Adenosine Kinase Expression in the Frontal Cortex in Schizophrenia

Schizophr Bull. 2020 Apr 10;46(3):690-698. doi: 10.1093/schbul/sbz086.


The adenosine hypothesis of schizophrenia posits that reduced availability of the neuromodulator adenosine contributes to dysregulation of dopamine and glutamate transmission and the symptoms associated with schizophrenia. It has been proposed that increased expression of the enzyme adenosine kinase (ADK) may drive hypofunction of the adenosine system. While animal models of ADK overexpression support such a role for altered ADK, the expression of ADK in schizophrenia has yet to be examined. In this study, we assayed ADK gene and protein expression in frontocortical tissue from schizophrenia subjects. In the dorsolateral prefrontal cortex (DLPFC), ADK-long and -short splice variant expression was not significantly altered in schizophrenia compared to controls. There was also no significant difference in ADK splice variant expression in the frontal cortex of rats treated chronically with haloperidol-decanoate, in a study to identify the effect of antipsychotics on ADK gene expression. ADK protein expression was not significantly altered in the DLPFC or anterior cingulate cortex (ACC). There was no significant effect of antipsychotic medication on ADK protein expression in the DLPFC or ACC. Overall, our results suggest that increased ADK expression does not contribute to hypofunction of the adenosine system in schizophrenia and that alternative mechanisms are involved in dysregulation of this system in schizophrenia.

Keywords: ACC; DLPFC; neuropsychiatric; postmortem.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine / metabolism*
  • Adenosine Kinase / drug effects
  • Adenosine Kinase / genetics
  • Adenosine Kinase / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Female
  • Gene Expression* / drug effects
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / enzymology
  • Gyrus Cinguli / metabolism*
  • Hep G2 Cells
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / enzymology
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Schizophrenia / drug therapy
  • Schizophrenia / enzymology
  • Schizophrenia / metabolism*
  • Tissue Banks


  • Antipsychotic Agents
  • Adenosine Kinase
  • Adenosine