- PROJECT 1 Childhood adversity is associated with greater risk for adulthood depression (MDD), aggressive traits and suicide. The overall goal of Project 1 is to define a biological phenotype for suicide and assess the contribution of reported childhood (before age 16) adversity. In MDD suicides, we find a higher rate of childhood adverse events. The biological basis of this relationship is mostly unknown, but recent studies, including finds from our previous Conte Center of thinner prefrontal cortex (PFC) and smaller hippocampus (HC) volume and reduced BDNF, suggest glucocorticoid excess and impaired trophic effect is a consequence of stress and contributes to suicide risk. Stress and suicide are also associated with fewer cells and dendritic shrinkage in prefrontal cortex (PFC) and hippocampus (HC). The thinner PFC and smaller HC volume may constitute a biological risk factor for stress-related psychopathology. We hypothesize that this neurobiological phenotype may result from neuroinflammation, environment and epigenetic effects. In the new Conte Center, we aim to determine in the PFC and HC, whether inflammatory cytokines are increased, whether neurons, glia or both express those inflammatory markers, and whether the presence of those markers is associated with changes in neuron number or morphology in 5 groups (n=15 per group) of age- and sex-matched MDD suicides and nonpsychiatric controls with and without reported childhood adversity (before 15y) and 10 non suicide MDDs, all with psychological autopsy and brain toxicology. We propose to measure: 1) 62 markers of the inflammasome in the dorsal PFC (dPFC), ACC and HC; we will estimate total number of neurons and glia in HC and neuronal and glial density in the dPFC and ACC, with neurons and glia double-labeled with select cytokines identified from the inflammasome assay; 2) we will count the number of microglia in the HC (at anterior, mid- and posterior levels) and the density of microglia in dPFC and ACC using microglia specific markers; and 3) Determine the dendrite length and branching as indices of neuron morphology. Exploratory aims will: 1) separate the effect of MDD from that of suicide or adversity on neuron and glia expression of select inflammatory markers comparing the suicide and non-suicide MDD groups; 2) compare cytokines from brain and blood; TSPO level in postmortem brain and measured by PET; cortical thickness and HC volume in postmortem brain and measured in vivo by MRI. The proposed studies will provide evidence whether CA and suicide are associated with a neuroinflammatory response. !
| Abreu, L N; Oquendo, M A; Galfavy, H et al. (2018) Are comorbid anxiety disorders a risk factor for suicide attempts in patients with mood disorders? A two-year prospective study. Eur Psychiatry 47:19-24 |
| Rizk, Mina M; Rubin-Falcone, Harry; Lin, Xuejing et al. (2018) Gray matter volumetric study of major depression and suicidal behavior. Psychiatry Res Neuroimaging 283:16-23 |
| Daray, Federico M; Mann, J John; Sublette, M Elizabeth (2018) How lipids may affect risk for suicidal behavior. J Psychiatr Res 104:16-23 |
| Rizk, Mina M; Galfalvy, Hanga; Singh, Tanya et al. (2018) Toward subtyping of suicidality: Brief suicidal ideation is associated with greater stress response. J Affect Disord 230:87-92 |
| Rubin-Falcone, Harry; Zanderigo, Francesca; Thapa-Chhetry, Binod et al. (2018) Pattern recognition of magnetic resonance imaging-based gray matter volume measurements classifies bipolar disorder and major depressive disorder. J Affect Disord 227:498-505 |
| Boldrini, Maura; Fulmore, Camille A; Tartt, Alexandria N et al. (2018) Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell 22:589-599.e5 |
| Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu et al. (2018) Association of BDNF Val66Met Polymorphism and Brain BDNF Levels with Major Depression and Suicide. Int J Neuropsychopharmacol 21:528-538 |
| Ganança, Licinia; Galfalvy, Hanga C; Oquendo, Maria A et al. (2017) Lipid correlates of antidepressant response to omega-3 polyunsaturated fatty acid supplementation: A pilot study. Prostaglandins Leukot Essent Fatty Acids 119:38-44 |
| Bernanke, J A; Stanley, B H; Oquendo, M A (2017) Toward fine-grained phenotyping of suicidal behavior: the role of suicidal subtypes. Mol Psychiatry 22:1080-1081 |
| Ceñido, Joshua F; Itin, Boris; Stark, Ruth E et al. (2017) Characterization of lipid rafts in human platelets using nuclear magnetic resonance: A pilot study. Biochem Biophys Rep 10:132-136 |
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