Psychiatry - Theses
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ItemEnvironment-by-brain development interactions as predictors of adolescent depressive symptoms and psychological well-being: structural brain development as a marker of responsivity to maternal parenting and socioeconomic status( 2019)Background Adolescence is widely reported to be a time of increased risk for depression and lower well-being. Importantly, however, outcomes are heterogeneous, and most adolescents do not develop mental health problems. In order to understand how these differences emerge, both environmental and biological factors have been examined in the literature. Evidence indicates that parenting behaviour, socioeconomic status and neurobiology may contribute and, further, that individual differences in brain development may moderate the extent to which contextual factors influence adolescents. That is, individual differences in brain development may confer ‘responsivity’ to context. Several developmental and evolutionary-developmental models provide frameworks with which to interpret such brain-by-environment interactions, and to describe biological responsivity – these are broadly associated with diathesis-stress and differential susceptibility/biological sensitivity frameworks. Broad PhD aim This thesis aims to investigate whether structural brain development moderates adolescent sensitivity to maternal parenting behaviour in the prediction of adolescent depressive symptoms and psychological well-being. Two empirical studies were completed to address this aim. Study 1 examined whether longitudinal change in brain structure modified adolescent vulnerability or susceptibility to aggressive and positive maternal parenting. Effects were assessed to infer evidence in support of either diathesis-stress or differential susceptibility frameworks. Study 2, in light of evidence that positive parenting protects against adversity, considered whether brain development moderated adolescent sensitivity to positive parenting, and whether this association was more pronounced for adolescents with low-socioeconomic status (SES). Methodology During early adolescence (age 13 years), participants completed observed interactions with their mothers, and the frequency of positive maternal behaviour was coded. At three time points (mean ages 13, 17 and 19 years), participants completed structural magnetic resonance imaging (MRI) scans. During late adolescence (age 19 years), participants completed self-report measures of depressive symptoms and psychological well-being. Two separate analyses (studies) were conducted in predicting late adolescent (age 19) outcomes (depressive symptoms and psychological well-being). For both studies, longitudinal brain development was indexed by changes in cortical thickness of structures within the frontal lobe, and volumetric changes of subcortical structures, from early to late adolescence. Study 1: Regression models analysed interactions between maternal behaviour and longitudinal brain development in the prediction of adolescent outcomes. Indices designed to distinguish between diathesis-stress and differential susceptibility effects were employed. Study 2: Regression models were used to investigate interactions between SES (parental occupation), positive maternal behaviour, and longitudinal brain development in the prediction of adolescent outcomes. Results Study 1: Results supported differential susceptibility, whereby less thinning of frontal regions (the left medial orbitofrontal, rostral middle frontal and superior frontal cortices, and the right pars opercularis) was associated with higher well-being in the context of low levels of aggressive maternal behaviour, and lower well-being in the context of high levels of aggressive maternal behaviour. Study 2: Results indicated that individual differences in structural brain development moderated the extent to which positive parenting impacted adolescents dependent on SES. High levels of positive parenting were associated with reduced depressive symptoms for low-SES adolescents with greater volumetric reduction of the right putamen. Further, low positive parenting was associated with reduced psychological well-being for individuals with greater neurobiological sensitivity, however, patterns of brain development that were associated with sensitivity differed by SES. Specifically, low positive parenting was associated with reduced psychological well-being for individuals with more thinning in the context of low-SES, but for individuals with less thinning in the context of high-SES. Significance Results across studies suggested that structural brain development may be associated with individual differences in how sensitive adolescents are to context. Study 1 indicated that reduced frontal cortical thinning during adolescence increased susceptibility to maternal aggressive behaviour in the prediction of well-being, for better and for worse. This finding is significant because it suggests that neither more or less cortical thinning is consistently good or bad for mental health. Results from Study 2 indicated that, although brain change was associated with responsivity to parenting behaviour, patterns of brain development associated with heightened responsivity to parenting were different for high- and low-SES. These results suggested that responsivity functions in a context dependent fashion and highlights the complex interactions that may occur across biological and multilevel environment factors. Results from these studies suggest that structural brain development may be a marker of responsivity to environmental influence. They also emphasise the importance of examining how brain development moderates the impact of multilevel environmental factors on mental health outcomes. Such study designs may better reflect the social settings in which adolescents develop.
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ItemThe neuropsychiatric disorders of focal epilepsy( 2017)Neuropsychiatric disorders commonly co-exist with focal epilepsy. Despite intense investigation there remains significant limitations to our current understanding of the aetiological relationship between these conditions, as well as the clinical and radiological factors that are associated with the development of mental illness in epileptic patients. To address these questions I assembled a large cohort of consecutive focal epilepsy patients reviewed at a large tertiary referral centre over an 11-year period, and analysed relevant clinical, radiological and demographic findings using both cross-sectional (baseline evaluation) and longitudinal (serial assessments) study designs. For cross-sectional analyses, psychiatric and epilepsy comorbidity were comprehensively identified and compared to baseline MRI-determined Deep Brain Structure (DSB) volumes. In the prospective study, standardised psychiatric and quality of life assessments were obtained in a subset of patients and the development of mental illness compared to interval changes in DSB volumes. I focus on depression and psychosis, as they represent the two most prevalent psychiatric disorders identified, and classify focal epilepsy patients according to the site of seizure origin and presence of a lesion. Contrary to the common medical belief, I found that the rates of neuropsychiatric disorders in temporal lobe epilepsy were equivalent to those in extratemporal lobe epilepsy. There were no differences between those with and without psychiatric disorder by age, gender, and laterality of seizure, epilepsy severity or duration. Patients with non-lesional epilepsy, both temporal and extratemporal, have double the rate of depression compared to those with lesional focal epilepsy. There were high rates of quality of life difficulties in people with epilepsy and comorbid psychiatric disorders but the pattern of subjective concerns does not match objective clinician ratings. The hippocampal and amygdalae volumes of epilepsy patients were reduced compared to normal controls. People with co-existing epilepsy and depression had a trend towards smaller reductions in temporal lobe structures, which may represent differential expressions of progression through inflammation, trauma or emotional processing needs with either relative sparing or volumetric increases. People with psychosis and epilepsy have bilaterally reduced hippocampi compared to those with epilepsy, where reductions are predominantly ipsilateral to seizure focus. There is less evidence for amygdala change in psychosis, but a small relative increased volume was observed compared to those with epilepsy alone. There was no evidence of progression over time at a population level over 3.9 years, although there was greater variability in size in all epilepsy subjects compared to normal controls. These results convincingly argue against assumptions about the primary role of temporal lobe foci in the pathogenesis of psychiatric comorbidities in patients with epilepsy, whilst allowing for the possibility that disruption to frontotemporal networks may be a component in the development of psychiatric disorders. Progression is not an inevitable part of the natural history, at least over a 4 year period but it is possible that individuals may exhibit marked changes. They highlight the as yet unexplored possibility that the absence of a lesion as an epileptic site may be associated with greater risks of neuropsychiatric illness and allow for speculation that this may be related to inhibitory surround impacts, more extensive underlying diffuse abnormalities and disruption to frontotemporal connectivity.
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ItemPersonality and care-related factors and their associations with depressive symptoms in older carers( 2016)With the rapidly ageing global population, there will be increased demand on informal older carers, who provide important roles in supporting older adults to live longer in their own homes. Depression in older carers is a well-known adverse outcome, however there is lack of consistent knowledge concerning factors associated with this outcome. The research reported in this thesis therefore investigated factors associated with depressive symptoms in a sample of older carers living at home with the older adults with whom they were caring for (the care-recipient, CR). This study differs from previous work in that a variety of different, but clinically relevant factors have been investigated. A convenience sample of 202 older carers were assessed cross-sectionally on their demographic characteristics, health measures, depressive symptoms, personality, attitudes to ageing, and CR factors (CR diagnosis and the hours spent caring). The cut-off score on the Geriatric Depression Scale (GDS-15) of ≥5 was used to delineate “depressed” and “non-depressed” carers, and a comparison of these characteristics was made between the 87 depressed, and 115 non-depressed carers. Female gender, but no other demographic factors were associated with a higher number of depressive symptoms. The CR diagnosis was not an independent factor associated with depressive symptoms. Higher levels of Neuroticism and more negative attitudes to ageing in the carers were associated with depressive symptoms. Depressed carers had worse physical health, participated in increased amounts of domestic physical activity (PA), but similar amounts of leisure-PA, compared to non-depressed carers. The regression analyses demonstrated that higher levels of Neuroticism, increased hours spent caring, and possibly increased amounts of domestic-PA, were independent factors associated with depressive symptoms. The findings of this study highlight the importance of carer-related factors when identifying risk factors for depressive symptoms in older carers. The clinical implications of this study, particularly that increased hours of care are a risk factor for depressive symptoms, suggest that in order to potentially reduce the risk of developing depression, older carers should be encouraged to “share the care” – that is the support of the CR should be preferably spread among more than one person, whether this be among other family members, and/or formal care services. Thus, being able to access support services such as “Home Help”, and respite is important. This approach may not be supported by the principles behind the current Victorian Active Services Model, which encourages self-reliance and enablement. Clinicians have an important role to encourage older carers to accept help, but this needs to be individually tailored, taking into account the carers’ personality structure.
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ItemA prospective longitudinal study of child development following in-utero exposure to antidepressant medication( 2014)Background: The recognition of the importance of treatment for depression in pregnancy to optimise both maternal and child outcomes parallels the increasing use of antidepressants in pregnancy across many countries in the world. However, there is also research to suggest that women are often reluctant to commence treatment or they abruptly cease antidepressant treatment on becoming pregnant due to concerns about long term safety of exposure for their unborn child. This thesis examines child developmental outcomes following in utero exposure to antidepressant medication using two data sets. These two data sets are distinct in methodology allowing a comparison of both methods and results when examining child outcomes following exposure in pregnancy. Methods: The first study is the Victorian Psychotropic Registry (VPR), a purpose designed, prospective, longitudinal study established by the candidate and where children have been followed from in utero to 5 years of age. The second study is the Longitudinal Study of Australian Children (LSAC), a large, normative, population based cohort across early childhood established by the Commonwealth Government of Australia. Both studies had an antidepressant exposed group of children and a control group and both studies had measures of maternal depression in pregnancy, postpartum and into childhood as well as measures of other exposures in pregnancy, such as alcohol and smoking. The VPR collected all data prospectively whereas the pregnancy measures for LSAC were retrospectively collected in the postpartum. The three areas of child development of focus in this thesis are: cognitive development, motor development and child adjustment and emotional development. Where possible, measures were chosen in LSAC, which closely matched those in age and domain to the VPR. Children were assessed at 4-7 years of age across the two studies. Results: This thesis found that in both data sets there was no evidence of an effect on cognitive development from antidepressant exposure in pregnancy. The results for both motor development and emotional development were more complex. For motor development there was a trend to lower scores in the VPR study on a specific neuropsychological measure of motor development: Movement ABC, without reaching a statistically significant difference but small effect sizes. There was no observational or task measures of motor development in LSAC. Both the VPR study and LSAC found a difference on a screening measure, Peds QL Physical Health Score, with exposed children having a lower score. However, when this was adjusted for the covariate of maternal depression this was no longer significant. Child adjustment and emotional development was examined in two areas. The first was internalizing and externalizing scores, within the VPR on the CBCL and within LSAC on SDQ, the second area was parenting and parent-child relational stress measured in VPR with PSI total stress score and within LSAC with the Parenting Efficacy Scale. VPR found there was no statistically significant difference on either measure for exposed children. Whereas, LSAC found both internalizing and externalizing scores and Parenting Efficacy Scale scores did show statistically significant differences, with higher externalizing and internalizing scores and lower Parenting Efficacy scores in exposed children. However, again when adjusted for the covariate of maternal depression these differences became non significant. Conclusions: Using two independent samples to examine antidepressant exposure in pregnancy on child developmental outcomes, no statistically significant difference was found between children exposed and controls on a range of cognitive, motor, child emotional and adjust outcomes at 4-6 years of age. There was also no difference in mothers who took antidepressants in pregnancy on parenting stress and efficacy at 4-6 years postpartum. However, the secondary findings within LSAC study was that maternal depression in the postpartum, as measured by the K6, was associated with poorer cognitive, language, emotional and parenting outcomes This suggests the very important role of maternal depression in examining longitudinal child outcomes. This thesis has contributed both original data to the limited information available on child developmental outcomes following antidepressant exposure across two distinct studies. By using two studies this thesis has also allowed a comparison of findings using different methodologies. This thesis has also been able to contribute data on the effects of maternal depression on child development. These findings support clinical recommendations and practices, which highlight the importance of detection and appropriate treatment of maternal depression in pregnancy.