OBJECTIVES Serum levels of brain-derived neurotrophic factor (BDNF) have been shown to be lower in patients with major depressive disorder (MDD) than in healthy persons. Although several studies have examined the associations between serum BDNF levels and broader categories of depression identified by psychiatrists or depressive symptoms measured with depression scales among nonpatient populations, some of these studies did not consider possible confounders and included mostly young or middle-aged subjects and nonrepresentative control subjects, such as volunteers and patients' relatives. Therefore, it remains unclear that whether MDD, broader categories of depression, or depressive symptoms in the elderly are associated with BDNF. The present study examined these associations in a community sample and controlled for confounders. METHODS The subjects were 538 women aged 78 to 88 years who had participated in a follow-up survey of a cohort and had scored 24 or more on the Mini-Mental State Examination. Two depression scales were administered, and, using the Structured Clinical Interview for DSM-IV, psychiatrists identified 53 persons having any mood disorder (AMD) - 8 with MDD and 45 with other types of depression according to the DSM-IV or its research criteria - and 106 healthy controls. RESULTS Subjects with MDD had serum BDNF levels lower than did controls but subjects with AMD did not. The severity of depressive symptoms assessed with either of the 2 depression scales was negatively correlated with serum BDNF levels in all subjects and in subjects remaining after persons with MDD or AMD were excluded. These associations were significant after controlling for possible confounders. CONCLUSION We have found an association between MDD and serum BDNF levels in old-old women, as has previously been found in younger patients. Although serum BDNF levels were not found to be associated with the broader category of depression, they were associated with depressive symptoms among subjects without clinical depression.