Nerve Growth Factor Serum Levels Are Associated With Regional Gray Matter Volume Differences in Schizophrenia Patients

Numerous neuroimaging studies have revealed structural brain abnormalities in schizophrenia patients and there is emerging evidence that dysfunctional nerve growth factor (NGF) signaling may contribute to structural brain alterations found in these patients. In this pilot study, we investigated whether there was a correlation between NGF serum levels and gray matter volume (GMV) in schizophrenia patients. Further, we investigated whether there was an overlap between the correlative findings and cross-sectional GMV differences between schizophrenia patients (n = 18) and healthy controls (n = 19) carrying out whole brain voxel-based morphometry (VBM) analysis. In schizophrenia patients, serum NGF levels were found to be positively correlated with GMV in the pons. Resorting to the BrainMap data base, functional characterization revealed a prominent conjunction between the cluster and functions of pain monitoring and pain discrimination. Two clusters were negatively correlated between NGF serum levels and GMV, one cluster located in the left mid orbital gyrus extending into the right hemisphere, and the other in the left MCC. Both clusters were found to be associated with reward related tasks. However, we did not find any correlations of NGF serum levels with GMV in healthy controls. Schizophrenia patients showed smaller GMV than healthy controls in brain regions located in the bilateral limbic system, bilateral parietal lobe, bilateral insula, bilateral primary auditory cortex, left frontal lobe, and bilateral occipital regions. The clusters showing reduced GMV in schizophrenia patients were associated with social cognition, reasoning, action execution and language-related processes. We did not find any increase in GMV in schizophrenia patients compared to healthy controls. In a conjunction analysis, GMV in the left midcingulate cortex (MCC) appears negatively correlated to NGF serum levels in the group of schizophrenia patients and also to be reduced compared to healthy controls. In conclusion, this pilot study offered hints about the influence of serum NGF on the brain structure of several regions in schizophrenia patients, while no comparable results had been found in healthy controls. Remarkably, changes correlated with NGF serum levels manifested also in the cingulate cortex, a region that also showed volume reductions our group comparison between patients and controls and has been repeatedly implicated in the literature as morphologically altered in schizophrenia. These results suggest an increased vulnerability of schizophrenia patients to changes in NGF levels compared to healthy controls and support a role for NGF signaling in the pathophysiology of schizophrenia