Association between olanzapine treatment and brain cortical thickness and gray/white matter contrast is moderated by cholesterol in psychotic disorders

Abstract

I would like to first and foremost acknowledge the contribution from all study participants for contributing with their time and providing valuable data for our research. I am very grateful to Professor Vidar M. Steen, my main supervisor, for including me in his research group, for allowing me the chance to take my PhD and the time to mature. I am also grateful to Professor Ingrid Melle, my co-supervisor, for her extensive knowledge of clinical areas and statistics. She has, without doubt, challenged me the most, asking critical questions, not letting me settle for anything less than my very best. Also, I would like to thank Silje Skrede and Professor Erik Johnsen, my other two co-supervisors, for their valuable inputs. From the TOP group in Oslo, I would like to extend my deepest gratitude to Professor Ole Andreassen for his time, comments for improving the articles, and in general for sharing his immense knowledge. Words cannot describe how deeply grateful I am for having psychiatrist Ingrid Dieseth and clinical psychologist Carmen Simonsen as collaborators and friends. With their positive attitudes and patience for all sorts of questions, they are truly the ideal combination for anyone venturing in the fields of biological psychiatry and neurocognition. I am also thankful to Professor Ingrid Agartz and postdoc Kjetil Jørgensen for navigating me through the fascinating world of neuroimaging. Kjetil has been like a co-supervisor for me, with his patience, steadiness, and expertise. I have genuinely appreciated our long discussions, even those at 2 o'clock in the night. Furthermore, I would like to thank all previous and present members of the Martens group for practical and social input during my years in the group. From the Statistical Department at Haukeland University Hospital, I also have to thank Professor Geir Egil Eide for introducing me to mixed-effects models and for double-checking the analyses. 7 My sincere thanks to Professor emeritus Knut Wester, as he was the one who first introduced me to research back when I was a medical student, and who encouraged me in perusing this PhD. Over the years he has always been available for both PhD-related discussions, but also for discussing any problems related to life in general. My clinical supervisor, Mildrid Clementsen, from my years as a resident doctor at Sandviken Hospital also deserves a huge thank, as she has been there through all the "ups and downs" in this PhD, giving wisdom and comfort when needed. Nevertheless, the most important and inspirational people in my life are my family. I wish to sincerely thank my husband, Åsmund, for his endless love and support. I am also eternally grateful for all the support and help from my mother, Sarva. This study would never have seen daylight had it not been for my mum and my husband. Finally, I owe my two children, Isak and Ivar the world. They have been there with their smiles, warm hugs,

Antipsychotic Effects on Cortical Morphology in Schizophrenia and Bipolar Disorders

“…In this study, cortical thinning in medicated patients relative to unmedicated patients provided preliminary evidence indicating negative effects of mid-to long-term atypical antipsychotic treatment on cortical thickness. Our results were consistent with studies showing the contribution of atypical antipsychotics to cortical thinning in the frontal, temporal, and parietal lobes, which has been repeatedly reported (Lesh et al, 2015;Zhang et al, 2018;Guo et al, 2019;Liu et al, 2020), and in the lateral orbitofrontal cortex (Gjerde et al, 2018;Akudjedu et al, 2020). Mid-to long-term treatment effects may be negative as a result of cumulative pharmacologic effects (Xiao et al, 2018).…”

“…Due to the challenges of conducting clinical trials to study atypical antipsychotic effects for more than 1 year, observations mostly come from cross-sectional studies and longitudinal studies with naturalistic designs. For example, crosssectional studies of SZ patients undergoing current or chronic (over 5 years) treatment suggest cortical loss (Haijma et al, 2013;Lesh et al, 2015;Gjerde et al, 2018;van Erp et al, 2018;Di Sero et al, 2019;Liu et al, 2020). Similar results were observed in BD patients (Gildengers et al, 2014;Birner et al, 2020), although other studies failed to replicate the finding, possibly due to differences in the duration (short, medium and long-term) of atypical antipsychotic treatment and variability in methodology and sample size (Hallahan et al, 2011;Hafeman et al, 2012;Hibar et al, 2018).…”

The benefits of the Mediterranean diet in first episode psychosis patients taking antipsychotics

“…In addition, both subgroups of FEPs had lower HDL levels than the HCs. Suboptimal levels of HDL, apart from increasing the risk of CVD complications [ 37 ], have been considered to play a role on brain myelination, with an increase of negative symptoms [ 38 ].…”

Sex-Specific Effect of Serum Lipids and Body Mass Index on Psychotic Symptoms, a Cross-Sectional Study of First-Episode Psychosis Patients

“…Impairments in myelination and synaptic communication have likewise been established in the pathophysiology of schizophrenia and related psychosis (71)(72)(73), and studies have further demonstrated sex difference in white matter abnormalities and its association with symptoms in schizophrenia (74). Given that antipsychotic drugs stimulate lipid biosynthesis with possible effects on myelin-related structures (24,26,75,76) and that estrogen regulates the synthesis of structural proteins essential for cholesterol formation (77), it is plausible that these two pathways interact to improve symptoms of psychosis. Supporting such an interpretation is that impairments in estrogen-and lipid metabolism have been implicated in the development of and in predicting the severity of schizophrenia (3,11,(78)(79)(80)(81)(82)(83).…”