Mechanisms in social anxiety disorder in the context of early developmental trauma : an imaging, neurocognitive and genetics study

[摘要] ENGLISH SUMMARY : The contribution of early developmental trauma (EDT) to the neurobiological mechanisms of social anxiety disorder (SAD) is poorly understood. A cross sectional study was conducted toexamine the effects of EDT on the pathophysiological mechanisms in SAD. The study assessed three groups: SAD with EDT, SAD without EDT and healthy controls matched for age, gender, ethnicity, education and handedness. We conducted neurocognitive testing, DNA sequencing from whole blood, structural magnetic resonance imaging and proton magnetic resonance imaging. Bayesian statistical analyses were conducted, as thephilosophical and theoretical underpinnings of Bayesian statistical methods account for many of the limitations inherent in traditional statistical methods. Bayesian statistical analysis was also used due to the limitations presented by the data in this study. The SAD with EDT group had a smaller left caudate nucleus compared with the SAD without EDT group and smaller left and right anterior cingulate cortex and left thalamus compared with controls. The SAD with EDT group had higher inositol (Ins) and lower N-Acetylaspartate (NAA) concentrationsin the amygdala compared with controls, and higher concentrations of Glutamine (Gln) andGlutamate (Glu) compared with controls. In contrast, the SAD without EDT group only had higher concentrations of Glu and Gln relative to controls. Further the SAD with EDT group had neurocognitive difficulties compared with controls spanning domains such as verbal immediate and delayed memory recall, executive functioning and fine motor functioning. The SAD without EDT group only demonstrated difficulties of immediate and delayed verbal memory compared with controls. Heterozygous (TG) carriers of the TPH2 gene had highertotal social anxiety scores and higher scores on the social fear and avoidance subscales than homozygous (GG) carriers. In addition individuals who carried at least one C allele of the RGS2 gene, compared with homozygous GG carriers, had higher concentrations of NAA and Ins; both metabolites are indicative of neuronal integrity. A number of correlations were observed between neurocognitive test findings and specific structural grey matter volumetricabnormalities, mainly in the SAD with EDT group. In the SAD with EDT group fine motor dexterity in the dominant hand was negatively correlated with the left caudate nucleus. In the SAD with EDT group executive functioning represented by non-perseverative errors negatively correlated with the right amygdala and conceptual level responses correlated positively with the right amygdala. No significant correlations were found in fine motor performance in the non-dominant hand and grey matter volumes. In the SAD without EDT group immediate memory recall was positively correlated with the left ACC and delayed verbal memory was positively correlated with the right ACC. In conclusion this study provides novel insights into the mechanisms of SAD within the context of EDT compared with SAD without EDT and healthy controls. A number of limbic circuitry volume differences, neurocognitive performance difficulties and more profuse dysregulated neurometabolism of the left amygdala characterizes individuals with SAD and EDT compared to individuals with SAD without EDT, demonstrating the additional influence of EDT on the pathophysiology of SAD.

[发布机构] Stellenbosch University