Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia

Schizophrenia and bipolar disorder have both been linked to structural abno rmalities of the hippocampus, which is consistent with a neurodevelopmental anomaly. One isoform of the neural cell adhesion molecule (N-CAM) protein, cytosolic N-CAM 105-115 kDa, was previously shown to be increased in schiz ophrenia in the hippocampus and prefrontal cortex. Another isoform of N-CAM , the variable alternative spliced exon of N-CAM, was also increased in the hippocampus and prefrontal cortex of bipolar disorder patients. In the pre sent study, the secreted isoform of N-CAM (SEC N-CAM), synaptophysin, and a ctin proteins were measured in the hippocampus of controls, suicide victims , and patients with bipolar disorder or schizophrenia by quantitative Weste rn immunoblotting. Previous measurements of cytosolic N-CAM (105-115 kDa) p rotein, from the same hippocampus samples, were used to calculate the NCAM (105-115 kDa)/synaptophysin ratio. An affinity purified antibody to SEC N-C AM recognized SEC N-CAM (108 kDa and 115 kDa) in brain but SEC N-CAM was no t detectable in CSF. In bipolar disorder, but not in schizophrenia, an incr eased SEC N-CAM 115 kDa/108 kDa ratio was found as compared to controls (P = 0.03). The synaptophysin/actin ratio was significantly decreased in schiz ophrenia (P = 0.014) as compared to controls. The cytosolic N-CAM 105-115 k Da/synaptophysin ratio was increased in patients with schizophrenia (P = 0. 017), but not in bipolar disorder. Thus, bipolar disorder patients show alt ered expression of SEC N-CAM in the hippocampus. Patients with schizophreni a show a decrease in synaptophysin and an increase in the cytosolic N-CAM 1 05-115 kDa/synaptophysin ratio. The results offer further evidence of diffe rences in protein expression between bipolar disorder and schizophrenia in the hippocampus, which is consistent with a distinct neuropathology for eac h neuropsychiatric disorder.