Ian PersaudMentor: Dr. Joshua ChiappelliMPRC Conte Research SymposiumAugust 5, 2016
Relationship of Cortisol to Brain
Morphological Abnormalities in
Schizophrenia
SZ and Brain Morphology In a study of 2028 patients and 2540 controls
volume decreases reported in: Hippocampus Amygdala Thalamus Accumbens Intracranial Volumes
Volume increases reported in Pallidum Lateral ventricles
(Van Erp, 2016)
Potential Biomarker?
IN a study of 596 individuals that compared SZ, SAD, BDP, 1° relatives and healthy controls Hippocampal volume supported as putative
biomarker for SZ (P = .007 - .02) and SAD (P = .003 - .14)
(Arnold S 2015)
Diathesis-Stress Model
Stess -events or experiences that jeopardize homeostasis (Chrousos & Gold 1992; Sapolsky, 1992)
Onset, exacerbation, and relapse ALL linked to multiple somatic/environmental stressors
Biological Mechanisms
KYN/A
Methods 91 Hi-res 3T structural MRI scans
48 healthy control, 43 SZ patients Controlled for age and sex
Whole blood samples collected Assays for cytokines, KYNA, and Cortisol
So far, only Cortisol is complete
Manual Hippocampal Volume measurements using Mango 4.0 software
Results No between group hippocampal volume differences
No correlation with cortisol
Significant decrease trend of vol. with age Trend more prominent in patient group
Hippocampal Volume and Age
Overall: (r=-.219, p=.037)Patients: (r=-.397, p=.008, n=43)Controls: (r=-.062, p=.67, n=48)
Accelerated Aging theory Patients with SZ have a faster rate of neural aging,
related to decay. Increased oxidative stress & inflammation
positive feedback mechanisms
Evidence supports Increased oxidative stress biomarkers (Okusaga O. O.
2014) Increased inflammatory biomarkers (Kirpatrick B. & Miller
B.J. 2013)
Allostatic Load Study “The term ‘allostasis’ refers to how an
organism accommodates to a stressor by adjusting homeostatic set points to maintain internal stability” (Nugent et al 2015)
Allostatic Load - 13 biomarkers vs. Cortical thickness
44 Schizophrenia Spectrum Disorder patients, 33 normal controls
Found patients had higher allostatic load, and lower cortical thickness (p=.008)
Hippocampal Volume and Urinary Cortisol
Spearman's rho=-.291, p=.033
Average Cortical Thickness and Plasma Cortisol
Overall: (r=-.198, p=.037)Patients: (r=-.276, p=.043)Controls: (r=-.152, p=.26)
Average Cortical Thickness and C-Reactive Protein
(rho=-.361, p=.005)
Plasma Cortisol and CRP Significant correlation in patients (rho=.429,
p=.013, n=33) but not in controls (rho=-.055,p=.81, n=21)
????????????
Moving Forward Move Forward with KYNA and Cytokine assays to
better explore relationships between these two circuits and neurodegeneration
Understanding the relationship these neurochemicals have with Hippocampal volume, and with patient vs control groups could offer insight to the interaction in the Diathesis-Stress model
Works CitedArnold, S. J. M., Ivleva, E. I., Gopal, T. A., Reddy, A. P., Jeon-Slaughter, H., Sacco, C. B., … Tamminga, C. A. (2015). Hippocampal volume is reduced in schizophrenia and schizoaffective disorder but not in psychotic bipolar i disorder demonstrated by both manual tracing and automated parcellation (FreeSurfer). Schizophrenia Bulletin, 41(1), 233–249. http://doi.org/10.1093/schbul/sbu009
Kirkpatrick, B., & Miller, B. J. (2013). Inflammation and schizophrenia. Schizophrenia Bulletin, 39(6), 1174–1179. http://doi.org/10.1093/schbul/sbt141
Nugent, K. L., Chiappelli, J., Rowland, L. M., & Hong, L. E. (2015). Cumulative stress pathophysiology in schizophrenia as indexed by allostatic load. Psychoneuroendocrinology, 60, 120–129. http://doi.org/10.1016/j.psyneuen.2015.06.009
Okusaga, O. O. (2014). Accelerated aging in schizophrenia patients: the potential role of oxidative stress. Aging and Disease, 5(4), 256–62. http://doi.org/10.14336/AD.2014.0500256
van Erp, T. G. M., Hibar, D. P., Rasmussen, J. M., Glahn, D. C., Pearlson, G. D., Andreassen, O. a, … Turner, J. a. (2016). Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Molecular Psychiatry, (October 2014), 1–7. http://doi.org/10.1038/mp.2015.63
Walker, E. F., & Diforio, D. (1997). Schizophrenia: A Neural Diathesis-Stress Model. Psychological Review, 104(4), 667–685. http://doi.org/10.1037/0033-295X.104.4.667
Acknowledgements
Dr. Ana Pocivavsek My mentor, Dr. Chiappelli Dr. Elliot Hong Neuroimaging staff, all of the Conte Staff
THANK YOU ALL!
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