Biological endophenotypes of prodromal psychosis and depression

Berger, Maximus (2018) Biological endophenotypes of prodromal psychosis and depression. PhD thesis, James Cook University.

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The identification of biomarkers to predict risk and clinical outcomes beyond clinical observation in psychiatry is a key priority in contemporary mental health research. Individuals at elevated risk for mental disorders have been the focus of such efforts as they represent a potentially viable target group for early intervention and indicated prevention. Early intervention and indicated prevention efforts for individuals at ultrahigh risk (UHR) for psychosis might benefit from such biomarkers to enable better risk prediction and to discern who will benefit from treatment. Alterations in neuroendocrine, immune and oxidative stress markers as well as abnormalities in lipid biology are robust findings in biological psychiatry. On the other hand, mounting evidence suggests that First Nations people including the Aboriginal and/or Torres Strait Islander people of Australia have a higher risk for common and severe mental illness, most likely attributable to social and environmental health determinants. However the role of stress-related biomarkers in this context remains poorly understood. Consequently, the aims of this thesis were to examine (1) a multisystem biomarker index known as allostatic load in two high-risk populations and to (2) examine the role of lipid biology in these groups.

The first part of this thesis explores the role of allostatic load (AL) and omega-3 (ω-3) polyunsaturated fatty acids (PUFA) in two clinical studies of patients with schizophrenia, first-episode psychosis and individuals at UHR for psychosis. The second part explores the role of AL and dietary ω-3 PUFA in a community-based study of Aboriginal and/or Torres Strait Islander people, who are at increased risk for mental ill-health according to recent national reports. The above aims are achieved through meta-analysis of existing studies of cortisol in psychotic disorders, secondary analysis of two clinical studies, and in a cross-sectional multi-site community-based study of Aboriginal and/or Torres Straight Islander adolescents and young adults attending a health check.

First, flattened cortisol-awakening response is reported in patients with schizophrenia and first-episode psychosis relative to controls, but not in UHR individuals, suggesting neuroendocrine dysregulation during some stages of the psychosis spectrum. Secondly, informed by these findings, a study of AL demonstrated elevated AL in patients with schizophrenia and first-episode psychosis that was positively correlated with positive psychotic symptoms and negatively correlated with functioning at trend level. No prospective association of AL and treatment response and symptomatic ix remission was identified. Next, secondary analysis of a multi-centre randomised controlled trial investigated AL in youth at UHR for psychosis. This study revealed prospective associations of high AL with impairments in social and occupational functioning. Next, the prospective association of PUFA status and clinical outcomes in a 12-month follow-up is reported, which demonstrated a selective relationship of low ω-3 PUFA levels with mood disorders and no association with psychotic or anxiety disorders. The second part of the thesis reports depression rates in three remote communities, explores the relationship of depression with hair cortisol and AL, and reports an association of low plasma levels of o ω-3 PUFA with depressive symptoms.

Collectively, the data presented in this thesis demonstrate complex associations of a multisystem biomarker index and ω-3 PUFA with mental ill-health. Ultimately, multisystem indices like AL may be used in future research to establish their utility as a clinical prognostic risk index. By studying membrane lipids in an ethnic minority group, this thesis was able to show an association of high dietary intake of ω-3 PUFA and low levels of depression, which may serve as a protective factor.

Item ID: 58931
Item Type: Thesis (PhD)
Keywords: Aboriginal and Torres Strait Islander, allostatic load, biomarker, CAR, cortisol, depression, DHA, EPA, first episode psychosisa, hair cortisol, HPA-axis, inflammation, Omega-3 fatty acids, PHQ-9, psychosis, screening, stress, ultra-high risk
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Copyright Information: Copyright © 2018 Maximus Berger.
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Chapter 2: Berger, Maximus, Kraeuter, Ann Katrin, Romanik, Daria, Malouf, Peter, Amminger, G. Paul, and Sarnyai, Zoltán (2016) Cortisol awakening response in patients with psychosis: systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 68. pp. 157-166.

Chapter 3: Berger, Maximus, Juster, Robert Paul, Westphal, Sabine, Amminger, G. Paul, Bogerts, Bernhard, Schiltz, Kolja, Bahn, Sabine, Steiner, Johann, and Sarnyai, Zoltan (2018) Allostatic load is associated with psychotic symptoms and decreases with antipsychotic treatment in patients with schizophrenia and first-episode psychosis. Psychoneuroendocrinology, 90. pp. 35-42.

Chapter 4: Berger, Maximus, Lavoie, Suzie, McGorry, Patrick D., Nelson, Barnaby, Markulev, Connie, Yuen, Hok-Pan, Schaefer, Miriam, Sarnyai, Zoltán, and Amminger, G. Paul (2018) Relationship between allostatic load and clinical outcomes in youth at ultra-high risk for psychosis in the NEURAPRO study. Schizophrenia Research. (In Press)

Chapter 5: Berger, M.E., Smesny, S., Kim, S-W., Davey, C.G., Rice, S., Sarnyai, Z., Schlöegelhofer, M., Schafer, M.R., Berk, M., McGorry, P.D., and Amminger, G.P. (2017) Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study. Translational Psychiatry, 7.

Chapter 6: Berger, Maximus, Taylor, Sean, Harriss, Linton, Campbell, Sandra, Thompson, Fintan, Jones, Samuel, Sushames, Ashleigh, Amminger, G. Paul, Sarnyai, Zoltan, and McDermott, Robyn (2019) Hair cortisol, allostatic load, and depressive symptoms in Australian Aboriginal and Torres Strait Islander people. Stress. (In Press)

Chapter 7: Berger, Maximus, Taylor, Sean, Harriss, Linton, Campbell, Sandra, Thompson, Fintan, Jones, Samuel, Makrides, Maria, Gibson, Robert, Amminger, G. Paul, Sarnyai, Zoltan, and McDermott, Robyn (2018) Cross-sectional association of seafood consumption, polyunsaturated fatty acids and depressive symptoms in two Torres Strait communities. Nutritional Neuroscience. (In Press)

Date Deposited: 16 Jul 2019 21:59
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 60%
11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 20%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110319 Psychiatry (incl Psychotherapy) @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 70%
92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920410 Mental Health @ 30%
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