ORIGINAL ARTICLES  NEU­RO­PHAR­MA­COL­O­GY 

The Quarterly Journal of Nuclear Medicine 1998 September;42(3):211-21

Copyright © 2000 EDIZIONI MINERVA MEDICA

language: English

Imaging dopamine transmission in schizophrenia. A review and meta-analysis

Laruelle M.

From the Brain Imaging Division New York State Psychiatric Istitute Columbia University College of Physicians and Surgeons New York, USA

Over the ­last ten ­years, sev­er­al posi­tron emis­sion tomog­ra­phy (PET) and sin­gle pho­ton com­pu­ter­ized tomog­ra­phy (­SPECT) stud­ies of the dop­a­mine (DA) ­system in ­patients ­with schizo­phre­nia ­were per­formed to ­test the hypoth­e­sis ­that DA hyper­ac­tiv­ity is asso­ciat­ed ­with ­this ill­ness. In ­this ­paper, we ­reviewed the ­results of fif­teen ­brain imag­ing stud­ies com­par­ing indi­ces of DA func­tion in ­drug ­naive or ­drug ­free ­patients ­with schizo­phre­nia and ­healthy con­trols: thir­teen stud­ies includ­ed meas­ure­ment of DA D2 recep­tors den­sity, two stud­ies com­pared amphet­a­mine-­induced DA ­release, and two stud­ies meas­ured ­DOPA decar­box­y­lase activ­ity, an ­enzyme ­involved in DA syn­the­sis. We con­duct­ed a ­meta-anal­y­sis of the stud­ies meas­ur­ing D2 recep­tor den­sity param­e­ters, ­under the assump­tion ­that all trac­ers ­labeled the ­same pop­u­la­tion of D2 recep­tors. This anal­y­sis ­revealed ­that, com­pared to ­healthy con­trols, ­patients ­with schizo­phre­nia ­present a sig­nif­i­cant but ­mild ele­va­tion of D2 recep­tor den­sity param­e­ters and a sig­nif­i­cant larg­er var­i­abil­ity of ­these indi­ces. We ­found no sta­tis­ti­cal evi­dence ­that stud­ies per­formed ­with radio­lab­eled buty­roph­e­nones detect­ed a larg­er ­increase in D2 recep­tor den­sity param­e­ters ­than stud­ies per­formed ­with oth­er radio­lig­ands, ­such as ben­za­mides. Studies of pre­syn­ap­tic activ­ity ­revealed an ­increase in DA trans­mis­sion ­response to amphet­a­mine chal­lenge, and an ­increase in ­DOPA decar­box­y­lase activ­ity. Together, ­these ­data are com­pat­ible ­with ­both pre- and ­post-syn­ap­tic alter­a­tions of DA trans­mis­sion in schizo­phre­nia. Future stud­ies ­should aim at a bet­ter char­ac­ter­iza­tion of ­these alter­a­tions, and at defin­ing ­their ­role in the pathoph­y­sio­lo­gy of the ill­ness.Over the ­last ten ­years, sev­er­al posi­tron emis­sion tomog­ra­phy (PET) and sin­gle pho­ton com­pu­ter­ized tomog­ra­phy (­SPECT) stud­ies of the dop­a­mine (DA) ­system in ­patients ­with schizo­phre­nia ­were per­formed to ­test the hypoth­e­sis ­that DA hyper­ac­tiv­ity is asso­ciat­ed ­with ­this ill­ness. In ­this ­paper, we ­reviewed the ­results of fif­teen ­brain imag­ing stud­ies com­par­ing indi­ces of DA func­tion in ­drug ­naive or ­drug ­free ­patients ­with schizo­phre­nia and ­healthy con­trols: thir­teen stud­ies includ­ed meas­ure­ment of DA D2 recep­tors den­sity, two stud­ies com­pared amphet­a­mine-­induced DA ­release, and two stud­ies meas­ured ­DOPA decar­box­y­lase activ­ity, an ­enzyme ­involved in DA syn­the­sis. We con­duct­ed a ­meta-anal­y­sis of the stud­ies meas­ur­ing D2 recep­tor den­sity param­e­ters, ­under the assump­tion ­that all trac­ers ­labeled the ­same pop­u­la­tion of D2 recep­tors. This anal­y­sis ­revealed ­that, com­pared to ­healthy con­trols, ­patients ­with schizo­phre­nia ­present a sig­nif­i­cant but ­mild ele­va­tion of D2 recep­tor den­sity param­e­ters and a sig­nif­i­cant larg­er var­i­abil­ity of ­these indi­ces. We ­found no sta­tis­ti­cal evi­dence ­that stud­ies per­formed ­with radio­lab­eled buty­roph­e­nones detect­ed a larg­er ­increase in D2 recep­tor den­sity param­e­ters ­than stud­ies per­formed ­with oth­er radio­lig­ands, ­such as ben­za­mides. Studies of pre­syn­ap­tic activ­ity ­revealed an ­increase in DA trans­mis­sion ­response to amphet­a­mine chal­lenge, and an ­increase in ­DOPA decar­box­y­lase activ­ity. Together, ­these ­data are com­pat­ible ­with ­both pre- and ­post-syn­ap­tic alter­a­tions of DA trans­mis­sion in schizo­phre­nia. Future stud­ies ­should aim at a bet­ter char­ac­ter­iza­tion of ­these alter­a­tions, and at defin­ing ­their ­role in the pathoph­y­sio­lo­gy of the ill­ness.