Reduction of the internal capsule in families affected with schizophrenia

Background: The anterior limb of the internal capsule (ALIC), connecting cortical and subcortical structures, is involved in functional important circuits. To detect volumetric changes in ALIC, including the influence of genetic factors, a magnetic resonance imaging (MRI) study of families affected with schizophrenia was performed. Methods: The study sample comprised 22 family members with schizophrenia (FM-SZ), 34 family members without schizophrenia (FM-NSZ), and 43 control subjects. In addition to manual tracing of ALIC, subjects underwent proton magnetic resonance spectroscopy in the left prefrontal cortex, psychopathological rating, and neuropsychological assessment of frontal lobe function. Results: Compared with controls, a significant reduction of right ALIC volume was seen in all family members (12%-16% reduction, p <.01) and a reduction of left ALIC volume in FM-NSZ (10% reduction, p =.028) was also observed. Both groups of family members showed a bilateral reduction in maximal cross sectional area of the ALIC. FM-SZ performed significantly worse on neurocognitive measures (Subject Ordered Pointing Task [SOPT] and Wisconsin Card Sorting Test), and performance correlated negatively with the ALIC volume (SOPT, r = -.6, p =.03). Conclusions: A reduced volume of ALIC in affected families supports the hypothesis of disturbed frontothalamic connectivity in schizophrenia and demonstrates functional relevance by an association with reduced neurocognitive performance.