title: Cortical opioid markers in schizophrenia and across postnatal development.
abstract: Certain cognitive deficits in schizophrenia have been linked to dysfunction of prefrontal cortical (PFC) γ-aminobutyric acid (GABA) neurons and appear neurodevelopmental in nature. Since opioids suppress GABA neuron activity, we conducted the first study to determine 1) whether the μ opioid receptor (MOR), δ opioid receptor (DOR), and opioid ligand proenkephalin are altered in the PFC of a large cohort of schizophrenia subjects and 2) the postnatal developmental trajectory in monkey PFC of opioid markers that are altered in schizophrenia. We used quantitative polymerase chain reaction to measure mRNA levels from 42 schizophrenia and 42 matched healthy comparison subjects; 18 monkeys chronically exposed to haloperidol, olanzapine, or placebo; and 49 monkeys aged 1 week-11.5 years. We found higher levels for MOR mRNA (+27%) in schizophrenia but no differences in DOR or proenkephalin mRNAs. Elevated MOR mRNA levels in schizophrenia did not appear to be explained by substance abuse, psychotropic medications, or illness chronicity. Finally, MOR mRNA levels declined through early postnatal development, stabilized shortly before adolescence and increased across adulthood in monkey PFC. In schizophrenia, higher MOR mRNA levels may contribute to suppressed PFC GABA neuron activity and might be attributable to alterations in the postnatal developmental trajectory of MOR signaling.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, W1655 BST, 3811 O’Hara Street, Pittsburgh, PA 15213, USA. volkdw@upmc.edu
authors.forename: David W
authors.initials: DW
authors.lastname: Volk
authors.forename: Polina V
authors.initials: PV
authors.lastname: Radchenkova
authors.forename: Erin M
authors.initials: EM
authors.lastname: Walker
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Sengupta
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D004745:Enkephalins / Q000096:biosynthesis*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D016133:Polymerase Chain Reaction; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D017465:Receptors, Opioid, delta / Q000096:biosynthesis*; D017450:Receptors, Opioid, mu / Q000096:biosynthesis*; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D014150:Antipsychotic Agents; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C029992:proenkephalin; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine