Psychiatry - Research Publications

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    Control of Neuronal Survival and Development Using Conductive Diamond
    Falahatdoost, S ; Prawer, YDJ ; Peng, D ; Chambers, A ; Zhan, H ; Pope, L ; Stacey, A ; Ahnood, A ; Al Hashem, HN ; De Leon, SE ; Garrett, DJ ; Fox, K ; Clark, MB ; Ibbotson, MR ; Prawer, S ; Tong, W (AMER CHEMICAL SOC, 2024-01-17)
    This study demonstrates the control of neuronal survival and development using nitrogen-doped ultrananocrystalline diamond (N-UNCD). We highlight the role of N-UNCD in regulating neuronal activity via near-infrared illumination, demonstrating the generation of stable photocurrents that enhance neuronal survival and neurite outgrowth and foster a more active, synchronized neuronal network. Whole transcriptome RNA sequencing reveals that diamond substrates improve cellular-substrate interaction by upregulating extracellular matrix and gap junction-related genes. Our findings underscore the potential of conductive diamond as a robust and biocompatible platform for noninvasive and effective neural tissue engineering.
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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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    Carer burden and behavioral disturbance is similar between younger-onset Alzheimer's disease and behavioral variant frontotemporal dementia
    Kang, MJY ; Farrand, S ; Evans, A ; Chiu, W-H ; Eratne, D ; Kelso, W ; Walterfang, M ; Velakoulis, D ; Loi, SM (CAMBRIDGE UNIV PRESS, 2023-02-09)
    OBJECTIVES: Carer burden is common in younger-onset dementia (YOD), often due to the difficulty of navigating services often designed for older people with dementia. Compared to Alzheimer's disease (AD), the burden is reported to be higher in behavioral variant frontotemporal dementia (bvFTD). However, there is little literature comparing carer burden specifically in YOD. This study hypothesized that carer burden in bvFTD would be higher than in AD. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary neuropsychiatry service in Victoria, Australia. PARTICIPANTS: Patient-carer dyads with YOD. MEASUREMENTS: We collected patient data, including behaviors using the Cambridge Behavioral Inventory-Revised (CBI-R). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI-12). Descriptive statistics and Mann-Whitney U tests were used to analyze the data. RESULTS: Carers reported high burden (ZBI-12 mean score = 17.2, SD = 10.5), with no significant difference in burden between younger-onset AD and bvFTD. CBI-R stereotypic and motor behaviors, CBI-R everyday skills, and total NUCOG scores differed between the two groups. There was no significant difference in the rest of the CBI-R subcategories, including the behavior-related domains. CONCLUSION: Carers of YOD face high burden and are managing significant challenging behaviors. We found no difference in carer burden between younger-onset AD and bvFTD. This could be due to similarities in the two subtypes in terms of abnormal behavior, motivation, and self-care as measured on CBI-R, contrary to previous literature. Clinicians should screen for carer burden and associated factors including behavioral symptoms in YOD syndromes, as they may contribute to carer burden regardless of the type.
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    Long-term effects of electroconvulsive therapy on brain structure in major depression.
    Borgers, T ; Enneking, V ; Klug, M ; Garbe, J ; Meinert, H ; Wulle, M ; König, P ; Zwiky, E ; Herrmann, R ; Selle, J ; Dohm, K ; Kraus, A ; Grotegerd, D ; Repple, J ; Opel, N ; Leehr, EJ ; Gruber, M ; Goltermann, J ; Meinert, S ; Bauer, J ; Heindel, W ; Kavakbasi, E ; Baune, BT ; Dannlowski, U ; Redlich, R (Cambridge University Press (CUP), 2023-09-08)
    BACKGROUND: Magnetic resonance imaging (MRI) studies on major depressive disorder (MDD) have predominantly found short-term electroconvulsive therapy (ECT)-related gray matter volume (GMV) increases, but research on the long-term stability of such changes is missing. Our aim was to investigate long-term GMV changes over a 2-year period after ECT administration and their associations with clinical outcome. METHODS: In this nonrandomized longitudinal study, patients with MDD undergoing ECT (n = 17) are assessed three times by structural MRI: Before ECT (t0), after ECT (t1) and 2 years later (t2). A healthy (n = 21) and MDD non-ECT (n = 33) control group are also measured three times within an equivalent time interval. A 3(group) × 3(time) ANOVA on whole-brain level and correlation analyses with clinical outcome variables is performed. RESULTS: Analyses yield a significant group × time interaction (pFWE < 0.001) resulting from significant volume increases from t0 to t1 and decreases from t1 to t2 in the ECT group, e.g., in limbic areas. There are no effects of time in both control groups. Volume increases from t0 to t1 correlate with immediate and delayed symptom increase, while volume decreases from t1 to t2 correlate with long-term depressive outcome (all p ⩽ 0.049). CONCLUSIONS: Volume increases induced by ECT appear to be a transient phenomenon as volume strongly decreased 2 years after ECT. Short-term volume increases are associated with less symptom improvement suggesting that the antidepressant effect of ECT is not due to volume changes. Larger volume decreases are associated with poorer long-term outcome highlighting the interplay between disease progression and structural changes.
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    Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers
    Boen, R ; Kaufmann, T ; van der Meer, D ; Frei, O ; Agartz, I ; Ames, D ; Andersson, M ; Armstrong, NJ ; Artiges, E ; Atkins, JR ; Bauer, J ; Benedetti, F ; Boomsma, DI ; Brodaty, H ; Brosch, K ; Buckner, RL ; Cairns, MJ ; Calhoun, V ; Caspers, S ; Cichon, S ; Corvin, AP ; Crespo-Facorro, B ; Dannlowski, U ; David, FS ; de Geus, EJC ; de Zubicaray, GI ; Desrivieres, S ; Doherty, JL ; Donohoe, G ; Ehrlich, S ; Eising, E ; Espeseth, T ; Fisher, SE ; Forstner, AJ ; Fortaner-Uya, L ; Frouin, V ; Fukunaga, M ; Ge, T ; Glahn, DC ; Goltermann, J ; Grabe, HJ ; Green, MJ ; Groenewold, NA ; Grotegerd, D ; Grontvedt, GR ; Hahn, T ; Hashimoto, R ; Hehir-Kwa, JY ; Henskens, FA ; Holmes, AJ ; Haberg, AK ; Haavik, J ; Jacquemont, S ; Jansen, A ; Jockwitz, C ; Joensson, EG ; Kikuchi, M ; Kircher, T ; Kumar, K ; Le Hellard, S ; Leu, C ; Linden, DE ; Liu, J ; Loughnan, R ; Mather, KA ; Mcmahon, KL ; Mcrae, AF ; Medland, SE ; Meinert, S ; Moreau, CA ; Morris, DW ; Mowry, BJ ; Muehleisen, TW ; Nenadic, I ; Noethen, MM ; Nyberg, L ; Ophoff, RA ; Owen, MJ ; Pantelis, C ; Paolini, M ; Paus, T ; Pausova, Z ; Persson, K ; Quide, Y ; Marques, TR ; Sachdev, PS ; Sando, SB ; Schall, U ; Scott, RJ ; Selbaek, G ; Shumskaya, E ; Silva, AI ; Sisodiya, SM ; Stein, F ; Stein, DJ ; Straube, B ; Streit, F ; Strike, LT ; Teumer, A ; Teutenberg, L ; Thalamuthu, A ; Tooney, PA ; Tordesillas-Gutierrez, D ; Trollor, JN ; Van't Ent, D ; van den Bree, MBM ; van Haren, NEM ; Vazquez-Bourgon, J ; Voelzke, H ; Wen, W ; Wittfeld, K ; Ching, CRK ; Westlye, LT ; Thompson, PM ; Bearden, CE ; Selmer, KK ; Alnaes, D ; Andreassen, OA ; Sonderby, IE (ELSEVIER SCIENCE INC, 2024-01-15)
    BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference. RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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    Improving perinatal sleep via a scalable cognitive behavioural intervention: findings from a randomised controlled trial from pregnancy to 2 years postpartum.
    Bei, B ; Pinnington, DM ; Quin, N ; Shen, L ; Blumfield, M ; Wiley, JF ; Drummond, SPA ; Newman, LK ; Manber, R (Cambridge University Press (CUP), 2023-01)
    BACKGROUND: Sleep disturbance is common in gestational parents during pregnancy and postpartum periods. This study evaluated the feasibility and efficacy of a scalable cognitive behavioural therapy (CBT) sleep intervention tailored for these periods. METHODS: This is a two-arm, parallel-group, single-blind, superiority randomised controlled trial. Nulliparous females without severe medical/psychiatric conditions were randomised 1:1 to CBT or attention- and time-matched control. All participants received a 1 h telephone session and automated multimedia emails from the third trimester until 6 months postpartum. Outcomes were assessed with validated instruments at gestation weeks 30 (baseline) and 35 (pregnancy endpoint), and postpartum months 1.5, 3, 6 (postpartum endpoint), 12 and 24. RESULTS: In total, 163 eligible participants (age M ± s.d. = 33.35 ± 3.42) were randomised. The CBT intervention was well accepted, with no reported adverse effect. Intention-to-treat analyses showed that compared to control, receiving CBT was associated with lower insomnia severity and sleep disturbance (two primary outcomes), and lower sleep-related impairment at the pregnancy endpoint (p values ⩽ 0.001), as well as at 24 months postpartum (p ranges 0.012-0.052). Group differences across the first postpartum year were non-significant. Participants with elevated insomnia symptoms at baseline benefitted substantially more from CBT (v. control), including having significantly lower insomnia symptoms throughout the first postpartum year. Group differences in symptoms of depression or anxiety were non-significant. CONCLUSIONS: A scalable CBT sleep intervention is efficacious in buffering against sleep disturbance during pregnancy and benefitted sleep at 2-year postpartum, especially for individuals with insomnia symptoms during pregnancy. The intervention holds promise for implementation into routine perinatal care.
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    Clinical outcomes of deep brain stimulation for obsessive-compulsive disorder: Insight as a predictor of symptom changes.
    Acevedo, N ; Rossell, S ; Castle, D ; Groves, C ; Cook, M ; McNeill, P ; Olver, J ; Meyer, D ; Perera, T ; Bosanac, P (Wiley, 2024-02)
    AIM: Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. METHODS: Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. RESULTS: Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6-9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. CONCLUSION: The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).
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    Combining Clinical With Cognitive or Magnetic Resonance Imaging Data for Predicting Transition to Psychosis in Ultra High-Risk Patients: Data From the PACE 400 Cohort.
    Hartmann, S ; Cearns, M ; Pantelis, C ; Dwyer, D ; Cavve, B ; Byrne, E ; Scott, I ; Yuen, HP ; Gao, C ; Allott, K ; Lin, A ; Wood, SJ ; Wigman, JTW ; Amminger, GP ; McGorry, PD ; Yung, AR ; Nelson, B ; Clark, SR (Elsevier BV, 2023-12-03)
    BACKGROUND: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging. METHODS: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231). RESULTS: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%-12%, brain age gap 7%, cognition 0%-16%). CONCLUSIONS: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis.
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    Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?
    Russell, SE ; Wrobel, AL ; Ashton, MM ; Turner, A ; Mohebbi, M ; Berk, M ; Cotton, S ; Dodd, S ; Ng, CH ; Malhi, GS ; Dean, OM (KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2023-08)
    OBJECTIVE: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. METHODS: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (+4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. RESULTS: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. CONCLUSION: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.
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    Genetic and Epigenetic Regulation in Lingo-1: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia
    Andrews, JL ; Zalesky, A ; Nair, S ; Sullivan, RP ; Green, MJ ; Pantelis, C ; Newell, KA ; Fernandez, F (MDPI, 2023-11)
    Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3'-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016-1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology.