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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ItemThe development and evaluation of guidelines and an information website for adult caregivers of adults with bipolar disorder( 2012)Background and aim: Bipolar disorder is a challenging and usually chronic illness associated with occupational and social consequences that affect the lives of both the person and those who care for them. Family members and friends with a primary role in supporting an adult with bipolar disorder (caregivers) are at risk of caregiver burden, depression and health problems. However, there is little evidence-based information to guide caregivers in ways to provide helpful support and maintain their own wellbeing. Thus, the aim of this project was to develop an easily accessible resource with relevant and useful information and suggestions for caregivers. Methods: The project was divided into two phases. In the first phase a Delphi consensus study was conducted with expert clinician, caregiver and consumer panel members to establish what information and suggestions to include in guidelines for adult caregivers of adults with bipolar disorder (N=143). In the second phase of the project, a web-based version of the guidelines www.bipolarcaregivers.org was developed to make this information easily accessible over the Internet. A formative evaluation of the website was conducted to establish the relevance and usefulness of the information to caregivers and how it could be improved. This involved an initial online survey for visitors to the website (N=536) and a more detailed follow-up email feedback survey, sent to interested caregivers of adults with bipolar disorder a month later (N=121). Results: There was mostly high consensus about what to include in the guidelines between the different Delphi panels. Out of a total of 626 survey items rated by the Delphi panels over three survey rounds, 537 (86%) were included in the guidelines. In the evaluation study, the majority of caregiver visitors who completed the initial feedback survey (97%) reported thinking that the information on www.bipolarcaregivers.org was “very useful” or “useful”. Similarly, between 86.4%-97.4% of caregivers who responded to the follow-up survey rated the information they read as “very useful" or “useful”. Nearly 93% found the information relevant and all participants said it gave them the impression that others were going through similar experiences. Over two thirds reported using the sections on providing support and working with the person to manage the illness and gave concrete examples of how they implemented the guidelines. Nevertheless, despite the overall positive results, qualitative feedback suggested practical ways the website could be further refined. Discussion: This project resulted in a publicly accessible information resource www.bipolarcaregivers.org that was reported to be relevant and useful by most of the users in the evaluation study. The website includes brief information summaries and a PDF of the guidelines that can easily be printed. The guidelines have been translated into booklets in Portugal and Brazil. According to Google Analytics, traffic to the website continues to increase. Www.bipolarcaregivers.org may form an initial step in providing basic information to caregivers caring for an adult with bipolar disorder. Those who care for people with more severe and complex illness presentations might benefit from additional support and training to cope with their caregiving role. Similarly, more detailed or tailored information and support may be suitable for caregivers who are already very experienced or well informed. A strength of this project is its consideration of the views of stakeholders and careful comparison and integration with the research literature. Future studies could combine stakeholder involvement with more rigorous evaluation of www.bipolarcaregivers.org and its long-term effect on caregiver and consumer outcomes. If funds become available, the website could be made more interactive to enhance learning of information and skills, and offer more tangible and tailored support. Background and aim: Bipolar disorder is a challenging and usually chronic illness associated with occupational and social consequences that affect the lives of both the person and those who care for them. Family members and friends with a primary role in supporting an adult with bipolar disorder (caregivers) are at risk of caregiver burden, depression and health problems. However, there is little evidence-based information to guide caregivers in ways to provide helpful support and maintain their own wellbeing. Thus, the aim of this project was to develop an easily accessible resource with relevant and useful information and suggestions for caregivers. Methods: The project was divided into two phases. In the first phase a Delphi consensus study was conducted with expert clinician, caregiver and consumer panel members to establish what information and suggestions to include in guidelines for adult caregivers of adults with bipolar disorder (N=143). In the second phase of the project, a web-based version of the guidelines www.bipolarcaregivers.org was developed to make this information easily accessible over the Internet. A formative evaluation of the website was conducted to establish the relevance and usefulness of the information to caregivers and how it could be improved. This involved an initial online survey for visitors to the website (N=536) and a more detailed follow-up email feedback survey, sent to interested caregivers of adults with bipolar disorder a month later (N=121). Results: There was mostly high consensus about what to include in the guidelines between the different Delphi panels. Out of a total of 626 survey items rated by the Delphi panels over three survey rounds, 537 (86%) were included in the guidelines. In the evaluation study, the majority of caregiver visitors who completed the initial feedback survey (97%) reported thinking that the information on www.bipolarcaregivers.org was “very useful” or “useful”. Similarly, between 86.4%-97.4% of caregivers who responded to the follow-up survey rated the information they read as “very useful" or “useful”. Nearly 93% found the information relevant and all participants said it gave them the impression that others were going through similar experiences. Over two thirds reported using the sections on providing support and working with the person to manage the illness and gave concrete examples of how they implemented the guidelines. Nevertheless, despite the overall positive results, qualitative feedback suggested practical ways the website could be further refined. Discussion: This project resulted in a publicly accessible information resource www.bipolarcaregivers.org that was reported to be relevant and useful by most of the users in the evaluation study. The website includes brief information summaries and a PDF of the guidelines that can easily be printed. The guidelines have been translated into booklets in Portugal and Brazil. According to Google Analytics, traffic to the website continues to increase. Www.bipolarcaregivers.org may form an initial step in providing basic information to caregivers caring for an adult with bipolar disorder. Those who care for people with more severe and complex illness presentations might benefit from additional support and training to cope with their caregiving role. Similarly, more detailed or tailored information and support may be suitable for caregivers who are already very experienced or well informed. A strength of this project is its consideration of the views of stakeholders and careful comparison and integration with the research literature. Future studies could combine stakeholder involvement with more rigorous evaluation of www.bipolarcaregivers.org and its long-term effect on caregiver and consumer outcomes. If funds become available, the website could be made more interactive to enhance learning of information and skills, and offer more tangible and tailored support.