Neurochemical and structural correlates of executive dysfunction in schizophrenia.

Background: Executive dysfunction is a core feature of schizophrenia. The neurochemical and structural changes associated with this deficit are, however, largely unclear. This study tested the hypothesis that changes in glutamate, glutamine and N-acetyl-aspartate (NAA) in hippocampal and dorsolateral prefrontal (DLPFC) regions as well as hippocampal, amygdalar and DLPFC volume reductions are associated with executive dysfunction.

Methods: Twenty-nine subjects with schizophrenia and 31 healthy controls were examined by short-echo single voxel magnetic resonance spectroscopy of the left anterior hippocampus and the left DLPFC. Volumes of the hippocampi, amygdalae and DLPFC were measured bilaterally using manual volumetry. Executive functioning was assessed by the Wisconsin Card Sorting Test (WCST).

Results: Poor WCST performance was associated with increased hippocampal glutamate concentrations among subjects with schizophrenia, not among healthy controls. Glutamate in the DLPFC as well as NAA or glutamine in the hippocampus or the DLPFC were not related to executive functioning in schizophrenia or healthy controls. Reduced amygdalar volume was associated with impaired executive functioning in subjects with schizophrenia (p=.06) and healthy controls (p=.04).

Conclusions: Altered hippocampal glutamatergic neurotransmission and amygdalar volume loss may be associated with executive dysfunction in schizophrenia.