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There is considerable evidence to indicate that depressive disorders may be associated with changes in regional cerebral blood flow (rCBF), and that successful treatment may reverse these changes. We studied patients with seasonal affective disorder (SAD) using 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) single photon emission tomography (SPET) to examine the effect of light therapy on rCBF. Ten depressed patients (8 females, 2 males) with a mean (± s.d.) age of 33.5 ± 11.3 years underwent 99Tcm-HMPAO SPET studies before and after light therapy. The treatment response was evaluated using the Structured Interview Guide for the Hamilton Depression Rating Scale - Seasonal Affective Disorders Version (SIGH-SAD). A patient was considered responsive to light therapy if the post-treatment SIGH-SAD score was reduced by 60 or more in comparison to the pre-treatment score (responders, n= 5; non-responders, n= 5). Pre- and post-treatment SIGH-SAD scores and SPET data were compared in each patient. An improvement in depressive symptoms after light therapy was associated with an increase in rCBF in the frontal and cingulate regions as well as the thalamus. Such changes were not seen in non-responsive subjects.