{
  "id": 6431852,
  "title": "The serotonin transporter genotype x cumulative early-life stress interaction has opposite effects on anxiety-like behaviors in male and female rats",
  "url": "https://urgent.news/2026/09/09/the-serotonin-transporter-genotype-x-cumulative-early-life-stress",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-09T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749397v1?rss=1"
  },
  "original_language": "en",
  "account": "A recent study has uncovered intriguing insights into how early-life stress and a specific serotonin transporter genotype interact differently in male and female rats. Early-life psychosocial adversity can set the stage for stress-related disorders, even prior to birth due to maternal stress. This research used a model of reduced serotonin transporter (SERT) expression to examine the impact of cumulative early-life stress (ELS) on behavioral phenotypes.\n\nDams were subjected to stress before, during, and after pregnancy, coupled with postnatal maternal separation. The offspring's cognitive, affective, and social behaviors were assessed in both wild-type (WT) and heterozygous SERT knockout (HET) rats, both male and female. Dams exposed to cumulative stress exhibited increased signs of anxiety in their offspring compared to controls.\n\nIn the offspring, HET rats displayed higher social investigation and tended to be more hyperactive than their WT counterparts. However, anxiety-like behavior was notably higher in HET females compared to WT females, with no significant difference in male rats. Importantly, independent of genotype, STR rats consumed less sucrose and showed impaired object recognition compared to CTR rats. Interestingly, HET-STR rats actually performed better in object recognition tests when compared to WT-STR rats.\n\nThe most striking finding came from a significant interaction between SERT genotype, cumulative ELS, and sex. This revealed opposing, sex-dependent effects on anxiety-like behavior. Specifically, HET-STR females exhibited more anxiety-like responses relative to both HET-CTR and WT-STR females, as well as HET-STR males. Conversely, HET-STR males displayed less anxiety compared to both HET-CTR and WT-STR males. The study also noted that reduced SERT expression correlated with increased social investigation and heightened anxiety, particularly in SERT+/- female rats.\n\nWhile cumulative ELS did not lead to robust anxiety-like or depressive-like phenotypes, it did impair memory performance, an effect that was partially mitigated in SERT+/- rats. Crucially, the SERT genotype modulated anxiety-like behavior differently in male versus female offspring. It increased vulnerability in SERT+/- females, while reducing it in SERT+/- males, an effect that was amplified by exposure to cumulative ELS. These findings emphasize the critical role of sex as a determinant in the interaction between genetic susceptibility and cumulative exposure to early-life adversity, shaping affective outcomes.",
  "summary": "Early-life psychosocial adversity increases vulnerability to stress-related disorders and may begin as early as prior to conception via maternal stress. Consequently, early-life stress (ELS) in offspring may accumulate across early development. The short-allele variant of the serotonin transporter (SERT) gene has been implicated in depression risk and higher anxiety sensitivity following stress…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}