Abstract
To examine the role of neuroplasticity in the pathology of psychiatric disorders, we measured cerebrospinal fluid (CSF) neuroplasticity-associated protein levels. Participants were 94 patients with schizophrenia, 68 with bipolar disorder (BD), 104 with major depressive disorder (MDD), and 118 healthy controls, matched for age, sex, and ethnicity (Japanese). A multiplex immunoassay (22-plex assay) was performed to measure CSF neuroplasticity-associated protein levels. Among 22 proteins, 11 were successfully measured in the assay. CSF amyloid precursor protein (APP) and glial cell-derived neurotrophic factor (GDNF) levels were significantly lower in patients with schizophrenia, and CSF APP and neural cell adhesion molecule (NCAM)-1 levels were significantly lower in patients with BD, than in healthy controls (all p < 0.05). Positive and Negative Syndrome Scale total, positive, and general scores were significantly and positively correlated with CSF hepatocyte growth factor (HGF) (p < 0.01) and S100 calcium-binding protein B (S100B) (p < 0.05) levels in patients with schizophrenia. Young mania-rating scale score was significantly and positively correlated with CSF S100B level in patients with BD (p < 0.05). Hamilton Depression Rating Scale, core, sleep, activity, somatic anxiety, and delusion subscale scores were significantly and positively correlated with CSF HGF level, while sleep subscale score was positively correlated with CSF S100B and VEGF receptor 2 levels in patients with MDD (p < 0.05). Our results suggest that CSF APP, GDNF, and NCAM-1 levels are associated with psychiatric disorders, and that CSF HGF, S100B, and VEGF receptor 2 levels are related to psychiatric symptoms.
Highlights
Impaired neuroplasticity, including synaptic plasticity, has been suggested in the pathophysiology of major psychiatric disorders, such as schizophrenia[1,2,3], bipolar disorder (BD)[4], and major depressive disorder (MDD)[5,6]
22 were chosen since they could be investigated using commercially available products. This multiplex immunoassay study aimed to measure protein levels simultaneously in a relatively large sample of cerebrospinal fluid (CSF) collected from patients with major psychiatric disorders, or healthy controls to investigate the role of neuroplasticity in the pathology of psychiatric disorders
CSF amyloid precursor protein (APP) and glial cell-derived neurotrophic factor (GDNF) levels were significantly lower in patients with schizophrenia {p = 0.019 and 0.035}, while CSF APP and neural cell adhesion molecule (NCAM)-1 levels were significantly lower in patients with BD {p = 0.002 and 0.017}, than in healthy controls (Fig. 1)
Summary
Impaired neuroplasticity, including synaptic plasticity, has been suggested in the pathophysiology of major psychiatric disorders, such as schizophrenia[1,2,3], bipolar disorder (BD)[4], and major depressive disorder (MDD)[5,6]. Above[19,20], we could not detect mature BDNF protein in the CSF, our western blotting assay found decreased CSF BDNF ‘pro-peptide’ levels in patients with MDD28. Other neuroplasticity-associated proteins remain to be quantified in the CSF collected from patients with psychiatric disorders, which warrants further comprehensive immunoassays. 22 were chosen since they could be investigated using commercially available products. This multiplex immunoassay study aimed to measure protein levels simultaneously in a relatively large sample of CSF collected from patients with major psychiatric disorders, or healthy controls to investigate the role of neuroplasticity in the pathology of psychiatric disorders. We tested the hypothesis that CSF neuroplasticity-associated protein levels would be reduced in patients with psychiatric disorders
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