Associations between psychosis endophenotypes across brain functional, structural, and cognitive domains.

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Psychosis is characterized by various endophenotypes, but their interrelationships remain underexplored.
• Understanding these connections is crucial for elucidating the underlying mechanisms of psychosis liability.

Purpose of the Study:

• To investigate the interrelationships between cognitive, electrophysiological, and neuroanatomical endophenotypes in psychosis.
• To determine if these relationships differ across individuals with psychotic disorders, unaffected relatives, and healthy controls.

Main Methods:

• A multi-center study involving 8754 participants: 2212 with psychotic disorders, 1487 unaffected relatives, and 5055 healthy controls.
• Assessment of cognition (digit span, block design, Rey Auditory Verbal Learning Test), electrophysiology (P300 amplitude and latency), and neuroanatomy (lateral ventricular volume).
• Linear regression analysis was employed to examine the associations between endophenotypes.

Main Results:

• P300 amplitude and latency were found to be independent endophenotypes.
• P300 amplitude was positively associated with block design performance.
• All cognitive endophenotypes demonstrated expected interrelationships (p < 0.001).

Conclusions:

• P300 amplitude and latency represent distinct endophenotypes, potentially indexing spatial visualization/working memory and processing speed, respectively.
• Consistent patterns of endophenotype associations were observed across all participant groups.
• Findings support a continuum of psychosis liability across the population.