UPTAKE OF TC-99M-EXAMETAZIME SHOWN BY SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY BEFORE AND AFTER LITHIUM WITHDRAWAL IN BIPOLAR PATIENTS - ASSOCIATIONS WITH MANIA

Background Early manic relapse following lithium discontinuation offer s an important opportunity to investigate the relationship between sym ptoms, effects of treatment and regional brain activation in bipolar a ffective disorder. Method Fourteen stable bipolar patients on lithium were examined with neuropsychological measures, clinical ratings and s ingle photon emission computed tomography (SPECT) before and after acu te double-blind withdrawal of lithium. Brain perfusion maps were spati ally transformed into standard stereo tactic space and compared pixel- by-pixel. A parametric analysis was used to examine the change in brai n perfusion on lithium withdrawal, and the relationship between sympto m severity and brain perfusion separately both between and within subj ects.Results Lithium withdrawal was associated with an important redis tribution of brain perfusion, with increases in inferior posterior reg ions and decreases in limbic areas, particularly anterior cingulate co rtex. Seven of the 14 patients developed manic symptoms during the pla cebo phase, correlating with relative increases in perfusion of superi or anterior cingulate and possibly left orbito-frontal cortex. Conclus ions The important effect of lithium withdrawal on brain perfusion imp lies that after withdrawal of lithium, the brain develops an abnormal state of activity in limbic cortex. The structures involved did not co -localise with those apparently modulated by manic symptoms.