Late-Life Depression
Status: | Completed |
---|---|
Conditions: | Depression |
Therapuetic Areas: | Psychiatry / Psychology |
Healthy: | No |
Age Range: | 60 - Any |
Updated: | 4/2/2016 |
Start Date: | September 2009 |
End Date: | April 2013 |
Contact: | Piotr Daranowski, MA |
Email: | pdaranowski@psych.uic.edu |
Phone: | 312-413-8223 |
Cortical/Subcortical Circuits in Late-Life Depression
The purpose of the study is to examine the relationship between brain structure and
depression in adults aged 60 or older. This relationship is determined using magnetic
resonance imaging technology (MRI), a scanner with a magnet that is used to create images of
the brain.
depression in adults aged 60 or older. This relationship is determined using magnetic
resonance imaging technology (MRI), a scanner with a magnet that is used to create images of
the brain.
Major depressive disorder (MDD) and other clinically significant forms of "minor depression"
are among the most common mental disorders in the elderly. Data from the Epidemiologic
Catchment Area Studies indicate that in the community dwelling elderly, the prevalence of
MDD is approximately 1-2 percent. The prevalence of dysthymia and "clinically significant"
depressive symptoms is estimated to be 2-3% and 5-10% respectively. Clinically significant
mood disorders are responsible for considerable medical and psychosocial morbidity. These
include frequent medical and psychiatric hospitalizations, visits to the emergency room,
suicide attempts, and use of alcohol, and other prescription medications with psychotropic
effects. The clinical impact of these disorders is comparable to those caused by other
chronic medical disorders.
The vast majority of patients with mood disorders are managed at ambulatory care/primary
care settings around the country. Ambulatory care clinics have become "defacto" settings for
the diagnosis and management of psychiatric problems, especially in the elderly. Depression,
particularly in the elderly, is associated with several chronic medical illnesses including
malignancies, chronic obstructive pulmonary disease, and gastrointestinal, vascular,
autoimmune and demyelinating disorders. Acknowledging the overall robust association between
medical illness and mood disorders, the NIH consensus statement on depression in the elderly
states, "The hallmark of depression in late-life is its association with medical
comorbidity." While the precise mechanisms by which coexisting medical illnesses contribute
to depression remain unclear, neuroanatomical, vascular, immunologic, psychosocial and /or a
combination of these mechanisms have been invoked as possible pathways by which medical
disorders may lead to depression in the elderly.
Late-life MDD is characterized by 1) Neuroanatomical changes in neocortical and subcortical
regions of the brain. These principally comprise a decrease in focal brain volumes and an
increase in the volume of high intensity lesions in the parenchyma; 2) The increase in high
intensity lesions occurs largely, though not exclusively, in the white matter; 3)
Preliminary studies suggest that there are abnormalities in white matter regions and tracts
even in areas that appear normal in MR images in patients with late-life MDD when compared
with controls; 4) Biochemical and biophysical changes in the white matter are likely related
to the pathophysiology of major psychiatric disorders independent of the impact of
cerebrovascular disease/risk factors.
TRIAL OBJECTIVES AND PURPOSE
Specific Aim 1: To estimate absolute levels and ratios (metabolite/creatine) of NAA, Ch and
Ml bilaterally in the dorsolateral white matter and subcortical nuclei in patients with MDD
and non-depressed controls.
Hypothesis: Absolute levels and ratios of Ch and Ml will be higher and levels of NAA will be
lower in the dorsolateral white matter and the subcortical nuclei in patients with MDD when
compared with controls.
Specific Aim 2: To estimate magnetization transfer ratios (MTR) bilaterally in the frontal
white matter/head of the caudate nucleus and the putamen in patients with MDD and controls
and to examine the relationship between MTR and MRS measures in the dorsolateral white
matter. Hypothesis a: MTR will be significantly lower in normal appearing dorsolateral white
matter regions and subcortical nuclei (caudate nucleus and putamen) in patients with MDD
when compared with controls.
Hypothesis b: There will be an inverse relationship between MTR and normalized levels of Ml
in patients diagnosed with MDD in the dorsolateral white matter bilaterally.
Specific Aim 3: To examine the neurocognitive correlates of frontal and striatal compromise
identified using MRS and MT ratio measures in patients with MDD and controls. The
associations between NAA and a global cognitive scale and MT ratios from the bilateral
dorsolateral white matter and subcortical nuclei and subscales targeted to dorsolateral and
striatal cognitive functioning will be examined.
Hypothesis a: Among healthy and depressed elderly, NAA/Cr with be positively related to a
global scale of cognitive function.
Hypothesis b: Among healthy and depressed elderly, MT ratios of the dorsolateral cortices
will be positively related to a subscale of dorsolateral function (working memory, executive
function, nonverbal recall).
Hypothesis c: Among healthy and depressed elderly, MT ratios of subcortical nuclei will be
positively related to a subscale of striatal function (processing, learning).
Exploratory analyses: In addition to the specific aims above, the investigators will conduct
two three exploratory analyses.
Analysis 1: A more finely grained analysis in which the investigators examine the
relationship of NAA, Ml and Cho ratios to dorsolateral and striatal subscales after
examining their relationship to global cognitive function. The investigators will also study
the relationship of the relative concentrations of NAA to Ml (NAA/MI) and Ch (NAA/Ch) to
global and regional subscales. In addition, the preliminary MTR data suggest that there may
be laterally effects, which the investigators will examine.
Analysis 2: A comparison of blood samples of the healthy versus depressed subject groups, to
see if there is evidence of differences in the neurotransmitter system,
hypothalamic-pituitary-adrenals (HAP) axis, and immune function between these two groups of
elderly persons.
Analysis 3: To examine whether neuroimaging and cognitive measures associated with major
depression are reversed by antidepressant treatment.
are among the most common mental disorders in the elderly. Data from the Epidemiologic
Catchment Area Studies indicate that in the community dwelling elderly, the prevalence of
MDD is approximately 1-2 percent. The prevalence of dysthymia and "clinically significant"
depressive symptoms is estimated to be 2-3% and 5-10% respectively. Clinically significant
mood disorders are responsible for considerable medical and psychosocial morbidity. These
include frequent medical and psychiatric hospitalizations, visits to the emergency room,
suicide attempts, and use of alcohol, and other prescription medications with psychotropic
effects. The clinical impact of these disorders is comparable to those caused by other
chronic medical disorders.
The vast majority of patients with mood disorders are managed at ambulatory care/primary
care settings around the country. Ambulatory care clinics have become "defacto" settings for
the diagnosis and management of psychiatric problems, especially in the elderly. Depression,
particularly in the elderly, is associated with several chronic medical illnesses including
malignancies, chronic obstructive pulmonary disease, and gastrointestinal, vascular,
autoimmune and demyelinating disorders. Acknowledging the overall robust association between
medical illness and mood disorders, the NIH consensus statement on depression in the elderly
states, "The hallmark of depression in late-life is its association with medical
comorbidity." While the precise mechanisms by which coexisting medical illnesses contribute
to depression remain unclear, neuroanatomical, vascular, immunologic, psychosocial and /or a
combination of these mechanisms have been invoked as possible pathways by which medical
disorders may lead to depression in the elderly.
Late-life MDD is characterized by 1) Neuroanatomical changes in neocortical and subcortical
regions of the brain. These principally comprise a decrease in focal brain volumes and an
increase in the volume of high intensity lesions in the parenchyma; 2) The increase in high
intensity lesions occurs largely, though not exclusively, in the white matter; 3)
Preliminary studies suggest that there are abnormalities in white matter regions and tracts
even in areas that appear normal in MR images in patients with late-life MDD when compared
with controls; 4) Biochemical and biophysical changes in the white matter are likely related
to the pathophysiology of major psychiatric disorders independent of the impact of
cerebrovascular disease/risk factors.
TRIAL OBJECTIVES AND PURPOSE
Specific Aim 1: To estimate absolute levels and ratios (metabolite/creatine) of NAA, Ch and
Ml bilaterally in the dorsolateral white matter and subcortical nuclei in patients with MDD
and non-depressed controls.
Hypothesis: Absolute levels and ratios of Ch and Ml will be higher and levels of NAA will be
lower in the dorsolateral white matter and the subcortical nuclei in patients with MDD when
compared with controls.
Specific Aim 2: To estimate magnetization transfer ratios (MTR) bilaterally in the frontal
white matter/head of the caudate nucleus and the putamen in patients with MDD and controls
and to examine the relationship between MTR and MRS measures in the dorsolateral white
matter. Hypothesis a: MTR will be significantly lower in normal appearing dorsolateral white
matter regions and subcortical nuclei (caudate nucleus and putamen) in patients with MDD
when compared with controls.
Hypothesis b: There will be an inverse relationship between MTR and normalized levels of Ml
in patients diagnosed with MDD in the dorsolateral white matter bilaterally.
Specific Aim 3: To examine the neurocognitive correlates of frontal and striatal compromise
identified using MRS and MT ratio measures in patients with MDD and controls. The
associations between NAA and a global cognitive scale and MT ratios from the bilateral
dorsolateral white matter and subcortical nuclei and subscales targeted to dorsolateral and
striatal cognitive functioning will be examined.
Hypothesis a: Among healthy and depressed elderly, NAA/Cr with be positively related to a
global scale of cognitive function.
Hypothesis b: Among healthy and depressed elderly, MT ratios of the dorsolateral cortices
will be positively related to a subscale of dorsolateral function (working memory, executive
function, nonverbal recall).
Hypothesis c: Among healthy and depressed elderly, MT ratios of subcortical nuclei will be
positively related to a subscale of striatal function (processing, learning).
Exploratory analyses: In addition to the specific aims above, the investigators will conduct
two three exploratory analyses.
Analysis 1: A more finely grained analysis in which the investigators examine the
relationship of NAA, Ml and Cho ratios to dorsolateral and striatal subscales after
examining their relationship to global cognitive function. The investigators will also study
the relationship of the relative concentrations of NAA to Ml (NAA/MI) and Ch (NAA/Ch) to
global and regional subscales. In addition, the preliminary MTR data suggest that there may
be laterally effects, which the investigators will examine.
Analysis 2: A comparison of blood samples of the healthy versus depressed subject groups, to
see if there is evidence of differences in the neurotransmitter system,
hypothalamic-pituitary-adrenals (HAP) axis, and immune function between these two groups of
elderly persons.
Analysis 3: To examine whether neuroimaging and cognitive measures associated with major
depression are reversed by antidepressant treatment.
Inclusion Criteria:
- Age: 60 years or greater
- Diagnosis of major depressive disorder using standard diagnostic and statistical
manual (DSM) criteria
- Score of 15 or greater on the 17-item Hamilton Depression rating scale
- Mini Mental Status Exam score of 24 or greater
- No evidence of clinical dementia or any other clinical brain disorder
- Free of psychotropic/psychoactive medications for at least 2 weeks
Exclusion Criteria:
- Presence of dementia or any other clinical brain disorder (Parkinson's, Alzheimer's)
- History of progressive cognitive decline and/or Mini Mental Status Exam score of less
than 24
- Lifetime diagnosis of substance abuse
- Unstable medical illness (grade 4 on the Cumulative Illness Rating Scale)
- Presence of any metallic implant that would preclude an MRI scan (pacemaker, etc.)
- Concurrent Axis 1 disorder (schizophrenia, bipolar)
- Psychotropic medication implicated in depression i.e. Reserpine, Alpha methyl dopa,
Beta blockers, multiple long acting benzodiazepines (valium, flurazepam,
chlordiazepoxide), neuroleptics;
- Seizure disorder
- Stroke/Transient Ischemic Attack
- Central nervous system disorder (Parkinson's disease, multiple sclerosis)
- Trauma to head/Loss of Consciousness
- Claustrophobia
- Eating disorder (anorexia, bulimia)
- Weight of over 350 pounds
- Learning disorder (dyslexia, ADHD)
- Psychosis, panic or anxiety disorder outside the context of depression
- Mood stabilizing agents such as lithium and Divalproex sodium and antidepressants -
as they have been shown to impact on brain levels of NAA, Ch and Ml
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