Researchers led by Mathias Schmidt at the Max Planck Institute of Psychiatry in Munich and Juan Pablo Lopez at the Karolinska Institutet in Stockholm published a study in June showing that an experimental compound blocked the social consequences of early-life stress in mice — but only when administered during the stressful period itself, not after.
Munich and Stockholm researchers prevent social consequences of early adversity in mice using experimental drug
Researchers led by Mathias Schmidt at the Max Planck Institute of Psychiatry in Munich and Juan Pablo Lopez at the Karolinska Institutet in Stockholm published a study in June showing that an experimental compound blocked the social consequences of early-life stress in mice — but only when administered during the stressful period itself, not after.
In the experiment, mother mice were provided with less nesting and bedding material than normal, making maternal behavior erratic and the first days of life unpredictable for offspring. Mice raised under those conditions appeared physically healthy but consistently ranked at the bottom of social hierarchies, first as adolescents and then again as adults.
The researchers identified a protein called FKBP51 as a key mechanism. Early hardship, according to the study, causes the body to produce excess FKBP51, which reduces the sensitivity of cortisol receptors. Because those receptors signal the body to wind down its stress response, reduced sensitivity means the stress response stays active longer than it otherwise would. Schmidt noted that this process is not perceptible to the individual: 'Your cortisol response is something you don't feel. You may think you're very stress resilient, but your body is pumping out cortisol, and you don't know.'
The compound used, SAFit2, blocks FKBP51. Administered to mothers during the stress period, it reached offspring through breast milk. Treated mice performed identically within their social groups to mice that had experienced no adversity. Gene activity screening across six stress-related brain regions found that early adversity had left a broad imprint; the drug largely reversed it, most clearly in the medial prefrontal cortex and the nucleus accumbens, regions the source identifies as involved in emotional control and reward.
The study tested male mice only. SAFit2 remains a research compound that has not been developed or safety-tested for human use. Existing treatments for stress-related disorders such as PTSD and trauma-linked depression rely heavily on selective serotonin reuptake inhibitors, or SSRIs, which target serotonin pathways and do not work for a significant portion of patients, according to the source.
- The source does not state the sample size of the mouse cohorts used in the study.
- The source does not state whether the findings have been peer-reviewed beyond the publication date of June.
- The source does not establish whether SAFit2 produces any adverse effects in animals.
- The source does not state what results other studies showed when SAFit2 was used in adult animals beyond noting that 'behavioral effects' were observed.
- The source does not include any position or response from Juan Pablo Lopez, who is identified as a co-lead of the study.
- The source does not state how researchers would identify at-risk individuals before harm occurs, and acknowledges this problem is not addressed by the current research.
- The source does not state whether the findings have been replicated by independent research groups.
Read the original at Deutsche Welle