Social defeat interacts with Disc1 mutations in the mouse to affect behavior

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Disrupted-in-schizophrenia 1 (DISC1) is a key gene linked to psychiatric disorders.
• Variable clinical presentations in families with DISC1 mutations suggest gene-environment interactions.
• Understanding these interactions is crucial for deciphering complex psychiatric disease heritability.

Purpose of the Study:

• To investigate the impact of gene-environment interactions on behavior in mutant Disc1 mouse models.
• To examine how chronic social defeat (CSD) stress affects behaviors relevant to psychiatric illness.

Main Methods:

• Two lines of mice with different Disc1 point mutations were exposed to CSD.
• Behavioral tests included open field (OF), pre-pulse inhibition (PPI), elevated plus maze (EPM), forced swim test (FST), sucrose consumption (SC), and social interaction (SSN).

Main Results:

• Disc1-L100P +/- and wild-type mice exhibited similar anxiety responses to CSD.
• Q31L +/- mice displayed a distinct anxiety response to CSD.
• Significant gene-environment interactions were observed in OF, EPM, and SSN tasks.

Conclusions:

• DISC1 gene variants modulate behavioral responses to environmental stressors.
• Gene-environment interactions play a significant role in the behavioral outcomes related to psychiatric illness.
• These findings contribute to understanding the genetic and environmental factors contributing to psychiatric disorders.