Centre for Youth Mental Health - Theses
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ItemAntecedents of incident bipolar disorder in youth( 2017)Background: Bipolar disorder (BD) is a serious mental illness characterised by episodes of mania and depression. The disability associated with this disorder and the observation that at least a sub-proportion have a progressive course suggests that early or preventive interventions may be an effective strategy to minimise the disability. However, prevention efforts for BD require characterisation of targets for such interventions. Aims and objectives: Thus, the overall aim of this research program was to describe the pre-onset illness stages related to the development of incident (hypo)manic episodes and their associated functional impairment. Specifically, we aimed to examine clinical populations where preventive efforts may be more feasible. The objectives included identification of i) baseline characteristics associated with later BD among non-bipolar help-seeking youth; ii) rates and predictors of transition from major depressive disorder (MDD) to BD in previously published studies; iii) instruments that have prospective predictive validity in identifying BD and iv) the precursors of functional impairment in the post-illness period. Methods: This thesis comprises five studies that have examined these issues using diverse methodologies – using systematic review, meta-analyses and longitudinal cohort designs. Three studies involved examining baseline characteristics associated with the development of later BD from non-bipolar states. One study identified the instruments that have been used to predict the later onset of BD using a systematic review, while the final study examined the pre-onset predictors of later functioning among young people with first episode BD. Main results: The characteristics associated with later BD in the two cohort studies included subthreshold manic symptoms, comorbid substance use, severity of depression, antidepressant use and lower functioning. Meta-analyses identified that family history of BD, comorbid psychotic symptoms and lower age of onset of depression was predictive of transition from MDD to BD. The systematic review identified few instruments with prospective validity for predicting BD onset that had been replicated in clinical cohorts. However, instruments with validity in non-clinical cohorts, or those without replication were described. Across the first four studies, combinations of risk factors were associated with a greater risk of transition to BD. Poor premorbid adjustment in the pre-onset phase was predictive of later functioning among youth with first episode mania. Discussion: The findings of these studies point to the need to use combinations of risk factors identified using validated instruments, particularly in young people to predict the onset of BD. This may then help develop preventive interventions that may be tested in studies that are feasible and have adequate statistical power. Incorporating functional precursors into pre-illness stages may help with prevention of functional impairments. A putative instrument which may decrease measurement bias is also proposed. The primary limitation of the included studies was in the post-hoc nature of analyses and the associated lack of availability of all possible baseline confounders. Additionally, low statistical power limited the ability to examine certain associations. Future studies should examine multiple confounding variables in longitudinal cohorts of youth and young adults. Larger cohorts that are enriched for multiple risk factors may help improve statistical power.
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ItemAn examination on cognitive functioning following a first episode of mania in people treated with lithium and quetiapine monotherapy: a 12-month follow-up study( 2016)Cognitive impairments that persist during remission in bipolar disorder have received intensive investigation over the past couple of decades. Nevertheless, the onset and extent of cognitive deficits that occur either prior to, or following, a first episode of mania (FEM), and the trajectory of cognitive functioning in the early stages of illness remain unclear. Moreover, the effect of treatment medication on cognitive functioning in people with bipolar disorder warrants systematic investigation. Specifically, lithium carbonate and quetiapine fumurate have shown to be effective in the treatment of mania and bipolar depression and are both postulated to have neuroprotective properties. The aims of this research program were to: (i) examine cognitive functioning in people following FEM; (ii) assess cognitive changes following FEM over a 12-month period; and (iii) compare the effects of lithium and quetiapine monotherapy on cognitive functioning over the same 12-months. A systematic review of all peer-reviewed studies on cognitive functioning in people with FEM during both the acute and remission phases of the illness was conducted. This involved a systematic search of the literature from three electronic databases from 1980 to 2014. The search identified seven studies on cognitive functioning in people with FEM. The limited studies in the acute phase focussed only on aspects of executive functioning, with findings of impairment in cognitive flexibility, but not in response inhibition or verbal fluency. Although deficits in several cognitive domains were identified during the remission phase, the findings between studies were largely inconsistent. Nevertheless, the most consistent finding during remission was a deficit in working memory, and that verbal fluency and nonverbal memory were not affected. The systematic review highlighted the need for further studies and clarification on the extent of cognitive impairment following FEM, and assisted in the formation of the hypotheses of the empirical studies. For the empirical studies, a total of 61 participants with FEM randomised to lithium or quetiapine monotherapy, and 21 demographically matched healthy controls (HCs) were recruited. FEM participants and HCs were compared on cognitive functioning using an extensive cognitive battery over a 12-month follow-up period. FEM participants were assessed on cognitive functioning at baseline, 3-months, and 12-months, whereas, cognitive functioning of HCs was assessed at baseline and 12-months. The cognitive assessment included measurements of processing speed, attention, sustained attention, verbal learning and memory, nonverbal memory, working memory, verbal fluency, executive functioning, and intelligence. The first empirical study involved a cross-sectional analysis comparing cognitive functioning in FEM participants following stabilisation relative to HCs. Although the groups were matched in age, sex and premorbid intelligence, the findings revealed that FEM participants had significantly lower full-scale IQ (FSIQ) and education level than HCs. However, the difference between groups in FSIQ was no longer significant after controlling for premorbid intelligence. FEM participants displayed cognitive deficits of medium to large effect in processing speed, verbal learning and memory, and working memory compared to HCs. There were no significant differences between groups on other measures of cognition after controlling for FSIQ, education and premorbid intelligence. The second empirical paper involved a longitudinal analysis that assessed the trajectory of cognitive functioning in the FEM participants relative to HCs over 12-months. The findings revealed a significant group by time interaction in one measure of processing speed (Trail Making Test – Part A), and immediate verbal recall (Rey Auditory Verbal Learning Test – trial 1), with a significant improvement observed in the FEM group relative to HCs over time. On the contrary, a significant group by time interaction was observed in a processing speed measure of focussed reaction time (CogstateTM Detection), with FEM participants showing a slower performance relative to HCs over time. A significant group by time interaction was also observed in one aspect of executive functioning - effortful inhibitory control (Stroop effect), revealing that HCs improved in performance over 12-months, whereas the FEM participants did not. There were no other group by time interactions for other measures of cognition. The final empirical study was a randomised-controlled trial, which examined the effects of lithium and quetiapine monotherapy in people following FEM over a 12-month period. The results showed a significant group by time interaction in phonemic verbal fluency, with an improved performance in lithium-treated participants compared to quetiapine-treated participants over time. There were no other significant group by time interactions after controlling for multiple comparisons. In conclusion, the findings from this research program revealed that FEM participants had poorer global intelligence relative to HCs, as well as impairments in some but not all cognitive domains following stabilisation from FEM. There appears to be stability in cognitive functioning for most domains over the 12-month period following FEM. However, an improvement was observed in immediate verbal memory and one measure of processing speed over time in FEM participants relative to HCs, although FEM participants performed slower over time on a simple processing speed test of focused reaction time. In addition, there may be a developmental arrest in effortful inhibitory control, as HCs showed an improvement in this function over the 12-month period that was not evident in the FEM group. There were no significant differences between lithium-treated and quetiapine-treated participants on most cognitive domains, apart from phonemic verbal fluency, in which lithium-treated participants showed a significant improvement relative to quetiapine-treated participants over the 12-month period. These findings suggest that neuroprotective properties of lithium may benefit aspects of cognitive functioning when commenced in the early stages of illness. The presence of cognitive deficits in FEM signifies that cognitive changes may occur very early in the illness course. The findings from this research program did not provide evidence for a progressive deterioration in cognitive functioning following FEM, although more rigorous longitudinal studies involving subgroup analysis are warranted. Future studies should examine the relationship between brain abnormalities and cognitive functioning in people following FEM, as well as assess the effects of lithium and quetiapine monotherapy on clinical and neuroanatomical changes over time.
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ItemPromotion of self-help strategies for sub-threshold depression: an e-mental health randomised controlled trial( 2012)Background: Sub-threshold depression refers to clinically relevant depressive symptoms that fall short of a diagnosis of major depression. Sub-threshold depression is very common in the general population, impairs functioning, increases the risk of developing major depression, and poses a significant burden at the population level. Public promotion of greater use of effective self-help strategies for depression has been proposed as one technique to reduce this population burden. Improving self-help strategies could reduce symptoms of sub-threshold depression and prevent major depression. Depression experts have identified several self-help strategies that are helpful for sub-threshold depression. The aim of the study was to develop messages based on these strategies that could be promoted to members of the public with sub-threshold depression, and to test whether their promotion was effective. Method: Twelve email messages (‘Mood Memos’) were developed, based on self-help strategies endorsed as effective and feasible by depression experts. The email messages were developed with reference to theories of behaviour change, persuasion, and health communication, in order to persuade recipients to engage in the self-help behaviours. The effectiveness of these emails was evaluated in a randomised controlled trial. Recruitment was via internet-based sources and participants joined the study by visiting the website www.moodmemos.com. Adults aged 18+ with sub-threshold depression who were not receiving professional treatment for depression were eligible to participate. Participants were randomly allocated to receive emails twice weekly for six weeks in a fully automated intervention. The active group received emails based on the effective self-help strategies and the control group received emails containing general information about depressive disorders. Assessment points were at baseline, midway through the intervention and at the end of the intervention (6 weeks post-baseline). The primary outcome was depression symptom score on the Patient Health Questionnaire-9 (PHQ-9). Secondary outcomes were psychological distress, assessed with the ten-item Kessler Psychological Distress Scale (K10), and level of functioning, assessed with the Work and Social Adjustment Scale. The primary hypotheses were that the emails containing self-help strategies would reduce depression symptoms and reduce the incidence of major depression more than the control emails post-intervention. Results: The study recruited an international sample of 1,326 adults with sub-threshold depression. There was a small, significant difference in depression symptoms post-intervention, favouring the active group (Cohen’s d = 0.17, 95% CI: 0.01 to 0.34). There was also a higher, though non-significant, risk of major depression in the control group (Relative Risk = 1.32, 95% CI: 0.89 to 1.98). A similar effect was found for psychological distress (d = 0.22, 95% CI: 0.05 to 0.38), but effects on functioning were less strong, with no significant difference between the active and control groups (d = 0.12, 95% CI: -0.05 to 0.28). A mediation analysis indicated that the effect of the emails on depression symptoms was completely mediated by the use of the self-help strategies promoted in the emails. Discussion: Overall, the results indicate that promoting effective self-help strategies to the public via automated emails was effective for sub-threshold depression. The improvement in depression was associated with use of the self-help strategies promoted in the emails. The delivery of self-help messages via email is a scalable, easily disseminated intervention. The study is a novel contribution with potential to reduce the large population burden of depression.
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ItemTreatment decision making for young people diagnosed with major depressive disorders( 2011)Adolescence is a crucial period of risk for depression, with one in every five people experiencing a depressive episode before the time they are 18 years old. Engaging young people in effective treatment during this time is essential to prevent potential long-term negative impact. Guidelines advocate for young people to be involved in treatment decision making, both in terms of receiving information about treatment options, and also making choices about their own care. These recommendations are in line with a model of decision making called ‘shared decision making’ (SDM), one of several models of medical decision making. Yet little is known about processes related to treatment decision making in this age group or young people’s preferred model of treatment decision making. What little literature that exists suggests young people would value involvement in treatment decision making and that such involvement may enhance engagement. In order to address this gap in our understanding of treatment decision making in young people, semi-structured, qualitative interviews were conducted with clients (n=10), caregivers (n=5) and clinicians (n=22) about their experiences and beliefs about treatment decision making for young people diagnosed with major depressive disorder (MDD). Thematic analysis was used to identify key themes in the data. Clients and caregivers reported a range of experiences regarding how involved they were in treatment decision making, yet, consistent with the small body of literature identified, they all wanted involvement of some sort. Clinicians also wanted clients, and caregivers as appropriate, to be involved. All participants (clients, caregivers and clinicians) reported a lack of information exchange (e.g. information about potential risks and benefits of different treatment options) and wanted resources to fill this gap. Overall, the findings from these interviews indicated a preference for involvement in treatment decision making that was in line with a SDM model. In response, an evidence-based decision aid that facilitates SDM was developed for young people diagnosed with MDD who are faced with the decision about which treatment option is best for them. The decision aid was developed according to international standards, and included field-testing with clients (n=5) and clinicians (n=3), who all found the tool acceptable and useful. The current study provides the basis from which an understanding of treatment decision making for young people diagnosed with MDD can be further built, and from which additional resources can be developed and tested in order to contribute to the emerging field of youth SDM. Approaches that support young people to make evidence-based and preference-based treatment decisions have the potential to increase guideline-concordant care, satisfaction, adherence and clinical outcomes.