Expression of Ca²⁺-dependent activator protein for secretion 2 is increased in the brains of schizophrenic patients

Prog Neuropsychopharmacol Biol Psychiatry. 2011 Aug 15;35(7):1738-43. doi: 10.1016/j.pnpbp.2011.05.004. Epub 2011 May 12.

Abstract

Ca(2+)-dependent activator protein for secretion 2 (CADPS2), a secretory granule associate protein, mediates monoamine transmission and the release of neurotrophins including brain-derived neurotrophic factor (BDNF) which have been implicated in psychiatric disorders. Furthermore, the expression of CADPS2deltaExon3, a defective splice variant of CADPS2, has been reported to be associated with autism. Based on these observations, we examined whether expression levels of CADPS2 and CADPS2deltaExon3 are altered in psychiatric disorders. Quantitative polymerase chain reaction analysis was performed for postmortem frontal cortex tissues (BA6) from 15 individuals with schizophrenia, 15 with bipolar disorder, 15 with major depression, and 15 controls (Stanley neuropathology consortium). The mean CADPS2 expression levels normalized to human glyceraldehyde-3phosphate dehydrogenase (GAPDH) or TATA-box binding protein levels was found to be significantly increased in the brains of the schizophrenia group, compared to the control group. On the other hand, the ratio of CADPS2deltaExon3 to total CADPS2 was similar in the 4 diagnostic groups. We then analyzed CADPS2 expression in blood samples from 121 patients with schizophrenia and 318 healthy controls; however, there was no significant difference between the two groups. Chronic risperidone treatment did not alter the expression of CADPS2 in frontal cortex of mice. The observed increase in the expression of CADPS2 may be related to the impaired synaptic function in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antipsychotic Agents / pharmacology
  • Autopsy
  • Brain / metabolism
  • Brain / physiopathology*
  • Calcium-Binding Proteins / biosynthesis*
  • Calcium-Binding Proteins / blood
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology*
  • Female
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / physiology
  • Humans
  • Male
  • Mental Disorders / metabolism
  • Mental Disorders / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Protein Isoforms / biosynthesis*
  • Protein Isoforms / genetics
  • RNA / blood
  • Risperidone / pharmacology
  • Schizophrenia / epidemiology
  • Schizophrenia / metabolism*
  • Schizophrenia / physiopathology
  • TATA-Box Binding Protein / physiology
  • Time Factors
  • Vesicular Transport Proteins / biosynthesis*
  • Vesicular Transport Proteins / blood
  • Vesicular Transport Proteins / genetics*
  • Vesicular Transport Proteins / metabolism

Substances

  • Antipsychotic Agents
  • CADPS2 protein, human
  • Calcium-Binding Proteins
  • Protein Isoforms
  • TATA-Box Binding Protein
  • Vesicular Transport Proteins
  • RNA
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
  • Risperidone