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.