JYEM Special Issue

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.

Keywords: Major Depressive Disorder (MDD), early life stress (ELS), emotional abuse, family conflict. bilateral DLPFC, ACC, HIP

References

1. 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.
2. 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.
3. 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.
4. Kessler, R.C. and W.J. Magee, Childhood family violence and adult recurrent depression. J Health Soc Behav, 1994. 35(1): p. 13-27.
5. 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.
6. 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.
7. 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.
8. Adolphs, R., Cognitive neuroscience of human social behaviour. Nat Rev Neurosci, 2003. 4(3): p. 165-78.
9. 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.
10. 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.
11. 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.
12. Critchley, H.D., et al., Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence. Brain, 2003. 126(Pt 10): p. 2139-52.
13. Devinsky, O., M.J. Morrell, and B.A. Vogt, Contributions of anterior cingulate cortex to behaviour. Brain, 1995. 118 ( Pt 1): p. 279-306.
14. Lisman, J., et al., Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nat Neurosci, 2017. 20(11): p. 1434-1447.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. Grigoryan, G. and M. Segal, Lasting Differential Effects on Plasticity Induced by Prenatal Stress in Dorsal and Ventral Hippocampus. Neural Plast, 2016. 2016: p. 2540462.
22. Demir-Lira, O.E., et al., Early-life stress exposure associated with altered prefrontal resting-state fMRI connectivity in young children. Dev Cogn Neurosci, 2016. 19: p. 107-14.
23. Zhang, K., et al., Molecular, Functional, and Structural Imaging of Major Depressive Disorder. Neurosci Bull, 2016. 32(3): p. 273-85.
24. Jaworska, N., et al., Subgenual anterior cingulate cortex and hippocampal volumes in depressed youth: The role of comorbidity and age. J Affect Disord, 2016. 190: p. 726-732.
25. van Tol, M.J., et al., Regional brain volume in depression and anxiety disorders. Arch Gen Psychiatry, 2010. 67(10): p. 1002-11.
26. Grieve, S.M., et al., Widespread reductions in gray matter volume in depression. Neuroimage Clin, 2013. 3: p. 332-9.
27. Fu, C., et al., Functional assessment of prefrontal lobes in patients with major depression disorder using a dual-mode technique of 3D-arterial spin labeling and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. Exp Ther Med, 2017. 14(2): p. 1058-1064.
28. Cohen, R.A., et al., Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biol Psychiatry, 2006. 59(10): p. 975-82.
29. Zhai, Z.W., et al., Childhood trauma moderates inhibitory control and anterior cingulate cortex activation during stress. Neuroimage, 2019. 185: p. 111-118.
30. Chocyk, A., et al., Impact of early-life stress on the medial prefrontal cortex functions - a search for the pathomechanisms of anxiety and mood disorders. Pharmacol Rep, 2013. 65(6): p. 1462-70.
31. Myers, B., J.M. McKlveen, and J.P. Herman, Glucocorticoid actions on synapses, circuits, and behavior: implications for the energetics of stress. Front Neuroendocrinol, 2014. 35(2): p. 180-196.
32. Daskalakis, N.P., et al., Early Life Stress Effects on Glucocorticoid-BDNF Interplay in the Hippocampus. Front Mol Neurosci, 2015. 8: p. 68.
33. Gupta, A., et al., Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females. Brain Struct Funct, 2016. 221(3): p. 1667-79.
34. Arnett, M.G., et al., The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior. Transl Psychiatry, 2015. 5: p. e542.
35. van der Doelen, R.H., et al., Early life stress and serotonin transporter gene variation interact to affect the transcription of the glucocorticoid and mineralocorticoid receptors, and the co-chaperone FKBP5, in the adult rat brain. Front Behav Neurosci, 2014. 8: p. 355.
36. Staffaroni, A.M., et al., The functional neuroanatomy of verbal memory in Alzheimer's disease: [(18)F]-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) correlates of recency and recognition memory. J Clin Exp Neuropsychol, 2017. 39(7): p. 682-693.
37. Verger, A., et al., Changes of metabolism and functional connectivity in late-onset deafness: Evidence from cerebral (18)F-FDG-PET. Hear Res, 2017. 353: p. 8-16.
38. Taylor, S.E., et al., Neural responses to emotional stimuli are associated with childhood family stress. Biol Psychiatry, 2006. 60(3): p. 296-301.
39. Wang, L., et al., Overlapping and segregated resting-state functional connectivity in patients with major depressive disorder with and without childhood neglect. Hum Brain Mapp, 2014. 35(4): p. 1154-66.
40. Yamamoto, T., et al., Increased amygdala reactivity following early life stress: a potential resilience enhancer role. BMC Psychiatry, 2017. 17(1): p. 27.
41. Davis, M. and P.J. Whalen, The amygdala: vigilance and emotion. Mol Psychiatry, 2001. 6(1): p. 13-34.
42. Merz, E.C., et al., Anxiety, depression, impulsivity, and brain structure in children and adolescents. Neuroimage Clin, 2018. 20: p. 243-251.
43. Belleau, E.L., M.T. Treadway, and D.A. Pizzagalli, The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology. Biol Psychiatry, 2019. 85(6): p. 443-453.
44. Phillips, J.L., et al., A Prospective, Longitudinal Study of the Effect of Remission on Cortical Thickness and Hippocampal Volume in Patients with Treatment-Resistant Depression. Int J Neuropsychopharmacol, 2015. 18(8).
45. Zuo, Z., et al., Altered Structural Covariance Among the Dorsolateral Prefrontal Cortex and Amygdala in Treatment-Naive Patients With Major Depressive Disorder. Front Psychiatry, 2018. 9: p. 323.
46. Malykhin, N.V., et al., Fronto-limbic volumetric changes in major depressive disorder. J Affect Disord, 2012. 136(3): p. 1104-13.
47. Colloby, S.J., et al., Cortical thickness and VBM-DARTEL in late-life depression. J Affect Disord, 2011. 133(1-2): p. 158-64.
48. Perlman, G., et al., Cortical thickness is not associated with current depression in a clinical treatment study. Hum Brain Mapp, 2017. 38(9): p. 4370-4385.
49. Yang, J., et al., Development and evaluation of a multimodal marker of major depressive disorder. Hum Brain Mapp, 2018. 39(11): p. 4420-4439.
50. Baeken, C., G.R. Wu, and R. De Raedt, Dorsomedial frontal cortical metabolic differences of comorbid generalized anxiety disorder in refractory major depression: A [(18)F] FDG PET brain imaging study. J Affect Disord, 2018. 227: p. 550-553.
51. Su, L., et al., Cerebral metabolism in major depressive disorder: a voxel-based meta-analysis of positron emission tomography studies. BMC Psychiatry, 2014. 14: p. 321.
52. Kennedy, S.H., et al., Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry, 2001. 158(6): p. 899-905.
53. Chaney, A., et al., Effect of childhood maltreatment on brain structure in adult patients with major depressive disorder and healthy participants. J Psychiatry Neurosci, 2014. 39(1): p. 50-9.
54. Saleh, A., et al., Effects of early life stress on depression, cognitive performance and brain morphology. Psychol Med, 2017. 47(1): p. 171-181.
55. Frodl, T., et al., Childhood adversity impacts on brain subcortical structures relevant to depression. J Psychiatr Res, 2017. 86: p. 58-65.
56. Hill, K.R., et al., Fully quantitative pretreatment brain metabolism does not predict depression response to Escitalopram or Placebo, a Randomized Trial. 2020.
57. Montgomery, S.A. and M. Asberg, A new depression scale designed to be sensitive to change. Br J Psychiatry, 1979. 134: p. 382-9.
58. First, M.B., et al., Structured clinical interview for DSM-IV axis I disorders. New York: New York State Psychiatric Institute, 1995.
59. Bernstein, D.P., et al., Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry, 1994. 151(8): p. 1132-6.
60. Negele, A., et al., Childhood Trauma and Its Relation to Chronic Depression in Adulthood. Depress Res Treat, 2015. 2015: p. 650804.