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    Psychosis and Hopelessness Mediate the Relationship Between Reduced Sleep and Suicidal Ideation in Schizophrenia Spectrum Disorders
    Carruthers, SP ; Lee, SJ ; Sankaranarayanan, A ; Sumner, PJ ; Toh, WL ; Tan, EJ ; Neill, E ; Van Rheenen, TE ; Gurvich, C ; Rossell, SL (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2022-01-01)
    OBJECTIVE: Suicide is a major cause of death amongst individuals with schizophrenia spectrum disorders (SSD). Despite numerous risk factors being identified, accurate prediction of suicidality and provision of tailored and effective treatment is difficult. One factor that may warrant particular attention as a contributor to increased psychopathology and suicidality in SSD is disturbed sleep. Sleep disturbances have been reliably linked to greater levels of suicidal ideation and are highly prevalent amongst individuals with SSD. This study aimed to examine if reduced sleep duration and psychopathology are associated with increased suicidal ideation. METHOD: One-hundred and eighteen adults with chronic SSD living within the community participated in this cross-sectional study. Psychosis symptoms were assessed using the Positive and Negative Syndrome Scale. Items 4 and 10 from the Montgomery-Asperg Depression Rating Scale and Item 2 from the Calgary Depression Scale for Schizophrenia were used to assess reduced sleep duration, current suicidal ideation, and hopelessness, respectively. All measures were rated concurrently. RESULTS: A hierarchical logistic regression revealed that greater acute sleep disturbances were associated with increased suicidal ideation and this relationship was found to be uniquely mediated by both positive symptom severity and hopelessness. CONCLUSION: These results suggest that individuals with SSD who exhibited disrupted or disordered sleep, positive symptoms and/or hopelessness should be routinely screened for suicidal thinking. Furthermore, interventions that effectively target sleep disruptions may provide much-needed action against suicidal ideation.HIGHLIGHTSReduced sleep found to be associated with increased suicidal ideationThis was uniquely mediated by both hopelessness and positive symptomsMore regular screening of sleep problems in schizophrenia is needed.
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    Characterisation of Deficits and Sex Differences in Verbal and Visual Memory/Learning in Bipolar Disorder
    Gogos, A ; Son, J ; Rossell, SL ; Karantonis, J ; Furlong, LS ; Felmingham, K ; Van Rheenen, TE (CAMBRIDGE UNIV PRESS, 2023-01)
    OBJECTIVE: Cognitive impairment is consistently reported in bipolar disorder (BD), but few studies have characterised which memory component processes are affected. Further, it is unknown whether the component processes underlying memory impairment are moderated by sex. The present study examined diagnosis and sex differences in both verbal and visual memory/learning domains in patients with BD and psychiatrically healthy controls. METHOD: Verbal and visual memory/learning were measured using the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). 114 patients with BD (n = 50 males, n = 64 females), were compared to 105 psychiatrically healthy controls (n = 42 males, n = 63 females). RESULTS: Patients with BD had worse performance in verbal and visual immediate and total recall, verbal and visual delayed free recall, and verbal recognition discrimination scores, but there were no group differences in learning slopes and cumulative learning index scores. There were trends for BD females to outperform BD males in visual memory/learning free recall and cumulative learning, but these results did not survive multiple testing correction. These findings did not change in a secondary sensitivity analysis comparing only strictly euthymic BD patients to controls (n = 64). CONCLUSION: The present study found trait-like verbal and visual memory/learning impairment in BD that was attributable to deficient encoding and/or consolidation processes rather than deficits in learning. We did not find marked sex differences in either visual or verbal memory/learning measures, although some trend level effects were apparent and deserve exploration in future studies.
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    Understanding familial liability for emotion regulation difficulties in bipolar disorder
    Van Rheenen, TE ; Miskowiak, K ; Karantonis, J ; Furlong, LS ; Murray, G ; Rossell, SL (CAMBRIDGE UNIV PRESS, 2022-10)
    BACKGROUND: There has been relatively limited work focused on understanding whether relatives of individuals with bipolar disorder (BD) have difficulties in the regulation of emotion, particularly in relation to perceptions about whether emotions can be effectively regulated, or trait behaviours that acknowledge emotions as self-regulators themselves. In this study, we assessed the presence and extent of difficulties in these dimensions of emotion regulation in individuals with BD compared to unaffected first-degree biological relatives (FDR) for the first time. METHODS: In total, 161 participants, including euthymic individuals with BD, unaffected FDRs, and healthy controls, were compared on the Difficulties in Emotion Regulation Scale (DERS) - a multi-dimensional measure of habitual emotion regulation. Clinical data were also collected and examined in relation to DERS scores in a secondary analysis. RESULTS: In the BD group, difficulties were evident for most dimensions of emotion regulation as measured by the DERS; and correlated with an earlier onset of illness and more mood episodes. FDRs displayed generally normal emotion regulation, except in terms of their beliefs that emotions can be effectively regulated; on this dimension, their reported difficulty was intermediate to the BD group and controls. CONCLUSION: Habitual emotion regulation difficulties in BD persist irrespective of mood state, are related to the course of illness, and should be targeted in psychological interventions. Further, the perception that emotions cannot be effectively regulated during times of distress seems to represent an endophenotype for BD.
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    Evidence that a working memory cognitive phenotype within schizophrenia has a unique underlying biology
    Dean, B ; Thomas, EHX ; Bozaoglu, K ; Tan, EJ ; Rheenen, TEV ; Neill, E ; Sumner, PJ ; Carruthers, SP ; Scarr, E ; Rossell, SL ; Gurvich, C (ELSEVIER IRELAND LTD, 2022-11)
    It is suggested studying phenotypes within the syndrome of schizophrenia will accelerate understanding the complex molecular pathology of the disorder. Supporting this hypothesis, we have identified a sub-group within schizophrenia with impaired working memory (WM) and have used Affymetrix™ Human Exon 1.0 ST Arrays to compare their blood RNA levels (n=16) to a group of with intact WM (n=18). Levels of 72 RNAs were higher in blood from patients with impaired WM, 11 of which have proven links to the maintenance of different aspects of working memory (cognition). Overall, changed gene expression in those with impaired WM could be linked to cognition through glutamatergic activity, olfaction, immunity, inflammation as well as energy and metabolism. Our data gives preliminary support to the hypotheses that there is a working memory deficit phenotype within the syndrome of schizophrenia with has a biological underpinning. In addition, our data raises the possibility that a larger study could show that the specific changes in gene expression we have identified could prove to be the biomarkers needed to develop a blood test to identify those with impaired WM; a significant step toward allowing the use of personalised medicine directed toward improving their impaired working memory.
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    Psychological-health correlates of physical activity and sedentary behaviour during the COVID pandemic
    Ringin, E ; Meyer, D ; Neill, E ; Phillipou, A ; Tan, EJ ; Toh, WL ; Sumner, PJ ; Owen, N ; Hallgren, M ; Dunstan, DW ; Rossell, SL ; Van Rheenen, TE (ELSEVIER SCI LTD, 2022-10)
    BACKGROUND: While physical inactivity is associated with adverse psychological outcomes, less is known about the psychological outcomes associated with sedentary behaviour, and specifically, its mentally active and passive forms. The COVID-19 pandemic represents a unique opportunity to study associations between these variables in light of widespread stay-at-home mandates and restrictions on outdoor exercise/social activities. Using a cross-sectional dataset acquired during the COVID-19 pandemic in Australia, we examined whether physical activity and sedentary behaviour were associated with subjective quality of life (sQoL) and subjective cognitive dysfunction, and whether these associations were mediated by depressive symptoms. METHODS: 658 participants (males = 169, females = 489) self-reported data on physical activity and sedentary behaviour in an online survey during May 2020-May 2021. Data on physical activity and sedentary behaviour (both mentally active and passive types) was compared according to whether it was collected during or out of a lockdown period. Regression models were used to test associations of physical activity and sedentary behaviour with sQoL and subjective cognitive dysfunction, and whether these associations were mediated by depression severity. RESULTS: Physical activity was beneficially associated with sQoL, whereas sedentary behaviour (both total hours and the reduction of mentally active/increase in mentally passive behaviour) was detrimentally associated with sQoL. These associations were mediated by depression severity. Physical activity and sedentary behaviour were also indirectly associated with subjective cognitive dysfunction by virtue of their associations with depression severity. CONCLUSIONS: There are important differences in the psychological correlates of mentally passive and active sedentary behaviours. Our findings suggest that health promotion strategies should focus on not only increasing physical activity but also reducing passive sedentary behaviours as a means of maintaining good psychological health.
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    Investigating predictors contributing to the expression of schizotypy during the COVID-19 pandemic
    Toh, WL ; Sumner, PJ ; Meyer, D ; Neill, E ; Phillipou, A ; Tan, EJ ; Van Rheenen, TE ; Rossell, SL (PERGAMON-ELSEVIER SCIENCE LTD, 2022-06)
    The coronavirus (COVID-19) pandemic has caused major disruptions to social and other forms of functioning, which may influence schizotypy expression. The current study aimed to explore possible distal and proximal predictors contributing to schizotypy in a sample of the Australian general population during the COVID-19 pandemic. The COvid-19 and you: mentaL heaLth in AusTralia now survEy (COLLATE) project is an online mental health study aimed at tracking key mental health indicators over the progression of the pandemic. Adults residing in Australia were invited to take part using non-discriminative snowball sampling. Demographic-clinical information was collected for 850 participants in either October 2020 or January 2021. To assess schizotypy facets, the Launay-Slade Hallucinations Scale-Extended (LSHS-E) and Peters Delusions Inventory (PDI-21) were used to measure hallucination and delusion proneness respectively. Generalised linear models (with gamma and negative binomial distributions) were employed. Age, negative emotions and loneliness significantly contributed to both hallucination and delusion proneness; gender, education and religiosity also significantly contributed to delusion proneness, in the final regression models. Our study corroborated the specific contribution of loneliness, amongst other factors, in the prediction of schizotypy facets. Tackling loneliness represents a public health challenge that needs to be urgently addressed, especially in the face of the ongoing COVID-19 pandemic.
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    No influence of sex on the relationship between schizotypy factors and executive control across the schizophrenia spectrum
    Gaillard, A ; Tan, EJ ; Carruthers, SP ; Gurvich, C ; Hughes, ME ; Neill, E ; Sumner, PJ ; Van Rheenen, TE ; Rossell, SL (PERGAMON-ELSEVIER SCIENCE LTD, 2022-04)
    Sex differences in symptoms and executive control across schizophrenia spectrum disorders (SSD) are consistently reported. Similarly, these findings of sex differences are also observed in schizotypy, that is, schizophrenia-like features occurring in healthy individuals in the absence of a clinical diagnosis. This study aimed to examine the relationships between performance on three major domains of executive control: performance monitoring, response inhibition, and cognitive set-shifting, and schizotypy factor scores in both SSD patients and healthy controls (HCs), and whether sex moderated any relationships observed. A total of 111 (67 males and 44 females) patients with SSD and 258 (129 males and 129 females) HCs were included in this study. Schizotypal personality traits (in both SSD and HC) was assessed using the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE). Executive control performance was assessed using seven tasks. Stepwise linear regressions revealed that performance on cognitive set-shifting tasks was significantly associated with the introvertive anhedonia, cognitive disorganisation, and unusual experiences subscales of the O-LIFE. When sex was examined as a moderator, it was not a significant moderator of any of the relationships between cognitive set-shifting tasks and schizotypy factors. The results suggest that independent of sex, cognitive set-shifting ability is associated to an increased vulnerability to schizotypal personality traits, although performance monitoring and response inhibition did not.
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    Mindfulness, mood symptom tendencies and quality of life in bipolar disorder: An examination of the mediating influence of emotion regulation difficulties
    Carruthers, SP ; Rossell, SL ; Murray, G ; Karantonis, J ; Furlong, LS ; Van Rheenen, TE (ELSEVIER, 2022-02-01)
    BACKGROUND: The aim of this cross-sectional study was to investigate dispositional mindfulness and its association with depression and manic tendencies, and subjective life quality in bipolar disorder (BD). Furthermore, this study sought to examine the potential mediating effects of emotion regulation difficulties on these relationships. METHOD: Twenty-eight healthy controls (HC) and 66 clinically stable outpatients with a DSM-IV-TR diagnosis of BD completed the Mindfulness Attention Awareness Scale (MAAS), Difficulties in Emotion Regulation Scale (DERS), Seven Up (7 Up) Seven Down (7 Down) and the Quality of Life in Bipolar Disorder Questionnaire (QoL.BD). These variables were compared between groups and entered into a series of mediation analyzes using PROCESS in the BD group only. RESULTS: Lower MAAS scores were detected amongst the BD patients compared to HCs. Lower MAAS scores in BD patients predicted higher 7 Up, 7 Down and lower QoL.BD scores. For the 7 Down and QoL.BD, the associations were completely mediated by DERS scores, with difficulties in strategy use and emotional clarity mediating the association between mindfulness and depressive tendencies and quality of life, respectively. No significant direct or indirect effects were detected for the 7 Up model. LIMITATIONS: The cross-sectional design precludes causal inference. The MAAS conceptualises mindfulness as unidimensional. Self-report scales of depressive and manic tendencies utilised. CONCLUSIONS: This study detected a significant association between dispositional mindfulness and depressive tendencies and life quality in BD, and found that these associations were influenced by emotion regulation difficulties. These findings encourage further investigation of mindfulness-based interventions in BD.
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    Virtual Ontogeny of Cortical Growth Preceding Mental Illness
    Patel, Y ; Shin, J ; Abe, C ; Agartz, I ; Alloza, C ; Alnaes, D ; Ambrogi, S ; Antonucci, LA ; Arango, C ; Arolt, V ; Auzias, G ; Ayesa-Arriola, R ; Banaj, N ; Banaschewski, T ; Bandeira, C ; Basgoze, Z ; Cupertino, RB ; Bau, CHD ; Bauer, J ; Baumeister, S ; Bernardoni, F ; Bertolino, A ; del Mar Bonnin, C ; Brandeis, D ; Brem, S ; Bruggemann, J ; Bulow, R ; Bustillo, JR ; Calderoni, S ; Calvo, R ; Canales-Rodriguez, EJ ; Cannon, DM ; Carmona, S ; Carr, VJ ; Catts, SV ; Chenji, S ; Chew, QH ; Coghill, D ; Connolly, CG ; Conzelmann, A ; Craven, AR ; Crespo-Facorro, B ; Cullen, K ; Dahl, A ; Dannlowski, U ; Davey, CG ; Deruelle, C ; Diaz-Caneja, CM ; Dohm, K ; Ehrlich, S ; Epstein, J ; Erwin-Grabner, T ; Eyler, LT ; Fedor, J ; Fitzgerald, J ; Foran, W ; Ford, JM ; Fortea, L ; Fuentes-Claramonte, P ; Fullerton, J ; Furlong, L ; Gallagher, L ; Gao, B ; Gao, S ; Goikolea, JM ; Gotlib, I ; Goya-Maldonado, R ; Grabe, HJ ; Green, M ; Grevet, EH ; Groenewold, NA ; Grotegerd, D ; Gruber, O ; Haavik, J ; Hahn, T ; Harrison, BJ ; Heindel, W ; Henskens, F ; Heslenfeld, DJ ; Hilland, E ; Hoekstra, PJ ; Hohmann, S ; Holz, N ; Howells, FM ; Ipser, JC ; Jahanshad, N ; Jakobi, B ; Jansen, A ; Janssen, J ; Jonassen, R ; Kaiser, A ; Kaleda, V ; Karantonis, J ; King, JA ; Kircher, T ; Kochunov, P ; Koopowitz, S-M ; Landen, M ; Landro, NI ; Lawrie, S ; Lebedeva, I ; Luna, B ; Lundervold, AJ ; MacMaster, FP ; Maglanoc, LA ; Mathalon, DH ; McDonald, C ; McIntosh, A ; Meinert, S ; Michie, PT ; Mitchell, P ; Moreno-Alcazar, A ; Mowry, B ; Muratori, F ; Nabulsi, L ; Nenadic, I ; Tuura, RO ; Oosterlaan, J ; Overs, B ; Pantelis, C ; Parellada, M ; Pariente, JC ; Pauli, P ; Pergola, G ; Piarulli, FM ; Picon, F ; Piras, F ; Pomarol-Clotet, E ; Pretus, C ; Quide, Y ; Radua, J ; Ramos-Quiroga, JA ; Rasser, PE ; Reif, A ; Retico, A ; Roberts, G ; Rossell, S ; Rovaris, DL ; Rubia, K ; Sacchet, M ; Salavert, J ; Salvador, R ; Sarro, S ; Sawa, A ; Schall, U ; Scott, R ; Selvaggi, P ; Silk, T ; Sim, K ; Skoch, A ; Spalletta, G ; Spaniel, F ; Stein, DJ ; Steinstrater, O ; Stolicyn, A ; Takayanagi, Y ; Tamm, L ; Tavares, M ; Teumer, A ; Thiel, K ; Thomopoulos, SI ; Tomecek, D ; Tomyshev, AS ; Tordesillas-Gutierrez, D ; Tosetti, M ; Uhlmann, A ; Van Rheenen, T ; Vazquez-Bourgon, J ; Vernooij, MW ; Vieta, E ; Vilarroya, O ; Weickert, C ; Weickert, T ; Westlye, LT ; Whalley, H ; Willinger, D ; Winter, A ; Wittfeld, K ; Yang, TT ; Yoncheva, Y ; Zijlmans, JL ; Hoogman, M ; Franke, B ; van Rooij, D ; Buitelaar, J ; Ching, CRK ; Andreassen, OA ; Pozzi, E ; Veltman, D ; Schmaal, L ; van Erp, TGM ; Turner, J ; Castellanos, FX ; Pausova, Z ; Thompson, P ; Paus, T (ELSEVIER SCIENCE INC, 2022-08-15)
    BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.