Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Bipolar disorder pathophysiology involves neurodevelopmental and neurodegenerative processes.
• Structural neuroimaging reveals brain alterations, but behavioral links are unclear.
• Multi-generational families with bipolar disorder offer a unique model to study these links.

Purpose of the Study:

• Characterize neurobehavioral correlates of bipolar disorder-implicated neuroanatomy.
• Identify differing brain-behavior associations between diagnostic groups.
• Examine age-related cognitive decline and brain-behavior correlations in bipolar disorder.

Main Methods:

• Structural neuroimaging and comprehensive neurocognitive/temperament assessments.
• Linear regression models to analyze brain-behavior associations.
• Study included 527 adults (153 with bipolar disorder) from 26 genetically enriched families.

Main Results:

• Total cortical and ventricular volumes correlated with multiple cognitive domains (memory, executive function).
• Cortical thickness linked to declarative memory, fluency, and processing speed.
• Unique association: increased prefrontal/parietal cortical thickness correlated with better declarative memory in bipolar disorder patients only.

Conclusions:

• Neuroanatomical traits in bipolar disorder are significantly associated with neurobehavioral domains.
• Brain-behavior relationships are mostly preserved, but prefrontal/parietal cortex shows unique cognitive resilience in bipolar disorder.
• No evidence of accelerated cognitive aging in bipolar disorder; larger global brain volume may protect against cognitive aging effects.