Psychiatry #200308003

 

Dr. Sergio Paradiso

 

Prediction of Late-Onset Depression using Emotion Probes and PET

 

Abstract:

 

Depression in older people constitutes a major public health problem that is often unrecognized and untreated. Even when depression is diagnosed the treatment response of older people is poor. Elderly depression carries a great risk of death by suicide. In 1998, the suicide rate for white men older than 85 years age was 62.7\100,000 in the US. Rates for all age groups in the US are 11.3\100,000. Most elderly victims of suicide have had a psychiatric disorder, most commonly late-onset depression. Studies of brain function using modern technology such as Positron Emission Tomography (PET) have lead to the discovery of pathological mechanisms of familial major depression with onset in young age. However, the systematic study of brain function in patients with late-onset depression has been almost completely overlooked. Therefore the essential pathologic mechanisms for late-life depression have not yet been successfully identified. The key pathological factors that precipitate the clinical syndrome of late-onset depression must be delineated before truly effective preventive and treatment strategies may be developed.

 

We propose to test the hypothesis that age-related functional changes in specific brain regions that support emotion perception will be predisposing pathological factors for late onset depression. At least two types of changes in emotion processing will be found to occur as a function of aging. One is “adaptive” and includes a moderated appreciation of the negative qualities of unpleasant stimuli. The “adaptive” pattern of emotion perception is hypothesized to be either a protective factor or a modifier of the presentation of elderly depression. The other, maladaptive, pattern leads to reduced perception of positive stimuli as enjoyable, and constitutes a risk factor for the development of late-onset depression. We expect it to be associated with a fundamental abnormality of an area of the brain’s frontal lobes called ventral pre-frontal cortex.

 

To test this hypothesis we will recruit 16 subjects with a history of late-onset depression who are currently in remission, 16 subjects with late-onset depression who are currently depressed, and 16 age and gender matched healthy controls without a family history of depression. Subjects will undergo our established limbic challenge while PET scanning will be performed using the 15O water method to evaluate the functioning of emotion processing systems in the brain. The limbic challenge will consist of an emotion-inducing paradigm using visual stimuli to engage limbic regions in the human brain. We have previously used this paradigm in young and elderly healthy volunteers, stroke victims, and patients with schizophrenia. These experiments have been able to identify changes in limbic system functioning across the aforementioned populations. Studying subjects with a history of late onset depression but who are currently non-symptomatic will inform us on the presence and entity of changes in emotional perception and background limbic (trait) abnormalities predisposing to depression. Studying subjects with a history of late onset depression but who are currently depressed will provide key information regarding limbic system abnormalities that are specific of an active depressed state (in addition to the changes due to trait features). Data from age-matched, never depressed volunteers will be acquired for comparison. All subjects will receive an assessment of their personal and family history, quality of life and cognitive function, and a magnetic resonance imaging study of the brain to examine group differences in brain atrophy and white matter changes and to exclude mass pathology.