Late-onset late life major depression (late-onset LLMD) is a heterogeneous disorder with respect to etiology and outcome. Both longitudinal and post-mortem studies have found that a subset of elderly individuals with late-onset LLMD who are cognitively intact at the time of their first depressive episode will develop progressive cognitive decline and/or a clinical and histopathologic diagnosis of Alzheimer's disease (AD) within relatively brief follow-up periods. The many decades required for the pathologic AD criteria to develop implies that the depressive episode may represent a preclinical or prodromal phase of AD in a subset of individuals. However, there are presently no biological markers to identify those individuals with late-onset LLMD who have prodromal AD. Results from studies in healthy elderly conducted by our group and others suggest that higher baseline plasma amyloid beta peptide-Ma (A/?42) level, higher A?42/A/?40 ratios and greater reductions in A?42 during longitudinal follow-up, are associated with greater cognitive decline and/or incident AD. There is also evidence from our cross-sectional pilot study of elevated plasma A/?42 and A$42/A?40 ratio in elderly individuals with LLMD, and elevated CSF A/?42 levels have also been reported previously in individuals with major depression. Based on these earlier suggestive findings, the major objectives of this proposal are: (1) to conduct a 3-year longitudinal study to test the hypothesis that elderly individuals with late-onset LLMD will have higher plasma A/942 level and A#42/A?40 ratio and greater reductions in A?42 during longitudinal follow-up relative to controls, and (2) to examine whether measures of A/042 will be associated with greater cognitive decline and/or the development of AD in elderly individuals with late-onset LLMD. Another goal is to determine if changes in plasma A/ff42 levels are paralleled by similar changes in cerebrospinal fluid (CSF) A/?42 in a subset of subjects. If these hypotheses are confirmed, then the determination of plasma A/?42 might become an easily obtainable marker to identify those individuals with late-onset LLMD who may have prodromal AD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH080405-05
Application #
8033160
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Evans, Jovier D
Project Start
2007-03-01
Project End
2014-02-28
Budget Start
2011-03-01
Budget End
2014-02-28
Support Year
5
Fiscal Year
2011
Total Cost
$273,981
Indirect Cost
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962
Khan, Atlas; Liu, Qian; Wang, Kai (2018) iMEGES: integrated mental-disorder GEnome score by deep neural network for prioritizing the susceptibility genes for mental disorders in personal genomes. BMC Bioinformatics 19:501
Giambartolomei, Claudia; Zhenli Liu, Jimmy; Zhang, Wen et al. (2018) A Bayesian framework for multiple trait colocalization from summary association statistics. Bioinformatics 34:2538-2545
Toker, Lilah; Mancarci, Burak Ogan; Tripathy, Shreejoy et al. (2018) Transcriptomic Evidence for Alterations in Astrocytes and Parvalbumin Interneurons in Subjects With Bipolar Disorder and Schizophrenia. Biol Psychiatry 84:787-796
Huckins, L M; Hatzikotoulas, K; Southam, L et al. (2018) Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Mol Psychiatry 23:1169-1180
Mitchell, A C; Javidfar, B; Pothula, V et al. (2018) MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice. Mol Psychiatry 23:123-132
Bryois, Julien; Garrett, Melanie E; Song, Lingyun et al. (2018) Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia. Nat Commun 9:3121
Fazio, Leonardo; Pergola, Giulio; Papalino, Marco et al. (2018) Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory. Proc Natl Acad Sci U S A 115:5582-5587
Gusev, Alexander; Mancuso, Nicholas; Won, Hyejung et al. (2018) Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. Nat Genet 50:538-548
Girdhar, Kiran; Hoffman, Gabriel E; Jiang, Yan et al. (2018) Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome. Nat Neurosci 21:1126-1136
Hauberg, Mads E; Fullard, John F; Zhu, Lingxue et al. (2018) Differential activity of transcribed enhancers in the prefrontal cortex of 537 cases with schizophrenia and controls. Mol Psychiatry :

Showing the most recent 10 out of 29 publications