Ovarian hormones shape brain structure, function, and chemistry: A neuropsychiatric framework for female brain health

There are robust sex differences in brain anatomy, function, as well as neuropsychiatric and neurodegenerative disease risk (1-6), with women approximately twice as likely to suffer from a depressive illness as well as Alzheimer’s Disease. Disruptions in ovarian hormones likely play a role in such disproportionate disease prevalence, given that ovarian hormones serve as key regulators of brain functional and structural plasticity and undergo major fluctuations across the female lifespan (7-9). From a clinical perspective, there is a wellreported increase in depression susceptibility and initial evidence for cognitive impairment or decline during hormonal transition states, such as the postpartum period and perimenopause (9-14). What remains unknown, however, is the underlying mechanism of how fluctuations in ovarian hormones interact with other biological factors to influence brain structure, function, and chemistry. While this line of research has translational relevance for over half the population, neuroscience is notably guilty of female participant exclusion in research studies, with the male brain implicitly treated as the default model and only a minority of basic and clinical neuroscience studies including a female sample (15-18). Female underrepresentation in neuroscience directly limits opportunities for basic scientific discovery; and without basic knowledge of the biological underpinnings of sex differences, we cannot address critical sexdriven differences in pathology. Thus, my doctoral thesis aims to deliberately investigate the influence of sex and ovarian hormones on brain states in health as well as in vulnerability to depression and cognitive impairment:Table of Contents List of Abbreviations ..................................................................................................................... i List of Figures .............................................................................................................................. ii Acknowledgements .....................................................................................................................iii 1 INTRODUCTION .....................................................................................................................1 1.1 Lifespan approach: Sex, hormones, and metabolic risk factors for cognitive health .......3 1.2 Reproductive years: Healthy models of ovarian hormones, serotonin, and the brain ......4 1.2.1 Ovarian hormones and brain structure across the menstrual cycle ........................4 1.2.2 Serotonergic modulation and brain function in oral contraceptive users .................6 1.3 Neuropsychiatric risk models: Reproductive subtypes of depression ...............................8 1.3.1 Hormonal transition states and brain chemistry measured by PET imaging ...........8 1.3.2 Serotonin transporter binding across the menstrual cycle in PMDD patients .......10 2 PUBLICATIONS ....................................................................................................................12 2.1 Publication 1: Association of estradiol and visceral fat with structural brain networks and memory performance in adults .................................................................................13 2.2 Publication 2: Longitudinal 7T MRI reveals volumetric changes in subregions of human medial temporal lobe to sex hormone fluctuations ..............................................28 2.3 Publication 3: One-week escitalopram intake alters the excitation-inhibition balance in the healthy female brain ...............................................................................................51 2.4 Publication 4: Using positron emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression ..........65 2.5 Publication 5: Increase in serotonin transporter binding across the menstrual cycle in patients with premenstrual dysphoric disorder: a case-control longitudinal neuro- receptor ligand PET imaging study ..................................................................................82 3 SUMMARY ...........................................................................................................................100 References ..............................................................................................................................107 Supplementary Publications ...................................................................................................114 Author Contributions to Publication 1 .....................................................................................184 Author Contributions to Publication 2 .....................................................................................186 Author Contributions to Publication 3 .....................................................................................188 Author Contributions to Publication 4 .....................................................................................190 Author Contributions to Publication 5 .....................................................................................191 Declaration of Authenticity ......................................................................................................193 Curriculum Vitae ......................................................................................................................194 List of Publications ................................................................................................................195 List of Talks and Posters ......................................................................................................19

A Remark on Quantum Group Actions and Nuclearity

Let H be a compact quantum group with faithful Haar measure and bounded counit. If H acts on a C*-algebra A, we show that A is nuclear if and only if its fixed-point subalgebra is nuclear. As a consequence H is a nuclear C*-algebra.Comment: 12 pages, LateX 2

Quantitative BT-Theorem and automatic continuity for standard von Neumann algebras

We prove a general criterion for a von Neumann algebra $M$ in order to be in standard form. It is formulated in terms of an everywhere defined, invertible, antilinear, a priori not necessarily bounded operator, intertwining $M$ with its commutant $M'$ and acting as the $*$-operation on the centre. We also prove a generalized version of the BT-Theorem which enables us to see that such an intertwiner must be necessarily bounded. It is shown that this extension of the BT-Theorem leads to the automatic boundedness of quite general operators which intertwine the identity map of a von Neumann algebra with a general bounded, real linear, operator valued map. We apply the last result to the automatic boundedness of linear operators implementing algebraic morphisms of a von Neumann algebra onto some Banach algebra, and to the structure of a $W^*$-algebra $M$ endowed with a normal, semi-finite, faithful weight $\varphi\,$, whose left ideal $\mathfrak N_\varphi$ admits an algebraic complement in the GNS representation space $H_\varphi\,$, invariant under the canonical action of $M$

Initial Semantics for higher-order typed syntax in Coq

Initial Semantics aims at characterizing the syntax associated to a signature as the initial object of some category. We present an initial semantics result for typed higher-order syntax together with its formalization in the Coq proof assistant. The main theorem was first proved on paper in the second author's PhD thesis in 2010, and verified formally shortly afterwards. To a simply-typed binding signature S over a fixed set T of object types we associate a category called the category of representations of S. We show that this category has an initial object Sigma(S). From its construction it will be clear that the object Sigma(S) merits the name abstract syntax associated to S. Our theorem is implemented and proved correct in the proof assistant Coq through heavy use of dependent types. The approach through monads gives rise to an implementation of syntax where both terms and variables are intrinsically typed, i.e. where the object types are reflected in the meta-level types. This article is to be seen as a research article rather than about the formalization of a classical mathematical result. The nature of our theorem - involving lengthy, technical proofs and complicated algebraic structures - makes it particularly interesting for formal verification. Our goal is to promote the use of computer theorem provers as research tools, and, accordingly, a new way of publishing mathematical results: a parallel description of a theorem and its formalization should allow the verification of correct transcription of definitions and statements into the proof assistant, and straightforward but technical proofs should be well-hidden in a digital library. We argue that Coq's rich type theory, combined with its various features such as implicit arguments, allows a particularly readable formalization and is hence well-suited for communicating mathematics.Comment: Article as published in JFR (cf. Journal ref). Features some more example

Psychometric properties and further validation of the emergency reaction questionnaire in a sample of Portuguese adults

Emergencies and disasters are abrupt, unexpected, dangerous events often traumatic. Individuals differ in the way they respond to this kind of adverse experience, depending on varied factors. This study used the Emergency Reaction Questionnaire (ERQ) to assess defensive mechanisms, feelings, and thoughts during emergency and disaster-related situations. The main objective of the present study was to confirm the factor structure and provide further support to the validity of the ERQ on a Portuguese sample. Here we replicated previous findings in showing that people who are more prone to react in an organized way in emergencies tend to have lower anxiety levels and a greater tendency for sensation seeking. We also found that females score lower than males; that ERQ specific readiness scores slightly increase with age and people who have risky jobs or routinely engage in extreme sports scored higher on the ERQ scales (meaning they act more readily and organized in an emergency). The ERQ and its Portuguese version show to be a psychometrically sound and valid measurement of emergency behavior, able to assess individual differences in the way people perform during various emergencies, and can be used in future research and in practice for screening or measuring training efficiency.info:eu-repo/semantics/publishedVersio

Fear inoculation among snake experts

Abstract Background Fear acquisition of certain stimuli, such as snakes, is thought to be rapid, resistant to extinction, and easily transferable onto other similar objects. It has been hypothesized that due to increased survival chances, preparedness to instantly acquire fear towards evolutionary threats has been hardwired into neural pathways of the primate brain. Here, we compare participants’ fear of snakes according to experience; from those who often deal with snakes and even suffer snakebites to those unfamiliar with snakes. Methods The Snake Questionnaire-12 (SNAQ-12) and Specific Phobia Questionnaire (SPQ) were administered to three groups of participants with a different level of experience with snakes and snakebites: 1) snake experts, 2) firefighters, and 3) college students. Results This study shows that individuals more experienced with snakes demonstrate lower fear. Moreover, participants who have suffered a snakebite (either venomous or not) score lower on fear of snakes (SNAQ-12), but not of all other potentially phobic stimuli (SPQ). Conclusions Our results suggest that a harmless benign exposure might immunize people to highly biologically prepared fears of evolutionary threats, such as snakes

Business Performance Evaluation, in the Light of Corporate Social Responsability

Global economic and social changes determined managers to change traditional strategies and to approach business performance from new and totaly different point of views. Future strategies should pursue the value creation to all stakeholders. The aim of the article is to draw attention to the increasingly important Corporate Social Responsability (CSR) and to make proposals to measure it and to accommodate it in the Financial Reports. As a first step, I will make on overview of the theoretical approach of the (CSR) subject, than, I will present and propose a group of indicators to measure the CSR activity. Regarding to the material and methods, I used several CSR Reports, internationally recognized and applied indicators (e.g.: DJSI), rates for a quantitative and qualitative performance analysis). This paper brings a possible alternative to evaluate the companie’s responsible behavior. Indicators are evaluating the companies accordig to different aspects. In addition to accounting and financial reporting, introducing the social (and environmental) reporting, would certainly have interest for local community (and not only), therefore the author recommend inclusion the results of corporate responsible evaluation in the notes to the Financial Statements mandatory for every enterprise