7 results
Structural brain correlates of childhood trauma with replication across two large, independent community-based samples
- Rebecca A. Madden, Kimberley Atkinson, Xueyi Shen, Claire Green, Robert F. Hillary, Emma Hawkins, Emma Såge, Anca-Larisa Sandu, Gordon Waiter, Christopher McNeil, Mathew Harris, Archie Campbell, David Porteous, Jennifer A. Macfarlane, Alison Murray, Douglas Steele, Liana Romaniuk, Stephen M. Lawrie, Andrew M. McIntosh, Heather C. Whalley
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- Journal:
- European Psychiatry / Volume 66 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 26 January 2023, e19
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Introduction
Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.
MethodsThe two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.
ResultsChildhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.
DiscussionAssociations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.
Associations of negative affective biases and depressive symptoms in a community-based sample
- Laura de Nooij, Mark J. Adams, Emma L. Hawkins, Liana Romaniuk, Marcus R. Munafò, Ian S. Penton-Voak, Rebecca Elliott, Amy R. Bland, Gordon D. Waiter, Anca-Larisa Sandu, Tina Habota, J. Douglas Steele, Alison D. Murray, Archie Campbell, David J. Porteous, Generation Scotland, Andrew M. McIntosh, Heather C. Whalley
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- Journal:
- Psychological Medicine / Volume 53 / Issue 12 / September 2023
- Published online by Cambridge University Press:
- 21 September 2022, pp. 5518-5527
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Background
Major depressive disorder (MDD) was previously associated with negative affective biases. Evidence from larger population-based studies, however, is lacking, including whether biases normalise with remission. We investigated associations between affective bias measures and depressive symptom severity across a large community-based sample, followed by examining differences between remitted individuals and controls.
MethodsParticipants from Generation Scotland (N = 1109) completed the: (i) Bristol Emotion Recognition Task (BERT), (ii) Face Affective Go/No-go (FAGN), and (iii) Cambridge Gambling Task (CGT). Individuals were classified as MDD-current (n = 43), MDD-remitted (n = 282), or controls (n = 784). Analyses included using affective bias summary measures (primary analyses), followed by detailed emotion/condition analyses of BERT and FAGN (secondary analyses).
ResultsFor summary measures, the only significant finding was an association between greater symptoms and lower risk adjustment for CGT across the sample (individuals with greater symptoms were less likely to bet more, despite increasingly favourable conditions). This was no longer significant when controlling for non-affective cognition. No differences were found for remitted-MDD v. controls. Detailed analysis of BERT and FAGN indicated subtle negative biases across multiple measures of affective cognition with increasing symptom severity, that were independent of non-effective cognition [e.g. greater tendency to rate faces as angry (BERT), and lower accuracy for happy/neutral conditions (FAGN)]. Results for remitted-MDD were inconsistent.
ConclusionsThis suggests the presence of subtle negative affective biases at the level of emotion/condition in association with depressive symptoms across the sample, over and above those accounted for by non-affective cognition, with no evidence for affective biases in remitted individuals.
Prediction of depression symptoms in individual subjects with face and eye movement tracking
- Aleks Stolicyn, J. Douglas Steele, Peggy Seriès
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- Journal:
- Psychological Medicine / Volume 52 / Issue 9 / July 2022
- Published online by Cambridge University Press:
- 09 November 2020, pp. 1784-1792
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Background
Depression is a challenge to diagnose reliably and the current gold standard for trials of DSM-5 has been in agreement between two or more medical specialists. Research studies aiming to objectively predict depression have typically used brain scanning. Less expensive methods from cognitive neuroscience may allow quicker and more reliable diagnoses, and contribute to reducing the costs of managing the condition. In the current study we aimed to develop a novel inexpensive system for detecting elevated symptoms of depression based on tracking face and eye movements during the performance of cognitive tasks.
MethodsIn total, 75 participants performed two novel cognitive tasks with verbal affective distraction elements while their face and eye movements were recorded using inexpensive cameras. Data from 48 participants (mean age 25.5 years, standard deviation of 6.1 years, 25 with elevated symptoms of depression) passed quality control and were included in a case-control classification analysis with machine learning.
ResultsClassification accuracy using cross-validation (within-study replication) reached 79% (sensitivity 76%, specificity 82%), when face and eye movement measures were combined. Symptomatic participants were characterised by less intense mouth and eyelid movements during different stages of the two tasks, and by differences in frequencies and durations of fixations on affectively salient distraction words.
ConclusionsElevated symptoms of depression can be detected with face and eye movement tracking during the cognitive performance, with a close to clinically-relevant accuracy (~80%). Future studies should validate these results in larger samples and in clinical populations.
Single-dose treatment for cutaneous leishmaniasis with an easily synthesized chalcone entrapped in polymeric microparticles
- Ariane J. Sousa-Batista, Natalia Arruda-Costa, Douglas O. Escrivani, Franceline Reynaud, Patrick G. Steel, Bartira Rossi-Bergmann
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- Journal:
- Parasitology / Volume 147 / Issue 9 / August 2020
- Published online by Cambridge University Press:
- 04 May 2020, pp. 1032-1037
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Cutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous injection with a slow-release formulation consisting of poly(lactide-co-glycolide) (PLGA) microparticles loaded with an antileishmanial 3-nitro-2-hydroxy-4,6-dimethoxychalcone (CH8) was demonstrated in mice model. In the search for more easily synthesized active chalcone derivatives, and improved microparticle loading, CH8 analogues were synthesized and tested for antileishmanial activity in vitro and in vivo. The 3-nitro-2′,4′,6′-trimethoxychalcone (NAT22) analogue was chosen for its higher selectivity against intracellular amastigotes (selectivity index = 1489, as compared with 317 for CH8) and more efficient synthesis (89% yield, as compared with 18% for CH8). NAT22 was loaded into PLGA / polyvinylpyrrolidone (PVP) polymeric blend microspheres (NAT22-PLGAk) with average diameter of 1.9 μm. Although NAT22-PLGAk showed similar activity to free NAT22 in killing intracellular parasites in vitro (IC50 ~ 0.2 μm), in vivo studies in Leishmania amazonensis – infected mice demonstrated the significant superior efficacy of NAT22-PLGAk to reduce the parasite load. A single intralesional injection with NAT22-PLGAk was more effective than eight injections with free NAT22. Together, these results show that NAT22-PLGAk is a promising alternative for single-dose localized treatment of CL.
Pragmatic neuroscience for clinical psychiatry
- J. Douglas Steele, Martin P. Paulus
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- Journal:
- The British Journal of Psychiatry / Volume 215 / Issue 1 / July 2019
- Published online by Cambridge University Press:
- 22 April 2019, pp. 404-408
- Print publication:
- July 2019
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Mental health and substance use disorders are the leading cause of long-term disability and a cause of significant mortality, worldwide. However, it is widely recognised that clinical practice in psychiatry has not fundamentally changed for over half a century. The Royal College of Psychiatrists is reviewing its trainee curriculum to identify neuroscience that relates to psychiatric practice. To date though, neuroscience has had very little impact on routine clinical practice. We discuss how a pragmatic approach to neuroscience can address this problem together with a route to implementation in National Health Service care. This has implications for altered funding priorities and training future psychiatrists. Five training recommendations for psychiatrists are identified.
Declaration of interestJ.D.S. receives direct funding from MRC Program Grant MR/S010351/1 aimed at developing machine learning-based methods for routinely acquired NHS data and indirect funding from the Wellcome Trust STRADL study. M.P.P. receives payments for an UpToDate chapter on methamphetamine and is principal investigator on the following grants: NIGMS P20GM121312 and NIDA U01 DA041089 and receives support from the William K. Warren Foundation.
13 - Other brain stimulation treatments
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- By Sarah Browne, University of Dundee, David Christmas, Ninewells Hospital and Medical School, Dundee, Douglas Steele, Ninewells Hospital and Medical School, Dundee, M. Sam Eljamel, Ninewells Hospital and Medical School, Dundee, Keith Matthews, Ninewells Hospital and Medical School, Dundee
- Edited by Jonathan Waite, Andrew Easton
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- Book:
- The ECT Handbook
- Published by:
- Royal College of Psychiatrists
- Published online:
- 25 February 2017, pp 113-125
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Summary
Electroconvulsive therapy prescribers, practitioners and many patients will be aware of an emerging clinical evidence base for non-ECT brain stimulation treatments. Although the previous edition of The ECT Handbook made no mention of brain stimulation treatments, a review of the status of the three most studied therapies is now relevant. These therapies are:
• repetitive transcranial magnetic stimulation
• vagus nerve stimulation
• deep brain stimulation.
In this chapter, we consider the use of these therapies in the management of depression and how they might relate to the ECT treatment pathway.
Repetitive transcranial magnetic stimulation (rTMS)
Repetitive transcranial magnetic stimulation is a non-invasive technique causing modification of brain activity by focal stimulation of the superficial layers of the cerebral cortex using a train of magnetic pulses via an external wire coil. The impetus for studies of rTMS in psychiatry has arisen from the need for a viable alternative to ECT with a lower burden of adverse effects and greater patient acceptability. A substantial literature, including several systematic reviews and meta-analyses, now exists on the use of rTMS in the management of depression. In 2008 the US Food and Drug Administration approved a TMS system ‘for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode’.
However, NICE published a technology appraisal in 2007, restating the core recommendations in the 2010 depression guideline update, which is consistent with the absence of convincing evidence of superior efficacy for rTMS over sham treatment and with the paucity of efficacy data extending beyond 4–6 weeks of treatment. The status of the technique is summarised as follows:
‘Current evidence suggests that there are no major safety concerns associated with transcranial magnetic stimulation (TMS) for severe depression. There is uncertainty about the procedure's clinical efficacy, which may depend on higher intensity, greater frequency, bilateral application and/or longer treatment durations than have appeared in the evidence to date. TMS should therefore be performed only in research studies designed to investigate these factors.’ (National Institute for Health and Clinical Excellence, 2007)
In our opinion, on the basis of current evidence, rTMS remains an interesting but experimental therapy which should not be considered a viable alternative to treatment with ECT.
13 - Other brain stimulation treatments
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- By Sarah Browne, Research Technician, Division of Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee, David Christmas, Consultant Psychiatrist, Advanced Interventions Service, Ninewells Hospital and Medical School, Dundee, Douglas Steele, Professor of Neuroimaging and Honorary Consultant Psychiatrist, Advanced Interventions Service, Ninewells Hospital and Medical School, Dundee, M. Sam Eljamel, Consultant Neurosurgeon, Advanced Interventions Service, Ninewells Hospital and Medical School, Dundee, Keith Matthews, Professor of Psychiatry and Honorary Consultant Psychiatrist, Division of Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee
- Edited by Jonathan Waite, Andrew Easton
-
- Book:
- The ECT Handbook
- Published online:
- 02 January 2018
- Print publication:
- 01 May 2013, pp 113-125
-
- Chapter
- Export citation
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Summary
Electroconvulsive therapy prescribers, practitioners and many patients will be aware of an emerging clinical evidence base for non-ECT brain stimulation treatments. Although the previous edition of The ECT Handbook made no mention of brain stimulation treatments, a review of the status of the three most studied therapies is now relevant. These therapies are:
• repetitive transcranial magnetic stimulation
• vagus nerve stimulation
• deep brain stimulation.
In this chapter, we consider the use of these therapies in the management of depression and how they might relate to the ECT treatment pathway.
Repetitive transcranial magnetic stimulation (rTMS)
Repetitive transcranial magnetic stimulation is a non-invasive technique causing modification of brain activity by focal stimulation of the superficial layers of the cerebral cortex using a train of magnetic pulses via an external wire coil. The impetus for studies of rTMS in psychiatry has arisen from the need for a viable alternative to ECT with a lower burden of adverse effects and greater patient acceptability. A substantial literature, including several systematic reviews and meta-analyses, now exists on the use of rTMS in the management of depression. In 2008 the US Food and Drug Administration approved a TMS system ‘for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode’.
However, NICE published a technology appraisal in 2007, restating the core recommendations in the 2010 depression guideline update, which is consistent with the absence of convincing evidence of superior efficacy for rTMS over sham treatment and with the paucity of efficacy data extending beyond 4–6 weeks of treatment. The status of the technique is summarised as follows:
‘Current evidence suggests that there are no major safety concerns associated with transcranial magnetic stimulation (TMS) for severe depression. There is uncertainty about the procedure's clinical efficacy, which may depend on higher intensity, greater frequency, bilateral application and/or longer treatment durations than have appeared in the evidence to date. TMS should therefore be performed only in research studies designed to investigate these factors.’ (National Institute for Health and Clinical Excellence, 2007)