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Background: Depressive symptoms have been found to accompany and develop following psychosis. Depression following psychosis has been associated with negative self-cognitions. Acceptance and Commitment Therapy (ACT) posits that avoidance of distressing internal experiences can lead to psychological inflexibility and the maintenance of distress. Aims: The study conducted a preliminary investigation into the effectiveness and acceptability of a brief ACT-based defusion intervention aimed at increasing psychological flexibility and reducing distress associated with negative self cognitions. This research also explored the extent to which levels of depression experienced by individuals with psychosis are associated with internal shame, psychological flexibility and emotion regulation difficulties. Method: A randomised controlled trial design was used in phase 1 of the study. Individuals were randomised to either a brief defusion intervention (N=8) or a control condition (N=8).An exploratory correlational design was used in phase 2 of the research. Sixteen participants completed questionnaires. Results: Levels of depression in individuals with psychosis were associated with internal shame, psychological inflexibility and difficulties with emotion regulation. A trend approaching significance suggested that the change in levels of distress related to a negative self cognition in the defusion group was greater than the corresponding change for the control group. Conclusions: Individuals randomised to a defusion exercise found the intervention acceptable and it appears to offer promise for reducing distress associated with negative self cognitions.

Mindfulness-Based Cognitive Therapy (MBCT) is hypothesised to reduce the risk of depressive relapse by teaching participants to adopt a mindful rather than a ruminative mode of information processing. This study aimed to examine the effects of state and trait ruminative and mindful modes of processing on Social Problem Solving (SPS) and affect in participants vulnerable to depressive relapse. Dysphoric participants with and without a history of depression were assessed for SPS and affect before and after manipulations designed to induce mindful (experiential) or ruminative (analytic) processing modes. Results indicated that increased trait rumination was associated with increased SPS ability following mindful processing only. Increased SPS ability was found following mindful processing for recovered depressed participants with less than three episodes of depression, but not for those with more than two. Trait mindfulness was found to influence SPS ability dependent upon processing condition and depression history. Processing conditions had equivalent effect on mood. These findings suggest that mindful processing may help reduce the risk of depressive relapse by increasing SPS in those with low mood and high levels of trait rumination. The influence of trait mindfulness and number of depressive episodes on the effectiveness of mindful processing inductions warrants further investigation.

Depression in older people is under recognized and under treated in primary care. This is despite symptoms being similar across the lifespan and many older people with depression regularly seeing their general practitioner (GP). Problems specific to its management set it apart from depression in younger people, and include both disparities in the way older people and GPs perceive depression and a shared view that it is a normal part of aging, as well as barriers to the way older people talk about it and the help GPs provide. This evidence indicates a lack of understanding about the ways both groups perceive depression, and how their different situations, positions and needs may influence what they say and do and ways they respond to each other in consultations. The research aim is therefore to explore how older people’s and GPs’ different positions and situations influence the ways they perceive depression. Particular focus is on influences reported by older people over ways they talk about depression and influences reported by GPs over ways they respond. In doing this the study seeks practical solutions to help GPs identify depression in older people and provide them with appropriate help. The methodology and methods of this study are informed by a recent version of grounded theory, Situational Analysis (Clarke, 2005), which is philosophically orientated between symbolic interactionism and social constructionism. Clarke (2005) builds on the work of Strauss and Corbin (1998), assuming a social constructionist approach to grounded theory to enable exploration of how people’s views are formed and how this influences their actions. Theory can be generated and located within changing and multi-faceted contexts by considering the wider situations of both the researcher and the researched and looking at the data from multiple perspectives such as historical, geographical and biographical. Semi structured interviews were conducted with older people and GPs as the main form of data, with the researcher’s (IG’s) observations of interviews as contextual data. Using this approach a theoretical model has been developed to explain how older people and GPs operate in consultations for depression, proposing how different types of older people and GPs are likely to respond to each other. The stories older people report telling about their depression and the ways GPs report responding show the “porous” and “flexible” (Clarke, 2005, p.111) positions they can take in consultations: the interview data suggests that older people can move between stages of understanding and accepting their depression, and GPs can move between styles of working and employ different combinations of skills in response to older people’s stories. This element of change is key to the findings of this study and indicates the fluidity of their positions, where they change depending on what they perceive to be influences over them at the time. This study highlights the importance of recognizing differences between ways older people and GPs operate in consultations and the different factors that influence ways they respond to each other. It suggests how GPs working in different styles might help older people based on the different ways they tell their stories, and a key message is that GPs who can adapt their skills to those needs are likely to be most successful in managing it. For example some older people may need GPs to help them make sense of their problems before they will accept treatment or therapy for depression and others may need GPs to take the lead on decisions when they are at rock bottom. The theoretical model suggests how GPs can quickly identify depression in older people and the stage of depression they are at by the stories they tell, and how they might adapt their skills in response to provide them with the most appropriate help. This is intended as a step towards understanding the reasons underlying what happens in consultations for depression in later life, and finding solutions for problems existing in its management.

Bibliography: leaves 286-305 / xiii, 305 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Psychology, 1985

Depression and schizophrenia are common psychiatric disorders that can be disabling and chronic. This thesis aimed to further elucidate the underlying neural substrates using functional magnetic resonance imaging (fMRI) based studies. Hypothesized impairments in reinforcement learning in depression and schizophrenia were investigated, as were the neural correlates of abnormalities of social information processing in schizophrenia. Computational models of reinforcement learning are based on the concept of a 'prediction error' (PE, discrepancy between the expected and actual outcome) signal to update predictions of rewards and improve action selection. It has been argued that the firing of dopamine neurons encode a reward PE signal that mediates the learning of associations and the attribution of motivational salience to reward-related stimuli. Using model-based fMRI, the encoding of neural PE signals in patients with depression and schizophrenia were investigated. Consistent with hypotheses, patients exhibited different abnormalities in neural PE signals, with the degree of abnormality correlating with increased anhedonia/psychotic symptoms in depression/schizophrenia. These findings are consistent with the suggestion that a disruption in the encoding of PE signals contributes to anhedonia symptoms in depression by disrupting learning and the acquisition of salience of rewarding events. In schizophrenia, abnormal PE signals may contribute to psychosis by promoting aberrant perceptions and abnormal associations. In a different study, the neural responses to social exclusion in schizophrenia were investigated. Schizophrenia patients failed to modulate activity in the medial prefrontal cortex with the degree of exclusion, unlike controls. This highlights the neural substrates of putatively impaired social information processing in schizophrenia. Overall, these findings are consistent with proposals that psychiatric syndromes reflect different disorders of neural valuation. This perspective may help bridge the gap between the biological and phenomenological levels of understanding of depression and schizophrenia, hopefully contributing in the long term to the development of more effective treatments.

Background: Depression and related phenotypes, such as anxiety and neuroticism are thought to have a common genetic background. The malfunction of the serotonergic system is likely to play an important role in the etiology of these phenotypes, with compelling evidence coming from animal and human studies. However, recent studies indicate that other factors should be investigated, such as environmental stress. Aim: To investigate the role of the serotonergic gene variants (HTR1A-7 and SLC6A4) in depression, anxiety and neuroticism, in interaction with each other and other factors, such as stressful events. Method: Two large independent Caucasian cohorts, haplotype tagging single nucleotide polymorphisms (htSNPs) and existing genome-wide genotype data were used. Phenotypes were assessed by detailed questionnaires about psychiatric phenotypes (depression, anxiety and neuroticism) as well as background information, such as physical health. Environmental stress factors were investigated in one cohort by self-reported life event (recent and childhood) questionnaires. Healthy participants from this cohort took part in a computerised task to measure the effect of a functional polymorphism in the HTR1A gene on threat-related emotional information processing. ResultsMy study confirmed the importance of stressful life events in depression and anxiety modulated via the 5-HT1A and 5-HT1B autoreceptor, but not via the SLC6A4. I found evidence for epistatic interaction between HTR2A and SLC6A4 genes and between different subunits of the HTR3 gene which may contribute towards the depressive phenotype. Finally, certain alleles of SNPs in other serotonergic receptors (5-HT4 and 5-HT6) were also associated with depression, anxiety and neuroticism however, this association was weak. On the other hand, my study did not provide evidence for the interaction between the serotonin transporter 5-HTTLPR polymorphism and stressful life events which is widely reported in the literature. Conclusion: This study provides further support for the serotonergic hypothesis of depression and confirms the role of the environment in the aetiology of depression. The results show evidence of possible epistatic interaction between the SLC6A4 and HTR2A genes. These results highlight the complex interactions between the members of the serotonergic pathway as well as the role of the environment on the individual.

Objectives: In this study, we examine the public’s knowledge about different levels of depression severity in Germany. Methods: Data stem from a national telephone survey in Germany. A total of 1,009 persons participated, response rate was 46.8%. A vignette was presented with signs of mild, moderate or severe depression. Participants were asked what they think the person has, which persons and services are helpful and how effective different treatment options are. Differences between the three vignettes were tested with 95% confidence intervals and χ 2 -tests. Results: 55.3% of the respondents identified depression as the health problem in question. Participants who heard the vignette with moderate symptomatology recognized depression more often. Across groups, a general practitioner was named most frequently concerning helpful persons/services. Effectiveness of psychotherapy received high levels of approval, online therapy and books were less often rated as effective. There were only few significant differences between the three vignettes. Conclusions: This is the first study examining public depression literacy for different severity levels. Small differences between severity levels indicate a lack of knowledge, which may have adverse consequences for adherence to treatment, especially for mild depression.

Inflammation appears to play a major role in the pathogenesis of Major Depression, and understanding the relationship between the immune system and mood disorders is a growing area of research. Patients undergoing cytokine therapy frequently develop depressive-like signs which cease upon termination of treatment. In addition, depressed patients often present with high levels of circulating pro-inflammatory cytokines. There are also significant behavioural correlates between inflammation-associated sickness behaviours and Major Depression, suggesting there is a bidirectional relationship between the immune system and central systems regulating behaviour. Both sickness behaviours in animals and cytokine-induced depression in humans can be reversed with antidepressants targeting the serotonergic (5-HT) system. Against this background, this thesis sought to investigate the role of inflammation in the development of certain specific characteristics of depressive-like states in animal models. Specifically, a single systemic endotoxin challenge (LPS) was used to model acute sickness behaviour and to study the behaviour and molecular effects of this challenge on the 5-HT system. These studies indicated that a single systemic challenge changed the function of the 5-HT system, as well as increasing expression levels of a number of 5-HT-related genes, and markers of inflammation in the CNS. A rodent chronic stress paradigm was employed to investigate whether these changes also occur in animals displaying depressive-like signs. Chronically stressed mice were shown to display significant features of rodent depression; decreased sucrose preference and increased forced swim immobility. These changes were also accompanied by increased expression of 5-HT-related genes and inflammatory markers within the CNS. Importantly, many of the molecular changes observed in LPS-induced sickness behaviour were conserved in the model of stress-induced Major Depression. In particular, increased TNF expression within the CNS was highlighted as a feature in both models. Novel anti-inflammatory agents were used to study the role of TNF in the development of sickness behaviours. Anti-TNF therapy, specifically the fusion protein etanercept, ameliorated sickness behaviour induced by LPS. Together, these data demonstrate that inflammation is capable of significantly changing the 5-HT system, and that stress per se is capable of inducing an inflammatory state within the CNS, which support the thesis that sickness and Major Depression are closely related at a molecular level.