Interaction of hippocampal volume and N-acetylaspartate concentration deficits in schizophrenia: A combined MRI and 1H-MRS study

BackgroundVolume deficits assessed with magnetic resonance imaging (MRI) and neurochemical dysfunctions (N-acetylaspartate, NAA) diagnosed using proton MR spectroscopy (1H-MRS) are reliable observations in the hippocampus of schizophrenic patients. NAA is an important cerebral amino acid in the synthesis pathways of glutamate, which has been implicated as a pathobiological core of schizophrenic symptomatology, of histological alterations and brain volume deficits in schizophrenia. However, the possible interaction between regional NAA reduction and volume deficits has been targeted only marginally in previous investigations.MethodsIn 29 schizophrenic patients and 44 control subjects, a multimodal imaging study with 1H-MRS and MRI volumetry of the left hippocampus was performed on a 3-Tesla scanner.ResultsCompared to the control group, the hippocampus of the patients exhibited a significant volume reduction and a significant NAA concentration decrease. In schizophrenic patients, but not in healthy controls, a significant negative correlation between hippocampal NAA concentration and volume (r = −0.455, p = 0.017) was observed. None of the imaging parameters was associated with clinical parameters.ConclusionsThe results argue for a coexistent neurochemical and structural deficit in the hippocampus of schizophrenic patients. The inverse relationship between the two parameters observed in patients only may reflect an interaction of neurochemistry and brain morphology as a pathobiological mechanism in schizophrenia. This observation is compatible with the important role of NAA in the synthesis of excitatory neurotransmitters and the hypothesized role of glutamate for brain morphology. The independence of the measured imaging parameters from clinical parameters is in line with the neurodevelopmental hypothesis of schizophrenia.

Research highlights► The NAA concentration in the hippocampus is significant reduced in patients with schizophrenia. ► The volume of the left and right hippocampus is significant reduced in patients with schizophrenia. ► A significant negative correlation between hippocampal NAA concentration and hippocampal volume was observed in patients with schizophrenia. ► Evidence for a coexistent structural and neurochemical dysfunction in the hippocampus of schizophrenic patients.