Centre for Youth Mental Health - Research Publications

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    Remote Control in Formation of 3D Multicellular Assemblies Using Magnetic Forces
    Jafari, J ; Han, X-L ; Palmer, J ; Tran, PA ; O'Connor, AJ (AMER CHEMICAL SOC, 2019-05)
    Cell constructs have been utilized as building blocks in tissue engineering to closely mimic the natural tissue and also overcome some of the limitations caused by two-dimensional cultures or using scaffolds. External forces can be used to enhance the cells' adhesion and interaction and thus provide better control over production of these structures compared to methods like cell seeding and migration. In this paper, we demonstrate an efficient method to generate uniform, three-dimensional cell constructs using magnetic forces. This method produced spheroids with higher densities and more symmetrical structures than the commonly used centrifugation method for production of cell spheroids. It was also shown that shape of the cell constructs could be changed readily by using different patterns of magnetic field. The application of magnetic fields to impart forces on the cells enhanced the fusion of these spheroids, which could be used to produce larger and more complicated structures for future tissue engineering applications.
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    MGLU5 receptors are necessary for extinction of drug associated cues and contexts
    Perry, C ; Reed, F ; Luikinga, S ; Zbukvic, I ; Kim, JH ; Lawrence, A (Wiley, 2017-08-01)
    Drug-associated cues and contexts are strong predictors of relapse. We used complex behavioural preparations to examine whether extinction of such cues reduces their capacity to trigger drug-seeking. We also examined whether the mGlu5 receptor is necessary for extinction learning. In Experiment 1, rats were trained to lever press for cocaine. Once stable responding was established, the context was extinguished by replacing the rats in the chambers, but with no opportunity to respond (levers were retracted). Control group remained in their home cage. An mGlu5 receptor negative allosteric modulator (MTEP) or vehicle was administered immediately after context extinction sessions. During subsequent drug-induced reinstatement, rats responded less if they had received context extinction; however, this effect was attenuated where MTEP had been applied. In Experiment 2, rats were trained to lever press for cocaine, now paired with a cue light. To extinguish the cue, half of the rats were placed in the chambers and given non-reinforced presentations of the cue, but with the levers retracted. Control rats remained in home cage. All rats received either MTEP or vehicle 20 minutes prior. Cue-induced reinstatement was tested the following day by re-pairing the lever with the light. Rats gave fewer drug-seeking responses following cue extinction. This effect was attenuated by MTEP. Experiment 3 followed the same protocol as Experiment 2, except that a positive allosteric modulator CDPPB or vehicle was administered 20 minutes before CS extinction. At reinstatement, cue-elicited cocaine seeking was lower for the animals that had previously been administered CDPPB, regardless of extinction condition. This study highlights the important role cues and contexts play in driving drug-seeking behaviour during reinstatement. It also shows that mGlu 5 signalling is necessary for extinction of drug-cue associations, and that mGlu5 positive allosteric modulators are promising targets for treating cocaine addiction.
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    Designing an App for Pregnancy Care for a Culturally and Linguistically Diverse Community
    Smith, W ; Wadley, G ; Daly, JO ; Webb, M ; Hughson, J ; Hajek, J ; Parker, A ; Woodward-Kron, R ; Story, DA (The Association for Computing Machinery, 2017)
    We report a study to design and evaluate an app to support pregnancy information provided to women through an Australian health service. As part of a larger project to provide prenatal resources for culturally and linguistically diverse groups, this study focused on the design and reception of an app with the local Vietnamese community and health professionals of a particular hospital. Our study had three stages: an initial design workshop with the hospital; prototype design and development; prototype-based interviews with health professionals and focus groups with Vietnamese women. We explore how an app of this sort must be designed for a range of different use scenarios, considering its use by consumers with a multiplicity of differing viewpoints about its nature and purpose in relation to pregnancy care.
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    The operational environment and rotational acceleration of asteroid (101955) Bennu from OSIRIS-REx observations
    Hergenrother, CW ; Maleszewski, CK ; Nolan, MC ; Li, J-Y ; d'Aubigny, CYD ; Shelly, FC ; Howell, ES ; Kareta, TR ; Izawa, MRM ; Barucci, MA ; Bierhaus, EB ; Campins, H ; Chesley, SR ; Clark, BE ; Christensen, EJ ; DellaGiustina, DN ; Fornasier, S ; Golish, DR ; Hartzell, CM ; Rizk, B ; Scheeres, DJ ; Smith, PH ; Zou, X-D ; Lauretta, DS ; Highsmith, DE ; Small, J ; Vokrouhlicky, D ; Bowles, NE ; Brown, E ; Hanna, KLD ; Warren, T ; Brunet, C ; Chicoine, RA ; Desjardins, S ; Gaudreau, D ; Haltigin, T ; Millington-Veloza, S ; Rubi, A ; Aponte, J ; Gorius, N ; Lunsford, A ; Allen, B ; Grindlay, J ; Guevel, D ; Hoak, D ; Hong, J ; Schrader, DL ; Bayron, J ; Golubov, O ; Sanchez, P ; Stromberg, J ; Hirabayashi, M ; Oliver, S ; Rascon, M ; Harch, A ; Joseph, J ; Squyres, S ; Richardson, D ; Emery, JP ; McGraw, L ; Ghent, R ; Binzel, RP ; Al Asad, MM ; Johnson, CL ; Philpott, L ; Susorney, HCM ; Cloutis, EA ; Hanna, RD ; Connolly, HC ; Ciceri, F ; Hildebrand, AR ; Ibrahim, E-M ; Breitenfeld, L ; Glotch, T ; Rogers, AD ; Ferrone, S ; Thomas, CA ; Fernandez, Y ; Chang, W ; Cheuvront, A ; Trang, D ; Tachibana, S ; Yurimoto, H ; Brucato, JR ; Poggiali, G ; Pajola, M ; Dotto, E ; Epifani, EM ; Crombie, MK ; Lantz, C ; de Leon, J ; Licandro, J ; Rizos Garcia, JL ; Clemett, S ; Thomas-Keprta, K ; Van Wal, S ; Yoshikawa, M ; Bellerose, J ; Bhaskaran, S ; Boyles, C ; Elder, CM ; Farnocchia, D ; Harbison, A ; Kennedy, B ; Knight, A ; Martinez-Vlasoff, N ; Mastrodemos, N ; McElrath, T ; Owen, W ; Park, R ; Rush, B ; Swanson, L ; Takahashi, Y ; Velez, D ; Yetter, K ; Thayer, C ; Adam, C ; Antreasian, P ; Bauman, J ; Bryan, C ; Carcich, B ; Corvin, M ; Geeraert, J ; Hoffman, J ; Leonard, JM ; Lessac-Chenen, E ; Levine, A ; McAdams, J ; McCarthy, L ; Nelson, D ; Page, B ; Pelgrift, J ; Sahr, E ; Stakkestad, K ; Stanbridge, D ; Wibben, D ; Williams, B ; Williams, K ; Wolff, P ; Hayne, P ; Kubitschek, D ; Deshapriya, JDP ; Fulchignoni, M ; Hasselmann, P ; Merlin, F ; Praet, A ; Billett, O ; Boggs, A ; Buck, B ; Carlson-Kelly, S ; Cerna, J ; Chaffin, K ; Church, E ; Coltrin, M ; Daly, J ; Deguzman, A ; Dubisher, R ; Eckart, D ; Ellis, D ; Falkenstern, P ; Fisher, A ; Fisher, ME ; Fleming, P ; Fortney, K ; Francis, S ; Freund, S ; Gonzales, S ; Haas, P ; Hasten, A ; Hauf, D ; Hilbert, A ; Howell, D ; Jaen, F ; Jayakody, N ; Jenkins, M ; Johnson, K ; Lefevre, M ; Ma, H ; Mario, C ; Martin, K ; May, C ; McGee, M ; Miller, B ; Miller, C ; Miller, G ; Mirfakhrai, A ; Muhle, E ; Norman, C ; Olds, R ; Parish, C ; Ryle, M ; Schmitzer, M ; Sherman, P ; Skeen, M ; Susak, M ; Sutter, B ; Tran, Q ; Welch, C ; Witherspoon, R ; Wood, J ; Zareski, J ; Arvizu-Jakubicki, M ; Asphaug, E ; Audi, E ; Ballouz, R-L ; Bandrowski, R ; Becker, KJ ; Becker, TL ; Bendall, S ; Bennett, CA ; Bloomenthal, H ; Blum, D ; Boynton, W ; Brodbeck, J ; Burke, KN ; Chojnacki, M ; Colpo, A ; Contreras, J ; Cutts, J ; Dean, D ; Diallo, B ; Drinnon, D ; Drozd, K ; Enos, HL ; Enos, R ; Fellows, C ; Ferro, T ; Fisher, MR ; Fitzgibbon, G ; Fitzgibbon, M ; Forelli, J ; Forrester, T ; Galinsky, I ; Garcia, R ; Gardner, A ; Habib, N ; Hamara, D ; Hammond, D ; Hanley, K ; Harshman, K ; Herzog, K ; Hill, D ; Hoekenga, C ; Hooven, S ; Huettner, E ; Janakus, A ; Jones, J ; Kidd, J ; Kingsbury, K ; Balram-Knutson, SS ; Koelbel, L ; Kreiner, J ; Lambert, D ; Lewin, C ; Lovelace, B ; Loveridge, M ; Lujan, M ; Malhotra, R ; Marchese, K ; McDonough, E ; Mogk, N ; Morrison, V ; Morton, E ; Munoz, R ; Nelson, J ; Padilla, J ; Pennington, R ; Polit, A ; Ramos, N ; Reddy, V ; Riehl, M ; Roper, HL ; Salazar, S ; Schwartz, SR ; Selznick, S ; Shultz, N ; Stewart, S ; Sutton, S ; Swindle, T ; Tang, YH ; Westermann, M ; Wolner, CW ; Worden, D ; Zega, T ; Zeszut, Z ; Bjurstrom, A ; Bloomquist, L ; Dickinson, C ; Keates, E ; Liang, J ; Nifo, V ; Taylor, A ; Teti, F ; Caplinger, M ; Bowles, H ; Carter, S ; Dickenshied, S ; Doerres, D ; Fisher, T ; Hagee, W ; Hill, J ; Miner, M ; Noss, D ; Piacentine, N ; Smith, M ; Toland, A ; Wren, P ; Bernacki, M ; Munoz, DP ; Watanabe, S ; Sandford, SA ; Aqueche, A ; Ashman, B ; Barker, M ; Bartels, A ; Berry, K ; Bos, B ; Burns, R ; Calloway, A ; Carpenter, R ; Castro, N ; Cosentino, R ; Donaldson, J ; Dworkin, JP ; Cook, JE ; Emr, C ; Everett, D ; Fennell, D ; Fleshman, K ; Folta, D ; Gallagher, D ; Garvin, J ; Getzandanner, K ; Glavin, D ; Hull, S ; Hyde, K ; Ido, H ; Ingegneri, A ; Jones, N ; Kaotira, P ; Lim, LF ; Liounis, A ; Lorentson, C ; Lorenz, D ; Lyzhoft, J ; Mazarico, EM ; Mink, R ; Moore, W ; Moreau, M ; Mullen, S ; Nagy, J ; Neumann, G ; Nuth, J ; Poland, D ; Reuter, DC ; Rhoads, L ; Rieger, S ; Rowlands, D ; Sallitt, D ; Scroggins, A ; Shaw, G ; Simon, AA ; Swenson, J ; Vasudeva, P ; Wasser, M ; Zellar, R ; Grossman, J ; Johnston, G ; Morris, M ; Wendel, J ; Burton, A ; Keller, LP ; McNamara, L ; Messenger, S ; Nakamura-Messenger, K ; Nguyen, A ; Righter, K ; Queen, E ; Bellamy, K ; Dill, K ; Gardner, S ; Giuntini, M ; Key, B ; Kissell, J ; Patterson, D ; Vaughan, D ; Wright, B ; Gaskell, RW ; Le Corre, L ; Molaro, JL ; Palmer, EE ; Siegler, MA ; Tricarico, P ; Weirich, JR ; Ireland, T ; Tait, K ; Bland, P ; Anwar, S ; Bojorquez-Murphy, N ; Christensen, PR ; Haberle, CW ; Mehall, G ; Rios, K ; Franchi, I ; Rozitis, B ; Beddingfield, CB ; Marshall, J ; Brack, DN ; French, AS ; McMahon, JW ; Jawin, ER ; McCoy, TJ ; Russell, S ; Killgore, M ; Bottke, WF ; Hamilton, VE ; Kaplan, HH ; Walsh, KJ ; Bandfield, JL ; Clark, BC ; Chodas, M ; Lambert, M ; Masterson, RA ; Daly, MG ; Freemantle, J ; Seabrook, JA ; Barnouin, OS ; Craft, K ; Daly, RT ; Ernst, C ; Espiritu, RC ; Holdridge, M ; Jones, M ; Nair, AH ; Nguyen, L ; Peachey, J ; Perry, ME ; Plescia, J ; Roberts, JH ; Steele, R ; Turner, R ; Backer, J ; Edmundson, K ; Mapel, J ; Milazzo, M ; Sides, S ; Manzoni, C ; May, B ; Delbo, M ; Libourel, G ; Michel, P ; Ryan, A ; Thuillet, F ; Marty, B (NATURE PUBLISHING GROUP, 2019-03-19)
    During its approach to asteroid (101955) Bennu, NASA's Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft surveyed Bennu's immediate environment, photometric properties, and rotation state. Discovery of a dusty environment, a natural satellite, or unexpected asteroid characteristics would have had consequences for the mission's safety and observation strategy. Here we show that spacecraft observations during this period were highly sensitive to satellites (sub-meter scale) but reveal none, although later navigational images indicate that further investigation is needed. We constrain average dust production in September 2018 from Bennu's surface to an upper limit of 150 g s-1 averaged over 34 min. Bennu's disk-integrated photometric phase function validates measurements from the pre-encounter astronomical campaign. We demonstrate that Bennu's rotation rate is accelerating continuously at 3.63 ± 0.52 × 10-6 degrees day-2, likely due to the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect, with evolutionary implications.
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    An investigation into the association of pre- and post-migration experiences on the self-rated health status among new resettled adult humanitarian refugees to Australia: a protocol for a mixed methods study.
    Dowling, A ; Enticott, J ; Kunin, M ; Russell, G (Springer Science and Business Media LLC, 2019-04-30)
    BACKGROUND: Refugees are one of the most vulnerable groups in our society. They are at risk of poor physical and mental health outcomes, much of this attributed to traumatic events prior to migration and the additional risk factors refugees face in the host nations. However, how migration factors shape the health of resettling refugees is not well understood. This study uses a mixed methods approach to examine how pre- and post-migration factors shape the self-rated health of resettling adult refugees in an effort to address the current knowledge gap. METHODS: This study will use a sequential explanatory mixed method study design. We begin by analyzing resettlement and health data from the 'Building a New Life In Australia' longitudinal study of humanitarian refugees resettled in Australia to identify significant associations between migration factors and refugee health. Then, a series of semi-structured interviews with resettled refugees will further explore the lived experiences of refugees with respect to the relationship between migration and refugee health. Finally, we will integrate both sets of findings to develop a detailed understanding of how and why migratory factors contribute to refugee health during resettlement. DISCUSSION: There is a paucity of studies that examine the multidimensional nature of refugee health during resettlement and as a result, little is understood about their resettlement health needs. This information is required to inform existing or new resettlement interventions to help promote or improve refugee health. To overcome these limitations in the research knowledge, this study will use a mixture of study methods to illustrate the complex and multifaceted determinants of refugee health during resettlement in Australia.
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    Improving access to primary healthcare for vulnerable populations in Australia and Canada: protocol for a mixed-method evaluation of six complex interventions.
    Russell, G ; Kunin, M ; Harris, M ; Levesque, J-F ; Descôteaux, S ; Scott, C ; Lewis, V ; Dionne, É ; Advocat, J ; Dahrouge, S ; Stocks, N ; Spooner, C ; Haggerty, J (BMJ, 2019-07-27)
    INTRODUCTION: Access to primary healthcare (PHC) has a fundamental influence on health outcomes, particularly for members of vulnerable populations. Innovative Models Promoting Access-to-Care Transformation (IMPACT) is a 5-year research programme built on community-academic partnerships. IMPACT aims to design, implement and evaluate organisational innovations to improve access to appropriate PHC for vulnerable populations. Six Local Innovation Partnerships (LIPs) in three Australian states (New South Wales, Victoria and South Australia) and three Canadian provinces (Ontario, Quebec and Alberta) used a common approach to implement six different interventions. This paper describes the protocol to evaluate the processes, outcomes and scalability of these organisational innovations. METHODS AND ANALYSIS: The evaluation will use a convergent mixed-methods design involving longitudinal (pre and post) analysis of the six interventions. Study participants include vulnerable populations, PHC practices, their clinicians and administrative staff, service providers in other health or social service organisations, intervention staff and members of the LIP teams. Data were collected prior to and 3-6 months after the interventions and included interviews with members of the LIPs, organisational process data, document analysis and tools collecting the cost of components of the intervention. Assessment of impacts on individuals and organisations will rely on surveys and semistructured interviews (and, in some settings, direct observation) of participating patients, providers and PHC practices. ETHICS AND DISSEMINATION: The IMPACT research programme received initial ethics approval from St Mary's Hospital (Montreal) SMHC #13-30. The interventions received a range of other ethics approvals across the six jurisdictions. Dissemination of the findings should generate a deeper understanding of the ways in which system-level organisational innovations can improve access to PHC for vulnerable populations and new knowledge concerning improvements in PHC delivery in health service utilisation.
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    The association of migration experiences on the self-rated health status among adult humanitarian refugees to Australia: an analysis of a longitudinal cohort study.
    Dowling, A ; Enticott, J ; Kunin, M ; Russell, G (Springer Science and Business Media LLC, 2019-08-22)
    BACKGROUND: Refugees are potentially at an increased risk for health problems due to their past and current migration experiences. How migration factors shape refugee health is not well understood. We examined the association between migration factors and the self-rated general health of adult humanitarian refugees living in Australia. METHODS: We analyzed the first three waves of data from the 'Building A New Life In Australia' longitudinal survey of 2399 humanitarian refugees resettled in Australia. The study outcome was self-rated health measured by the 36-Item Short Form Health Survey. Predictors were migration process and resettlement factors. We used generalized linear mixed models to investigate the relationship between predictor and outcome variables. RESULTS: Poor general health persisted among this refugee population at high levels throughout the three-year follow-up. At baseline, 35.7% (95% CI: 33.8-37.7%) of the study population reported poorer general health. Female gender, increasing age and post-migration financial stressors were positively associated with poorer general health. Having a university degree and absence of chronic health conditions were seemingly protective against declining general health (OR: 0.50; 95% CI: 0.65-1.81 and OR: 0.15, 95% CI: 0.09-1.04, respectively). CONCLUSION: Our results show that there is persisting high prevalence of poorer general health among adult refugees across the initial years of resettlement in Australia. This finding suggests unmet health needs which may be compounded by the challenges of resettlement in a new society, highlighting the need for increased clinical awareness of this sustained health burden to help inform and prepare refugee health care and settlement service providers.
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    Neurocognitive and neuroanatomical maturation in the clinical high-risk states for psychosis: A pattern recognition study
    Kambeitz-Ilankovic, L ; Haas, SS ; Meisenzahl, E ; Dwyer, DB ; Weiske, J ; Peters, H ; Moeller, H-J ; Falkai, P ; Koutsouleris, N (ELSEVIER SCI LTD, 2019)
    BACKGROUND: Findings from neurodevelopmental studies indicate that adolescents with psychosis spectrum disorders have delayed neurocognitive performance relative to the maturational state of their healthy peers. Using machine learning, we generated a model of neurocognitive age in healthy adults and investigated whether individuals in clinical high risk (CHR) for psychosis showed systematic neurocognitive age deviations that were accompanied by specific structural brain alterations. METHODS: First, a Support Vector Regression-based age prediction model was trained and cross-validated on the neurocognitive data of 36 healthy controls (HC). This produced Cognitive Age Gap Estimates (CogAGE) that measured each participant's deviation from the normal cognitive maturation as the difference between estimated neurocognitive and chronological age. Second, we employed voxel-based morphometry to explore the neuroanatomical gray and white matter correlates of CogAGE in HC, in CHR individuals with early (CHR-E) and late (CHR-L) high risk states. RESULTS: The age prediction model estimated age in HC subjects with a mean absolute error of ±2.2 years (SD = 3.3; R2 = 0.33, P < .001). Mean (SD) CogAGE measured +4.3 (8.1) years in CHR individuals compared to HC (-0.1 (5.5) years, P = .006). CHR-L individuals differed significantly from HC subjects while this was not the case for the CHR-E group. CogAGE was associated with a distributed bilateral pattern of increased GM volume in the temporal and frontal areas and diffuse pattern of WM reductions. CONCLUSION: Although the generalizability of our findings might be limited due to the relatively small number of participants, CHR individuals exhibit a disturbed neurocognitive development as compared to healthy peers, which may be independent of conversion to psychosis and paralleled by an altered structural maturation process.
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    Correcting for cell-type effects in DNA methylation studies: reference-based method outperforms latent variable approaches in empirical studies
    Hattab, MW ; Shabalin, AA ; Clark, SL ; Zhao, M ; Kumar, G ; Chan, RF ; Xie, LY ; Jansen, R ; Han, LKM ; Magnusson, PKE ; van Grootheest, G ; Hultman, CM ; Penninx, BWJH ; Aberg, KA ; van den Oord, EJCG (BIOMED CENTRAL LTD, 2017-01-30)
    Based on an extensive simulation study, McGregor and colleagues recently recommended the use of surrogate variable analysis (SVA) to control for the confounding effects of cell-type heterogeneity in DNA methylation association studies in scenarios where no cell-type proportions are available. As their recommendation was mainly based on simulated data, we sought to replicate findings in two large-scale empirical studies. In our empirical data, SVA did not fully correct for cell-type effects, its performance was somewhat unstable, and it carried a risk of missing true signals caused by removing variation that might be linked to actual disease processes. By contrast, a reference-based correction method performed well and did not show these limitations. A disadvantage of this approach is that if reference methylomes are not (publicly) available, they will need to be generated once for a small set of samples. However, given the notable risk we observed for cell-type confounding, we argue that, to avoid introducing false-positive findings into the literature, it could be well worth making this investment.Please see related Correspondence article: https://genomebiology.biomedcentral.com/articles/10/1186/s13059-017-1149-7 and related Research article: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0935-y.
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    Brain Aging in Major Depressive Disorder: Results From the ENIGMA MDD Consortium
    Schmaal, L ; Han, L ; Dinga, R ; Thompson, P ; Veltman, D ; Penninx, B (ELSEVIER SCIENCE INC, 2018-05-01)
    Background: Major Depressive Disorder has been associated with accelerated biological aging. From a brain perspective, normal aging is associated with significant loss of grey matter and depression may have an accelerating effect on age-related brain atrophy. Here, data on brain aging in MDD from the ENIGMA MDD Working Group will be presented. Methods: A normative model of brain-based age was devel- oped in 4708 healthy controls by applying a Gaussian Process Regression analysis with 10-fold cross-validation to estimate chronological age from structural MRI scans, separately for males and females. This model was then applied to 2924 MDD individuals to predict their brain-based age. Accelerated brain aging was measured as the difference between predicted brain-based age and actual chronological age (brain age gap). Results: The brain age model explained 92% and 93% of the age variance in female and male healthy controls, respectively. The mean absolute error (MAE) was 6.79 years in females and 6.60 in males. Application of the model to MDD patients showed a mean brain age gap of 0.75 years in females (MAE¼6.82) and 0.64 in males (MAE¼6.68), which were significantly lower than brain age gap estimates in healthy controls in both females (F(1,4379)¼6.10,P¼0.01) and males (F(1,3166)¼4.07,P¼0.04). Our preliminary analysis also showed greater brain age gap associations with various clinical characteristics. Conclusions: We found preliminary evidence for accelerated brain aging in MDD, however, the brains of patients were estimated to be only <1 years older than healthy controls. The impact of different methods, feature selection and potential confounding effects will also be discussed.