The negative symptoms of psychosis and depressive symptomatology share several features e.g. low motivation, apathy and reduced activity. Understanding the links between these two sets of symptoms will inform the development of future interventions targeting these difficulties in people with psychosis. The aim of this systematic review and meta-analysis is to quantify the relationship between these two clusters of symptoms, as measured in studies to date. Further analyses investigate potential moderating variables. PsycInfo, Embase and Medline were systematically searched to identify eligible studies. Inclusion criteria measured both depression and negative symptoms using validated measures in a sample with non-affective psychosis diagnoses. 2020 records were initially screened and 56 were included in the meta-analysis and review. Both meta-analyses and meta-regressions were conducted to explore the main effect and potential moderating variables. The findings showed a significant but small relationship between negative and depressive symptoms (Effect Size = 0.19). This did not vary greatly with the measures used and was not moderated by demographic variables or quality ratings. Depression and negative symptom severity showed an inverse reciprocal relationship. Heterogeneity was high across these analyses. The findings show that there is a relationship between depression and negative symptoms in people with psychosis. This is taken as support for the dimensional approach to understanding symptoms in this population.

Aims: Childhood trauma (CT) is increasingly recognised as a potential risk factor for the development of positive symptoms of psychosis. As a result, studies are beginning to investigate potential psychological factors that may mediate this relationship. This review sought to identify, summarise and critically evaluate studies that investigated psychological factors as mediating processes between CT and positive symptoms in people with psychosis. Method: The following computerised databases were searched up to March 2015; ISI Web of Science, PsychInfo and Pubmed. These were supplemented with manual searches. After screening, papers relevant to the review question were examined in more detail and quality assessment ratings were completed. Results: A total of 44 papers were identified comprising 10,161 participants. Two papers examined anomalous experiences, 2 attachment, 2 theory of mind (ToM), 9 neurocognitive functioning, 7 post-traumatic stress disorder (PTSD) and 22 dissociation. Quality varied across studies and some frequent methodological limitations were identified. Conclusion: There is some evidence to support a mediating role of dissociative experiences and attachment anxiety in the relationship between CT and positive symptoms. It is not possible to draw conclusions concerning the other factors under review. Future research should aim to address methodological limitations of existing studies and should consider multiple factors within a single sample.

Background: An association between type 2 diabetes (T2DM) and depression has been reported in epidemiological studies. The mechanisms underlying the T2DM-depression link remain unclear. One possible question is whether the co-occurrence of T2DM and depression is due to common genetic and/or common environmental vulnerabilities. A genetic overlap between T2DM and depression will provide evidence supporting a common biological pathway to both disorders. Method: This thesis applied three methodological approaches: i) structural equation modelling of twin data, ii) polygenic score analysis and iii) linkage disequilibrium score regression using genome-wide association studies (GWAS) data. For the first approach, the primary dataset was the Swedish Twin Registry with replication in the Danish Twin Registry and Colombo Twin and Singleton Study (COTASS-2). For the second and third approach, the population cohorts deCODE and UK Biobank, and the Psychiatric Genomics Consortium Major Depressive Disorder (PGC-MDD-29) dataset were used. Result: In the twin studies, a genetic overlap between T2DM and depression was observed in the Swedish Twin Registry and the finding was replicated in the Danish Twin Registry and COTASS-2. In the GWAS datasets, T2DM-polygenic scores were not a major contribution to depression nor depression-polygenic scores for T2DM in both deCODE and UK Biobank. A small, negative but statistically significant association was observed between feelings of guilt/worthlessness and T2DM-polygenic scores in the PGC-MDD-29 dataset. Conclusion: Twin studies have suggested a genetic overlap between T2DM and depression. There are many reasons to explain the discrepancies in findings between twin studies and GWAS. Clarifying the shared heritability between these two complex traits is an important next step while gene-environment interaction is an area that needs to be explored, given genotypes can affect an individual’s responses to the environment and environment can differentially affect genotypes expression.

Background: Measurement of awareness plays an important role in adjustment following a brain injury and is noted to impact on engagement with and outcome of rehabilitation. Aim: To systematically review all instruments used to assess intellectual awareness of deficits following TBI and evaluate study design, instrument properties and methods adopted and explore associated factors. Results: Thirty-four studies, all rated as fair to good quality, were identified and within these twenty-three different assessment tools were adopted. The most common method of assessment was patient-proxy discrepancy with the AQ, PCRS and FrSBe instruments being most frequently employed. However, variability was noted regarding the type of assessment method dependent on various sample demographics (e.g. age of sample) and injury characteristics (e.g. time post injury). Exploration of the association between non-cognitive factors and awareness was more common than cognitive factors and awareness. Cognitive functioning appeared to be worse when there was increased unawareness. By comparison greater variation was found in non-cognitive associates. Conclusions: The findings reveal that there still lacks a consensus about the preferred instrument to assess intellectual awareness of deficits after TBI specifically. Recommendations for future research to aid comparability across studies and continued tool development ideas are discussed.

Background: Evidence suggests that certain inequalities in care provision may result from differential access to services according to ethnic minority membership. Hearn (2006) identified that the Croydon Memory Service (CMS) showed good penetration into the local Black and Ethnic minority (BME) community. This audit aims to replicate Hearn’s aims and objectives with an updated data set; to investigate whether the range of referrals that the CMS receive continue to accurately reflect the ethnic composition of Croydon’s older adult population. In addition, the distribution pattern of diagnostic outcome across ethnic groups, the waiting time (between the receipt of referral and date of initial assessment) and the severity of cognitive impairment at initial presentation for seven ethnic groups will be considered. Method: Information from 3264 referrals was utilised within the analysis, replicating and expanding upon Hearn’s (2006) methodology. Expected frequency data was calculated, categorised according to the self-report ethnicity labels available, and compared with the observed frequency data for the corresponding local population, using one-way classifications. Descriptive statistics are utilised to test the assumption that four categories of dementia (Alzheimer’s disease, Dementia in Alzheimer’s disease - mixed type, Vascular, Other Dementia Subtypes) - in addition to the outcomes of no diagnosis given and psychiatric-based diagnoses - would be distributed evenly across ethnic groups. The mean waiting times (in days) and mean MMSE scores at assessment were calculated and compared across superordinate ethnic groups by means of one-way ANOVA’s. Results: Statistical analysis did not demonstrate a significant difference between the ethnic composition of the referrals assessed by the CMS and the Croydon data set. Waiting times did not differ across ethnic groupings. The mean MMSE scores obtained at assessment only differed significantly between the ‘White British - Black’ and ‘Black - Asian’ groups. Alzheimer’s was the most prevalent diagnosis observed across all ethnic groups within the sample; the remaining outcomes differ in proportion across groups. Conclusions: These results indicate good penetration into local BME communities, demonstrating good practice and service equality across the different ethnic categories referred to the CMS. The results illustrate achievement of the standards created by the Memory Services National Accreditation Programme (MSNAP) and emphasise that the CMS provides a good prototype of what works in National Health Memory Services. The importance of a specialised service structure and liaison with both the community and primary care is highlighted, in order to increase access to BME communities.

The present PhD project investigated the role of psychophysiological stress-function and adversity exposure in auditory verbal hallucinations and the clinical status of voice-hearers. Psychosis is associated with several alterations in biological stress systems, including the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis, as well as subjective stress levels and -reactivity. Exposure to childhood trauma has been particularly linked to the emergence of auditory verbal hallucinations in psychosis, as well as a dysregulation of stress-psychophysiology. However, it remains unclear whether changes in stress-function and -reactivity are related to auditory hallucinations specifically, or only to psychosis more generally. Further, auditory verbal hallucinations occur in both clinical and non-clinical populations. Voices in healthy and clinical voice-hearers share many characteristics, including phenomenological (such as loudness) and neurophysiological correlates of auditory verbal hallucinations. However, healthy voice-hearers do not experience distress in response to their voices, and their voices contain less negative content. It remains unknown whether psychophysiological stress-function may also discriminate clinical and non-clinical voice-hearers, and whether dysregulated stress-function is associated with the experience of hearing voices, and/or need for care. Evidence suggests there is increased childhood trauma exposure in healthy voice-hearers, at similar rates to clinical voice-hearers. However, adolescence/adulthood adversity remains largely unexplored in healthy voice-hearers, as does exposure to other risk factors including socioeconomic adversity and substance use. A more recent version of the diathesis-stress model, the three hit model, has highlighted the role of adversity after childhood in shaping pathological trajectories, which may partially explain the difference in distress and need for care in clinical and healthy voice-hearers. Lastly, it is not known whether, and to what degree, voice content contributes to psychophysiological dysregulation in clinical voice-hearers. To address these issues, the present project investigated three key research questions: 1. Does adolescent/adulthood adversity exposure differ between healthy voice-hearers and clinical voice-hearers, and is the differential adversity exposure associated with increased stress-sensitivity? 2. Does the content of voices exacerbate stress-reactivity? 3. Does psychophysiological stress-function in clinical voice-hearers differ from those of healthy voice-hearers and healthy controls without voices? Methods: Three individual studies are reported to assess these research questions: 1. A cross-sectional study of clinical and healthy voice-hearers was carried out to assess the role of familial risk and adversity exposure in childhood, and adolescence/adulthood in the context of the three hit model. Further, the association of adversity exposure with perceived stress was examined. 2. A cross-sectional design with a healthy non-voice hearing sample was carried out using simulated auditory hallucinations with negative and neutral content to assess their impact on psychophysiological stress-reactivity during psychosocial stress exposure. The potential buffering effects of mindful appraisals of voices on psychophysiological stress-reactivity were also assessed. 3. A cross-sectional study of clinical and healthy voice-hearers, as well as a healthy control group with no voices, was carried out comparing the three groups on diurnal HPA and ANS activity, HPA response to pharmacologically induced negative feedback, and HPA and ANS responses, as well as subjective reactivity, to a psychophysiological stress paradigm. Results: The cross-sectional study on adversity exposure showed that, unexpectedly, victimisation and discrimination experiences were similar in clinical and healthy voice-hearers in both childhood and adolescence/adulthood. However, the two groups differed on familial psychosis risk, adolescence/adulthood socioeconomic status, and substance use, with the clinical group reporting greater rates of adversity exposure. These variables were further predictive of perceived stress, after controlling for group. The analogue voice study demonstrated that negative voices exacerbated subjective, but not physiological, stress-reactivity, compared to neutral voices and ambient sounds. Having a mindful stance towards the voices during the task was associated with lessened stress-reactivity. Finally, as predicted, clinical voice-hearers showed several indices of aberrant psychophysiological stress-function of the HPA axis, compared to both healthy voice-hearers and controls without voices, although not always in the predicted direction. Contrary to our predictions, there were no differences between groups on parameters of the ANS. However, there was some evidence to suggest stress-function in healthy voice-hearers also diverges from non-voice-hearing controls on some HPA parameters, including reduced cortisol levels during stress exposure, slower speed of cortisol recovery from the stressor, and lower HPA negative feedback capacity. Conclusion: The present thesis found evidence to suggest that specific types of adversity exposure and stress-function are related to the need for care of clinical voice-hearers and may be involved in pathological outcomes of voice-hearing. Differential adversity exposure, and its relationship to stress-sensitivity may therefore partially relate to psychopathological trajectories in voice-hearing. The negative content of voices may further contribute to the maintenance of need for care through exacerbated stress-reactivity. Finally, dysregulated psychophysiological stress-function is present in clinical voice-hearers, and partially discriminates them from healthy voice-hearers. Overall, the present findings identified specific potential psychophysiological markers of risk and resilience in auditory verbal hallucinations and need for care. This thesis provides an initial stepping stone for future research developments to explore precise causal and mechanistic relationships of adversity exposure, psychophysiological stress-function and need for care in voice-hearing.

Background and aims: The aim of this study was to review whether (and which) impulsivity sub-domains are elevated in groups of non-dependent alcohol misusers (e.g., heavy/hazardous drinkers, binge drinkers, etc.), relative to healthy drinking comparison groups. It set out to answer this by reviewing studies comparing groups on impulsivity multi-dimensionally – that is, via more than one index (at least one self-report and at least one behavioural). Comprehensively profiling non-dependent alcohol misusers’ impulsivity may increase understanding of the potential mechanism(s) involved in the initial development to and maintenance of such misuse (and possibly to subsequent dependence). Methods: The search was performed via three scientific databases (Embase, Medline and PsycINFO) and was limited to empirical studies comparing non-clinical groups of drinkers aged 18-25 years and published in English language journals. The titles and abstracts of all non-duplicate returns were screened in order to determine eligibility. A subsequent ancestry search involved screening the (titles and abstracts of papers in the) references sections of all eligible papers. Grey literature was not included. The findings of the included papers were qualitatively reviewed, before each was rated using the National Institutes for Health quality assessment tool for observational cohort and cross-sectional studies. Results: Just eight studies were found to have compared impulsivity multidimensionally in groups of young adult (i.e. 18-25) non-clinical alcohol misusers, relative to comparison groups. Collectively, findings indicate that self-reported rash impulsivity is elevated in the quasi-experimental groups, whilst behavioural inhibitory control and delay discounting are not. Due to insufficient amounts of data, it is unclear whether response-initiation, risk-taking and reflection impulsivity may be elevated in non-clinical alcohol misusers. The quality of the eight studies included in the final review was generally rated ‘fair’, none being rated ‘good’, due to a range of potential sources of confound. Conclusions: Across all impulsivity sub-domains assessed in these studies, only selfreported rash impulsivity appears a reliable risk factor for the maintenance (and possibly, initial development) of non-clinical patterns of alcohol misuse, at least in young adults. However, the potential inclusion of dependent drinkers across the included studies represents a serious limitation, raising questions about findings/conclusions. Overall, more studies are needed that assess impulsivity multidimensionally in groups of alcohol misusers, relative to healthy drinkers; these studies should ensure better control of possible sources of confound.

People suffering with depression often do not respond sufficiently to current treatments. A wealth of research suggests that mood disorders are associated with higher levels of inflammation, yet this literature currently provides an inadequate description of the nature of the depressive disorders studied and involves extensive heterogeneity between patients and study methodologies. This thesis comprises three studies examining a broad spectrum of circulating pro-inflammatory proteins before and after interventions for depression, to test specific hypotheses that raised inflammatory markers predict a poor response to treatment, and to detect inflammatory changes in relation to clinical response. Firstly, a systematic review and meta-analysis of inflammatory markers and treatment-response was undertaken (Study 1). Subsequently, investigations of inpatients with treatment-resistant depression (Study 2) and outpatients undertaking psychological therapy (Study 3) assessed 33 biomarkers alongside treatment and clinical outcome. Interleukin-6 (IL-6), Tumour necrosis factor (TNFα) and c-reactive protein (CRP) represent the most studied biomarkers. In meta-analyses, these were higher in depressed participants than controls and showed decreases with antidepressant treatment. In both subsequent studies, numerous biomarkers were higher in depressed patients than a non-depressed control group; few were lower in depression. IL-6, CRP and TNFα were predictive of treatment outcomes. Both inpatient and outpatient studies indicate increases in inflammatory levels with treatment. Results suggest that overall, inflammation is more closely linked with refractory or somatic depression but that age and other sociodemographic constructs also affect inflammatory activity. These results support previous evidence that inflammatory responses are dysregulated in mood disorders and provide novel candidates for future study. Reports of psychological interventions and those for treatment-resistant populations are scarce. Our findings provide promising indications that, if validated in future research, measures of inflammation may be useful in identifying patients less likely to respond to standard treatments or defining more homogenous subpopulations within affective disorders.

Excessive and debilitating worry is a core feature of generalised anxiety disorder. A number of cognitive constructs have been highlighted as being relevant to the initiation and maintenance of worry, but the extent and quality of the evidence to support these links has never been systematically reviewed. The present review systematically examines the evidence for a causal relationship between the following cognitive constructs and worry: interpretation and attention biases, attentional control, mentation style (verbal vs. imagery), intolerance of uncertainty, positive and negative beliefs about worry, and goal directed worry stop rules. PsycINFO and Web of Science databases were searched and after removal of duplicates and extraction of studies that did not meet inclusion criteria, 13 studies remained. Evidence was found to support a causal relationship between all examined constructs and worry, except positive and negative beliefs about worry. The experimental psychopathology techniques employed to manipulate cognitive constructs are discussed, as are methods of measuring worry and the quality of the studies in the review. Suggestions for future research in this area are made.

Engagement in activity, an aspect of social functioning, is important to good mental health. In adults, perceived mental health stigma has been shown to limit functioning, and is therefore implicated in the development and maintenance of a range of mental health conditions. Recovery-oriented interventions have started to focus on reducing stigma, to promote improved functioning. There is growing interest in early intervention in mental health, to address vulnerability and emerging difficulties, and promote engagement in developmental opportunities, with a view to reducing future morbidity. Stigma-focused interventions could be important components of early support. Despite this, little is known about the impact of self-stigma amongst young people with mental health problems and its association with activity levels and social functioning. This is the first systematic review to investigate this relationship in children and young people. The purpose was to consider the potential for stigma-focused early intervention to promote better functioning in this group. Five electronic data bases were searched up to January 2017; PsychINFO, PubMed, Embase, Medline and Web of Science. A total of 4001 citations were screened and seven quantitative studies were identified that met inclusion criteria. Four studies showed a significant relationship between mental health stigma and aspects of social functioning in young people. However, interpretation of the findings is restricted by the small number and poor methodological quality of identified studies. In particular, the range of conceptualisations of self-stigma and social functioning, and the methods of measurement utilised, limit the potential to compare studies. There is a need for more studies investigating self-stigma experiences with young people with mental health problems, using well-conceptualised, developmentally appropriate measures, of social functioning in particular.