Elevated concentration of N-CAM VASE isoforms in schizophrenia

Marquis P. Vawter, Mark A Frye, John J. Hemperly, Dale M. Vanderputten, Nsima Usen, Patrick Doherty, Jane L. Saffell, Fuad Issa, Robert M. Post, Richard Jed Wyatt, William J. Freed

Research output: Contribution to journalArticle

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Abstract

Neural cell adhesion molecule (N-CAM) is a cell recognition molecule, four major isoforms (180, 140, 120, and 105-115 kDa) of which are present in brain. N-CAM has several roles in cellular organization and CNS development. Previously we have found an elevation in CSF N-CAM 120 kDa in the CSF of patients with schizophrenia, bipolar disorder, and depression. We now report an increase in the variable alternative spliced exon (VASE), a 10 amino acid sequence inserted into the fourth N-CAM domain, in the CSF of patients with schizophrenia, but not in bipolar disorder or depression. VASE-immunoreactive (VASE-ir) bands were measured in CSF from patients with schizophrenia (n=14), bipolar disorder I (n=7), bipolar disorder II (n=9), unipolar depression (n=17) and matched controls (n=37) by Western immunoblotting. Three VASE-ir bands were distinguished in lumbar CSF corresponding to heavy (165 kDa), medium (155 kDa) and low (140 kDa) MW. A logarithmic transformation was applied to the VASE protein units and analyzed with a MANOVA. There was a 51% and 45% increase in VASE heavy (p=0.0008) and medium (p=0.04) MW protein, respectively, in patients with schizophrenia as compared with normal controls. Current neuroleptic treatment in patients with schizophrenia had no effect on CSF VASE concentrations. VASE concentration correlated significantly with behavioral ratings in patients with schizophrenia but not affective disorders. Thus, VASE immunoreactivity is increased in schizophrenia but not in affective disorders. These results provide further evidence of an abnormality of N-CAM protein in chronic schizophrenia and suggest differences between schizophrenia and affective disorders in regulation of N-CAM. Copyright (C) 1999.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalJournal of Psychiatric Research
Volume34
Issue number1
DOIs
StatePublished - Jan 2000
Externally publishedYes

Fingerprint

Neural Cell Adhesion Molecules
Exons
Schizophrenia
Protein Isoforms
Bipolar Disorder
Mood Disorders
Proteins
Depressive Disorder
Antipsychotic Agents
Amino Acid Sequence
Western Blotting

Keywords

  • Bipolar disorder
  • Cerebrospinal fluid
  • Electrophoresis
  • Hamilton depression rating scale
  • Neural cell adhesion molecule
  • Psychiatric symptom assessment scale
  • Schizophrenia
  • Variable alternative spliced exon
  • Western immunoblot

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Psychology(all)

Cite this

Vawter, M. P., Frye, M. A., Hemperly, J. J., Vanderputten, D. M., Usen, N., Doherty, P., ... Freed, W. J. (2000). Elevated concentration of N-CAM VASE isoforms in schizophrenia. Journal of Psychiatric Research, 34(1), 25-34. https://doi.org/10.1016/S0022-3956(99)00026-6

Elevated concentration of N-CAM VASE isoforms in schizophrenia. / Vawter, Marquis P.; Frye, Mark A; Hemperly, John J.; Vanderputten, Dale M.; Usen, Nsima; Doherty, Patrick; Saffell, Jane L.; Issa, Fuad; Post, Robert M.; Wyatt, Richard Jed; Freed, William J.

In: Journal of Psychiatric Research, Vol. 34, No. 1, 01.2000, p. 25-34.

Research output: Contribution to journalArticle

Vawter, MP, Frye, MA, Hemperly, JJ, Vanderputten, DM, Usen, N, Doherty, P, Saffell, JL, Issa, F, Post, RM, Wyatt, RJ & Freed, WJ 2000, 'Elevated concentration of N-CAM VASE isoforms in schizophrenia', Journal of Psychiatric Research, vol. 34, no. 1, pp. 25-34. https://doi.org/10.1016/S0022-3956(99)00026-6
Vawter, Marquis P. ; Frye, Mark A ; Hemperly, John J. ; Vanderputten, Dale M. ; Usen, Nsima ; Doherty, Patrick ; Saffell, Jane L. ; Issa, Fuad ; Post, Robert M. ; Wyatt, Richard Jed ; Freed, William J. / Elevated concentration of N-CAM VASE isoforms in schizophrenia. In: Journal of Psychiatric Research. 2000 ; Vol. 34, No. 1. pp. 25-34.
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abstract = "Neural cell adhesion molecule (N-CAM) is a cell recognition molecule, four major isoforms (180, 140, 120, and 105-115 kDa) of which are present in brain. N-CAM has several roles in cellular organization and CNS development. Previously we have found an elevation in CSF N-CAM 120 kDa in the CSF of patients with schizophrenia, bipolar disorder, and depression. We now report an increase in the variable alternative spliced exon (VASE), a 10 amino acid sequence inserted into the fourth N-CAM domain, in the CSF of patients with schizophrenia, but not in bipolar disorder or depression. VASE-immunoreactive (VASE-ir) bands were measured in CSF from patients with schizophrenia (n=14), bipolar disorder I (n=7), bipolar disorder II (n=9), unipolar depression (n=17) and matched controls (n=37) by Western immunoblotting. Three VASE-ir bands were distinguished in lumbar CSF corresponding to heavy (165 kDa), medium (155 kDa) and low (140 kDa) MW. A logarithmic transformation was applied to the VASE protein units and analyzed with a MANOVA. There was a 51{\%} and 45{\%} increase in VASE heavy (p=0.0008) and medium (p=0.04) MW protein, respectively, in patients with schizophrenia as compared with normal controls. Current neuroleptic treatment in patients with schizophrenia had no effect on CSF VASE concentrations. VASE concentration correlated significantly with behavioral ratings in patients with schizophrenia but not affective disorders. Thus, VASE immunoreactivity is increased in schizophrenia but not in affective disorders. These results provide further evidence of an abnormality of N-CAM protein in chronic schizophrenia and suggest differences between schizophrenia and affective disorders in regulation of N-CAM. Copyright (C) 1999.",
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AU - Usen, Nsima

AU - Doherty, Patrick

AU - Saffell, Jane L.

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AB - Neural cell adhesion molecule (N-CAM) is a cell recognition molecule, four major isoforms (180, 140, 120, and 105-115 kDa) of which are present in brain. N-CAM has several roles in cellular organization and CNS development. Previously we have found an elevation in CSF N-CAM 120 kDa in the CSF of patients with schizophrenia, bipolar disorder, and depression. We now report an increase in the variable alternative spliced exon (VASE), a 10 amino acid sequence inserted into the fourth N-CAM domain, in the CSF of patients with schizophrenia, but not in bipolar disorder or depression. VASE-immunoreactive (VASE-ir) bands were measured in CSF from patients with schizophrenia (n=14), bipolar disorder I (n=7), bipolar disorder II (n=9), unipolar depression (n=17) and matched controls (n=37) by Western immunoblotting. Three VASE-ir bands were distinguished in lumbar CSF corresponding to heavy (165 kDa), medium (155 kDa) and low (140 kDa) MW. A logarithmic transformation was applied to the VASE protein units and analyzed with a MANOVA. There was a 51% and 45% increase in VASE heavy (p=0.0008) and medium (p=0.04) MW protein, respectively, in patients with schizophrenia as compared with normal controls. Current neuroleptic treatment in patients with schizophrenia had no effect on CSF VASE concentrations. VASE concentration correlated significantly with behavioral ratings in patients with schizophrenia but not affective disorders. Thus, VASE immunoreactivity is increased in schizophrenia but not in affective disorders. These results provide further evidence of an abnormality of N-CAM protein in chronic schizophrenia and suggest differences between schizophrenia and affective disorders in regulation of N-CAM. Copyright (C) 1999.

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