Thesis (Ph.D.) - University of Queensland, 2003. / Includes bibliography.

published_or_final_version / Clinical Psychology / Master / Master of Social Sciences

This thesis addresses the effects of pharmacological manipulations of brain 5- hydroxytryptamine (5-HT, serotonin) and it's precursor, tryptophan, on appetite and mood in humans. Chapter 1 is a presentation of the literature reviewed in order to carry out the studies contained within this thesis. General methods are described in Chapter 2; these include biochemical methods for analysis of plasma tryptophan, and measures and assessment methodologies for analysis of appetite and mood. This chapter also contains a pilot study of the methodology adopted for lowering plasma tryptophan levels. The first experiment (Chapter 3) examines the effects of calorie controlled dieting on plasma tryptophan, mood and appetite using a longitudinal design. Dieters were compared with a matched control group, and the results demonstrated that whilst dieting does not appear to alter mood or responses to food in a laboratory setting, it does lower levels of plasma tryptophan compared with baseline and with controls. In view of the confounding variables of dieting on mood and appetite, the second experiment (Chapter 4) examined the effects of an acute, laboratory based depletion of plasma tryptophan on these parameters in healthy female volunteers acting as their own controls. Significant depletion of plasma tryptophan was not associated with alterations in mood or appetite. The third experiment (Chapter 5) addresses the issue of predisposing factors in the effects of tryptophan depletion on mood and appetite. This was carried out with a group of women who had recovered from an eating disorder (bulimia nervosa). These subjects were acting as their own controls but were also compared directly with the non-clinical group of subjects from the previous experiment. This experiment demonstrated interesting differences in the eating behaviour of the two groups, and a significant difference in baseline levels of total plasma tryptophan. There were, however, no effects of tryptophan depletion on mood or appetite in the women who had recovered from bulimia nervosa. In view of the apparent lack of effect of tryptophan depletion on mood or appetite, the remaining two experiments examine the role of specific 5-HT receptor subtypes in the control of appetite. Chapter 6 examines the effect of meta-chlorophenylpiperazine (mCPP), a 5-HT_2C receptor agonist on appetite, and Chapter 7 examines the effect of 5-HT₃ receptor blockade on amphetamine anorexia. Whilst the data from these experiments do not support a role for these receptor subtypes in appetite, it is suggested that this is a potentially fruitful area for future research. The results generated by the above experiments are discussed in Chapter 8 in the light of other research findings. The methodologies adopted for these experiments and the implications of these studies for future research are discussed.

Thesis (M.A.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on May 11, 2009) Includes bibliographical references.

Thesis (M. Soc. Sc.)--University of Hong Kong, 2008. / Includes bibliographical references (p.54-66).

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xiv, 110 p. : ill. Includes bibliographical references (p. 106-110). Available online via OhioLINK's ETD Center

As much as 10% of the US population will experience at least one bout of depression within their lifetime. It has been reported that an increased time spent with major depressive disorder (MDD) results in a decreased volume in the hippocampus. This decreased volume is the result of apoptosis, or programmed cell death. In recent years it has become known that new neurons (neurogenesis) are continuously born in the hippocampus of humans. In fact, it now appears that antidepressant drug efficacy may be dependent on adult neurogenesis in the hippocampus. At least six epidemiological studies have shown an inverse correlation between seafood intake and prevalence of mood disorders (p [less than]0.05 or better). There is mounting evidence that this result is due to fish oils containing the long-chain, poly-unsaturated, omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Although extensive study has been undertaken using both of these omega-3s together, very little has been done to determine which fatty acid has the greater effect. Although previously thought to be readily interconvertible, there is mounting evidence that these two lipids are not treated equally in the body. EPA has produced greater cell proliferation over DHA in the B-lymphocyte cells, and DHA has even been known to cause a decrease at higher concentrations. Differences have also been reported in both molecular and behavioral outcomes. This research tested the hypothesis that EPA facilitates proliferation and survival of neuronal precursor cells to a greater extent than does DHA. Human neuronal precursor cells were grown in the presence of EPA, DHA, and varying ratios of EPA and DHA to determine their dose-response relationships. While there were no large effects on proliferation or differentiation, EPA, but not DHA, protected cells from iron-induced oxidative stress. This protection appears to be, at least in part, the result of altered p53 translocation in EPA-treated cells. Future work will be needed to determine the role of this molecular protection in the antidepressant activity of EPA. / A Dissertation submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Master of Science. / July 16, 2009. / Includes bibliographical references. / Cathy Levenson, Professor Directing Theis; Jodee Dorsey, Committee Member; Michael Meredith, Committee Member.

Das serotonerge System bildet schon seit Jahrzehnten einen Schwerpunkt in der psychiatrischen Grundlagenforschung. Seinen weit verzweigten Leitungsbahnen wird eine global-modulatorische Eigenschaft für die Aufrechterhaltung des Gleichgewichts zwischen unterschiedlichen Hirnregionen und unterschiedlichen Neurotransmitter-systemen zugeschrieben (Hüther und Rüther, 2000). Darüber hinaus ist die serotonerge Neurotransmission ein Hauptmodulator emotionalen Verhaltens, das Angst und Ängstlichkeit ebenso umfasst wie Aggression und Impulsivität (Lesch et al., 2003). In der vorliegenden Arbeit wurden im Sinne eines Kandidatengenansatzes zwei Assoziationsstudien durchgeführt. Im ersten Teil wurde versucht, eine mögliche Assoziation zwischen der Erkrankung an affektiven Störungen und drei vorbeschriebenen SNPs des FEV-Gens aufzudecken. FEV ist das humane Homolog des in mehreren Tierversuchen untersuchten Pet-1-Gens, dem vor allem eine zentrale Bedeutung in der embryonalen Entwicklung des serotonergen Systems zugeschrieben wird. Zusätzlich wurde ein 286 bp langer Abschnitt des Exon 3 sequenziert, um die Häufigkeit der sieben in diesem Abschnitt beschriebenen SNPs bei unipolar depressiven Patienten abzuschätzen und ggf. neue Varianten zu detektieren. Der zweite Teil untersuchte das Auftreten zweier bereits von anderen Autoren beschriebener SNPs des TPH2-Gen bei an der adulten Form des ADHS leidenden Patienten im Vergleich zu einer Kontrollgruppe. Die im zentralen serotonergen System dominierende Tryptophanhydroxylase 2 (TPH2) ist das erste, geschwindigkeitsbegrenzende Enzym der Serotonin-Biosynthese. Die Genotypisierung der einzelnen SNPs erfolgte mit unterschiedlichen Methoden. So kam sowohl die PCR, der Restriktionsenzymverdau, die Minisequenzierung (SNaPshot®) als auch die MALDI-ToF Massenspektrometrie und die Sequenzierung zum Einsatz, die Auftrennung einzelner Schnittprodukte erfolgte durch die Gelelektrophorese. Die erste Stichprobe umfasste 270 Patienten (davon 179 weiblich) mittleren Alters mit einer Diagnose aus dem affektiven Formenkreis (180 mit bipolar-affektiver Störung gemäß den DSM-IV Kriterien, weitere 90 Patienten mit einer rezidivierenden unipolaren depressiven Störung) sowie 362 (davon 174 weibliche) Kontrollpersonen. Die Stichproben der zweiten Studie umfassten 284 am adulten ADHS (Diagnose nach DSM IV) leidende Patienten (140 davon weiblich) und 120 Kontrollpersonen (61 davon weiblich). Statistisch wurden die Daten sowohl auf Einzelmarker- als auch auf Haplotypniveau ausgewertet. In beiden Studien konnte keine Assoziation der untersuchten Polymorphismen des FEV- bzw. TPH2-Gens mit der jeweiligen Erkrankung (affektive Störung / adultes ADHS), weder auf Einzelmarker- noch auf Haplotypniveau, nachgewiesen werden. Die Sequenzierung des 286 bp langen Abschnitts von Exon 3 des FEV-Gens zeigt eine ausgeprägte Konservierung der Sequenz dieses Gens, wie sie auch von anderen Autoren beschrieben wurde. Die hier untersuchten Kandidatengene FEV und TPH2 sind auch weiterhin interessante Ansatzpunkte für die psychiatrische Grundlagenforschung. Die Aufklärung der genauen Wirkungsweise von FEV und seine Rolle in der Entwicklung des menschlichen serotonergen Systems erscheint jedoch vordergründig, um zunächst Funktion, Interaktionen und mögliche pathogenetische Mechanismen aufzudecken und dann gezielter die Einflüsse bestimmter Polymorphismen zu untersuchen. / Since decades, the serotonergic system is one major focus of basic research in psychiatry. The widely branched serotonergic network is thought to have global-modulatory impact on diverse brain regions and transmitter systems (Hüther & Rüther, 2000). Moreover, serotonergic neurotransmission plays a key modulatory role in emotional behavior, including for example fear, anxiety, aggression and impulsivity (Lesch et al., 2003). Within the present manuscript, two association studies focussing on two candidate genes of the serotonergic system are presented. The first study aimed at investigating the association between affective disorders and three previously described SNPs of the FEV gene. FEV is considered the human homolog of the murine Pet-1-gene and has been suggested to be of key importance for the embryonic development of the serotonergic system. In addition, the study aimed at detecting new variants, and therefore assessed the frequency of seven new SNPs located on a 286 bp long part of the Exon 3, and tested for their association with unipolar depressive disorder. The second study aimed to compare the frequency of two previously described SNPs of the TPH2- gene between a sample of adult ADHD patients and a sample of healthy controls. TPH2 is thought to be the dominating speed reducing enzyme to central serotonergic biosynthesis. While genotyping of the respective SNPs was done using different methods, i.e. PCR, restriction enzyme digest, SNaPshot®, MALDI-ToF mass spectrometry as well as sequencing, all cleavage products were separated using gel-electrophoresis. The first studies‘ sample consisted of N=270 middle-aged patients (179 female) diagnosed for affective disorders according to DSM-IV criteria (i.e. n=180 bipolar disorder, n=90 unipolar depression), and N=362 (174 female) healthy controls. Within the second study, N=284 patients suffering from adult ADHD (140 female) and 120 healthy controls (61 female) were investigated. Data within both studies have been analyzed for single-marker as well as for haplotype associations. In both studies, no associations between the polymorphisms under investigation and the respective disorders were found (neither on the single-marker nor on the haplotype level). In accordance with previous reports, a marked conservation of a section of the Exon 3 sequence (286 bp) of the FEV gene was found. Although both candidate genes (FEV, TPH2) are of further interest for basic research into Psychiatry, unraveling the role of FEV in the development of the human serotonergic system seems to be of primary importance. Once the functional associations, interactions and pathogenic mechanisms have been discovered, future research might be able to more specifically target the role of single polymorphisms within the serotonergic network.

Thesis--PlanB (M.S.)--University of Wisconsin--Stout, 2004. / Includes bibliographical references.

Title from PDF of title page (University of Missouri--Columbia, viewed on Feb. 18, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dr. Stanislav Kolenikov, Thesis Supervisor Includes bibliographical references.