Correlations between stress-associated anxiety and physiological determinants of health in adolescents

Viljoen, Monet (2016-03)

Thesis (PhD)--Stellenbosch University, 2016.

Thesis

ENGLISH ABSTRACT: Anxiety disorders are among the most prevalent of psychiatric disorders across age groups, with onset typically in childhood or early adolescence, and risk for developing an anxiety disorder increasing with trauma/childhood maltreatment. Little is known about biomarkers of resilience/vulnerability in relation to subclinical anxiety, especially when trauma-exposed adolescents are implicated. Therefore, better elucidation of the neuro-endocrine and -immunological underpinnings relative to anxiety and trauma, may highlight specific avenues to target with more effective diagnosis, monitoring and/or treatment strategies in the context of youth at risk for later development of anxiety disorders. Thus, our aims were to elucidate the central and peripheral neuroendocrine and immunological profiles in association with anxiety proneness, in comparison to childhood trauma, in older adolescents, and to assess potential outcome modulators. A total of 43 participants, aged 15-18, were selected from an initial cohort of 1149 adolescents. Participants were delineated into four groups based on levels of anxiety proneness and trauma exposure, using questionnaires and a structured diagnostic interview. Blood obtained from each participant was analysed for an HPA-axis hormone profile (cortisol, prolactin, testosterone and dehydroepiandrosterone-sulphate (DHEAs) and immune status (total white blood cell count, leukocyte glucocorticoid receptor (GR) expression and serum cytokine and myeloperoxidase (MPO) levels). Resilience (coping capacity), self-esteem and handedness were assessed via questionnaires. Verbal- and visuospatial working memory, as well as executive neurocognitive function, were assessed by means of the administration of neurocognitive tests. A structural Magnetic Resonance Imaging (MRI) was performed to determine left versus right grey matter volumes of the thalamus, amygdala, hippocampus, and Prefrontal cortex (PFC). Finally, HPA-axis responsivity and concurrent state anxiety to an in vivo Bexamethasone suppression test, in conjunction with as a psychosocial stress test (TSST), were assessed. In terms of neurophysiological maladaptations, main findings included a relatively larger association with anxiety proneness, compared to childhood maltreatment. Specifically, anxiety proneness was associated with poorer neurocognitive function, increased right amygdala volume, lower serum DHEAs levels, lower peripheral leukocyte counts, and increased GR expression. In terms of potential outcome modifying factors (OMFs), resilience and self-esteem were affected by trauma, but not anxiety proneness, while a higher degree of right handedness was associated with poorer neurophysiological outcomes. Furthermore, increased serum IL-12p70 and MPO (suggesting relatively more pro-inflammatory state) were associated with anxiety scales and emotional/physical abuse. Also, better PFC neurocognitive function and larger left PFC volumes were associated with better physiological outcome as indicated by levels of GR expression and DHEAs. In conclusion, this is the first study to have investigated neurophysiological adaptations, as well as psycho-physiological responses to HPA-axis suppression and a psychosocial stress test, in association with anxiety proneness and trauma exposure, in adolescents of low socio-demographic background. Results suggest for the study population, a) chronic hypo-activity and acute hypo-reactivity of the lower HPA-axis, b) neurophysiological perturbations associated relatively closely with anxiety proneness, when compared to trauma exposure, c) central correlates associated with physiological outcome, and d) a higher degree of consistent right handedness to be a potential marker of vulnerability in terms of neurophysiology and anxiety.

AFRIKAANSE OPSOMMING: Angsversteurings is van die algemeenste van al die psigiatrise afwykings oor al die ouderdomsgroepe heen, met die aanvang gewoonlik tydens kindertyd of vroë adolessensie, en met die risiko om n angsversteuring te ontwikkel toenemend met kinder trauma/mishandeling. Min is tans bekend aangaande biomerkers van weerstandigheid/kwesbaarheid in verhouding tot sub-kliniese angs, veral wanneer trauma-blootgestelde adolessente ge-impliseer is. Daarom sal beter toeligting van die neuro-endokriene en –immuun merkers, relatief tot angs en trauma, mag bydra tot die ontwikkeling van meer effektiewe voorkoming, monitering en/of behandeling strategieë in die konteks van jeug wat die risiko loop vir latere ontwikkeling van angsversteurings. Ons doelstelling was om die sentrale en perifere neuro-endokriene en immunologiese profiele wat ge-assosieer is met angsvatbaarheid , in teenstelling met kinder trauma, in ouer adolessente te bepaal, en om ook potensiële gevolge modulerende (OMFs) te bepaal. ‘n Totaal van 43 deelnemers, ouderdom tussen 15 en 18 jaar, was gesellekteer uit n aanvanklike kohort van 1149 adolessente. Deelnemers is ingedeel in vier groepe gebasseer op vlakke van angsvatbaarheid en kinder trauma, deur gebruik te maak van vraelyste en ‘n gestruktureerde diagnostisie onderhoud. Bloed monsters van elke deelmener was ge-analiseer vir ‘n HPA-axis hormoon profiel (kortisol, prolaktien, testosteroon en dehidroepiandrosteroon-sulfaat (DHEAs) en immuun status (totale witbloedsel telling, leukosiet glucocorticoid reseptor (GR) uitdrukking en serum sitokien en myeloperoxidase (MPO) vlakke). Weerstandigheids (uithouvermoë), selfwaarde/selfvertroue, en handedness was bepaal via vraelyste. Verbale- en visieruimtelike werkende geheue, asook uitvoerbare neurokognitiewe funksie was bepaal deur middel van neurokognitiewe toetse. ‘n Strukturele Magnetiese Resonans Skandering (MRS) was verrig om links versus regs grysstof volumes van die thalamus, amygdala, hippocampus en prefrontale korteks (PFK) te bepaal. Laastens, HPA-axis reaksie kapasiteit en gesamentlike toestand angs as n gevolg van ‘n Bexamethasone onderdrukking toets, in kombinasie met n psigososiale stres toets (TSST), is vasgestel. In terme van neurofisiologiese wanaanpassings, sluit primêre bevindinge in ‘n relatiewe groter assosiasie met angsvatbaarheid, in vergelyking met kinder trauma. Meer spesifiek, angsvatbaarheid was ge-assosieer met swakker neurokognitiewe funksies, vergrote regter amygdala volume, laer serum DHEAs vlakke, laer periferale leukosiete tellings en verhoogde GR uitdrukking. In terme van potensiele OMFs, was weerstandigheid en selfwaarde/selfvertroue ge-affekteer deur trauma en nie angsvatbaarheid nie, terwyl n hoër graad van regshandigheid ge-assosieer was met swakker neurofisiologiese resultate. Vervolgens was verhoogde serum IL-12p70 en MPO (wat n relatiewe meer pro-inflammatoriese toestand suggereer), ge-assosieer met hoër angs eindtellings en emosionele/fisiese mishandeling. Verder was beter PFK neurokognitiewe funksie en groter linker PFK volumes ge-assosieer met beter fisiologiese gevolge, aangedui deur vlakke van GR uitdrukking en DHEAs. Ter afsluiting, die huidige studie is die eerste om neurofisiolgiese aanpassings te bestudeer, asook psigofisiologiese reaksies tot HPA-axis onderdrukking en ‘n psigososiale stres toets, in verband met angsvatbaarheid en kinder trauma, in adolessente met lae sosio-demografiese agtergronde. Die resultate vir die huidige studie populasie suggereer, a) kroniese hipo-aktiwiteit en kortstondige hipo-reaktiwiteit van die laer HPA-axis, b) neurofisiologiese verstorings relatief hoog ge-assosieer met angs vatbaarheid, in vergelyking met kinder trauma, c) sentrale merkers ge-assosieer met fisiolgiese gevolge, en d) a hoër graad van konstante regs handigheid wat n potensiële merker van vatbaarheid kan wees, in terme van neurofisiologie en angs.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/98419
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