Dissecting causal relationships between cortical morphology and neuropsychiatric disorders: a bidirectional Mendelian...

Area of Science:

• Neurogenetics
• Neuroimaging
• Psychiatry

Background:

• Brain cortical morphology (surface area and thickness) is highly heritable.
• Previous studies suggest links between cortical morphology and neuropsychiatric phenotypes, but establishing causality is challenging due to confounders.

Purpose of the Study:

• To investigate causal relationships between 70 brain cortical morphology measures and 199 neuropsychiatric, behavioral, and metabolic phenotypes.
• To identify specific morphological traits influencing various health outcomes.

Main Methods:

• Generalized Summary-data-based Mendelian Randomization (GSMR) was employed.
• Sensitivity analyses were conducted to validate findings.
• Investigated causal links between cortical morphology and 199 phenotypes.

Main Results:

• Total brain cortical surface area (TSA) causally influences 18 phenotypes, notably enhancing cognitive performance.
• Global mean cortical thickness (MTH) causally affects five phenotypes, including reducing schizophrenia risk.
• Bidirectional causality observed between MTH and smoking initiation; regional analyses showed TSA and thickness influencing cognition and schizophrenia.

Conclusions:

• Significant bidirectional associations exist between brain morphology (TSA, MTH) and neuropsychiatric traits.
• Findings suggest potential intervention strategies for improving brain health.
• Cortical morphology plays a causal role in cognitive function and psychiatric conditions.