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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    Development of harmonized and co‐calibrated scores for memory, executive functioning, language, and visuospatial in the AIBL Study, ADNI, and NACC datasets
    Crane, PK ; Trittschuh, EH ; Mez, JB ; Saykin, AJ ; Sanders, RE ; Gibbons, LE ; Lee, ML ; Scollard, P ; Choi, S ; Rainey‐Smith, S ; Chooi, CK ; Gavett, BE ; Maruff, P ; Ames, D ; Culhane, JE ; Gauthreaux, K ; Chan, KCG ; Biber, S ; Stephens, K ; Kukull, WA ; Dumitrescu, L ; Hohman, TJ ; Mukherjee, S (Wiley, 2022-12)
    Background The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study is a prospective study collecting extensive cognitive, clinical, fluid, and imaging biomarkers data from older adults living in Australia. Integration of outcomes between large prospective studies of AD will provide greater precision in models of AD brain‐behavior relationships, so it is important to align composite scores for cognitive domains between such studies. Methods Detailed methods for AIBL, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the National Alzheimer’s Coordinating Center (NACC) have been published. Briefly, AIBL participants had cognition assessed with an extensive neuropsychological test battery alongside health and biomarker assessments at entry and each 18‐months thereafter. Granular‐level cognitive data were obtained and an expert panel of two neuropsychologists and a behavioral neurologist categorized each element as assessing memory, executive functioning, language, visuospatial, or none of these, exactly as we have done previously. We also identified elements we had previously calibrated from other studies; after careful quality control and confirmation these served as anchors enabling co‐calibration. We used confirmatory factor analysis bi‐factor models to calibrate the AIBL battery with other studies. We used those calibrations to obtain co‐calibrated scores for all AIBL participants at every study visit. Here we show descriptive statistics for baseline visits, separately by diagnosis (normal cognition, mild cognitive impairment (MCI), dementia) for two enrollment waves for AIBL as well as for each phase of ADNI and across the Uniform Data Set (UDS) 1 & 2 (UDS1/2) and UDS3 time periods for NACC. Results Box plots for memory, executive functioning, language, and visuospatial for people with normal cognition are in Figure 1, MCI in Figure 2, and dementia in Figure 3. These figures show there is substantial cognitive variation across waves within these disease stage groups and across studies. Conclusion Co‐calibrated neuropsychological domain scores provide a common metric for integrating cognitive data across studies. Co‐calibrated scores aggregated across large prospective AD studies such as AIBL, ADNI, and NACC provide a foundation for large‐scale models of the development of AD and can serve as phenotypes for genetics studies. Co‐calibrated scores are available from AIBL, ADNI, and from NACC.
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    Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from ‘phenocopy’ non‐progressors
    Keem, MH ; Eratne, D ; Lewis, C ; Kang, M ; Walterfang, M ; Loi, SM ; Kelso, W ; Cadwallader, C ; Berkovic, SF ; Li, Q ; Masters, CL ; Collins, S ; Santillo, A ; Velakoulis, D (Wiley, 2022-12)
    Background Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non‐neurodegenerative ‘non‐progressor’, ‘phenocopy’ mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay. Method Cerebrospinal fluid (CSF) NfL, amyloid beta 1‐42 (AB42), total and phosphorylated tau (T‐tau, P‐tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow up information, patients were categorised as Progressors. Non‐Progressors were subtyped in to Phenocopy Non‐Progressors (non‐neurological/neurodegenerative final diagnosis), and Static Non‐Progressors (static deficits, not fully explained by non‐neurological/neurodegenerative causes). Result Forty‐three patients were included: 20 Progressors, 23 Non‐Progressors (15 Phenocopy, 8 Static), 20 controls. NfL concentrations were lower in Non‐Progressors (Non‐Progressors Mean, M=554pg/mL, 95%CI:[461, 675], Phenocopy Non‐Progressors M=459pg/mL, 95%CI:[385, 539], Static Non‐Progressors M=730pg/mL, 95%CI:[516, 940]), compared to bvFTD Progressors (M=2397pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non‐Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Static Non‐Progressors tended to have higher T‐tau and P‐tau levels compared to Phenocopy Non‐Progressors. Conclusion This study demonstrated strong diagnostic utility of CSF NfL in distinguishing bvFTD from phenocopy non‐progressor variants, at baseline, with high accuracy, in a real‐world clinical setting. This has important clinical implications to improve outcomes for patients and clinicians facing this challenging clinical dilemma, as well as for healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non‐progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL.
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    Maintain Your Brain: a 3‐year online randomized controlled trial to reduce cognitive decline in 55‐77 year olds
    Brodaty, H ; Heffernan, M ; Singh, MAF ; Valenzuela, M ; Lautenschlager, NT ; Anstey, KJ ; Sachdev, PS ; Jorm, L ; McNeil, J ; Maeder, A ; Ginige, JA ; Chau, T ; Jose, JCS ; Millard, M ; Welberry, H (Wiley, 2022-12)
    Background Technology and web‐based approaches potentially provide scalable population‐based interventions to reduce modifiable risk factors for dementia such as physical inactivity, suboptimal nutrition and low cognitive activity. Our aim was to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months followed by monthly boosters for 24 months. The trial was completed in November 2021. Method Invitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). Participants were required to be eligible for at least two of four modules. The modules addressed physical inactivity and health risks associated with inactivity (Physical Activity), adherence to a Mediterranean‐type diet and health risks associated with poor nutrition (Nutrition), cognitive activity (Brain Training) and mental well‐being (Peace of Mind). All participants received modules based on their risks, with randomized allocation to active personalised coaching modules (intervention) or static information‐based modules (control). The primary outcome was change in an online combined multi‐domain cognitive score measured using COGSTATE and Cambridge Brain Sciences tests. Secondary outcomes included ANU‐ADRI risk score, specific cognitive domain scores and diagnoses of dementia. Result From 96,418 invitations, 14,064 (14%) consented; 12,281 (13%) were eligible. Of these, 6,236 (6%) completed all 10 baseline assessments and were enrolled in the trial. Nearly 70% or 4,365 participants provided follow‐up data. At final 36‐months’ follow‐up, 3,482 (55.8%) completed the primary outcome and 2594 (41.6%) had returned informant‐rated Amsterdam‐Instrumental Activities of Daily Living Scale questionnaires. Conclusion Online strategies to prevent cognitive decline in 55‐77 year olds are feasible and appear acceptable for more than half of participants. Analysis of group*time effects will be presented.
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    Objectively measured physical activity and cognition in cognitively normal older adults: A longitudinal analysis of the Australian Imaging Biomarkers and Lifestyle (AIBL) study
    Sewell, KR ; Rainey‐Smith, S ; Villemagne, VL ; Peiffer, JJ ; Sohrabi, HR ; Taddei, K ; Ames, D ; Maruff, P ; Laws, SM ; Masters, CL ; Rowe, C ; Martins, RN ; Erickson, KI ; Brown, BM (Wiley Open Access, 2022-12)
    Background Physical inactivity is one of the greatest modifiable risk factors for dementia and research shows physical activity can delay cognitive decline in older adults. However, much of this research has used subjective physical activity data and a single follow‐up cognitive assessment. Further studies using objectively measured physical activity and comprehensive cognitive data measured at multiple timepoints are required. Methods Participants were 199 community‐dwelling cognitively normal older adults (68.7 5.9 years) from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Actigraphy was used to measure physical activity at baseline, yielding measures of intensity (peak counts), total activity (total counts) and energy expenditure (kilocalories; k/cal). Cognitive function was assessed using a cognitive battery administered every 18‐months from baseline (3‐11 years follow‐up), yielding composite scores for episodic memory, executive function, attention and processing speed, and global cognition. Results Higher baseline energy expenditure predicted improvements in episodic memory and maintained global cognition over time (β = 0.011, SE = 0.005, p = 0.031; β = 0.009, SE = 0.004, p = 0.047, respectively). Both physical activity intensity and total activity predicted global cognition, such that those with higher peak and total counts had better cognition over time (β = 0.012, SE = 0.004, p = 0.005; β = 0.012, SE = 0.004, p = 0.005, respectively). Finally, higher total activity predicted improved episodic memory over time (β = 0.011, SE = 0.005, p = .022). Conclusion These results suggest that physical activity is associated with preserved cognitive function over time, and that activity intensity may play an important role. This research further highlights the importance of early intervention to prevent cognitive decline and may aid in informing lifestyle interventions for dementia prevention.
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    Plasma glial fibrillary acidic protein is associated with reactive astrogliosis assessed via 18F-SMBT-1 PET
    Chatterjee, P ; Dore, V ; Pedrini, S ; Krishnadas, N ; Thota, RN ; Bourgeat, P ; Rainey‐Smith, S ; Burnham, SC ; Fowler, C ; Taddei, K ; Mulligan, RS ; Ames, D ; Masters, CL ; Fripp, J ; Rowe, C ; Martins, RN ; Villemagne, VL (Wiley, 2022-12)
    Background Reactive astrogliosis is an early event along the Alzheimer’s disease (AD) continuum. We have shown that plasma glial fibrillary acidic protein (GFAP), reflecting reactive astrogliosis, is elevated in cognitively unimpaired individuals with preclinical AD (Chatterjee et al., 2021). We reported similar findings using 18F‐SMBT‐1, a PET tracer for monoamine oxidase B (MAO‐B) (Villemagne et al., 2022). To provide further evidence of their relationship with reactive astrogliosis we investigated the association between GFAP and 18F‐SMBT‐1 in the same participants. Method Plasma GFAP, Aβ42 and Aβ40 levels were measured using the Single Molecule Array platform in 71 participants comprising 54 healthy controls (12 Aβ+ and 42 Aβ‐), 11 MCI(3 Aβ+ and 8 Aβ‐) and 6 probable AD(5 Aβ+ and 1 Aβ‐) patients from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing cohort. These participants also underwent 18F‐SMBT‐1 and Aβ PET imaging. Aβ imaging results were expressed in Centiloids (CL; ≥20 CL classified as Aβ+). 18F‐SMBT‐1 Standard Uptake Value Ratio (SUVR) were generated using the subcortical white matter as reference region. Linear regression analyses were carried out using plasma GFAP levels as the dependent variable and regional 18F‐SMBT‐1 SUVR as the independent variable, before and after adjusting for age, sex, soluble Aβ (plasma Aβ1‐42/Aβ1‐40 ratio) and insoluble Aβ (Aβ PET). Result Plasma GFAP was significantly associated with 18F‐SMBT‐1 SUVR in brain regions of early Aβ deposition, such as the supramarginal gyrus (SG, β=.361, p=.002), posterior cingulate (PC, β=.308, p=.009), lateral temporal (LT, β=.299, p=.011), lateral occipital (LO, β=.313, p=.008) before adjusting for any covariates. After adjusting for covariates age, sex and soluble Aβ, GFAP was significantly associated with 18F‐SMBT‐1 PET signal in the SG (β=.333, p<.001), PC (β=.278, p=.005), LT (β=.256, p=.009), LO (β=.296, p=.004) and superior parietal (SP, β=.243, p=.016). On adjusting for age, sex and insoluble Aβ, GFAP was significantly associated with SMBT‐1 PET in the SG (β=.211, p=.037) however only a trend towards significance was observed in the PC (β=.186, p=.052) and LT (β=.171, p=.067) (Figure 1). Conclusion There is an association between plasma GFAP and regional SMBT‐1 PET that is primarily driven by brain Aβ load.
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    BRINGING THE BENCH TO THE BEDSIDE: UPDATES ON THE MIND STUDY AND WHAT A ROUTINELY AVAILABLE SIMPLE BLOOD TEST FOR NEUROFILAMENT LIGHT WOULD MEAN AT THE CLINICAL COAL FACE FOR PATIENTS AND FAMILIES, PSYCHIATRISTS, NEUROLOGISTS, GERIATRICIANS AND GENERAL PRACTITIONERS
    Eratne, D ; Lewis, C ; Cadwallader, C ; Kang, M ; Keem, M ; Santillo, A ; Li, QX ; Stehmann, C ; Loi, SM ; Walterfang, M ; Watson, R ; Yassi, N ; Blennow, K ; Zetterberg, H ; Janelidze, S ; Hansson, O ; Berry-Kravitz, E ; Brodtmann, A ; Darby, D ; Walker, A ; Dean, O ; Masters, CL ; Collins, S ; Berkovic, SF ; Velakoulis, D (SAGE PUBLICATIONS LTD, 2022-05)
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    Early interventions for youth at high risk for bipolar disorder
    Miklowitz, DJ ; Berk, M ; DelBello, MP (WILEY, 2022-12)
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    NICE guideline for depression ranks short-term psychodynamic psychotherapy (STTP)
    Malhi, GS ; Bell, E ; Boyce, P ; Mulder, R ; Bassett, D ; Hamilton, A ; Morris, G ; Bryant, R ; Hazell, P ; Hopwood, M ; Lyndon, B ; Porter, R ; Singh, AB ; Murray, G (WILEY, 2022-08)
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    A psychological group intervention for high-risk pregnant women: a protocol of a feasibility and acceptability study of the STAR Mums program
    Bellhouse, C ; Komiti, A ; Temple-Smith, M ; Bilardi, J ; Newman, L (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2022-07-04)
    BACKGROUND: In pregnancy, the attachment relationship between a mother and her baby begins to develop and women are more motivated and willing to make changes to become more engaged and responsive mothers and have better relationships with their children. A transgenerational framework has proposed that dysfunctional relationship patterns are often repeated across generations and this has broadened the understanding of early difficulties in parenting. Despite this there has been little research specifically examining high-risk perinatal women and how their interactions with their infants are related to attachment or relational outcomes. METHODS: This pilot study aims to evaluate, and to explore the acceptability and feasibility, of participating in the Supporting Transitions, Attachment and Relationships (STAR Mums) program, a psychodynamic attachment-based group intervention, for pregnant women with risk factors for attachment difficulties. The STAR Mums program aims to intervene during pregnancy to assist women with risk factors in the transition to parenthood with the desired outcome to improve the quality of mother-infant emotional interactions, regulation and the attachment relationship. This is a mixed-methods design study incorporating both qualitative and quantitative assessments of five groups of five first-time mothers over a 12-month period. CONCLUSIONS: This paper outlines the STAR Mums intervention and protocol for assessing acceptability and feasibility. The STAR Mums program takes a preventative approach and supports early intervention for parents at risk of attachment difficulties with their infants. The results of this study will inform revisions to the current treatment manual and a larger-scale program evaluation to further examine the efficacy of this intervention.