Geriatric depression is associated with disability, a dramatic increase in the rate of completed suicide, higher mortality in the medically ill elderly, and greater risk of Alzheimer’s dementia (AD). Depression in the elderly is a clinically and neurobiologically heterogeneous disorder.The clinical management of geriatric depression is complicated by age- related changes in cognition and neurochemical function, in addition to neurodegenerative and cerebrovascular disease (CVD) processes. More than half of geriatric depressed patients are partial responders or refractory to antidepressant treatment. Even after mood symptom remission, persistent cognitive impairment is commonly observed, which may be associated with increased risk of AD. An understanding of mechanisms underlying affective and cognitive symptoms in geriatric depression, and their failure to respond to treatment, is a priority for research in this area.
Over the past decade we have incorporated molecular imaging studies (including Positron Emission Tomography [PET] imaging) into antidepressant treatment studies to understand the neurobiological mechanisms underlying treatment response variability in geriatric depression. This strategy provides a unique opportunity to assess the functional integrity of neurochemical systems and the capacity of the brain to compensate for age and disease related (neurochemical and neuropathological) changes. Studies of the functional neuroanatomy of geriatric depression have shown elevated glucose metabolism in cortico-cortico networks that include regions that comprise the ‘default network’. Antidepressant (the SSRI, citalopram) treatment decreased metabolism in a subcortical-limbic-frontal network that was associated with improvement in affect (depression and anxiety), while decreases in a medial temporal-parietal- frontal network was associated with improvement in cognition (verbal memory and verbal fluency). Having identified the functional neuroanatomy, the next step is to examine the underlying pathophysiology. Our recent molecular imaging studies using high resolution PET (HRRT) and well-established radiotracers have focused on the role of the serotonin transporter (5-HTT) and beta-amyloid deposition (Aβ) as mechanisms underlying affective and cognitive network dysfunction, respectively, in geriatric depression. Late Life depressed patients demonstrate lower 5-HTT concentrations than controls. Further, greater 5-HTT occupancy in the regions implicated in the affective network correlated with better mood symptom improvement. Region of interest (ROI) and voxel-wise analyses demonstrated decreased baseline 5-HTT in cortical (superior and middle frontal, superior and middle temporal, precuneus and posterior cingulated gyri), limbic (parahippocampal gyrus) and subcortical (striatum, thalamus, midbrain [raphe] regions. Voxel-based morphometry (VBM) analyses of the magnetic resonance (MR) imaging scans did not show significant differences between the patients and controls, which suggests that lower 5-HTT in the patients was not explained by cerebral atrophy. Significant correlations between 5-HTT occupancy by citalopram and improvement of depressive symptoms (change in Hamilton Depression Rating Scale Scores) were observed in these regions, as well the anterior cingulate (BA 24). Aβ is observed in the regions implicated in the cognitive network and associated with less antidepressant related improvement in cognition. Significantly greater cortical Aβ was observed in the patients than controls in superior and middle frontal, anterior and posterior cingulate, superior temporal and parahipppocampal gyri. The selective vulnerability of the serotonin system has been demonstrated in transgenic amyloid mouse models. Thus, lower 5-HTT availability and less occupancy in late life depression (associated with treatment resistance) may be associated with Aβ deposition, as suggested by the neuroimaging data.
CURRICULUM VITAE PERSONAL INFORMATION Lecturer, Department of Biomedical Engineering International University, Vietnam National Uni RESEARCH INTERESTS Controlled bioavailability of poorly water-soluble drugs, solubilization techniques, and development of nano-drug delivery systems. EDUCATION BACKGROUND From 2008 to 2011: Ph.D. Degree in Pharmaceutics , College of Pharmacy, Kangw
Treatment of Menorrhagia BARBARA S. APGAR, MD, MS, AMANDA H. KAUFMAN, MD, UCHE GEORGE-NWOGU, MD, and ANNE KITTENDORF, MD, University of Michigan Medical Center, Ann Arbor, Michigan Menorrhagia is defined as excessive uterine bleeding occurring at regular intervals or prolonged uterine bleeding lasting more than seven days. The classic definition of menorrhagia (i.e., greater than 80 mL of