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(2022) Shvetcov, ArturThesisRodents learn to fear a stimulus (e.g., a light) that signals the imminent arrival of an innate source of danger (typically an aversive foot shock). They also learn to fear a stimulus (e.g., a noise) that signals a learned source of danger (e.g., the already conditioned fear-eliciting light). Following Pavlov (1927), the former type of fear is termed first-order conditioned fear, because the stimulus is paired with an aversive unconditioned stimulus (US). The latter is termed second-order conditioned fear, because the stimulus is paired, not with a US, but with an already conditioned stimulus. There are both commonalities and differences in the neural substrates underlying these two forms of fear. Both require neuronal activity in the basolateral amygdala complex (BLA), including activation of NMDA receptors, for their encoding, and both require CaMK signalling, gene expression and DNA methylation for their consolidation. However, de novo protein synthesis is required for consolidation of first-order fear but not for consolidation of second-order fear.
(2022) Joubert, AmyThesisTargeting and reducing the processes underlying the development and maintenance of depression and anxiety disorders, such as repetitive negative thinking (RNT), is a promising approach suggested to improve the efficacy and durability of psychological treatment. Delivering treatment online overcomes many of the barriers to accessing mental health treatment and improves treatment coverage. This thesis therefore involved the development and evaluation of a novel internet-delivered treatment targeting RNT. Study 1 involved an online qualitative survey to gain insight into how individuals define, experience, and understand rumination and worry. The findings from Study 1 were used to inform the development of the online intervention evaluated in subsequent chapters. Study 2 outlines the pilot evaluation of the online intervention. The results of Study 2 demonstrated the preliminary efficacy and acceptability of the intervention in adults, with significant reductions in participants self-reported levels of RNT, rumination, and worry, as well as symptoms of depression and generalised anxiety. Treatment effects were maintained at 1-month follow-up. Study 3 aimed to extend these preliminary findings using a randomised controlled trial design and compared the intervention when it was delivered with and without clinician guidance to a treatment-as-usual (TAU) control group. Participants in both the clinician guided and self-help groups had significantly lower levels of RNT, rumination, and worry, as well as symptoms of depression and anxiety compared to TAU at both post-treatment and 3-month follow-up. Treatment effects were significantly larger in the clinician guided group compared to self-help. This thesis provided the first evidence that targeting rumination and worry, both types of RNT, using an online intervention is efficacious, feasible, and acceptable in adults. This thesis also provided the first direct comparison of treatment outcomes and adherence between guided and self-help intervention formats and, in doing so, is the first to demonstrate the superiority of the clinician guided format. These findings add to the growing body of literature suggesting that internet-delivered interventions can successfully simultaneously target rumination and worry and that doing so is associated with significant improvements in depression and anxiety symptoms.