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

Abstract

Numerous neuroimaging studies have revealed structural brain abnormalities in schizophrenia patients. 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). Serum NGF was significantly correlated to GMV in the left prefrontal lobe, the left midcingulate cortex, and the brainstem in schizophrenia patients. 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. 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. 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. As our pilot study is exploratory in nature, further studies enrolling larger sample sizes will be needed to further corroborate our findings and to investigate the influence of additional covariates.

BDNF Serum Levels are Associated With White Matter Microstructure in Schizophrenia - A Pilot Study

“…As described previously, we found significant reductions of grey matter volume in schizophrenia patients in a widespread fronto-temporo-parietal network (44).…”

“…The study protocol was approved by the institutional review board of RWTH Aachen University Hospital, Aachen, Germany. A total of 20 healthy volunteers (12 male and 8 female) recruited from the local community and 19 patients with schizophrenia (11 male and 8 female) recruited at the Department of Psychiatry, Psychotherapy, and Psychosomatics, RWTH Aachen University Hospital, were enrolled in this study, as, in part, previously reported by Neugebauer and colleagues (44). Two of the patients had to be excluded due to abnormalities in their MRI data sets (one because of grossly enlarged lateral ventricles, most likely due to infantile hypoxia, and another one due to technical artifacts).Written informed consent was given by all participants prior to inclusion.…”

A Meta-Analysis of Brain-Derived Neurotrophic Factor Effects on Brain Volume in Schizophrenia: Genotype and Serum Levels

“…BDNF may therefore contribute to observed brain volume reductions in schizophrenia, especially in regions of significant BDNF function such as the hippocampal and frontal regions. It is likely, however, that BDNF works synergistically with other neurotrophins, growth factors, and immune response parameters that have similarly shown associations with frontal and hippocampal volume [68][69][70]. The current meta-analysis adds to existing evidence of the status of BDNF as a biomarker of schizophrenia with multiple pleiotropic effects including the incidence of the illness, predisposing factors, cognitive functions, and clinical status [37,50,[71][72][73][74][75][76][77][78][79][80][81].…”

Neuro-Immune Aspects of Schizophrenia with Severe Negative Symptoms: New Diagnostic Markers of Disease Phenotype

“…Among them, there are acute-phase proteins, anti-inflammatory proteins, macrophage and lymphocyte pro-inflammatory factors, including cytokines and chemokines of cells of natural and adaptive immunity. These deviations from the normal status can be combined in various ways to create numerous immune patterns affecting the signaling and metabolic pathways in the periphery and in the brain [ 14 ]. On this general background, the immune profiles of patients with schizophrenia with severe negative symptoms have not been studied enough.…”