Basic Science and Pathogenesis.

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Adversity and trauma can lead to psychiatric disorders years later, potentially via oxidative stress and epigenetic changes.
• Trauma-induced epigenetic imprints on the Hypothalamic-Pituitary-Adrenal Axis may alter the lateral habenula, increasing dementia risk.
• Generational trauma transmission is hypothesized to increase dementia risk in subsequent generations.

Purpose of the Study:

• To investigate the epigenetic mechanisms linking generational trauma to increased dementia risk.
• To explore how parental adversity impacts offspring neuroanatomy and behavior, potentially influencing dementia susceptibility.

Main Methods:

• Utilize murine models to study the neuroanatomical effects of trauma on prenatal mice and their offspring's behavior.
• Analyze lateral habenula structure and perform methylation assays in murine models, comparing them to control groups.
• Compare findings with human longitudinal cohorts experiencing extreme adversity to assess dementia frequency and outcomes.

Main Results:

• Corroborate the link between trauma and disrupted nervous system development.
• Establish if offspring of parents with extreme adversity face a higher risk of dementia-related conditions.
• Translate findings between murine and human models using common variables to understand intergenerational effects.

Conclusions:

• Investigate the extent and mechanisms by which generational trauma increases dementia likelihood.
• Provide insights into generational studies of dementia and inform proactive risk reduction strategies.