Centre for Youth Mental Health - Research Publications
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ItemGenetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks(SOC NEUROSCIENCE, 2011-03-02)The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09-0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization.
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ItemIs it all in the reward? Peers influence risk-taking behaviour in young adulthood(WILEY, 2017-05)The presence of peers is suggested to increase risk-taking behaviour by heightening response to reward. The current study investigated this using a computerized financial risk-taking task which was performed twice by a group of young adults (n = 201, median age 19.8 years): once alone and once while in the presence of two peers. An overall increase in risk-taking was observed when with peers compared to when alone (CHANGE). CHANGE was positively associated with self-reported levels of reward responsiveness and fun seeking while older age and lack of perseverance were associated with reduced CHANGE. The association between risk-taking when with peers and both resistance to the influence of peers and age was indirect through reward responsiveness. Reward responsiveness was positively associated with impulsiveness. Only in those who showed a peer-related decrease in risk-taking (1/3 of participants), risk-taking in the presence of peers was associated with increased impulsiveness. The current findings suggest an important role for reward responsiveness in risk-taking behaviour and demonstrate the influence of peers. Increased understanding of these processes has direct implications for prevention and intervention efforts. Placing risk-taking behaviour within varying (social) contexts with an eye for differences in personality, development, and emotions provides ample scope for future research.
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ItemResilience as a multimodal dynamic process(WILEY, 2019-08)AIM: Resilience is rapidly gaining momentum in mental health literature. It provides a new understanding of the highly variable trajectories of mental illness, and has consistently been linked with improved mental health outcomes. The present review aims to clarify the definition of resilience and to discuss new directions for the field. METHODS: After discussing the definition of resilience, this narrative review synthesizes evidence that identifies the specific protective factors involved in this process. This review also addresses the mechanisms that underlie resilience. RESULTS: Recent literature has clarified the three core components of resilience, which are the presence of an adversity or specific risk for mental illness; the influence of protective factors that supersede this risk; and finally, a subsequently more positive outcome than expected. Now that these are largely agreed upon, the field should move on to addressing other topics. Resilience is a dynamic process by which individuals utilize protective factors and resources to their benefit. It can vary within one individual across time and circumstance. It can also refer to good functional outcomes in the context of diagnosable illness. While previous research has focused on psychological resilience, it is essential that resilience is conceptualized across modalities. CONCLUSIONS: The field should move towards the development of a multimodal model of resilience. Researchers should now focus on producing empirical research which clarifies the specific protective factors and mechanisms of the process, aligning with the core concepts of resilience. This growing, more homogeneous evidence base, can then inform new intervention strategies.
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ItemAuditory verbal hallucinations in first-episode psychosis: a phenomenological investigation(CAMBRIDGE UNIV PRESS, 2016-01)
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ItemThe impact of psychotic experiences in the early stages of mental health problems in young people(BMC, 2018-06-28)BACKGROUND: Anxiety and depressive symptoms and psychotic experiences constitute common features of emerging mental disorders in young people. Psychotic experiences and the ultra-high risk (UHR) state for psychosis appear to have a particular importance for clinical presentation, progression of symptomatology, quality of life and functioning, but the impact of psychotic experiences in individuals seeking help at non-UHR services, compared to UHR services, is under-researched. METHODS: Sixty-nine young people (Mage ± SD at baseline = 20.8 ± 2.6, range 16-26 years, 48 females) presenting to mental health services were grouped according to UHR and non-UHR status. They were assessed at baseline for anxiety and depressive symptoms, psychological distress, psychosocial functioning and quality of life. They were followed up at three, six, and 12 months. Data were analysed using mixed linear modelling. RESULTS: UHR individuals reported higher levels of depressive symptoms and psychological distress, and lower levels of role functioning and quality of life compared to non-UHR individuals. No differences were reported for anxiety symptoms or social functioning. Decline in psychosocial functioning was not associated with clinical deterioration or reduction of quality of life. CONCLUSIONS: Psychotic experiences appear to be particularly associated with depressive symptoms and psychological distress, impaired role functioning and quality of life in help-seeking young people in the medium-term. It is therefore important to pay special attention to psychotic experiences in the early stages of mental health problems even if psychotic symptoms are not the main motivation for help-seeking.
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ItemContribution of Brain Size to IQ and Educational Underperformance in Extremely Preterm Adolescents(PUBLIC LIBRARY SCIENCE, 2013-10-09)OBJECTIVES: Extremely preterm (EP) survivors have smaller brains, lower IQ, and worse educational achievement than their term-born peers. The contribution of smaller brain size to the IQ and educational disadvantages of EP is unknown. This study aimed (i) to compare brain volumes from multiple brain tissues and structures between EP-born (< 28 weeks) and term-born (≥ 37 weeks) control adolescents, (ii) to explore the relationships of brain tissue volumes with IQ and basic educational skills and whether this differed by group, and (iii) to explore how much total brain tissue volume explains the underperformance of EP adolescents compared with controls. METHODS: Longitudinal cohort study of 148 EP and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic resonance imaging-determined brain volumes of multiple tissues and structures were calculated. IQ and educational skills were measured using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT-4), respectively. RESULTS: Brain volumes were smaller in EP adolescents compared with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%] for total brain tissue volume). The largest relative differences were noted in the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]), spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of total brain tissue and other brain tissues and structures correlated positively with IQ and educational skills, a relationship that was similar for both the EP and controls. Total brain tissue volume explained between 20-40% of the IQ and educational outcome differences between EP and controls. CONCLUSIONS: EP adolescents had smaller brain volumes, lower IQs and poorer educational performance than controls. Brain volumes of multiple tissues and structures are related to IQ and educational outcomes. Smaller total brain tissue volume is an important contributor to the cognitive and educational underperformance of adolescents born EP.
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ItemEffects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis(NATURE PUBLISHING GROUP, 2013-04)Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4-14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37-4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05-2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of 3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.
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ItemDivergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis(CAMBRIDGE UNIV PRESS, 2015-02)BACKGROUND: Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses. METHOD: Cortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined. RESULTS: The effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms. CONCLUSIONS: Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.
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ItemMulti-center MRI prediction models: Predicting sex and illness course in first episode psychosis patients(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2017-01-15)Structural Magnetic Resonance Imaging (MRI) studies have attempted to use brain measures obtained at the first-episode of psychosis to predict subsequent outcome, with inconsistent results. Thus, there is a real need to validate the utility of brain measures in the prediction of outcome using large datasets, from independent samples, obtained with different protocols and from different MRI scanners. This study had three main aims: 1) to investigate whether structural MRI data from multiple centers can be combined to create a machine-learning model able to predict a strong biological variable like sex; 2) to replicate our previous finding that an MRI scan obtained at first episode significantly predicts subsequent illness course in other independent datasets; and finally, 3) to test whether these datasets can be combined to generate multicenter models with better accuracy in the prediction of illness course. The multi-center sample included brain structural MRI scans from 256 males and 133 females patients with first episode psychosis, acquired in five centers: University Medical Center Utrecht (The Netherlands) (n=67); Institute of Psychiatry, Psychology and Neuroscience, London (United Kingdom) (n=97); University of São Paulo (Brazil) (n=64); University of Cantabria, Santander (Spain) (n=107); and University of Melbourne (Australia) (n=54). All images were acquired on 1.5-Tesla scanners and all centers provided information on illness course during a follow-up period ranging 3 to 7years. We only included in the analyses of outcome prediction patients for whom illness course was categorized as either "continuous" (n=94) or "remitting" (n=118). Using structural brain scans from all centers, sex was predicted with significant accuracy (89%; p<0.001). In the single- or multi-center models, illness course could not be predicted with significant accuracy. However, when reducing heterogeneity by restricting the analyses to male patients only, classification accuracy improved in some samples. This study provides proof of concept that combining multi-center MRI data to create a well performing classification model is possible. However, to create complex multi-center models that perform accurately, each center should contribute a sample either large or homogeneous enough to first allow accurate classification within the single-center.
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ItemDisrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: findings from the LYRIKS study(CAMBRIDGE UNIV PRESS, 2016-10)BACKGROUND: Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression. METHOD: We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis. RESULTS: ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years. CONCLUSIONS: Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.