DISC1 mouse models as a tool to decipher gene-environment interactions in psychiatric disorders

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Disrupted-In-Schizophrenia 1 (DISC1) gene identified in a Scottish pedigree with psychiatric disorders.
• Genetic studies confirm DISC1's role as a susceptibility gene for neuropsychiatric disorders.
• Numerous DISC1 mouse models have been developed to investigate its neuronal functions and associated phenotypes.

Purpose of the Study:

• To explore the impact of gene-environment interactions on neuropsychiatric disorder development using DISC1 mouse models.
• To investigate how genetic and environmental factors determine the clinical manifestation of psychiatric disorders.
• To summarize existing research on DISC1 mouse models combined with environmental stressors.

Main Methods:

• Utilized five distinct DISC1 mouse models.
• Applied environmental stressors including early immune activation and social paradigms across neurodevelopmental stages (prenatal to adulthood).
• Employed molecular, anatomical, and behavioral assessments; some studies included rescue strategies.

Main Results:

• DISC1 mouse models exhibit varied phenotypes relevant to schizophrenia and depression.
• Environmental stressors, when combined with DISC1 models, influence neurodevelopmental trajectories.
• Studies highlight the potential for gene-environment interactions to shape disorder-specific outcomes.

Conclusions:

• DISC1 is a crucial gene for understanding gene-environment interactions in psychiatric disorders.
• Further research using DISC1 models and controlled environmental exposures can elucidate the mechanisms underlying disorder etiology.
• Investigating differential responses of DISC1 models to specific stressors is key to understanding clinical variability.