PRODYNORPHIN MESSENGER-RNA EXPRESSION IS INCREASED IN THE PATCH VS MATRIX COMPARTMENT OF THE CAUDATE-NUCLEUS IN SUICIDE SUBJECTS

Experimental and clinical studies suggest an involvement of the opioid neuropeptide system in psychiatric disorders. Notably, opioid peptide immunoreactivity is altered in the cerebrospinal fluid of chronic sch izophrenics and manic-depressive subjects.(1-3) Despite these clinical findings, few postmortem investigations(4,5) have examined the associ ation of endogenous opioid neuropeptides with schizophrenia and suicid e. Anatomically, a tight interaction exists within the neostriatum bet ween the opioid peptide (dynorphin and enkephalin) system and classica l neurotransmitters such as dopamine(6) which has been implicated in b oth the psychotic symptoms and the cognitive deficits that characteriz e schizophrenia (see review).(7) The neostriatum is differentially org anized into patch and matrix neurochemical mosaic compartments anatomi cally connected to limbic-and sensorimotor-related brain regions, resp ectively.(6,8) Moreover, the human neostriatum is characterized by a h eterogenous expression of the prodynorphin opioid gene: high in the pa tch, but low in the matrix compartment.(9,10) The present results show for the first time a differential alteration of prodynorphin within d istinct striatal compartments in postmortem tissue from nonschizophren ic suicide subjects. The prodynorphin patch/matrix mRNA expression was elevated in the caudate nucleus of suicide subjects as compared to no rmal controls and schizophrenics in which no alterations in opioid pep tides or D-1 and D-2 mRNA expression were apparent. Altogether the fin dings suggest that discrete dysfunction of the endogenous opioid dynor phin system might contribute to depression and the risk of suicide in nonschizophrenic subjects.