This thesis has examined what long-term psychological and neurological effects that are apparent in children and adults who have experienced parental divorce. It was predicted that significantly more children and adult children from divorced families would have increased symptoms of mental disorders than children and adult children from married homes e.g., anxiety, depression, panic disorder, and generalized anxiety disorder. It was further predicted that parental divorce would negatively affect the neurological system in the offspring. The correlation between children of divorce and negative neurological effects was not found to be true. However, adult children of divorce have significantly lower baseline cortisol levels compared to adult children of marriage. Dysregulated cortisol levels are highly associated with the development of e.g., anxiety, depression, and brain damage. Parental divorce did not only influence how secretion of the hormone cortisol is regulated within adult children of divorce, but how both children and adult children of divorce psychologically adapt postdivorce. Children of divorce have for instance lower general well-being, more symptoms of anxiety and depression, lower self-esteem, and feel more stress than children of marriage. Adult children of divorce are more likely to experience marital discord, getting divorced themselves, anxiety and depression, lower academic performance, and substance abuse, etc. The result of the thesis suggests that children and adult children from divorced families are negatively affected, both psychologically and neurologically, regardless of age. Parental divorce and supplementary effects make it more likely for children and adult children to experience more symptoms of mental disorders.

This report describes the use of small molecule probes in the modulation of brain chemistry with the ultimate goal of developing novel therapeutics for the treatment of mood disorders. With an increasing number of people suffering from depression, there is a need to explore more diverse mechanisms of these diseases to better understand their cause and therefore provide insight into their treatment. Chapter 1 serves as an introduction and describes the current understanding of depression mechanisms, as well as a history of antidepressant therapeutics. The chapter then goes on to discuss, in depth, the mechanisms of G Protein-Coupled Receptor (GPCR) function and the implications of biased signaling. There is also an introductory overview of basic pharmacological terms. The chapter finishes with a summary of current technology available to measure GPCR function, including those utilized in the rest of this report. The remainder of the report is broken up into two parts. In the first part, I will describe my work to understand the opioid receptor system in the context of mood disorders. In Chapter 2, the atypical antidepressant tianeptine is discovered to act through the mu-opioid receptor (MOR), and a biochemical exploration is reported including an exploration of its unique properties in the context of G protein-dependent and -independent signaling, as well as preliminary in vivo and structure activity relationship studies into the mechanism of action. In Chapter 3, I will describe the biological characterization of the Mitragyna speciosa alkaloids at the opioid receptors. In particular, the major alkaloids mitragynine and 7-OH mitragynine are found to be partial agonists at the MOR and antagonists at the kappa-opioid receptor (KOR) with apparent G protein bias. In Chapter 4, alkaloids inspired by those found in Tabernanthe iboga, such as ibogaine, are synthesized and characterized at the opioid receptors. Through a novel 12- hydroxy-oxaibogamine scaffold, opioid activity is uncovered that is greatly increased in comparison to the ibogaine metabolite noribogaine. Analogs tested have varying degrees of potency and efficacy at all three opioid receptors, and one analog in particular is found to be a selective G protein biased partial KOR agonist. In Chapter 5, I will conclude the opioid section by taking a critical examination of commonly used assays for measuring arrestin recruitment by dissecting assay components and analyzing what is necessary to determine accurate calculations of bias within a cellular system. The alleged G protein bias of KOR agonist dynorphin is studied at great length, and a discussion on the future of understanding ligand bias is presented. In the second part of this report, I move away from opioids and instead focus on the growth factor signaling system as a second approach to uncovering novel therapeutics for depression. In Chapter 6, I describe a second potential mechanism of action of the natural product ibogaine in the context of glial cell line-derived neurotrophic factor (GDNF) signaling. The deconstructed iboga analog XL-008 is studied that is a superior releaser of GDNF and potentiates the signaling of a second growth factor, fibroblast growth factor 2 (FGF2). In the final Chapter 7, I look to the FGF family, both receptor and growth factor, as a novel target for depression. In order to identify small molecule modulators of the FGF receptor 1 (FGFR1), cell- based assays are developed and validated in a pilot screen. The strength of these assays are assessed, and the initial results from a full high throughput screen are presented.

Bibliography: leaves 317-350 / 350 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, 1986

Thesis (Ph. D.)--Florida State University, 2003. / Advisor: Jeanette Taylor, Florida State University, College of Arts and Sciences, Dept. of Psychology. Title and description from dissertation home page (Apr. 9, 2004). Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. Linköping : Univ., 1999.

Thesis (Ph. D.)--University of Texas at El Paso, 2008. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

Thesis (M.S.)--Florida State University, 2005. / Advisor: James Joiner, Florida State University, College of Arts and Sciences, Dept. of Psychology. Title and description from dissertation home page (viewed Feb.1, 2006). Document formatted into pages; contains vi, 23 pages. Includes bibliographical references.

This two-part study investigates the effectiveness of neurofeedback training for reducing behavioral problems commonly observed in abused/neglected children, and compares its efficacy to other treatment interventions with this population. Neuro-developmental sequelae of early relationship trauma are explored as an etiological framework for understanding disturbed affect-regulation, which appears central to the behavioral and emotional difficulties commonly experienced by this pediatric population. It is suggested that neurofeedback teaches children to self-regulate brain rhythmicity mechanisms, which in turn affects global improvements in behavior and mood. The pilot study utilizes records of 20 children removed from their biological homes by Child Protective Services. Children were assessed prior to treatment using the Child Behavior Checklist (CBCL) and the Test of Variables of Attention (TOVA), and again after 30 sessions of individualized, qEEG-guided neurofeedback training. A t-test analysis of pre- and post-scores was computed, and indicated significant improvements following treatment. A meta-analysis of existing literature on treatment interventions with abused/neglected children provides individual and aggregate effect sizes for 33 outcome studies with this clinical population, and contextualizes the results of the present pilot study within other empirically validated treatment modalities. Establishment of an overall effect size for treatment for this pediatric population provides a needed method of comparing research results across studies when control groups may not be ethical or feasible.

Individuals are becoming more dependent on medication for conditions such as chronic-pain, anxiety, and depression. It is reported that patients are often overprescribed medication while health outcomes do not improve. The medicalization of society is distracting attention from the possibility of other therapies such as complementary or alternative medicine (CAMs) that can improve health outcomes if they were as supported as pharmacological research and better received by the medical community. Yoga and meditation, the components of Mindfulness Based Stress Reduction (MBSR) and yoga therapy, have been shown as effective CAMs for cases of anxiety and depression related to chronic illness or chronic pain. There is little agreement in research, among yoga practitioners, and in the medical community on how to prescribe the delivery of yoga therapy interventions to reduce pain, depression, or anxiety. The purpose of this quantitative study and, to address this gap in the literature, is to provide the medical community protocols for the delivery of yoga therapy and to discover a “dose response” for yoga therapy among 6 individuals suffering pain and related affective disorders such as anxiety and depression. The findings of this study showed no significant difference among individuals who practice yoga therapy at the rate of one or three times per week on reported levels of depression, anxiety, pain, perceived stress or quality of life depending on the rate of practice. This study could impact the over-prescription of medication and reduce the dependence on psychopharmacology for management of affective disorders