Intentional forgetting in depressed states

The aim of this thesis was to extend previous research on intentional forgetting in depressed states. The first experiment used the think/no-think paradigm, and found that although dysphoric individuals were significantly worse at suppressing emotional (positive and negative) words than non-dysphoric individuals, both groups were unsuccessful at direct thought suppression. However, there was no effect of rumination on dysphoric individuals' ability to intentionally forget material. Furthermore, there was also no group differences in attentional measures of Stroop and IDEO. The second experiment involved modifying the TNT task, by including the use of substitute words in the suppression phase, in order to determine whether recalling substitute words during suppression would increase the level of forgetting. The findings from the study revealed that both dysphoric and non-dysphoric individuals were successful at intentionally forgetting neutral words using a thought substitution strategy. However, both groups were impaired at suppressing words in the direct thought substitution condition. The third experiment investigated the influence of thought substitution on intentional forgetting of emotional words in dysphoria. The study replicated experiment two, but used emotional (i.e. positive and depression-relevant) words instead of neutral words. The study found that dysphoric individuals were still impaired in their ability to suppress emotional material. Furthermore, dysphoric individuals were recalling significantly more depression­ relevant respond and previously-suppressed words. The fourth experiment examined the role of executive control in intentional forgetting. In the study, dysphoric and non­ dysphoric participants were categorised as having good or poor executive control based on their scores on the operation span with words task (OSPAN). The study found that non-dysphoric individuals with good control demonstrated successful suppression. However, dysphoric individuals with good control were unsuccessful at suppression. The fifth experiment investigated whether experimentally induced changes in mood state would alter an individual's ability to intentionally forget emotional material. Non-dysphoric healthy participants were given a positive or negative autobiographical memory and music mood induction. They completed two modified think/no-think tasks, one prior to the mood induction and one after the mood induction. The study found that transient negative mood state impaired intentional forgetting of depression-relevant material. Summary: Taken together, the findings suggest that individuals in a depressed mood are impaired in their ability to intentionally forget emotional material, even with the use of a thought substitution strategy. Furthermore, the findings implicate poor executive control and negative mood state in impaired intentional forgetting. An important theme emerging from the findings was the role of an inhibitory mechanism in intentional forgetting. The findings reported in this thesis suggest that thought substitution involves engaging an inhibitory control mechanism that contributes to successful intentional forgetting. The findings have clear implications on depressed individuals everyday functioning, and suggest that even with the presence of effective distraction, dysphoric indivduals are imapired in their ability to suppress emotional material. Furthermore, it is suggested that impaired intentional forgetting of emotional material may contribute to the maintenance of depressed mood, and could potentially worsen ongoing depression.

A novel multilocus sequence typing scheme for the opportunistic pathogen Propionibacterium acnes and characterisation of type 1 cell surface-associated antigens

We have developed a novel multilocus sequence typing (MLST) scheme and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and random amplification of polymorphic DNA typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (STs). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB1), representing 64?% of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants, which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore support an association between acne and P. acnes strains from the type IA cluster and highlight the role of a widely disseminated clonal genotype in this condition. Characterization of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.