Depressive disorders are common and debilitating conditions; however, current methods of diagnosis and treatment are suboptimal, largely due to a lack of understanding of the biological basis of these disorders. Neuroimaging has provided substantial insights in this area, but one particularly understudied area is the relationship between unipolar and bipolar depression. These disorders have similar symptom profiles but require different treatment strategies, making their diagnosis and management challenging for clinicians. The overarching aim of this thesis is to understand differences and similarities in the structure and neurochemistry of neurobiological systems underlying unipolar and bipolar depression. This question is addressed in three ways: Firstly meta-analyses structural neuroimaging studies looking at alterations in grey and white matter were performed to identify patterns of changes that were common or specific to either disorder. Secondly, an original investigation was carried out to identify patterns of neurochemical alteration that differ between unmedicated patients with unipolar and bipolar depression. Lastly, the appropriateness of a dimensional approach to bipolarity in depression was evaluated by looking for structural neural correlates of bipolar symptoms within patients with unip9olar and bipolar depression. The results of these studies show that although many neurobiological alterations are common to unipolar and bipolar depression, there are changes in grey matter volume that are specific to unipolar depression, and changes in white matter volume that are specific to bipolar depression. However, alterations in grey matter volume do not correlate with bipolarity when treated as a dimensional characteristic. These results contribute to our understanding of structural and neurochemical alterations in depressive disorders, and provide targets for future research into improved diagnosis of these conditions.

The majority of schizophrenia patients exhibit significant, diffuse cognitive impairment. Understanding the course and nature of this impairment is essential to elucidating etiology and treatment. Previous studies have been unable to trace the course of cognition from infancy to adulthood and assess true developmental change. Cognitive deficits in individuals with subclinical psychotic experiences may provide important clues about clinical psychotic disorders. Yet, developmental change and the effects of age, sociodemographic and familial factors have not been examined. Moreover, while there is evidence for connection abnormalities in the brains of schizophrenia patients, little is known about the structure of cognitive functioning across the psychosis spectrum i.e. in subclinical psychotic experiences and clinical psychotic disorders. The first study examined the association between subclinical psychotic experiences and cognitive functioning in a general population sample. Adults with psychotic experiences showed significant verbal and memory, but not processing speed deficits. Only older adults with psychotic experiences showed medium to large verbal and memory deficits when adjusting for sociodemographic factors, psychiatric morbidity and cannabis use. First-degree relatives showed a significant verbal, but not memory impairment. The second and third studies used data from a longitudinal cohort to examine 1) the course of cognitive functioning from infancy to adulthood and 2) cognitive network structure in childhood and adulthood. Individuals with depression, psychotic experiences, affective psychotic disorder and non-affective psychotic disorder were compared to controls. Affective psychotic disorder, psychotic experiences and depression groups showed a degree of cognitive impairment across infancy and adulthood, but only those with non-affective psychosis showed large, progressive deficits across multiple domains. Individuals with non-affective, affective and subclinical psychosis also showed qualitative and quantitative abnormalities in cognitive network structure, with the two clinical groups showing larger, widespread anomalies. Controls showed increasing reliance on working memory between childhood and adulthood, while all other groups remained reliant on low-level cognitive processes. Altogether, these findings suggest that the course of cognitive impairment differs across the psychosis spectrum. Despite distinct profiles of impairment, abnormalities in cognitive network structure were seen across the spectrum, highlighting the importance of looking beyond cognitive deficits to how performance is achieved.

Background and Aims: Caring for someone with dementia can be a source of significant stress, with many experiencing depression and anxiety (Pinquart & Sorensen, 2006). Despite showing promise for informal care-givers of people with dementia Cognitive Behavioural Therapy has received little systematic appraisal in isolation from other intervention models. The current review aimed to provide a systematic and quantitative appraisal of the evidence for CBT interventions with a primary focus upon anxiety outcomes, and secondary focus upon depression. Methods: A systematic search of relevant databases was conducted. Study characteristics and effect size data were extracted. A series of random-effects meta-analyses were conducted. Subgroup analysis and meta-regression were performed to evaluate impact of intervention and care-giver characteristics. Publication bias and sensitivity analyses were examined. Results: Fourteen studies comparing CBT to active or passive comparators for anxiety in informal dementia care-givers were identified. For both anxiety and depression significant “small” effect sizes, Hedge’s g=-0.15 and g=-0.21 respectively, were identified in favour of CBT over comparators combined. Effect sizes were generally reduced when studies deemed to be outliers were excluded. No significant treatment effects were found for anxiety or depression when CBT was compared to psychoeducation in isolation. Subgroup analysis for anxiety outcomes suggested that care-giver gender and relationship to care-receiver did not impact upon CBT intervention effectiveness. Interventions did not differ significantly according to delivery format; however, the magnitude of the effect was increased when studies without a relaxation component were excluded. Subgroup analyses were limited by lack of clear reporting within studies and therefore should be treated as preliminary. Conclusions: There is a primary need to better understand whether dementia care-givers want help for anxiety and if they do then there is a need to establish what factors are driving their anxiety, specifically whether these factors lend themselves to the CBT model. If the answer is yes to both these questions then further methodologically rigorous clinical trials exploring the effectiveness of CBT for anxiety in informal dementia care-givers are warranted. In particular there is a need for trials employing CBT interventions specifically designed to target anxiety, with theoretically linked and well-defined primary outcomes, with attention given to baseline anxiety symptomatology.

Background: Movement in Children‘s hospices in the UK has seen the introduction of various ‘cold’ facilities, which allow families to spend time with their baby after they have died. To date, only two studies have explored the use of these facilities. This thesis aims to understand the experiences of parental grief and how this is expressed through a systematic review and explore the experiences of parents who have used ‘cold’ facilities within a paediatric hospice after the death of their infant. Methods: A qualitative thematic synthesis of the literature was conducted using electronic databases and relevant reference sections of papers to evaluate parental grieving patterns. Alongside this, a qualitative study was conducted using semi-structured interviews with seven parents who had used ‘cold’ facilities at a regional children‘s hospice. Data were transcribed and analysed using thematic analysis. Results: The systematic review found 7 studies which met the inclusion criteria. Quality was appraised, and data was analysed using thematic synthesis. Three themes identified: Affective vs. non-affective expression of grief; a reciprocal negotiation of grief; the pointlessness and importance of words. The thematic analysis of the qualitative study identified eight key themes. Conclusions: The research highlighted the unique experiences of parental grief and the experience of using ‘cold’ facilities. It highlighted the need for education, discussion and openness about death and grief within the wider community. Limitations and directions for future research are considered.

Objective: The thesis portfolio aimed to explore the effect of mindfulness on cognition in an acquired neurodisability population. Methods: A systematic review of the literature was conducted to determine the effect of mindfulness-based interventions on cognition for those with acquired brain injury, traumatic brain injury and multiple sclerosis. Further to this, a parallel randomised control design was used to explore the effect of a 10-minute mindfulness exercise on stimulus over-selectivity and selective attention to threat in a sample of 42 individuals with acquired brain injury, compared to an unfocused control condition. Computerised measures of stimulus over-selectivity and selective attention to threat (an emotional Stroop) were administered pre- and post-intervention. Results: Six studies met criteria for the systematic review and included participants who had experienced traumatic brain injury, stroke or unspecified acquired brain injury. Results across studies were mixed with regards to effects on different cognitive domains, with the most promising results for selective and sustained attention. However, all papers were at moderate-high risk of bias. In the empirical paper, mindfulness was not found to improve stimulus over-selectivity or selective attention to threat in this sample of individuals with acquired brain injury. Conclusions: More good-quality research is needed to investigate the effect of mindfulness on cognition following acquired neurodisability. It would be particularly beneficial to identify mechanisms of change to establish which aspects of mindfulness work on which cognitive processes for whom. Additionally, more research is needed to further understand specific attentional biases in this population, such as stimulus over-selectivity and selective attention to threat.

A significant proportion of the population experience adverse events in childhood. For some, the literature demonstrates that these adverse events contribute towards the later development of severe and enduring mental health problems such as psychosis and borderline personality disorder (BPD). These diagnoses are associated with poor outcomes including reduced Quality of Life (QoL). Whilst we are making progress in our understanding though the advances in theoretical models, reviews of current literature, and new research, the multi-faceted mechanisms and influence of different variables require further exploration. The first aim of this research was to ascertain if coping mechanisms were related to QoL in individuals diagnosed with schizophrenia. The second aim was to explore whether BPD, psychosis and control populations differ in their trauma history, symptomatology (psychotic and BPD), attachment style and difficulties in emotion regulation; to assess if trauma type and severity relate to symptomatology, attachment and emotion regulation; and finally, to assess if attachment or emotion regulation influence the relationship between trauma and symptomatology. A systematic review of the literature generated 2795 studies. Nine studies met inclusion criteria for data synthesis. A quantitative questionnaire-based empirical study involved 120 adult participants (28 BPD, 29 psychoses and 63 controls). Synthesis demonstrated evidence for a small to medium positive correlation between problem-focused coping and QoL. Between group differences were found for all variables and trauma correlated with all variables. Only emotion regulation mediated the influence of trauma on both BPD and psychotic symptomatology. More research is required for conclusions to be determined about how coping relates to QoL in schizophrenia. The empirical results evidence the necessity of further research and development towards multifactorial models which incorporate the complex interacting influences of trauma, attachment and emotion regulation. Models should be integrative and be applied beyond diagnostic boundaries to best promote recovery.

Aims: Two meta-analyses of under-researched areas within the eating disorder field are presented. The first explored whether people with binge eating disorder (BED) exhibit greater deficits in attentional bias (AB) when attending to food stimuli compared to controls. The second explored whether eating disorder-focused family therapy (ED-FT) for young people with anorexia nervosa and bulimia nervosa is effective when compared to other forms of family therapy (FT). Methods: The first meta-analysis produced 13 studies, which were analysed using a Hedges’s g random effects model. The second meta-analysis identified 15 papers for ED-FT and seven for multifamily therapy (MFT). The analysis of ED-FT compared with other forms of FT was conducted using an Odds ratio random effects model; the analysis of changes in weight for MFT was conducted using a Hedges’s g random effects model. Results: The first meta-analysis yielded a pooled Hedges’s g effect size of -.12 (95% CI: -.36, .12), indicating no statistically significant difference between groups (p = .339). The second meta-analysis found a non-significant pooled Odds ratio effect of .64 (95% CI: .36, 1.12) indicating that ED-FT was not as efficacious when compared with other forms of FT. The effect of MFT on changes in weight yielded a pooled medium Hedges’s g effect of .64 (95% CI: .23, 1.05), indicating that MFT may be a promising alternative treatment to ED-FT. Conclusions: The results of the first meta-analysis do not support the theory that ABs are greater in BED. Future research is needed to produce higher quality research which tests other components of ABs in BED. The second meta-analysis highlights the need for research into the efficacy of other forms of FT or modifications to ED FT. Patients receiving MFT appear to gain weight; however, the lack of comparison groups limits the ability to draw firm conclusions.

The primary aims of this thesis were to examine the prevalence of depression and burden among informal caregivers of people with dementia (PwD) and the effectiveness of mindfulness and acceptance based interventions (MABIs) at reducing these difficulties. The thesis consists of a meta-analysis on the prevalence of depression and burden among informal caregivers of PwD, a bridging chapter detailing the rationale behind the second meta-analysis set within the context of the first, a meta-analysis on the effectiveness of MABIs on depressive symptoms and burden among informal caregivers of PwD, an additional methodology chapter on the random-effects model, and an overall discussion and critical appraisal. The first meta-analysis identified 43 studies, examining a total of 16 911 participants. The adjusted pooled prevalence of depression was 31.2% (95% CI 27.7% to 35.0%) and burden was 49.3% (95% CI 37.2% to 61.5%). The second meta-analysis included 12 studies, providing data on 321 caregivers. MABIs proved largely and moderately effective at reducing depressive symptoms and burden among informal caregivers of PwD, respectively. There was, however, significant heterogeneity amongst almost all effect estimates reported. The first meta-analysis found the prevalence of depression differed according to the instrument used and the continent in which the study was conducted. The second meta-analysis was unable to explain the observed heterogeneity of effect sizes. Many of the included studies in the first and second meta-analysis were rated as having a ‘high risk’ of bias. The impact of heterogeneity and study quality is critically explored. The thesis indicates that there is a great need within this population for interventions that are effective at reducing burden and depressive symptoms, with MABIs appearing acceptable and beneficial. However, further higher quality research is needed to improve the robustness of the evidence bases and enable a meta-analysis to thoroughly examine and quantify moderator variables.

Background: It is possible to identify young people who are at an increased risk of developing psychosis, often referred to as having an At Risk Mental State (ARMS). Research shows that psychological interventions offered to these individuals, can reduce the risk that they will go on to develop psychosis, whilst also reducing their distress. However, the availability of such interventions within the NHS is limited, and those services that do support these individuals are characterised by high levels of disengagement. Aims: The current portfolio aimed to explore how young people with ARMS experience mental health services, to identify ways of increasing the acceptability of these services to them. It also aimed to develop and trial a brief, benign psychological intervention that could be offered to young people with ARMS by non-registered practitioners, which could ultimately be used to increase the availability of psychological interventions for this population. Methods: A systematic review was conducted. A thematic synthesis analysed existing qualitative articles to consider young peoples’ experience of ARMS, the services offered to them and of being labelled in this way. A feasibility study was also conducted, to assess the viability of offering the intervention, developed for the current portfolio, within the NHS and in a future Randomised Controlled Trial (RCT). Results: The current findings suggest that young people with ARMS experience high-levels of self-stigma, which delay their help seeking. They highlight the importance of services offering young people the space to talk about and understand their psychotic-like experiences, within a safe and normalising therapeutic relationship. The intervention developed was acceptable to young people and mental health practitioners, with feasible rates of attrition. Recruitment rates were poorer than intended, recommendations for addressing this in future research are made. Conclusion: Implications for services are highlighted, as are ways of improving the intervention developed. A future RCT evaluating the intervention is recommended.

A significant minority of children and adolescents experience symptoms of acute stress following exposure to a traumatic event, some of whom will meet criteria for Acute Stress Disorder (ASD) within the first month post-trauma. Current estimates of ASD prevalence vary greatly. In order to reach a more reliable estimate, a meta-analysis of ASD prevalence was conducted which comprised of 17 studies. The impact of moderators, including trauma type and method by which ASD was assessed, provided significant. Results are discussed within the context of the relatively small number of studies that met inclusion criteria, high levels of heterogeneity, and risk of bias. Many children and adolescents who have ASD will experience a period of natural recovery in the months that follow. However, previous research has identified that for a minority of youth, ASD symptoms will remain persistent beyond the first month; meeting criteria for Post-Traumatic Stress Disorder (PTSD). The trajectory to either recovery or PTSD in youth who met criteria for ASD was explored, based upon their initial symptom profile. Of youth who met full ASD criteria, sleeping difficulties in the acute phase were associated with later PTSD. However, when using subthreshold ASD criteria, two additional symptoms showed an association. These findings are discussed with relation to the screening and assessment of children and adolescents, as well as early selective interventions, following exposure to a traumatic event.