Abstract
Early experiments in nonhuman primates established the relation between disruption of filial attachment and depressive-like outcomes. Subsequent studies in rats and mice have been instrumental in linking depressive-like outcomes to disturbances in maternal behavior. Another aspect of attachment disruption, absence of the attachment object per se, may be studied more effectively in a different laboratory rodent—the guinea pig. Here, we discuss the rationale for using guinea pigs for this work. We then review guinea pig studies providing evidence for inflammatory mechanisms mediating both depressive-like behavior during separation as well as sensitization of stress responsiveness such as is thought to lead to increased vulnerability to depression at later ages. Finally, we discuss recent complementary work in adult monkeys that suggests cross-species generalizability of broad principles derived from the guinea pig experiments. Overall, the findings provide experimental support for human research implicating inflammatory mechanisms in the development of increased stress responsiveness and vulnerability to depression following attachment disruption and other forms of early-life stress. Specifically, the findings suggest inflammatory mechanisms may set in motion a cascade of underlying processes that mediate later increased stress responsiveness and, therefore, depression susceptibility.
Highlights
Experiments in nonhuman primates established the relation between disruption of filial attachment and depressive-like outcomes
We review guinea pig studies providing evidence for inflammatory mechanisms mediating both depressive-like behavior during separation as well as sensitization of stress responsiveness such as is thought to lead to increased vulnerability to depression at later ages
The findings provide experimental support for human research implicating inflammatory mechanisms in the development of increased stress responsiveness and vulnerability to depression following attachment disruption and other forms of early-life stress
Summary
A recent PubMed search for the term ‘‘early life stress’’ yielded over 17,000 hits. The roots of this enormous body of scientific study can largely be traced back to three lines of research from the mid 20th century: studies of infantile ‘‘handling’’ in rats and mice, experiments in which infant monkeys were separated from their mothers, and observations of institutionalized children. Extreme by today’s standards of animal welfare and acceptable experimental manipulation, these studies offered crucial empirical support for the work of other investigators examining children lacking normal maternal or substitute affectionate care in orphanages, hospitals, and other institutions (Spitz and Wolf, 1946; Robertson and Bowlby, 1952) The conclusion that such children were suffering serious emotional and depressive effects due to separation from their attachment figure flew in the face of prevailing professional consensus of that era that affectionate interaction was irrelevant or even harmful for normal child development (Watson and Watson, 1928; Blum, 2002). These studies have been extremely productive and illuminating, showing that disrupted maternal care can produce counterparts to many of the symptoms/responses of human adolescents and adults who have undergone early-life stress (e.g., Walker et al, 2017)
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