Psychiatry - Research Publications

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    The use of component-wise gradient boosting to assess the possible role of cognitive measures as markers of vulnerability to pediatric bipolar disorder.
    Bauer, IE ; Suchting, R ; Van Rheenen, TE ; Wu, M-J ; Mwangi, B ; Spiker, D ; Zunta-Soares, GB ; Soares, JC (Informa UK Limited, 2019-03)
    BACKGROUND AND AIMS: Cognitive impairments are primary hallmarks symptoms of bipolar disorder (BD). Whether these deficits are markers of vulnerability or symptoms of the disease is still unclear. This study used a component-wise gradient (CGB) machine learning algorithm to identify cognitive measures that could accurately differentiate pediatric BD, unaffected offspring of BD parents, and healthy controls. METHODS: 59 healthy controls (HC; 11.19 ± 3.15 yo; 30 girls), 119 children and adolescents with BD (13.31 ± 3.02 yo, 52 girls) and 49 unaffected offspring of BD parents (UO; 9.36 ± 3.18 yo; 22 girls) completed the CANTAB cognitive battery. RESULTS: CGB achieved accuracy of 73.2% and an AUROC of 0.785 in classifying individuals as either BD or non-BD on a dataset held out for validation for testing. The strongest cognitive predictors of BD were measures of processing speed and affective processing. Measures of cognition did not differentiate between UO and HC. CONCLUSIONS: Alterations in processing speed and affective processing are markers of BD in pediatric populations. Longitudinal studies should determine whether UO with a cognitive profile similar to that of HC are at less or equal risk for mood disorders. Future studies should include relevant measures for BD such as verbal memory and genetic risk scores.
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    Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings
    Russo, M ; Van Rheenen, TE ; Shanahan, M ; Mahon, K ; Perez-Rodriguez, MM ; Cuesta-Diaz, A ; Larsen, E ; Malhotra, AK ; Burdick, KE (CAMBRIDGE UNIV PRESS, 2017-12)
    BACKGROUND: Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters. METHODS: Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71). RESULTS: Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs. CONCLUSIONS: This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.
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    FRONTOSTRIATAL CONNECTIVITY IN TREATMENT-RESISTANT SCHIZOPHRENIA: RELATIONSHIP TO POSITIVE SYMPTOMS AND COGNITIVE FLEXIBILITY
    Cropley, V ; Ganella, E ; Wannan, C ; Zalesky, A ; Van Rheenen, T ; Bousman, C ; Everall, I ; Fornito, A ; Pantelis, C (OXFORD UNIV PRESS, 2018-04)
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    Affective cognition in bipolar disorder: A systematic review by the ISBD targeting cognition task force
    Miskowiak, KW ; Seeberg, I ; Kjaerstad, HL ; Burdick, KE ; Martinez-Aran, A ; del Mar Bonnin, C ; Bowie, CR ; Carvalho, AF ; Gallagher, P ; Hasler, G ; Lafer, B ; Lopez-Jaramillo, C ; Sumiyoshi, T ; McIntyre, RS ; Schaffer, A ; Porter, RJ ; Purdon, S ; Torres, IJ ; Yatham, LN ; Youn, AH ; Kessing, L ; Van Rheenen, TE ; Vieta, E (WILEY, 2019-12)
    BACKGROUND: Impairments in affective cognition are part of the neurocognitive profile and possible treatment targets in bipolar disorder (BD), but the findings are heterogeneous. The International Society of Bipolar Disorder (ISBD) Targeting Cognition Task Force conducted a systematic review to (i) identify the most consistent findings in affective cognition in BD, and (ii) provide suggestions for affective cognitive domains for future study and meta-analyses. METHODS: The review included original studies reporting behavioral measures of affective cognition in BD patients vs controls following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Searches were conducted on PubMed/MEDLINE, EMBASE, and PsychInfo from inception until November 2018. RESULTS: A total of 106 articles were included (of which nine included data for several affective domains); 41 studies assessed emotional face processing; 23 studies investigated reactivity to emotional words and images; 3 investigated explicit emotion regulation; 17 assessed implicit emotion regulation; 31 assessed reward processing and affective decision making. In general, findings were inconsistent. The most consistent findings were trait-related difficulties in facial emotion recognition and implicit emotion regulation, and impairments in reward processing and affective decision making during mood episodes. Studies using eye-tracking and facial emotion analysis revealed subtle trait-related abnormalities in emotional reactivity. CONCLUSION: The ISBD Task Force recommends facial expression recognition, implicit emotion regulation, and reward processing as domains for future research and meta-analyses. An important step to aid comparability between studies in the field would be to reach consensus on an affective cognition test battery for BD.
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    Sex differences in schizophrenia, bipolar disorder, and post-traumatic stress disorder: Are gonadal hormones the link?
    Gogos, A ; Ney, LJ ; Seymour, N ; Van Rheenen, TE ; Felmingham, KL (WILEY, 2019-11)
    In this review, we describe the sex differences in prevalence, onset, symptom profiles, and disease outcome that are evident in schizophrenia, bipolar disorder, and post-traumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men. By contrast, women with post-traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. This review details the clinical evidence that oestradiol and progesterone are dysregulated in these psychiatric disorders. Notably, existing data on oestradiol, and to a lesser extent, progesterone, suggest that low levels of these hormones may increase the risk of disease development and worsen symptom severity. We argue that future studies require a more inclusive, considered analysis of gonadal steroid hormones and the intricacies of the interactions between them, with methodological rigour applied, to enhance our understanding of the roles of steroid hormones in psychiatric disorders. LINKED ARTICLES: This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc.
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    The International Consortium Investigating Neurocognition in Bipolar Disorder (ICONIC-BD)
    Burdick, KE ; Millett, CE ; del Mar Bonnin, C ; Bowie, CR ; Carvalho, AF ; Eyler, LT ; Gallagher, P ; Harvey, PD ; Kessing, LV ; Lafer, B ; Langenecker, SA ; Lewandowski, KE ; Lopez-Jaramillo, C ; Marshall, DF ; Martinez-Aran, A ; McInnis, MG ; McIntyre, RS ; Miskowiak, KW ; Porter, RJ ; Purdon, SE ; Ryan, KA ; Sumiyoshi, T ; Torres, IJ ; Van Rheenen, TE ; Vieta, E ; Woodward, ND ; Yatham, LN ; Young, A (WILEY, 2019-02)
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    A Prospective Cohort Study of Antipsychotic Medications in Pregnancy: The First 147 Pregnancies and 100 One Year Old Babies
    Kulkarni, J ; Worsley, R ; Gilbert, H ; Gavrilidis, E ; Van Rheenen, TE ; Wang, W ; McCauley, K ; Fitzgerald, P ; McKenna, PJ (PUBLIC LIBRARY SCIENCE, 2014-05-02)
    BACKGROUND: Many women diagnosed with varying psychiatric disorders take antipsychotic medications during pregnancy. The safety of antipsychotic medications in pregnancy is largely unknown. METHODS: We established the National Register of Antipsychotic Medications in Pregnancy in 2005. Women who are pregnant and taking an antipsychotic medication are interviewed every 6 weeks during pregnancy and then followed until their babies are one year old. The baby's progress is closely followed for the first year of life. FINDINGS: As of April 18 2012, 147 pregnancies had been followed through to completion. There were 142 live births and data is available for 100 one year old babies. 18% of babies were born preterm, with a higher dose of antipsychotic medication correlating to an increased likelihood of premature delivery; 43% of babies required special care nursery or intensive care after birth; 37% had any degree of respiratory distress and 15% of babies developed withdrawal symptoms. Congenital anomalies were seen in eight babies. Most pregnancies resulted in the birth of live, healthy babies. The use of mood stabilisers or higher doses of antipsychotics during pregnancy increased the likelihood of babies experiencing respiratory distress or admission to Special Care Nursery or Neonatal Intensive Care Units. CONCLUSION: There is a great need for safety and efficacy information about the use of antipsychotic medications in pregnancy. Live, healthy babies are the most common outcome following the use of antipsychotic medication in pregnancy, but clinicians should be particularly mindful of neonatal problems such as respiratory distress.
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    The Role of Estrogen in the Treatment of Men with Schizophrenia
    Kulkarni, J ; Gavrilidis, E ; Worsley, R ; Van Rheenen, T ; Hayes, E (KOWSAR CORP, 2013)
    Schizophrenia is a debilitating and pervasive mental illness with devastating effects on many aspects of psychological, cognitive and social wellbeing. Epidemiological and life-cycle data point to significant differences in the incidence and course of schizophrenia between men and women, suggesting that estrogen plays a "protective" role . Adjunctive estrogen therapy has been shown to be effective in enhancing the treatment of schizophrenia in women. In men, consideration of estrogen therapy has been impacted by concerns of feminisation, however, clinical trials using estrogen to treat prostate cancer, bone density loss and even aggression in men with dementia or traumatic brain injury, show estrogen to be a safe and effective therapy. Findings do, however, suggest that further exploration of a therapeutic role for adjunctive estradiol treatment in men with schizophrenia is warranted. The development of the new estrogen compounds - Selective Estrogen Receptor Modulators (SERMs) which do not cause feminisation - opens up the possibility of using a different type of estrogen for a longer period of time at higher doses. Estrogen could therefore prove to be an important component in the treatment of psychotic symptoms in men with schizophrenia. This review explains the scientific rationale behind the estrogen hypothesis and how it can be clinically utilised to address concerns unique to the care of men with schizophrenia.
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    Hippocampal subfields and visuospatial associative memory across stages of schizophrenia-spectrum disorder
    Wannan, CMJ ; Cropley, VL ; Chakravarty, MM ; Van Rheenen, TE ; Mancuso, S ; Bousman, C ; Everall, I ; McGorry, PD ; Pantelis, C ; Bartholomeusz, CF (CAMBRIDGE UNIV PRESS, 2019-10)
    BACKGROUND: While previous studies have identified relationships between hippocampal volumes and memory performance in schizophrenia, these relationships are not apparent in healthy individuals. Further, few studies have examined the role of hippocampal subfields in illness-related memory deficits, and no study has examined potential differences across varying illness stages. The current study aimed to investigate whether individuals with early and established psychosis exhibited differential relationships between visuospatial associative memory and hippocampal subfield volumes. METHODS: Measurements of visuospatial associative memory performance and grey matter volume were obtained from 52 individuals with a chronic schizophrenia-spectrum disorder, 28 youth with recent-onset psychosis, 52 older healthy controls, and 28 younger healthy controls. RESULTS: Both chronic and recent-onset patients had impaired visuospatial associative memory performance, however, only chronic patients showed hippocampal subfield volume loss. Both chronic and recent-onset patients demonstrated relationships between visuospatial associative memory performance and hippocampal subfield volumes in the CA4/dentate gyrus and the stratum that were not observed in older healthy controls. There were no group by volume interactions when chronic and recent-onset patients were compared. CONCLUSIONS: The current study extends the findings of previous studies by identifying particular hippocampal subfields, including the hippocampal stratum layers and the dentate gyrus, that appear to be related to visuospatial associative memory ability in individuals with both chronic and first-episode psychosis.