Characterizing massa intermedia morphology in schizophrenia: associations with aging, neuropsychological functioning, and atypical hippocampal development

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