Aging Brain Changes, Executive Dysfunction and Depression

Age-related brain changes have been associated with development of late-life depression. Prominent among aging-related changes is decline in white matter disproportionately affecting frontal structures.Based on previous findings, we conceptualized treatment resistance, disability, and executive dysfunction as clinical phenomena contributed, at least in part, by compromised integrity of frontal neural systems. The study focuses on frontal white matter abnormalities in geriatric depression and their relationship to treatment response, disability,and executive dysfunction.

Inclusion criteria

• Age: Two strata: 60-74 years (n=60) subjects and 75-84 years (n=60).
• Diagnosis: Major depression, unipolar (by DSM-IV criteria); or, for control subjects, no diagnosis of major depression, no history of depression or other psychiatric conditions.
• Severity of depression: A 24-Item HDRS above 19; Level of Executive Dysfunction: Two strata within each age stratum: Stroop Color-Word scores below and above 24 (1 SD below the median of our normal elderly sample).

Exclusion criteria

• Psychotic depression by DSM-IV, i.e., presence of delusions with a score higher than 2 (questionable delusion) rated by the Scale for Assessment of Positive Symptoms (SAPS; 51).
• High suicide risk, i.e. intent or plan to attempt suicide in near future.
• Presence of any Axis I psychiatric disorder or substance abuse other than unipolar major depression.
• Axis II diagnosis of antisocial personality (by SCID-P and DSM-IV).
• History of psychiatric disorders other than unipolar major depression or generalized anxiety disorder (bipolar disorder, hypomania, are exclusion criteria).
• Cognition: MMSE scores below 24 or diagnosis of dementia by DSM-IV.
• Acute or severe medical illness, i.e., delirium, metastatic cancer, decompensated cardiac, liver or kidney failure, major surgery, stroke or myocardial infarction during the three months prior to entry; or drugs known to cause depression, e.g., reserpine, alpha-methyl-dopa, steroids.
• Failure to respond to an adequate trial of escitalopram (10 mg/day or more for 6 weeks or longer) during the current or previous depressive episodes.
• Current involvement in psychotherapy.
• History of hypersensitivity to escitalopram or need to receive drugs that may interact with escitalopram.
• Inability to perform any of the ADLs (MAI: ADL subscale) even with assistance, e.g. walking with a cane is not an exclusion criterion.
• Inability to speak English.
• Aphasia.
• Residence outside a 45-minute drive from Cornell's clinical facilities.
• Patients taking MAOI's and Fluoxetine will be excluded.