Investigating the biological basis of emotion: Brain structure, function and genetics

Stjepanovic, Daniel (2013). Investigating the biological basis of emotion: Brain structure, function and genetics PhD Thesis, Queensland Brain Institute, The University of Queensland.

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Author Stjepanovic, Daniel
Thesis Title Investigating the biological basis of emotion: Brain structure, function and genetics
School, Centre or Institute Queensland Brain Institute
Institution The University of Queensland
Publication date 2013
Thesis type PhD Thesis
Supervisor Mark Bellgrove
Jason Mattingley
Ottmar Lipp
Total pages 207
Total colour pages 13
Total black and white pages 197
Language eng
Subjects 170101 Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
110903 Central Nervous System
060410 Neurogenetics
Formatted abstract
It would be impossible to imagine a world devoid of emotion. Emotions enrich our lives with experiences of joy, such as the smile of a loved one, and warn us of possible danger, such as the burning of anger in another’s eyes. The last few decades have seen a blossoming in research attempting to understand the neural and psychological basis of emotion. The aim of this thesis was to elucidate the influence of genetic variation on the biological underpinnings of emotion. To achieve this, the tools available to modern neuroscience—namely molecular genetics, imaging of brain structure and function, and cognition—were utilised.

It has long been known that the amygdala, a complex grey matter structure in the medial temporal lobes, is critical for the experience and recognition of emotional stimuli in healthy individuals, with damage to the amygdala often resulting in difficulties experiencing and perceiving emotion. One question that remains open is the extent to which the amygdala automatically processes emotional stimuli. Building on behavioural work showing preferential processing of emotional stimuli, theoretical accounts have proposed that the amygdala is able to rely on specific subcortical pathways to process emotional stimuli without the usual constraints of the attention system. That is, whereas the processing of unvalenced stimuli depends on the availability of attention resources, it has been argued that the amygdala processes valenced stimuli free of this constraint.

When this assertion was tested directly in the past using functional neuroimaging, the results provided support for this view that the amygdala is independent of attention. This work, however, was criticised for using a simple manipulation of spatial attention, which may have been insufficiently demanding to fully exhaust attentional capacity and influence amygdala processing. Subsequent work that has attempted to resolve this issue with more stringent manipulations of attentional load has found amygdala responding to depend on attentional resources. Subsequent studies, however, have suffered from methodological shortcomings such as attentional capacity manipulations that varied spatial attention in tandem with load, making it difficult to conclude which of those two factors is important in determining amygdala responding. Despite a large number of studies on this topic, it is still not clear if amygdala responding can be influenced by manipulations of attentional capacity. The study detailed in Chapter 2 sought to address this question using a novel behavioural paradigm. This study proceeded by first validating this paradigm by demonstrating the influence of increasing attentional load on the processing of task-irrelevant stimuli. Following this, the paradigm was then applied to functional neuroimaging, demonstrating that when extraneous factors such as spatial attention were controlled, there was an effect of attentional load on amygdala responding with a significant reduction in the response of the amygdala as load increased.

Importantly, in addressing the thesis aim of elucidating the genetic basis of emotion processing, the study in Chapter 2 also sought to understand the influence of variation in a functional insertion/deletion polymorphism within the promoter region of the serotonin transporter gene (the so-called 5-HTTLPR) on amygdala processing of emotion under load. This question was motivated by the extensive and consistent literature demonstrating an influence of 5-HTTLPR variation on amygdala function. Results reported herein indicate that increasing copies of the s allele in this polymorphism were associated with significant reductions in the effectiveness of the load effect (i.e., the difference between low and high load). This finding extends the current view of a hyperactive amygdala in individuals carrying an s allele at this polymorphism, and suggests that the influence of 5-HTTLPR on amygdala responding is more pervasive than has been previously shown, continuing to influence the amygdala during the performance of a cognitive task.

Developing in parallel to the extensive amygdala functional neuroimaging work, research has shown the importance in studying individual variation in amygdala morphology. Changes in amygdala volume have been associated with increased risk for a number of psychiatric disorders, with recent work demonstrating that amygdala volume is able to predict increased risk and symptom severity in a number of disorders. Further to this, variation in amygdala volume has also been associated with changes in personality and cognitive functioning in healthy individuals. It is surprising then that despite the high heritability of amygdala volume in health there is little work that has sought to establish the molecular genetic influences on amygdala volume. A small number of reports have demonstrated an influence of 5-HTTLPR variation, as well as variation in other neurotransmitter genes, on amygdala volume. The aim of Chapter 3 was, therefore, to further this understanding by testing the influence of 5-HTTLPR and a number of other prominent polymorphisms within candidate genes in their association with amygdala volume. Results from this work failed to replicate existing associations of 5-HTTLPR and amygdala volume, despite the larger sample size in this study than previous work. Significant associations were, however, found between a variant in the serotonin transporter and a variant in the human stathmin gene and amygdala volume. Furthermore, these findings were partially replicated using automated amygdala tracing methods, providing partial validation for this increasingly common analysis tool.

Lastly, the work described in Chapter 4 sought to extend the burgeoning work examining the influence of genetic variation on cognitive emotion processing. Work to date has associated variation in the 5-HTTLPR polymorphism with attention to emotional stimuli as measured using the dot-probe paradigm. This work has consistently found that the s allele at this polymorphism is associated with biased attention to negatively valenced stimuli such as anxiolytic words and fear- relevant faces and animal stimuli. Consistent with the aims of the thesis, and to expand upon this literature, Chapter 4 tested the influence of 5-HTTLPR and the variants associated with amygdala volume in Chapter 3 in their association with measures of biased attention to emotional stimuli. The results indicated associations between allelic variation in the serotonin transporter and stathmin genes and biased attention to emotion. These findings represent the first associations of these markers with biased attention to emotion in healthy individuals.

Together, these studies extend our understanding of the influence of genetic variation upon emotion processing at the levels of cognition, functional neuroimaging and structural morphology. Results demonstrate an expanded influence of 5-HTTLPR in biasing amygdala responding under differential levels of attentional load. Variants in the serotonin transporter and stathmin genes are shown to influence amygdala volume, and to also influence responding to emotional stimuli in a cognitive dot-probe paradigm.
Keyword Emotion
Face processing

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Created: Mon, 18 Nov 2013, 10:50:37 EST by Mr Daniel Stjepanovic on behalf of Scholarly Communication and Digitisation Service