Genetic aetiology of anxiety disorders

Benecke, Rohan Meerholz (2016-12)

Thesis (MSc)--Stellenbosch University, 2016

Thesis

ENGLISH SUMMARY: Anxiety disorders are among the most prevalent psychiatric disorders among both adults and adolescents. Comorbidity with other psychiatric disorders, including other anxiety disorders, is common and it is clear that a high degree of burden of distress and impairment is associated with the condition. Substantial evidence has been presented to suggest a strong genetic component in the aetiology of anxiety disorders. Twin and family studies suggest that panic disorder, general anxiety disorder, phobias and obsessive-compulsive disorder (OCD) aggregate in families. Twin studies in particular shown greater intrapair resemblance between monozygotic twins compared to dizygotic twins, suggesting a strong genetic component. Several genes have been implicated in the genetic aetiology of anxiety disorders, the most prominent of which are BDNF and SCL6A4. Furthermore, the role of the HPA axis in the regulation of the normal response to fear and stress may be influenced by genes contributing to cortisol functions such as FKBP5 and CRHR1. The severity of childhood trauma can contribute to the development of anxiety disorders by modulating gene expression. In this study anxiety sensitivity (AS) is investigated as a possible predictive marker for development of anxiety disorders. Adolescents (13-18 years of age) were recruited from senior secondary schools in the Cape Town area of the Western Cape. Participants were subjected to psychological screening, which included the childhood anxiety sensitivity index (CASI) as well as the childhood trauma questionnaire (CTQ), and saliva samples were collected and genotyping conducted. Gene-environment (G × E) interactions, focussing on the severity of childhood trauma and selected genetic variants, were investigated to determine how levels of AS in a South African adolescent population were modulated. Our cohort consisted of predominantly Xhosa and Coloured individuals and analysis was done on both ethnic groups separately. Significant findings in FKBP5 and CRHR1 in males of both ethnic groups suggests sex linked effect in genes regulating cortisol function. The severity of childhood trauma was found to modulate selected variants which is in line with previous literature. AS may be seen as a precursor to the development of anxiety- and anxiety-related disorders, and a potential clinical marker for early diagnoses of anxiety disorders.

AFRIKAANSE OPSOMMING: Angsversteurings is een van die mees algemene psigiatriese versteurings onder beide volwassenes en tieners. Medemorbiditeit met ander psigiatriese versteurings asook medemorbiditeit onder angsversteurings is algemeen. Verder is dit duidelik dat 'n hoë graad van las van nood en gebrek verband hou met die lyding van angsversteurings. ‘n Aansienlike hoeveelheid bewyse is beskikbaar in die literatuur dat daar 'n sterk genetiese komponent as deel van die etiologie van angsversteurings bestaan. Tweeling en familie studies dui daarop dat paniekversteuring, algemene angsversteuring, fobies en obsessiewe kompulsiewe versteuring in families meer algemeen vertoon. Tweeling studies veral wys groter intra-paar ooreenkoms tussen monosigotiese tweelinge in vergelyking met disigotiese tweelinge, wat dui dat die ooreenkoms geneties is eerder as die omgewing waarin die tweelinge hul self bevind. Verskeie gene word geïmpliseer by die genetiese etiologie van angsversteurings waarvan die mees prominente gene BDNF en SCL6A4 is. Verder, die rol van die HPA-as in die regulering van die normale reaksie op vrees en stres, kan beïnvloed word deur gene wat bydra tot kortisol funksie beheer soos FKBP5 en CRHR1. Kinderjare trauma kan ook bydra tot die ontwikkeling van angsversteurings, asook 'n modulerende uitwerking hê op gene. In hierdie studie word angs sensitiwiteit (AS) ondersoek as 'n moontlike voorspellende merker vir die ontwikkeling van angsversteurings. Adolessente (13-18 jaar oud) is gewerf uit senior sekondêre skole in die Kaapstad-omgewing van die Wes-Kaap om aan die studie deel te neem. Deelnemers is blootgestel aan sielkundige vraelyste soos die kinderjare angs sensitiwiteit indeks (CASI) asook die kinderjare trauma vraelys (CTQ), en speeksel monsters is ingesamel en genotipering is gedoen. Geen-omgewing (G × E) interaksies, met die fokus op die erns van kinderjare trauma en gekose genetiese variante is ondersoek, om ten einde vas te stel hoe vlakke van AS in 'n Suid-Afrikaanse adolessente bevolking is gemoduleer word. Ons studie groep bestaan uit oorwegend Xhosa en Bruin deelnemers en ontleding is gedoen op beide etniese groepe afsonderlik. Beduidende bevindinge in FKBP5 en CRHR1 by mans van beide etniese groepe dui op 'n geslagsgekoppelde effek in gene wat kortisol funksie reguleer. Kinderjare trauma is ook gevind om sekere variante te beïnvloed wat in lyn is met die vorige literatuur bevindings. AS kan gesien word as 'n voorloper tot die ontwikkeling van angs- en-angs verwante versteurings, en dus as 'n potensiële kliniese merker gebruik kan word tot die vroeë diagnoseering van angs versteurings.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/100444
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