Archived Issues

We congratulate you on acceptance of your manuscript.

Evaluation of Brain Structure and Function in Currently Depressed Adults with a History of Early Life Stress

January 26, 2024

Abstract: Even though Major Depressive Disorder (MDD) is the leading cause of disability worldwide impacting over 300 million individuals, early detection and intervention is hindered by the limited knowledge of its underlying mechanisms. One association found to be significant within MDD is the presence of early life stress (ELS), such as sexual abuse, emotional abuse and family conflict. However, the biological mechanism linking ELS and MDD are unknown.

To properly assess the function consequences of ELS within MDD and address these open questions, we propose an analysis of the metabolism of AMY, ACC, HIP, and DLPFC through FDG PET in addition to a structural MRI in MDD patients with and without ELS. We hypothesize that in MDD patients with prior history of ELS, compared to those without ELS, will have a smaller volume/cortical thickness as measured by MRI and decreased metabolism as measured by PET scans in the bilateral DLPFC, ACC, HIP, and AMY. This study would for the first time, assess both structure and function of critical regions of the HPA axis in MDD, while accounting for the common confounder of ELS.


References:

Fitzgerald, P.B., et al., A meta-analytic study of changes in brain activation in depression. Hum Brain Mapp, 2008. 29(6): p. 683-95.

Kaplow, J.B. and C.S. Widom, Age of onset of child maltreatment predicts long-term mental health outcomes. J Abnorm Psychol, 2007. 116(1): p. 176-87.

Martins, C.M., et al., Emotional abuse in childhood is a differential factor for the development of depression in adults. J Nerv Ment Dis, 2014. 202(11): p. 774-82.

Kessler, R.C. and W.J. Magee, Childhood family violence and adult recurrent depression. J Health Soc Behav, 1994. 35(1): p. 13-27.

Teicher, M.H., et al., The effects of childhood maltreatment on brain structure, function and connectivity. Nat Rev Neurosci, 2016. 17(10): p. 652-66.

Parr, L.A., et al., Early life stress affects cerebral glucose metabolism in adult rhesus monkeys (Macaca mulatta). Dev Cogn Neurosci, 2012. 2(1): p. 181-93.

Harkness, K.L., A.E. Bruce, and M.N. Lumley, The role of childhood abuse and neglect in the sensitization to stressful life events in adolescent depression. J Abnorm Psychol, 2006. 115(4): p. 730-41.

Adolphs, R., Cognitive neuroscience of human social behaviour. Nat Rev Neurosci, 2003. 4(3): p. 165-78.

Hari, R. and M.V. Kujala, Brain basis of human social interaction: from concepts to brain imaging. Physiol Rev, 2009. 89(2): p. 453-79.

Quaedflieg, C.W., et al., Temporal dynamics of stress-induced alternations of intrinsic amygdala connectivity and neuroendocrine levels. PLoS One, 2015. 10(5): p. e0124141.

van Marle, H.J., et al., From specificity to sensitivity: how acute stress affects amygdala processing of biologically salient stimuli. Biol Psychiatry, 2009. 66(7): p. 649-55.

Critchley, H.D., et al., Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence. Brain, 2003. 126(Pt 10): p. 2139-52.

Devinsky, O., M.J. Morrell, and B.A. Vogt, Contributions of anterior cingulate cortex to behaviour. Brain, 1995. 118 ( Pt 1): p. 279-306.

Lisman, J., et al., Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nat Neurosci, 2017. 20(11): p. 1434-1447.

van Bodegom, M., J.R. Homberg, and M. Henckens, Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure. Front Cell Neurosci, 2017. 11: p. 87.

McEwen, B.S., C. Nasca, and J.D. Gray, Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex. Neuropsychopharmacology, 2016. 41(1): p. 3-23.

Kim, E.J., B. Pellman, and J.J. Kim, Stress effects on the hippocampus: a critical review. Learn Mem, 2015. 22(9): p. 411-6.

Carballedo, A., et al., Brain-derived neurotrophic factor Val66Met polymorphism and early life adversity affect hippocampal volume. Am J Med Genet B Neuropsychiatr Genet, 2013. 162B(2): p. 183-90.

Vyas, A., et al., Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci, 2002. 22(15): p. 6810-8.

Hanson, J.L., et al., Behavioral problems after early life stress: contributions of the hippocampus and amygdala. Biol Psychiatry, 2015. 77(4): p. 314-23.