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Characterizing interthalamic adhesion morphology in schizophrenia: associations with aging, neuropsychological functioning, and atypical hippocampal development.

Zachary Bergson,Maxwell J. Roeske,B. Rogers,Anna S. Huang,Victoria Fox,S. Heckers,N. D. Woodward

Published 2025 in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

ABSTRACT

BACKGROUND The interthalamic adhesion (IA) is a midline structure connecting the left and right thalamus that typically develops during the 2nd trimester of pregnancy. Missing and smaller IA has been linked to neurodevelopmental disorders, including schizophrenia, and subtle deficits in cognition. However, findings are inconsistent and the association between IA and other anatomical variants linked to atypical brain development in schizophrenia, including incomplete hippocampal inversion (IHI), is unclear. METHODS Presence/absence and morphology of the IA were ascertained on structural T1-weighted MRI images obtained at 3T in individuals with schizophrenia spectrum disorder (SSD; n = 223) and healthy individuals (n = 194) and compared between groups. Associations between IA morphology, cognitive function, and incomplete hippocampal inversion (IHI) were assessed. RESULTS Prevalence of missing IA was 1.7% and did not differ between groups. IA was significantly smaller in SSD (p <.001). However, follow-up analyses revealed that smaller IA size in SSD was due to a significant Diagnosis x Age interaction characterized by a stronger negative age effect in SSD. IHI was significantly more common in individuals with missing IA. Neurocognition was not correlated with IA size when controlling for age and diagnosis. CONCLUSIONS Stronger effects of age on IA size in SSD suggests that abnormal IA size measured in adulthood may not be a reliable static indicator of atypical neurodevelopment, but may reflect disease progression or accelerated aging. Missing IA was rare in our sample. Conversely, missing IA was associated with IHI suggesting a shared neurodevelopmental disruption in the 2nd trimester.

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