward but instead by a gradual, continent-wide process whose mode and tempo varied widely.
ch 8: This chapter reviews evidence associated with the Neanderthals, extinct hominins who lived in Europe and Western Asia before humans settled these regions after 40–50 Ka. It compares evidence for Neanderthals’ survival strategies with those Ancient Africans practiced. Many of the differences between Neanderthals and Ancient Africans seem to have arisen from Neanderthals’ living in small, highly mobile groups and from their investing less time and energy in technology.