Table 4.
Early-life manipulations associated with anxiety behaviors and epigenetic modifications
| Brain region | Manipulation | Primary findings | Findings by sex | Species | Reference | |
|---|---|---|---|---|---|---|
| Males | Females | |||||
| Hippocampus | Maternal separation | ↑ Avp methylation | ✓ | ns | C57BL/6J & | (Kember et al., 2012) |
| ↓ Nr4a1 methylation | ✓ | ✓ | DBA/2J mice | |||
| ↑ Nr3c1 methylation | ✓ | ✓ | C57Bl/6J mice | |||
| Low maternal care | ↑ Nr3c1 methylation | ✓ | ✓ | DBA/2J mice | (Weaver et al., 2004) | |
| ↓ H3K4 acetylation | ✓ | ✓ | LE rats | |||
| ↓ Nr3c1 methylation | -- | ✓ | LE rats | (Pan et al., 2014) | ||
| Litter gender composition |
↑ Nr3c1 methylation | ns | ✓ | (Kosten et al., 2014) | ||
| ↑ Bdnf methylation | ✓(ss) | ns | SD rats | |||
| ↑ Oprm1 methylation | ✓(ss) | ✓(ss) | SD rats | (Hao et al., 2011) | ||
| Amygdala | Maternal separation | ↑ Ntsr1 methylation | ✓ | -- | SD rats | (Toda et al., 2014) |
| ↑ Syn1 methylation | ✓ | ✓ | SD rats | (Park et al., 2014) | ||
| Low maternal care | ↑ Dnmt1 expression | ✓ | ✓ | SD rats | (Zhong et al., 2015) | |
| ↑ Total methylation | ✓ | ✓ | ||||
| Anxious temperament | ↑ BCL11A & JAG1 methylation |
✓ | -- | RM monkeys | (Alisch et al., 2014) | |
| Striatum | Litter gender composition |
↑ Nr3c1 methylation | ns | ✓(ss) | SD rats | (Kosten et al., 2014) |
| ↓ Egr1 methylation | ✓(ss) | ns | ||||
| ↑ Oprm1 methylation | ✓(ss) | ns | SD rats | (Hao et al., 2011) | ||
| Hypothalamus | Maternal separation | ↓ Avp methylation | ✓ | -- | C57BL/6N mice | (Murgatroyd et al., 2009) |
| Maternal separation | ↓ Crh methylation | ✓ | ✓ | SD rats | (Chen et al., 2012) | |
| Pituitary | Maternal separation | ↓ Pomc methylation | ✓ | -- | C57BL/6N mice | (Wu et al., 2014) |
| Prefrontal cortex |
Low maternal care | ↑ Bdnf methylation | ✓ | ✓ | LE rats | (Roth et al., 2009) |
| Whole brain | Low Paternal Care | ↓ Dnmt3a expression | ✓ | ✓ | SB fish | (McGhee and Bell, 2014) |
| Blood | Variable Foraging Demand |
↑ 5-HTT methylation | -- | ✓ | RM monkeys | (Kinnally et al., 2011) |
| ↑ global methylation | ||||||
✓ = Significant; NS = Not Significant; -- = Not Included; SS = Single Sex; SD = Sprague Dawley; TG = Transgenic; LE = Long Evans; RM = Rhesus Macaques; SB = Stickleback.