Abstract
BACKGROUND: The interthalamic adhesion (IA) is a midline structure connecting the left and right thalamus that typically develops during the second trimester of pregnancy. Missing and smaller IA have been linked to neurodevelopmental disorders, including schizophrenia, and subtle deficits in cognition. However, the 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: The presence/absence and morphology of IA were ascertained on structural T1-weighted magnetic resonance images obtained at 3T in individuals with schizophrenia spectrum disorders (SSDs) (n = 223) and healthy individuals (n = 194) and compared between groups. Associations between IA morphology, cognitive function, and IHI were assessed. RESULTS: The prevalence of missing IA was 1.7% and did not differ between groups. IA was significantly smaller in the SSD group (p < .001). However, follow-up analyses revealed that smaller IA size in SSD was due to a significant diagnosis × 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 SSDs suggests that abnormal IA size measured during 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 during the second trimester.