Centre for Youth Mental Health - Theses

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Characterising and Evaluating Use of Moderated Online Social Therapy Interventions as Blended Models of Care for Serious Mental Illness

O'Sullivan, Shaunagh ( 2023-08)

Digital interventions provide a unique opportunity to overcome the current limitations in youth mental health treatment and to extend treatment effects for long-term social and functional recovery in mental health disorders such as first-episode psychosis and borderline personality disorder. However, attrition is high in existing short-term digital interventions and most do not typically extend beyond a three-month period to focus on long-term recovery. Although digital interventions have shown efficacy in improving mental health outcomes, limitations still exist such as high attrition rates and lack of integration with face-to-face interventions and clinical services. Moderated online social therapy (MOST) interventions are innovative, multi-component blended models of care for complex mental disorders, which aim to address the limitations of the first generation of digital interventions described above. MOST interventions aim to increase engagement and improve long-term outcomes by adding an additional intervention component; a moderated private social network. This research program focused on two MOST interventions; (i) Horyzons; and (ii) eOrygen. Horyzons is an 18-month sequential blended intervention aiming to maintain treatment effects and improve social functioning, recovery and prevent relapses in first-episode psychosis (FEP) after two years of specialised care. However, as it is a long-term intervention with multiple intervention components, it is important to understand how young people engage with intervention components over time and how engagement relates to treatment outcomes. Horyzons provides a unique opportunity to examine the relationship between multidimensional patterns of use, treatment outcomes and subsequent use by categorising the use of multiple intervention components, such as therapeutic and social networking components. By gaining a better understanding of system usage and user trajectories, and how they relate to treatment outcomes and subsequent usage, multicomponent blended digital interventions could be further optimized to improve long-term outcomes, a key limitation of both face to face and digital interventions. The eOrygen intervention was developed as an integrated blended transdiagnostic intervention for first-episode psychosis and borderline personality disorder. Transdiagnostic interventions may provide more effective and personalised treatment, targeting common symptoms across multiple disorders. eOrygen aims to provide transdiagnostic care across a range of mental health disorders, and to integrate this within mental health services to increase accessibility and continuity of care. As transdiagnostic integrated blended interventions for first-episode psychosis and borderline personality disorder have not yet been evaluated, a 3-month pilot study of eOrygen first needs to be conducted. As such, the aims of this PhD research program were to: (1) examine the association between user profiles and treatment outcomes on Horyzons, a sequential blended intervention aimed at maintaining treatment effects and improving social functioning for young people following discharge from a specialised FEP service; (2) test the direction of relationships between the core components of the Horyzons intervention, namely the therapeutic and social network components, in order to predict what elements of the intervention drive long-term engagement; and (3) test the feasibility, safety, effectiveness and preliminary effectiveness of eOrygen, an integrated blended transdiagnostic intervention for first-episode psychosis and borderline personality disorder. This thesis contributes to the understanding of moderated online social therapy interventions as blended models of care for mental illness. Continued engagement with both therapy and social components of such interventions might be key in achieving long-term recovery. Maintained use of the social network and low use outcomes were broadly comparable with treatment as usual, emphasising the importance of maintaining engagement for improved treatment outcomes. Although the social network may be a key ingredient to increase sustained engagement, as users engaged with this more consistently, it should be leveraged as a tool to engage young people with therapeutic content to bring about social and clinical benefits. Future research could leverage online social networks to engage young people with therapeutic content to ensure treatment effects are maintained and to create virtuous cycles between all intervention components to maintain engagement. Furthermore, novel integrated blended models of care for serious mental illness have the potential to increase therapeutic intensity, continuity, engagement, and effectiveness. Future research will need to examine the effectiveness of integrated blended models of care, as well as determine how to successfully implement such models of care into clinical services.
Normative modelling in large-scale multi-site neuroimaging data sets to investigate brain abnormalities in depression

Bayer, Johanna ( 2023-09)

The search for diagnostic biomarkers using cortical thickness alterations in depression has been impeded by a combination factors, including small sample sizes underpowered to detect small effect sizes in cortical thickness differences, clinical and pathogenic between-subject heterogeneity, group average comparisons and brain ageing effects. Sample sizes in clinical neuroimaging can be increased by creating data sets by pooling. However, pooling studies across acquisition sites can create site effects, which stem from differences in during image acquisition and pre-processing. Site effects can induce biases into the estimates of cortical thickness measures and can interact with the effects of additional variables on cortical thickness, which can make their removal difficult. The aim of this thesis is to 1) Provide an educational review of retrospective site effect correction methods, their benefits, drawbacks and use cases, including normative modelling 2) Develop and test a normative model based on the covariates age, sex and site that allows to correct for site effects on cortical thickness measures in a pooled, public normative modelling data set 3) apply the best performing normative model to cortical thickness data of a large pooled depression neuroimaging data set, in order to compare z-score deviations of depressed individuals to those of healthy controls and link those deviations to clinical characteristics. Regarding aim 1) I summarise several retrospective site effect correction methods that have been published. The evaluation of the statistical foundation of each method reveals that each method has different used cases, advantages and disadvantages that the user should be aware of when choosing a method. To address aim 2), linear and non-linear versions of a normative model based on Hierarchical Bayesian Regression were developed and tested against alternative common site-effect correction methods. All models were evaluated based on their interference with making predictions from cortical thickness measures in a test set containing 35 cortical measures (34 bilateral regions and one whole brain average). ComBat 1–3, regressing out site and predictions from raw data led to a shrinkage of variance when predicting cortical thickness measures from the test set, which suggests the removal of both site variance and shared co-variation with other variables, such as age and sex. Normative modelling, in contrast, was able to retain a larger spectrum of variation. 3) Finally, the non-linear version of the normative model was applied to a large, pooled neuroimaging data set in that contained the same 35 cortical thickness measures of 5300 healthy individuals (training set: n = 3181, test set: n = 2119) and 3645 individuals with depression. The results show large between subject variability in cortical thickness alterations within depression and a large overlap of alterations with healthy controls. This thesis highlights the large between -subject variability in brain measures in clinical cohorts, that may be partially due to site effects in pooled neuroimaging studies. The findings of this thesis stress the need for methods and models in clinical neuroimaging that allow for individualised predictions and for site effect correction, stepping beyond the average patient. Last, the large overlap in the distribution of cortical thickness measures between individuals with depression and healthy controls suggests that cortical thickness might not be a suitable marker for the diagnosis of depression.
Young people’s experiences of completing a trauma and PTSD screening tool when attending an early psychosis program

Dryden-Mead, Tracey ( 2022-07)

It is well established that many people with psychosis have experienced trauma in childhood. Young people with a first episode psychosis (FEP), who receive a service from an early psychosis program, have been identified as having high levels of trauma exposure in their childhood with up to 82% reporting this history. Research findings suggest that childhood trauma is not only a risk factor for psychosis but that this exposure to traumatic experiences is associated with psychosis in a dose-response fashion with increased reports of trauma increasing the risk or severity of psychosis. As there is now a known correlation between trauma experiences and the development of psychosis it is essential that the mental health services provide appropriate interventions following a thorough assessment of the young person’s needs. Best practice guidelines identify that screening for trauma occurs at introduction to mental health services to provide tailored clinical interventions, however the reality is many services do not routinely conduct these assessments. One of the main reasons cited for this is that clinicians are concerned about the potentially distressing and destabilising effect screening would have on the young person. Despite these concerns it is currently unclear how young people experience screening and/or trauma assessments as their voices have not been sought in research around trauma experiences, screening and assessments in early psychosis programs to date. This research therefore focused on exploring how young people experienced a screening process relating to their experiences of trauma and possible post-traumatic stress disorder (PTSD) symptoms. Participants were all engaged in an early psychosis service and had completed trauma and PTSD screening questionnaires in their first three months in the service. The researcher conducted interviews with ten young people and then analysed this data using an interpretative phenomenological analysis (IPA) approach to synthesise data and relay these findings. Four super-ordinate themes are presented in the format of one published journal manuscript and the exploration of these are further reviewed during the discussion section. Whilst most of the participants found the completion of the screening tools to be confronting, with some reporting levels of mild distress during the completion, they were all able to complete them and none of the young people reported ongoing distress following the completion of them. These findings reinforce the recommendations for young people to be screened for trauma experiences when they are engaged in a mental health service and allow the clinicians to have more confidence in being able to support young people during this process.
Psychological Interventions for Interpersonal Trauma in Young People with symptoms of Posttraumatic Stress, Anxiety and Depression

Peters, Wilma Luther ( 2022-08)

Worldwide exposure to potentially traumatic events is highly prevalent among young people aged 12 to 25 years, with international data indicating that approximately two-thirds of adolescents experience exposure to a traumatic event before age 16. In addition to interpersonal trauma inflicted by a caregiver, such as abuse (sexual, physical, and emotional), neglect, and maltreatment, young people are often exposed to family violence, physically assaulted or intimidated by siblings or peers, and are bullied. Unfortunately, subsequent exposure to a different interpersonal trauma type is not uncommon, with nearly 65% of young people experiencing multiple exposures once exposed to one interpersonal trauma. Exposure to interpersonal trauma during this developmentally sensitive period is associated with pervasive and long-lasting psychological, physical, behavioural, social, and economic costs accounting for between 28% and 45% of the population attributable risk for the early onset of youth psychological disorders. In addition to posttraumatic stress, anxiety, depression, problematic substance use, emotional dysregulation, lack of impulse control, poor interpersonal relationships, dissociation, as well as attention and cognition, dysfunctions are highly prevalent and associated with increased incidents of self-harming behaviours and suicidal thoughts and behaviours. Although evidence-based interventions and guideline recommendations exist for the treatment of PTSD in children/adolescents and adults, none of the recommended interventions has been developmentally adapted for transitional-aged youth aged 15 to 25 years exposed to interpersonal trauma, and it remains unclear what the most effective and safe treatment is for these young people. This thesis sought to address this significant gap in the literature with the ultimate aim of evaluating the evidence for psychological interventions for posttraumatic stress disorder (PTSD) and comorbidities in young people exposed to interpersonal trauma and understanding if trauma-focused cognitive behavioural therapy ([TF-CBT]; Cohen et al., 2017), specifically are potentially suitable for this group of young people. The research reported in this thesis had three main aims. Aim 1: To collect, interpret and synthesise quantitative research about the efficacy of psychological interventions for treating anxiety, depression, and substance use in addition to posttraumatic stress symptoms in young people exposed to interpersonal trauma. Aim 2: To understand if trauma-focused cognitive behavioural therapy (TF-CBT) is feasible, acceptable, and potentially clinically effective for young people impacted by interpersonal trauma and symptoms of posttraumatic stress disorder (PTSD). Aim 3: To understand if TF-CBT is safe and tolerable, with a specific focus on determining whether the exposure component of TF-CBT (known as trauma narration) is associated with an elevation in distress or an increase in self-harming behaviours or suicidal thoughts and behaviours. Three studies were conducted to address these aims. Study 1: To achieve the first aim, Study 1 used a meta-analytical approach to evaluate the efficacy of psychological interventions in reducing PTSD, anxiety, depression, and substance use symptoms in young people exposed to interpersonal trauma. Until now, the largest meta-analysis of young people is the study conducted by Gutermann et al. (2016). Unfortunately, the results of this study were affected by incomplete age-data (i.e., no mean age or age range) and poorly reported trauma data (i.e., reported mixed types, not specific types). I was interested in overcoming these two issues in order to provide specific evidence of treatment effects for young people (aged 12–25 years) and those exposed to a wide range of interpersonal trauma types (i.e., beyond physical and sexual abuse). Therefore, I conducted a new review, selecting only those studies where participants’ mean age fell between 12 and 25 years, with at least 80% of the sample exposed to one or more interpersonal traumas. Large significant effect sizes were observed for psychological interventions versus controls for outcomes of PTSD, and there were small significant effect sizes for anxiety and small trend-level non-significant effect sizes for depression. TF-CBT outperformed other treatments in the sub-group analysis for PTSD. However, results need to be interpreted within the context of the small sample size and heterogeneity. Study 2: To achieve the second aim, Study 2 employed a single-arm pre vs post study design, with two additional assessment points at the start and end of the trauma narration phase of TF-CBT for transitional-aged young people aged 15- 25. The sample included 20 young people (65% female, n = 13) who participated in up to 20 sessions of TF-CBT over 30 weeks. Two female participants dropped out of treatment (one after the first session and the other before the start of trauma narration. The remaining participants attended a mean of 15 sessions of TF-CBT over 25 weeks. TF-CBT was implemented with fidelity, and young people reported that they would recommend the intervention to a friend experiencing a similar issue. Quantitative data supported the relative clinical efficacy of TF-CBT. At the end of treatment, only one of the 16 participants with a baseline PTSD diagnosis met the diagnostic criteria. Significant improvements were also noted in self-reported PTSD, anxiety, and depression outcomes. Study 3: To achieve the third aim, distress, self-harm and suicide from Study 2 were analysed and interrogated to investigate if TF-CBT was safe and tolerable. The young people enrolled in Study 2 completed the Subjective Units of Distress Scale (SUDS) at the start and end of each session and were also asked question 6 of the C-SSRS, which inquired about their suicidal thoughts and behaviours in the week between therapy sessions. In addition, data from the Deliberate Self Harm Inventory (DSHI) and Adult Suicide Ideation Questionnaire (ASIQ) were also analysed. Across the 279 sessions of TF-CBT (M = 15.5 sessions), there were 16 incidents of elevated distress in seven participants, 15 incidents of self-harming behaviour in seven participants, and one of both elevated distress and suicide ideation. Results indicated there might be a relationship between distress and self-harming behaviours. Conclusion: This thesis used quantitative methods to understand the relative efficacy of psychological interventions for PTSD, anxiety, and depression in transitional-aged young people exposed to interpersonal trauma. The results of the meta-analysis and data from the pilot study demonstrated the potential safety and efficacy of TF-CBT for transitional-aged young people. This new knowledge is timely given the expansion in specialised mental health service delivery and the need to better accommodate the needs of transitional-aged young people with a history of trauma exposure.
Characteristics and Predictors of Suicidality in Young People with Depressive Disorders

Moller, Carl Ian ( 2023)

Depression is one of the most prevalent and disabling mental health conditions among young people worldwide. Suicidality and depression are closely intertwined, yet the specific factors that contribute to the nature and severity of suicidality, or changes in suicidality over time, are not perfectly understood. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. In order to reduce the burden of suicidality in young people with depression, we need to improve our understanding of its underlying constructs and contributory elements. This has the potential to contribute to improved prevention and early intervention efforts across multiple stages of suicidality, in addition to informing more targeted clinical treatment approaches. Aims and Objectives The broad aim of this research program was to contribute towards an improved understanding of suicidal thoughts and behaviours in young people with clinically diagnosed depressive disorders. More specifically, the aim was to identify modifiable intervention targets, which could inform clinical treatment approaches, and suicide prevention and early intervention efforts more broadly. Methods This research program comprises four studies each addressing different research questions. Study 1 is a comprehensive systematic review of contributors to suicidality in young people with unipolar and bipolar depression. Study 2 is an analysis of the dimensionality of a widely used measure of suicidal ideation, including associations between this measure’s latent factors and actual suicidal behaviour in young people with major depressive disorder (MDD). Study 3 is an investigation of how different dimensions of social support are associated with suicidal ideation in a treatment seeking cohort of young people with MDD; and Study 4 is a longitudinal analysis of associations between a range of psychosocial correlates and suicidal ideation severity in this same cohort of young people MDD, assessed over a 12-week period. Main Results Several key themes can be drawn from the findings of this research program. First, there is a lack of consensus regarding how the construct of suicidality should be defined, highlighting the need for international collaboration in the development of a standardised, validated classification system for suicidal ideation and suicidal behaviours. The second key finding is that suicidality in young people with depressive disorders is multidimensional in nature. That is, the way in which suicidality manifests in an individual is multifaceted. Suicidality is comprised of multiple constructs encompassing both active and passive ideation, intrapersonal cognitions such as hopelessness and lack of self-worth, and interpersonal factors such as perceived burdensomeness. The third key finding is that there are multiple determinants of suicidality in young people with depressive disorders; in addition to depressive symptoms, there are numerous other predictors of the nature and severity of suicidality. Notably, familial support is an important protective factor, while psychopathological features such as state and trait anxiety contribute to suicidality severity. Discussion Outcomes of this research program reinforce the notion that suicidality is complex and multideterminant in nature. Depression symptomatology is an important contributor, suggesting that regular monitoring of depression symptom severity should be a core aspect of the clinical management of suicidality in young people with depressive disorders. Suicidality is not driven by depression symptomatology alone and it is clear that suicide prevention and intervention efforts need to go beyond simply reducing depression severity. Psychiatric comorbidity with depression, particularly comorbid anxiety, is an important determinant of suicidality. Anxiety and depression, in particular, share many clinical features and risk factors. Interventions targeting transdiagnostic features could have clinical utility in reducing the burden of suicide in young people. In addition, methodological assessment of personality features and carefully targeted intervention approaches such as dialectal behaviour therapy, or mentalization-based therapy, could be a beneficial component of the clinical management of depression and suicidality in young people. An important clinical implication of this research program is that there is likely substantial variability underlying the mechanisms for suicidality from one depressed young person to the next. This suggests that there is perhaps a similarly high degree of variability with respect to potentially effective treatment targets for suicidality. It raises the question of how useful it is to consider a diagnosis of depression as a specific risk factor for suicidality in young people. Alternative approaches to identifying aetiological mechanisms of suicidality, such as a specific symptom approach, could be warranted. It is crucial to develop and employ early intervention approaches for suicidality in young people which focus on the earliest stage of suicidality. Potential targets for early intervention, such as increasing adaptive social support to reduce severity of suicidal ideation, are likely to be beneficial in preventing transition to suicidal behaviour. This highlights the need to assess and monitor suicidality early in young people presenting with mental health symptoms, irrespective of the specific diagnosis. This requires the use of age-appropriate suicidality assessment tools designed for use in young people. Given the fluctuating nature of suicidality, real-time symptom monitoring could perhaps be implemented as part of routine clinical care. The use of transdiagnostic interventions aimed at modifying common cognitive processes underlying depression, anxiety, and suicidality could be an effective treatment approach. Although suicidality is a complex phenomenon and no single approach to prevention or intervention is likely to be universally effective, the findings of this research program do have the potential to help reduce the suicidality-related health burden in this particularly vulnerable population.
Using Machine Learning to Disentangle Heterogeneity Within and Between Psychosis and Depression: Improving Pathways for Precision Medicine in Psychiatry

Lalousis, Paris Alexandros ( 2022)

The aim of this PhD was to examine the clinical and biological -primarily structural brain- heterogeneity within and between depression and psychosis and provide tools for the improvement of diagnosis and targeted treatment. In chapter 3, a systematic review of structural neuroimaging studies in depression and psychosis identified potential transdiagnostic patterns of gray matter volume (GMV) and white matter volume (WMV) reductions in areas including the middle frontal gyrus, hippocampus, and left-sided posterior subgenual prefrontal cortex. In chapter 4, clinical/neurocognitive and neuroanatomical support vector machine (SVM) learning models demonstrated separability of prototypic depression from psychosis. Psychosis patients with affective comorbidity aligned more strongly to depressive rather than psychotic disease processes. In chapter 5, we identified two transdiagnostic neuroanatomically informed clusters which are clinically and biologically distinct, challenging current diagnostic boundaries in recent onset mental health disorders. In chapter 6, five clusters of schizophrenia with distinct immune signatures, associated with differing GMV and neurocognitive function were identified, with potential to inform the development of novel, targeted treatments. Overall, machine learning was utilised to elucidate and reduce heterogeneity within and between psychosis and depression, and identify biologically relevant and transdiagnostic subtypes that could become potential candidates for targeted treatment. The results are promising and challenge the current nosological system.
Predicting onset and identifying subtypes of major depressive disorder (MDD) - Examining (neuro) biological predictors and correlates of (subtypes of) MDD

Toenders, Yara Jo ( 2022)

Major depressive disorder (MDD) is amongst the leading causes of burden of disease in young people. The onset of MDD peaks during adolescence and young adulthood and this early onset of MDD can have long-term negative consequences. In addition, treatment in young people with MDD shows limited effectiveness. Identifying who is at risk for developing MDD and what risk factors are predictive of MDD onset in young people could help the development of prevention strategies. Besides knowing who is at risk for MDD, developing more effective treatments for MDD is equally important. MDD shows heterogeneous symptoms, and refining people into more homogeneous symptom subtypes might help the identification of underlying biological mechanisms and treatments targeted at specific subtypes of depression. Therefore, the aims of this thesis were to 1) better understand who will develop MDD, 2) identify subtypes of MDD and 3) examine the biological mechanisms underlying MDD. The most consisting finding in the existing literature on neuroimaging predictors of depression in young people, was that blunted ventral striatum to reward processing was predictive of depression onset. In the second study, in 544 young people aged 14, structural neuroimaging data was combined with information from other modalities, including cognitive, environmental, clinical and demographic measures to predict depression onset using a machine learning approach. Penalised logistic regression was used to predict depression onset over a 5-year follow-up period. The model predicted depression onset moderately well based on neurobiological, environmental, clinical and psychosocial risk factors. However, the model was also predictive of risky substance use. For the second aim, data-driven symptom subtypes of MDD were identified in 275 young people using k-means clustering. Three subtypes were identified that mainly differed on neurovegetative symptoms; an increased appetite subtype, decreased appetite subtype and moderate severity subtype. Only the increased appetite subtype showed structural brain alterations, as it showed lower surface area of the anterior insula compared to healthy controls. The association between structural brain alterations and clinical symptom profiles of depression was also studied in 451 adults. The symptom profile in adults related to the increased appetite symptom subtype, was not associated with structural brain alterations. With regard to biological mechanisms involved in MDD, our systematic review including 109 studies provided evidence for inflammatory dysregulation in young people with depression. The findings were heterogeneous and they were affected by factors such as early life or chronic stress, being female, and neurovegetative symptoms of depression. This thesis highlights the importance of stratified psychiatry, with a more general approach at early stages of psychopathology, because of the overlap in risk factors in psychiatric disorders, and a more specific approach as depression develops because of the heterogeneous nature of the disorder.

Centre for Youth Mental Health - Theses

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