Psychiatry - Research Publications

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    The Early Mid-Career Committee (EMCC) of the International Society for Bipolar Disorders: Aspirations and goals
    Huber, RS ; Douglas, KM ; Sperry, SH ; Gomes, FA ; Van Rheenen, TE ; Xu, N ; Hosang, GM (Wiley, 2022-12)
    In 2021, the International Society for Bipolar Disorders (ISBD) launched a new global initiative to support researchers and clinicians specializing in bipolar disorder who are still in the process of establishing their careers. To capture the needs of this group, an Early and Mid-Career Committee (EMCC) was formed and tasked with the development of activities and initiatives to address this objective. To this end, the committee conducted a needs assessment survey in early 2022 that was distributed and completed worldwide. This paper, authored by members of the committee, outlines the rationale, process, goals, and aspirations of the EMCC and summarizes the development of the needs survey.
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    Genetic variation in glutamatergic genes moderates the effects of childhood adversity on brain volume and IQ in treatment-resistant schizophrenia.
    Mohamed Saini, S ; Bousman, CA ; Mancuso, SG ; Cropley, V ; Van Rheenen, TE ; Lenroot, RK ; Bruggemann, J ; Weickert, CS ; Weickert, TW ; Sundram, S ; Everall, IP ; Pantelis, C (Springer Science and Business Media LLC, 2023-09-14)
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    Pathways from threat exposure to psychotic symptoms in youth: The role of emotion recognition bias and brain structure
    Thomas, M ; Whittle, S ; Tian, YE ; van Rheenen, TE ; Zalesky, A ; Cropley, VL (ELSEVIER, 2023-11)
    BACKGROUND: Research supports an association between threatening experiences in childhood and psychosis. It is possible that early threat exposure disrupts the development of emotion recognition (specifically, producing a bias for facial expressions relating to threat) and the brain structures subserving it, contributing to psychosis development. METHODS: Using data from the Philadelphia Neurodevelopmental Cohort, we examined associations between threat exposure and both the misattribution of facial expressions to fear/anger in an emotion recognition task, and gray matter volumes in key emotion processing regions. Our sample comprised youth with psychosis spectrum symptoms (N = 304), control youth (N = 787), and to evaluate specificity, youth with internalizing symptoms (N = 92). The moderating effects of group and sex were examined. RESULTS: Both the psychosis spectrum and internalizing groups had higher levels of threat exposure than controls. In the total sample, threat exposure was associated with lower left medial prefrontal cortex (mPFC) volume but not misattributions to fear/anger. The effects of threat exposure did not significantly differ by group or sex. CONCLUSIONS: The findings of this study provide evidence for an effect of threat exposure on mPFC morphology, but do not support an association between threat exposure and a recognition bias for threat-related expressions, that is particularly pronounced in psychosis. Future research should investigate factors linking transdiagnostic alterations related to threat exposure with psychotic symptoms, and attempt to clarify the mechanisms underpinning emotion recognition misattributions in threat-exposed youth.
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    Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness
    Wenzel, J ; Badde, L ; Haas, SS ; Bonivento, C ; Van Rheenen, TE ; Antonucci, LA ; Ruef, A ; Penzel, N ; Rosen, M ; Lichtenstein, T ; Lalousis, PA ; Paolini, M ; Stainton, A ; Dannlowski, U ; Romer, G ; Brambilla, P ; Wood, SJ ; Upthegrove, R ; Borgwardt, S ; Meisenzahl, E ; Salokangas, RKR ; Pantelis, C ; Lencer, R ; Bertolino, A ; Kambeitz, J ; Koutsouleris, N ; Dwyer, DB ; Kambeitz-Ilankovic, L (SPRINGERNATURE, 2024-02)
    Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (NROP = 79, NROD = 30, NCHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (NROP = 61, NROD = 100, NCHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. CLINICAL TRIAL REGISTRY NAME: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042.
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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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