Feature Finding Figure
Certain cognitive deficits in schizophrenia have been linked to dysfunction of prefrontal cortical (PFC) g-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 to 11.5 years. We found higher levels for MOR mRNA (127%) in schizophrenia but no differences in DOR or roenkephalin 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. Because MOR activation suppresses GABA release from axon terminals and hyperpolarizes the cell body (reducing responsiveness to excitatory input), higher MOR mRNA levels in schizophrenia may contribute to suppressed PFC GABA neurotransmission (Figure). These abnormalities may reflect alterations in the postnatal developmental trajectory of MOR signaling.
Volk, DW, Radchenkova PV, Walker EM, Sengupta EJ, Lewis DA: Cortical opioid markers in schizophrenia and across postnatal development. Cereb Cortex, ePub August 1, 2011.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
Pittsburgh, Pennsylvania 15213-2593
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