Early life stress leads to sex differences in development of depressive-like outcomes in a mouse model.
Haley L Goodwill, Gabriela Manzano-Nieves, Meghan Gallo, Hye-In Lee, Esther Oyerinde, Thomas Serre, Kevin G Bath
Neuropsychopharmacology September 6, 2018 DOI: 10.1038/s41386-018-0195-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Population | Mice (C57BL/6 background implied by field context), exposed to early life stress via limited bedding versus controls |
| Intervention | Ketamine |
| Duration | Early life stress from postnatal day 4 to 11; behavioral testing in early adolescence and young adulthood; home cage monitoring over 5-10 days |
| Measures | Automated home cage behavioral recognition system, traditional assays for depressive-like behavior (not specified) |
| Topics | Depression Ketamine |
| Keywords | Animals Mice, inbred c57bl Disease models, animal Antidepressive agents Behavior, animal Stress, psychological Age factors Sex characteristics Female |
| Key findings | Early life stress from limited bedding produced a female-specific depression-like phenotype in mice that emerged in adolescence and worsened in adulthood; males were unaffected. A novel automated home cage monitoring system detected robust, continuous behavioral markers in stressed females that resemble human depression, and ketamine rapidly reversed these effects. |
Abstract
Childhood trauma and neglect influence emotional development and increase the risk for and severity of mental illness. Women have a heightened susceptibility to the effects of early life stress (ELS) and are twice as likely as men to develop debilitating, stress-associated disorders later in life, such as major depressive disorder (MDD). Until now, mouse models of depression have been largely unsuccessful at replicating the diverse symptomatology of this disease and the sex bias in vulnerability. From P4 to P11, a limited bedding model that leads to fragmented maternal care, was used to induce ELS. Early adolescent and young adult mice were tested on an array of assays to test for depressive-like behavior. This included our newly developed automated home cage behavioral recognition system, where the home cage behavior of ELS and control mice could be monitored over a continuous 5-10 day span. ELS females, but not males, exhibited depressive-like behaviors on traditional assays. These effects emerged during adolescence and became more severe in adulthood. Using the novel home cage video monitoring method, we identified robust and continuous markers of depressive-like pathology in ELS females that phenocopy many of the behavioral characteristics of depression in humans. ELS effects on home cage behavior were rapidly rescued by ketamine, a fast-acting antidepressant. Together, these findings highlight that limited bedding ELS (1) produces an early emerging, female-specific depressive phenotype that responds to a fast-acting antidepressant and (2) this model has the potential to inform sex-selective risk for the development of stress-induced mental illness.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.