11 results
Will new brain stimulation techniques precipitate a new wave of therapies?
- Ian B. Hickie, Paul B. Fitzgerald, Elizabeth Scott
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- Journal:
- Research Directions: Depression / Volume 1 / 2024
- Published online by Cambridge University Press:
- 11 October 2023, e10
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The field of therapeutic interventions available for depression and other mood disorders has been radically transformed over the last decade by the introduction of a range of new brain stimulation therapies. There is strong professional and public interest in the relative efficacy, and side effect profiles, of these approaches compared with conventional pharmacotherapy and older methods such as electro-convulsive therapy (Brunoni et al., 2022; Fitzgerald, 2021; Fitzgerald et al., 2022).
Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial
- Colleen Loo, Nick Glozier, David Barton, Bernhard T. Baune, Natalie T. Mills, Paul Fitzgerald, Paul Glue, Shanthi Sarma, Veronica Galvez-Ortiz, Dusan Hadzi-Pavlovic, Angelo Alonzo, Vanessa Dong, Donel Martin, Stevan Nikolin, Philip B. Mitchell, Michael Berk, Gregory Carter, Maree Hackett, John Leyden, Sean Hood, Andrew A. Somogyi, Kyle Lapidus, Elizabeth Stratton, Kirsten Gainsford, Deepak Garg, Nicollette L. R. Thornton, Célia Fourrier, Karyn Richardson, Demi Rozakis, Anish Scaria, Cathrine Mihalopoulos, Mary Lou Chatterton, William M. McDonald, Philip Boyce, Paul E. Holtzheimer, F. Andrew Kozel, Patricio Riva-Posse, Anthony Rodgers
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- Journal:
- The British Journal of Psychiatry / Volume 223 / Issue 6 / December 2023
- Published online by Cambridge University Press:
- 14 July 2023, pp. 533-541
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- December 2023
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Background
Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.
AimsTo assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.
MethodThis phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
ResultsThe final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
ConclusionsAdequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Obsessive–compulsive disorder (OCD) is associated with increased engagement of frontal brain regions across multiple event-related potentials
- M. Prabhavi N. Perera, Sudaraka Mallawaarachchi, Neil W. Bailey, Oscar W. Murphy, Paul B. Fitzgerald
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- Journal:
- Psychological Medicine / Volume 53 / Issue 15 / November 2023
- Published online by Cambridge University Press:
- 24 April 2023, pp. 7287-7299
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Background
Obsessive–compulsive disorder (OCD) is a psychiatric condition leading to significant distress and poor quality of life. Successful treatment of OCD is restricted by the limited knowledge about its pathophysiology. This study aimed to investigate the pathophysiology of OCD using electroencephalographic (EEG) event-related potentials (ERPs), elicited from multiple tasks to characterise disorder-related differences in underlying brain activity across multiple neural processes.
MethodsERP data were obtained from 25 OCD patients and 27 age- and sex-matched healthy controls (HCs) by recording EEG during flanker and go/nogo tasks. Error-related negativity (ERN) was elicited by the flanker task, while N200 and P300 were generated using the go/nogo task. Primary comparisons of the neural response amplitudes and the topographical distribution of neural activity were conducted using scalp field differences across all time points and electrodes.
ResultsCompared to HCs, the OCD group showed altered ERP distributions. Contrasting with the previous literature on ERN and N200 topographies in OCD where fronto-central negative voltages were reported, we detected positive voltages. Additionally, the P300 was found to be less negative in the frontal regions. None of these ERP findings were associated with OCD symptom severity.
ConclusionsThese results indicate that individuals with OCD show altered frontal neural activity across multiple executive function-related processes, supporting the frontal dysfunction theory of OCD. Furthermore, due to the lack of association between altered ERPs and OCD symptom severity, they may be considered potential candidate endophenotypes for OCD.
The impact of age at onset of bipolar I disorder on functioning and clinical presentation
- Frances Biffin, Steven Tahtalian, Kate Filia, Paul B. Fitzgerald, Anthony R. de Castella, Sacha Filia, Michael Berk, Seetal Dodd, Pam Callaly, Lesley Berk, Katarina Kelin, Meg Smith, William Montgomery, Jayashri Kulkarni
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- Acta Neuropsychiatrica / Volume 21 / Issue 4 / August 2009
- Published online by Cambridge University Press:
- 24 June 2014, pp. 191-196
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Objectives:
Recent studies have proposed the existence of three distinct subgroups of bipolar 1 disorder based on age at onset (AAO). The present study aims to investigate potential clinical and functional differences between these subgroups in an Australian sample.
Methods:Participants (n = 239) were enrolled in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal, observational, cross-sectional study. Assessment measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ-5D). Participants were also asked about their age at the first major affective episode.
Results:Three AAO groups were compared: early (AAO < 20, mean = 15.5 ± 2.72; 44.4% of the participants); intermediate (AAO 20–39, mean = 26.1 ± 4.8; 48.14% of the participants) and late (AAO > 40, mean = 50.6 ± 9.04; 7.4% of the participants). Higher rates of depression, suicidal ideation and binge drinking were reported by the early AAO group. This group also reported poorer quality of life in a number of areas. The early AAO group had a predominant depressive initial polarity and the intermediate group had a manic predominance.
Conclusion:Early AAO is associated with an adverse outcome.
Spreading activation: the origins of brain stimulation in psychiatry
- Kate E. Hoy, Paul B. Fitzgerald
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- Journal:
- Acta Neuropsychiatrica / Volume 22 / Issue 6 / December 2010
- Published online by Cambridge University Press:
- 24 June 2014, pp. 302-304
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Prediction of fat-free mass and percentage of body fat in neonates using bioelectrical impedance analysis and anthropometric measures: validation against the PEA POD
- Barbara E. Lingwood, Anne-Martine Storm van Leeuwen, Angela E. Carberry, Erin C. Fitzgerald, Leonie K. Callaway, Paul B. Colditz, Leigh C. Ward
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- Journal:
- British Journal of Nutrition / Volume 107 / Issue 10 / 28 May 2012
- Published online by Cambridge University Press:
- 15 September 2011, pp. 1545-1552
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- 28 May 2012
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Accurate assessment of neonatal body composition is essential to studies investigating neonatal nutrition or developmental origins of obesity. Bioelectrical impedance analysis or bioimpedance analysis is inexpensive, non-invasive and portable, and is widely used in adults for the assessment of body composition. There are currently no prediction algorithms using bioimpedance analysis in neonates that have been directly validated against measurements of fat-free mass (FFM). The aim of the study was to evaluate the use of bioimpedance analysis for the estimation of FFM and percentage of body fat over the first 4 months of life in healthy infants born at term, and to compare these with estimations based on anthropometric measurements (weight and length) and with skinfolds. The present study was an observational study in seventy-seven infants. Body fat content of infants was assessed at birth, 6 weeks, 3 and 4·5 months of age by air displacement plethysmography, using the PEA POD body composition system. Bioimpedance analysis was performed at the same time and the data were used to develop and test prediction equations for FFM. The combination of weight+sex+length predicted FFM, with a bias of < 100 g and limits of agreement of 6–13 %. Before 3 months of age, bioimpedance analysis did not improve the prediction of FFM or body fat. At 3 and 4·5 months, the inclusion of impedance in prediction algorithms resulted in small improvements in prediction of FFM, reducing the bias to < 50 g and limits of agreement to < 9 %. Skinfold measurements performed poorly at all ages.
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. 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Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. 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Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- The Cambridge Dictionary of Christianity
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- 05 August 2012
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- 20 September 2010, pp xi-xliv
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A Randomized-Controlled Trial of Bilateral rTMS for Treatment-Resistant Depression
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- By Paul B. Fitzgerald, Alfred Psychiatry Research Centre, The Alfred and Monash University School of Psychiatry, Psychology and Psychological Medicine, Commercial Road, Melbourne, Victoria, Australia
- Edited by Jeffrey L. Cummings
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- Progress in Neurotherapeutics and Neuropsychopharmacology
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- 13 May 2010
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- 06 March 2008, pp 211-226
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Summary
ABSTRACT
Background: Antidepressant effects have been demonstrated with both highfrequency left-sided repetitive transcranial magnetic stimulation (rTMS) (HFL-TMS) and low-frequency stimulation to the right prefrontal cortex (LFR-TMS). However, doubts remain about the extent of these reported treatment effects. Design and Methods: The study was a 6 week double-blind randomized sham-controlled trial of sequential bilateral rTMS (SBrTMS) in depression. The method consisted of 3 trains of LFR-TMS of 140 s duration at 1 Hz being applied daily followed immediately by 15 trains of 5 s duration of HFL-TMS at 10 Hz. Sham stimulation was applied using identical parameters, but with the coil angled at 45 degrees from the scalp resting on the side of one wing of the coil. Results: There was a significant difference in response between the two groups at the 2-week time-point (F(1,25) = 25.5, p < 0.001) and for the full duration of the study (F(5,44) = 3.9, p = 0.005). A significant proportion of the active study group met response (11/25) and remission criteria (9/25) by study end compared to the sham group (2 and 0/22). Interpretation: Bilateral rTMS treatment, involving the sequential application of both HFL-TMS and LFR-TMS, has substantial treatment efficacy in patients with treatment-resistant depression. The treatment response is clinically significant following 4–6 weeks of active treatment. Therefore this novel style of bilateral rTMS has the potential to become a substantive clinical intervention, although the study requires replication.
A Randomized-Controlled Trial of Bilateral rTMS for Treatment-Resistant Depression
- Paul B. Fitzgerald
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- Journal:
- Progress in Neurotherapeutics and Neuropsychopharmacology / Volume 3 / Issue 1 / January 2008
- Published online by Cambridge University Press:
- 22 August 2007, pp. 211-226
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- January 2008
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ABSTRACT
Background: Antidepressant effects have been demonstrated with both high-frequency left-sided repetitive transcranial magnetic stimulation (rTMS) (HFL-TMS) and low-frequency stimulation to the right prefrontal cortex (LFR-TMS). However, doubts remain about the extent of these reported treatment effects. Design and Methods: The study was a 6 week double-blind randomized sham-controlled trial of sequential bilateral rTMS (SBrTMS) in depression. The method consisted of 3 trains of LFR-TMS of 140 s duration at 1 Hz being applied daily followed immediately by 15 trains of 5 s duration of HFL-TMS at 10 Hz. Sham stimulation was applied using identical parameters, but with the coil angled at 45 degrees from the scalp resting on the side of one wing of the coil. Results: There was a significant difference in response between the two groups at the 2-week time-point (F(1,25) = 25.5, p < 0.001) and for the full duration of the study (F(5,44) = 3.9, p = 0.005). A significant proportion of the active study group met response (11/25) and remission criteria (9/25) by study end compared to the sham group (2 and 0/22). Interpretation: Bilateral rTMS treatment, involving the sequential application of both HFL-TMS and LFR-TMS, has substantial treatment efficacy in patients with treatment-resistant depression. The treatment response is clinically significant following 4–6 weeks of active treatment. Therefore this novel style of bilateral rTMS has the potential to become a substantive clinical intervention, although the study requires replication.
Using transcranial magnetic stimulation to investigate the cortical origins of motor overflow: a study in schizophrenia and healthy controls
- KATE E. HOY, NELLIE GEORGIOU-KARISTIANIS, ROBIN LAYCOCK, PAUL B. FITZGERALD
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- Journal:
- Psychological Medicine / Volume 37 / Issue 4 / April 2007
- Published online by Cambridge University Press:
- 16 January 2007, pp. 583-594
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Background. Previous research has confirmed the presence of increased motor overflow in schizophrenia. There are essentially two theories regarding the cortical origins of overflow. Recent research suggests that both may be correct, and that the cortical origin of overflow is highly dependent upon the population in which it presents. Motor overflow, due to an abnormally active ipsilateral corticospinal tract, may indicate a potentially severe brain abnormality arising in early development. In contrast, bilaterally active corticospinal tracts accounting for overflow probably represent a naturally occurring response during fatiguing contractions.
Method. The cortical origins of motor overflow in 20 participants with schizophrenia and 20 normal controls were investigated through the use of a number of transcranial magnetic stimulation (TMS) protocols.
Results. Each of the experimental protocols employed independently supported the contention that overflow was originating in the hemisphere contralateral to the involuntary movement.
Conclusions. Results indicated that the origins of overflow in schizophrenia are the same as those seen in the normal control group, i.e. motor overflow seems to be due to the presence of bilaterally active corticospinal tracts. Potential explanations for greater motor overflow seen in schizophrenia are discussed.
The influence of attention and age on the occurrence of mirror movements
- YASMIN BALIZ, CHRISTINE ARMATAS, MAREE FARROW, KATE E. HOY, PAUL B. FITZGERALD, JOHN L. BRADSHAW, NELLIE GEORGIOU-KARISTIANIS
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- Journal:
- Journal of the International Neuropsychological Society / Volume 11 / Issue 7 / November 2005
- Published online by Cambridge University Press:
- 16 December 2005, pp. 855-862
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This study utilised a finger force task to investigate the influence of attention and age on the occurrence of motor overflow in the form of mirror movements in neurologically intact adults. Forty right-handed participants were recruited from three age groups: 20–30 years, 40–50 years, and 60–70 years. Participants were required to maintain a target force using both their index and middle fingers, representing 50% of their maximum strength capacity for that hand. Attention was directed to a hand by activating a bone conduction vibrator attached to the small finger of that hand. Based on Cabeza's (2002) model of hemispheric asymmetry reduction in older adults, it was hypothesised that mirror movements would increase with age. Furthermore, it was expected that when the attentional demands of the task were increased, motor overflow occurrence would be exacerbated for the older adult group. The results obtained provide support for the model, and qualified support for the hypothesis that increasing the attentional demands of a task results in greater motor overflow. It is proposed that the association between mirror movements and age observed in this study may result from an age-related increase in bihemispheric activation that occurs in older adults, who, unlike younger adults, benefit from bihemispheric processing for task performance. (JINS, 2005, 11, 855–862.)