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Depression: HELP
Articles from Ninewells Hospital and Medical School
Based on 31 articles published since 2010
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These are the 31 published articles about Depression that originated from Ninewells Hospital and Medical School during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines. 2015

Cleare, Anthony / Pariante, C M / Young, A H / Anderson, I M / Christmas, D / Cowen, P J / Dickens, C / Ferrier, I N / Geddes, J / Gilbody, S / Haddad, P M / Katona, C / Lewis, G / Malizia, A / McAllister-Williams, R H / Ramchandani, P / Scott, J / Taylor, D / Uher, R / Anonymous40830. ·Professor of Psychopharmacology & Affective Disorders, King's College London, Institute of Psychiatry, Psychology and Neuroscience, Centre for Affective Disorders, London, UK anthony.cleare@kcl.ac.uk. · Professor of Biological Psychiatry, King's College London, Institute of Psychiatry, Psychology and Neuroscience, Centre for Affective Disorders, London, UK. · Professor of Psychiatry and Chair of Mood Disorders, King's College London, Institute of Psychiatry, Psychology and Neuroscience, Centre for Affective Disorders, London, UK. · Professor and Honorary Consultant Psychiatrist, University of Manchester Department of Psychiatry, University of Manchester, Manchester, UK. · Consultant Psychiatrist, Advanced Interventions Service, Ninewells Hospital & Medical School, Dundee, UK. · Professor of Psychopharmacology, Psychopharmacology Research Unit, Neurosciences Building, University Department of Psychiatry, Warneford Hospital, Oxford, UK. · Professor of Psychological Medicine, University of Exeter Medical School and Devon Partnership Trust, Exeter, UK. · Professor of Psychiatry, Honorary Consultant Psychiatrist, School of Neurology, Neurobiology & Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne, UK. · Head, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. · Director of the Mental Health and Addictions Research Group (MHARG), The Hull York Medical School, Department of Health Sciences, University of York, York, UK. · Consultant Psychiatrist, Cromwell House, Greater Manchester West Mental Health NHS Foundation Trust, Salford, UK. · Division of Psychiatry, University College London, London, UK. · Consultant in Neuropsychopharmacology and Neuromodulation, North Bristol NHS Trust, Rosa Burden Centre, Southmead Hospital, Bristol, UK. · Reader in Clinical Psychopharmacology, Institute of Neuroscience, Newcastle University, Royal Victoria Infirmary, Newcastle upon Tyne, UK. · Reader in Child and Adolescent Psychiatry, Centre for Mental Health, Imperial College London, London, UK. · Professor of Psychological Medicine, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Professor of Psychopharmacology, King's College London, London, UK. · Associate Professor, Canada Research Chair in Early Interventions, Dalhousie University, Department of Psychiatry, Halifax, NS, Canada. ·J Psychopharmacol · Pubmed #25969470.

ABSTRACT: A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made.

2 Editorial Editor's reply. 2015

Chien, P. ·Ninewells Hospital & Medical School, Dundee, UK. ·BJOG · Pubmed #25702558.

ABSTRACT: -- No abstract --

3 Review Assessing the Risks Associated with Antidepressant Use in Plastic Surgery: A Systematic Review. 2015

Teo, Isabel / Song, Christopher Tam. ·Dundee and Edinburgh, United Kingdom From Ninewells Hospital and the University of Edinburgh. ·Plast Reconstr Surg · Pubmed #26182175.

ABSTRACT: BACKGROUND: Antidepressant use has increased dramatically over the past decade. Although there is no question about the benefits of these medications, uncertainty exists with regard to the implications of antidepressant treatment surrounding plastic surgery. This systematic review collates all of the available literature that evaluates the risks of patient antidepressant treatment, in relation to plastic surgery. METHODS: A comprehensive literature review of the PubMed and Cochrane databases was conducted. Articles were assessed by two independent reviewers using predefined data fields and selected using specific inclusion criteria. The two authors independently reviewed the literature and extracted data from included reviews, and discrepancies were resolved by consensus. RESULTS: Twenty-six articles were included in the analysis and were categorized into five groups for comparison: risk of bleeding, risk of breast cancer, risk of breast cancer recurrence, breast enlargement, and miscellaneous (unique complications). Extracted information included study type, statistical analyses, conclusion, and limitations. CONCLUSIONS: This review does not support the cessation of antidepressants in patients before plastic surgery, as the numbers needed to harm are low and the implications of withdrawal may prove to be detrimental to postoperative management. However, the use of antidepressants for mental disorders may also implicate key patient risk factors for surgical complications, and sufficient exploration into the patient's indications for the prescription is crucial. Evidence so far does not suggest that antidepressants increase the risk of breast cancer or recurrence in general, but caution should be exercised for those specifically on concurrent tamoxifen and paroxetine treatment.

4 Review GABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response. 2015

Gunn, Benjamin G / Cunningham, Linda / Mitchell, Scott G / Swinny, Jerome D / Lambert, Jeremy J / Belelli, Delia. ·Division of Neuroscience, Medical Research Institute, Dundee University, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Institute for Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, UK. · Division of Neuroscience, Medical Research Institute, Dundee University, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. Electronic address: d.belelli@dundee.ac.uk. ·Front Neuroendocrinol · Pubmed #24929099.

ABSTRACT: Regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity by stress is a fundamental survival mechanism and HPA-dysfunction is implicated in psychiatric disorders. Adverse early life experiences, e.g. poor maternal care, negatively influence brain development and programs an abnormal stress response by encoding long-lasting molecular changes, which may extend to the next generation. How HPA-dysfunction leads to the development of affective disorders is complex, but may involve GABAA receptors (GABAARs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABAARs and exhibit stress-protective properties. Importantly, neurosteroid levels rise rapidly during acute stress, are perturbed in chronic stress and are implicated in the behavioural changes associated with early-life adversity. We will appraise how GABAAR-active neurosteroids may impact on HPA axis development and the orchestration of the stress-evoked response. The significance of these actions will be discussed in the context of stress-associated mood disorders.

5 Review Association between depression and non-fatal overdoses among drug users: a systematic review and meta-analysis. 2014

Bartoli, Francesco / Carrà, Giuseppe / Brambilla, Giulia / Carretta, Daniele / Crocamo, Cristina / Neufeind, Julia / Baldacchino, Alex / Humphris, Gerry / Clerici, Massimo. ·Department of Surgery and Interdisciplinary Medicine, University of Milano Bicocca, Milano 20126, Italy. · Mental Health Sciences Unit, Faculty of Brain Sciences, University College London, W1W 7EJ, UK. Electronic address: g.carra@ucl.ac.uk. · Department of Mental Health, San Gerardo Hospital, Monza 20900, MB, Italy. · Medical and Biological Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9TF, UK. · Division of Neuroscience, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. ·Drug Alcohol Depend · Pubmed #24210424.

ABSTRACT: BACKGROUND: Assessing factors associated with non-fatal overdose is important as these could be useful to identify individuals with substance use disorders at high risk of adverse outcomes and consequences. Depression may play an important role in terms of overdose risk. We aimed to test if drug users suffering from a depressive disorder might have significantly higher risk of non-fatal overdose as compared with drug users without depression. METHODS: We conducted a systematic review and meta-analysis. PubMed, Embase and Web of Knowledge were searched. The pooled analyses were based on prevalence rates, risk difference (RD) and odds ratio (OR), reporting 95% confidence intervals (CIs). The combined estimates were obtained weighting each study according to random effects model for meta-analysis. RESULTS: Seven articles, involving 12,019 individuals, and run in the US, Canada, Sweden, Norway, and Australia, were included. Pooled analyses comparing depressed with not depressed individuals highlighted a RD (95% CIs) for non-fatal overdose of 7.3% (4.8-9.7%) and an OR (95% CIs) of 1.45 (1.17-1.79). The subgroups analyses based on specific characteristics of included studies confirmed the association between depression and overdose. CONCLUSIONS: Depressive disorders seem to be important factors associated to the risk of non-fatal overdose. Longitudinal studies might appropriately clarify causal inference issues. Future research should address the role of depressive disorders as predictors of subsequent non-fatal overdoses.

6 Clinical Trial Cognitive Behavioural Analysis System of Psychotherapy (CBASP) for chronic depression: clinical characteristics and six month clinical outcomes in an open case series. 2014

Swan, John S / Macvicar, Robert / Christmas, David / Durham, Rob / Rauchhaus, Petra / McCullough, James P / Matthews, Keith. ·Division of Neuroscience, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, UK. Electronic address: johnswan@nhs.net. ·J Affect Disord · Pubmed #24182417.

ABSTRACT: BACKGROUND: Evidence-based guidance on how best to treat chronic depression is limited. Cognitive Behavioural Analysis System of Psychotherapy (CBASP) has shown some promise with this 'difficult-to-treat' clinical group. This case series was designed to assess the acceptability and utility of this novel treatment in routine clinical practice within the U.K. National Health Service. METHODS: We offered an open trial of CBASP to a cohort of 115 referred patients within primary and secondary care. Diagnostic interview and standardised outcome measures were administered before and after 6 months of CBASP with a trained, accredited therapist. RESULTS: Seventy-four patients entered therapy, with 46 completing. 30% met criteria for remission (≤ 8 HRSD-24 score) and a further 30% met criteria for clinically significant change (> 8 and ≤15 HRSD-24 plus 50% reduction in baseline score). Thirty-nine per cent made "No change". Group measures of quality of life, social functioning and interpersonal functioning also improved. LIMITATIONS: This was an open study design with a moderate sample size and no control group. Ratings were not completed using a blinded procedure. CONCLUSIONS: CBASP is an acceptable therapy for a large proportion of patients with chronic depression and was associated with clinically significant change in 60% of completers.

7 Article Effects of Opioid Dependence on Visuospatial Memory and Its Associations With Depression and Anxiety. 2019

Tolomeo, Serenella / Davey, Fleur / Steele, J Douglas / Baldacchino, Alexander Mario. ·Department of Psychology, National University of Singapore, Singapore, Singapore. · Centre for Family and Population Research, National University of Singapore, Singapore, Singapore. · NHS Fife, Queen Margaret Hospital, Dunfermline, United Kingdom. · School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom. · Division of Population and Behavioural Science, Medical School, University of St Andrews, St Andrews, United Kingdom. ·Front Psychiatry · Pubmed #31708811.

ABSTRACT:

8 Article The role of depression in unnatural death: A case-based retrospective study. 2019

Gilchrist, Eilidh E A / Sadler, David W. ·School of Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee, DD1 9SY, United Kingdom. Electronic address: e.e.a.gilchrist@dundee.ac.uk. · University of Dundee, Police Mortuary, United Kingdom. ·J Affect Disord · Pubmed #31437704.

ABSTRACT: BACKGROUND: Depression affects the life of millions around the globe and perhaps also the manner of death. This study examined the role of depression in specific causes of unnatural death and whether alcohol and substance use affect this relationship, in one locality in Scotland. METHODS: The research used a retrospective case-based study approach to analyse 168 cases, quantifying data reported in mortuary files to allow for quantitative statistical analysis of associations and differences amongst the variables. RESULTS: A diagnosis of depression was associated with a higher likelihood of unnatural death due to suicide, drugs or homicide. A diagnosis of substance abuse was associated with a diagnosis of depression and with an increased likelihood of death due to suicide or drugs. A diagnosis of alcohol abuse was associated with a reduced likelihood of a diagnosis of depression but was associated with an increased likelihood of suicide. LIMITATIONS: This study relied on a small sample from one locality in Scotland which limited the ability to generalise the results and the retrospective case-based design also limited the potential for checking data accuracy or to consider temporal relationships, which limited the ability to interpret causality. CONCLUSIONS: This study found that there was a relationship between depression and unnatural death, which was mediated by alcohol and substance use. The importance of this study lies within the recognition of these relationships which identified the complexities of these relationships but suggested that some unnatural deaths within this population could be prevented.

9 Article Insulin resistance: Genetic associations with depression and cognition in population based cohorts. 2019

Frangou, Sophia / Shirali, Masoud / Adams, Mark J / Howard, David M / Gibson, Jude / Hall, Lynsey S / Smith, Blair H / Padmanabhan, Sandosh / Murray, Alison D / Porteous, David J / Haley, Chris S / Deary, Ian J / Clarke, Toni-Kim / McIntosh, Andrew M. ·Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: sophia.frangou@mssm.edu. · Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK. · Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. · Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, UK. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Generation Scotland, Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK. · Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK. ·Exp Neurol · Pubmed #30965038.

ABSTRACT: Insulin resistance, broadly defined as the reduced ability of insulin to exert its biological action, has been associated with depression and cognitive dysfunction in observational studies. However, it is unclear whether these associations are causal and whether they might be underpinned by other shared factors. To address this knowledge gap, we capitalized on the stability of genetic biomarkers through the lifetime, and on their unidirectional relationship with depression and cognition. Specifically, we determined the association between quantitative measures of cognitive function and depression and genetic instruments of insulin resistance traits in two large-scale population samples, the Generation Scotland: Scottish Family Health Study (GS: SFHS; N = 19,994) and in the UK Biobank (N = 331,374). In the GS:SFHS, the polygenic risk score (PRS) for fasting insulin was associated with verbal intelligence and depression while the PRS for the homeostasis model assessment of insulin resistance was associated with verbal intelligence. Despite this overlap in genetic architecture, Mendelian randomization analyses in the GS:SFHS and in the UK Biobank samples did not yield evidence for causal associations from insulin resistance traits to either depression or cognition. These findings may be due to weak genetic instruments, limited cognitive measures and insufficient power but they may also indicate the need to identify other biological mechanisms that may mediate the relationship from insulin resistance to depression and cognition.

10 Article Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin. 2018

McGregor, Gemma / Clements, Leigh / Farah, Adham / Irving, Andrew J / Harvey, Jenni. ·Division of Neuroscience, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · School of Biomolecular and Biomedical Science, The Conway Institute, University College Dublin, Dublin, Ireland. · Division of Neuroscience, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. Electronic address: j.z.harvey@dundee.ac.uk. ·Neurobiol Aging · Pubmed #29860205.

ABSTRACT: The hippocampus is a key target for the hormone leptin and leptin regulation of excitatory synaptic transmission at Schaffer-collateral-CA1 synapses during aging are well documented. However, little is known about the age-dependent actions of leptin at the temporoammonic (TA) input to CA1 neurons. Here we show that leptin induces a novel form of N-methyl-D-aspartate receptor-dependent long-term depression (LTD) at adult (12-24 weeks old) TA-CA1 synapses. Leptin-induced LTD requires activation of canonical Janus tyrosine kinase 2- signal transducer and activator of transcription signaling and removal of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors from synapses. Moreover, leptin-induced LTD is occluded by activity-dependent LTD at TA-CA1 synapses. By contrast, leptin has no effect on excitatory synaptic transmission at aged (12-14 months old) TA-CA1 synapses, and low-frequency stimulation also fails to induce LTD at this age. These findings demonstrate clear age-related alterations in the leptin sensitivity of TA-CA1 synapses and provide valuable information on how the leptin system alters with age. As leptin has been linked to Alzheimer's disease, these findings have important implications for understanding of age-related disorders such as Alzheimer's disease.

11 Article Long-range temporal correlations of broadband EEG oscillations for depressed subjects following different hemispheric cerebral infarction. 2017

Hou, Dongzhe / Wang, Chunfang / Chen, Yuanyuan / Wang, Weijie / Du, Jingang. ·Neurorehabilitation Department, Tianjin Huanhu Hospital, Tianjin, People's Republic of China. · 0000 0004 1758 2086 · grid.413605.5 · Rehabilitation Medical Department, Tianjin Union Medical Center, Tianjin, 300121 People's Republic of China. · 0000 0004 1799 2675 · grid.417031.0 · Rehabilitation Medical Research Center of Tianjin, Tianjin, 300121 People's Republic of China. · Lab of Neural Engineering and Rehabilitation, Department of Biomedical Engineering, Tianjin University, Tianjin, People's Republic of China. · 0000 0004 1761 2484 · grid.33763.32 · Tayside Orthopaedics and Rehabilitation Technology Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · 0000 0004 0397 2876 · grid.8241.f ·Cogn Neurodyn · Pubmed #29147145.

ABSTRACT: Abnormal long-range temporal correlation (LRTC) in EEG oscillation has been observed in several brain pathologies and mental disorders. This study examined the relationship between the LRTC of broadband EEG oscillation and depression following cerebral infarction with different hemispheric lesions to provide a novel insight into such depressive disorders. Resting EEGs of 16 channels in 18 depressed (9 left and 9 right lesions) and 21 non-depressed (11 left and 10 right lesions) subjects following cerebral infarction and 19 healthy control subjects were analysed by means of detrended fluctuation analysis, a quantitative measurement of LRTC. The difference among groups and the correlation between the severity of depression and LRTC in EEG oscillation were investigated by statistical analysis. The results showed that LRTC of broadband EEG oscillations in depressive subjects was still preserved but attenuated in right hemispheric lesion subjects especially in left pre-frontal and right inferior frontal and posterior temporal regions. Moreover, an association between the severity of psychiatric symptoms and the attenuation of the LRTC was found in frontal, central and temporal regions for stroke subjects with right lesions. A high discriminating ability of the LRTC in the frontal and central regions to distinguish depressive from non-depressive subjects suggested potential feasibility for LRTC as an assessment indicator for depression following right hemispheric cerebral infarction. Different performance of temporal correlation in depressed subjects following the two hemispheric lesions implied complex association between depression and stroke lesion location.

12 Article Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. 2017

Holtzheimer, Paul E / Husain, Mustafa M / Lisanby, Sarah H / Taylor, Stephan F / Whitworth, Louis A / McClintock, Shawn / Slavin, Konstantin V / Berman, Joshua / McKhann, Guy M / Patil, Parag G / Rittberg, Barry R / Abosch, Aviva / Pandurangi, Ananda K / Holloway, Kathryn L / Lam, Raymond W / Honey, Christopher R / Neimat, Joseph S / Henderson, Jaimie M / DeBattista, Charles / Rothschild, Anthony J / Pilitsis, Julie G / Espinoza, Randall T / Petrides, Georgios / Mogilner, Alon Y / Matthews, Keith / Peichel, DeLea / Gross, Robert E / Hamani, Clement / Lozano, Andres M / Mayberg, Helen S. ·Department of Psychiatry and Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. Electronic address: paul.e.holtzheimer@dartmouth.edu. · Department of Psychiatry, Neurology and Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Psychiatry and Behavioral Science, Duke University School of Medicine, Durham, NC, USA. · National Institute of Mental Health, Rockville, MD, USA. · Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. · Neurological Surgery, Radiation Oncology, Department of Neurological Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. · Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Psychiatry and Behavioral Science, Duke University School of Medicine, Durham, NC, USA. · Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA. · Department of Psychiatry, Division of Experimental Therapeutics, Columbia University College of Physicians & Surgeons, New York, NY, USA. · Department of Neurosurgery, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA. · Department of Neurosurgery, Neurology, Anesthesiology and Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. · Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA. · Department of Neurosurgery and Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. · Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA. · Department of Neurosurgery, Virginia Commonwealth University, Richmond, VA, USA. · Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. · Department of Surgery (Neurosurgery), University of British Columbia, Vancouver, BC, Canada. · Department of Neurological Surgery, University of Louisville, Louisville, KY, USA. · Stanford Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. · Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA. · Department of Psychiatry, University of Massachusetts Medical School and UMass Memorial HealthCare, Worcester, MA, USA. · Department of Neuroscience and Experimental Therapeutics and the Department of Neurosurgery, Albany Medical College, Albany, NY, USA. · Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · The Zucker Hillside Hospital, Northwell Health System, Glen Oaks, NY, USA; Hofstra Northwell School of Medicine, Hempstead, NY, USA. · Department of Neurosurgery, Center for Neuromodulation, NYU Langone Medical Center, New York, NY, USA. · Division of Neuroscience, School of Medicine, University of Dundee, Dundee, UK; Advanced Interventions Service, NHS Tayside, Ninewells Hospital and Medical School, Dundee, UK. · Clinical Studies Department, Abbott (previously St Jude Medical), Plano, TX, USA. · Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA. · Behavioural Neurobiology Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Division of Neurosurgery, Toronto Western Hospital, Toronto, ON, Canada. · Department of Neurosurgery and Neuroscience, Toronto Western Hospital, Toronto, ON, Canada. · Department of Psychiatry and Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA. ·Lancet Psychiatry · Pubmed #28988904.

ABSTRACT: BACKGROUND: Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. METHODS: Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. FINDINGS: Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. INTERPRETATION: This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. FUNDING: Abbott (previously St Jude Medical).

13 Article Physical and mental health comorbidities of epilepsy: Population-based cross-sectional analysis of 1.5 million people in Scotland. 2017

Weatherburn, Christopher J / Heath, Craig A / Mercer, Stewart W / Guthrie, Bruce. ·Quality, Safety and Informatics Research Group, Population Health Sciences Division, Ninewells Hospital and Medical School, University of Dundee, Mackenzie Building, Kirsty Semple Way, Dundee DD2 4BF, UK. · Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, UK. · Institute of Health and Wellbeing, General Practice and Primary Care, University of Glasgow, 1 Horselethill Road, Glasgow G12 9LX, UK. · Quality, Safety and Informatics Research Group, Population Health Sciences Division, Ninewells Hospital and Medical School, University of Dundee, Mackenzie Building, Kirsty Semple Way, Dundee DD2 4BF, UK. Electronic address: B.Guthrie@dundee.ac.uk. ·Seizure · Pubmed #28024199.

ABSTRACT: PURPOSE: To measure the prevalence of physical and mental health comorbidities in people with epilepsy in a large population cohort, and to examine the prevalence of depression accounting for other physical comorbidity. METHODS: Population-based, cross-sectional descriptive epidemiology analysis of primary care electronic records for 1,510,742 people aged 14+ years, examining the prevalence of 39 comorbidities. RESULTS: 12,720 people with epilepsy were identified (prevalence 8.4/1000 population, 95% CI 8.3-8.5). Physical and mental health comorbidity was more common with epilepsy (mean of an additional 1.02 physical conditions difference, 95% CI 0.99-1.06). 69.9% of people with epilepsy had one or more comorbid health conditions and 18.6% had four or more, compared to 46.9% and 9.0% of people without epilepsy. Depression was present in 16.3% of people with epilepsy compared to 9.5% of those without (adjusted OR 1.57, 95% CI 1.49-1.65). The prevalence of comorbid depression in epilepsy increased as the number of physical comorbidities increased (OR 5.82, 95% CI 4.90-6.91 for 4+ physical comorbidities vs none) and with increasing deprivation, similar to the patterns observed in other common physical conditions. CONCLUSION: People with epilepsy have higher rates of both physical and mental health comorbidity than people without even after adjustment for age, gender and levels of deprivation. Depression is more common than in the general population but the prevalence is similar to other physical health conditions, and is strongly associated with the total burden of physical conditions. This study highlights the complexity in caring for people with epilepsy.

14 Article Conditioned task-set competition: Neural mechanisms of emotional interference in depression. 2017

Stolicyn, Aleks / Steele, J Douglas / Seriès, Peggy. ·Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, 10 Crichton Street, Edinburgh, EH8 9AB, UK. · School of Medicine (Neuroscience), University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. · Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, 10 Crichton Street, Edinburgh, EH8 9AB, UK. pseries@inf.ed.ac.uk. ·Cogn Affect Behav Neurosci · Pubmed #27943159.

ABSTRACT: Depression has been associated with increased response times at the incongruent-, neutral-, and negative-word trials of the classical and emotional Stroop tasks (Epp et al., Clinical Psychology Review, 32, 316-328, 2012). Response-time slowdown effects at incongruent- and negative-word trials of the Stroop tasks were reported to correlate with depressive severity, indicating strong relevance of the effects to the symptomatology. This study proposes a novel integrative computational model of neural mechanisms of both the classical and emotional Stroop effects, drawing on the previous prominent theoretical explanations of performance at the classical Stroop task (Cohen, Dunbar, & McClelland, Psychological Review, 97, 332-361, 1990; Herd, Banich, & O'Reilly, Journal of Cognitive Neuroscience, 18, 22-32, 2006), and in addition suggesting that negative emotional words represent conditioned stimuli for future negative outcomes. The model is shown to explain the classical Stroop effect and the slow (between-trial) emotional Stroop effect with biologically plausible mechanisms, providing an advantage over the previous theoretical accounts (Matthews & Harley, Cognition & Emotion, 10, 561-600, 1996; Wyble, Sharma, & Bowman, Cognition & Emotion, 22, 1019-1051, 2008). Simulation results suggested a candidate mechanism responsible for the pattern of depressive performance at the classical and the emotional Stroop tasks. Hyperactivity of the amygdala, together with increased inhibitory influence of the amygdala over dopaminergic neurotransmission, could be at the origin of the performance deficits.

15 Article Organic vs. functional neurological disorders: The role of childhood psychological trauma. 2017

Karatzias, Thanos / Howard, Ruth / Power, Kevin / Socherel, Florentina / Heath, Craig / Livingstone, Alison. ·Edinburgh Napier University, School of Health & Social Care, Edinburgh, UK; NHS Lothian, Rivers Centre for Traumatic Stress, Edinburgh, UK. Electronic address: t.karatzias@napier.ac.uk. · Edinburgh Napier University, School of Health & Social Care, Edinburgh, UK. · NHS Tayside, Psychological Therapies Service, Dundee, UK; University of Stirling, School Of Natural Sciences, Stirling, UK. · NHS Tayside, Psychological Therapies Service, Dundee, UK. · Department of Neurology, Institute of Neurological Sciences, Glasgow, UK. · Department of Clinical Neuropsychology, Ninewells Hospital, Dundee, UK. ·Child Abuse Negl · Pubmed #27886517.

ABSTRACT: Although the relationship between psychological trauma and medically unexplained symptoms (MUS) is well established, this relationship is less well understood in people with medically unexplained neurological symptoms. In the present study, we set out to compare people with functional neurological disorders, and organic neurological disorders, in terms of childhood and adulthood traumatic events, traumatic stress, emotional dysregulation and symptoms of depression and anxiety. We have hypothesised that those with functional neurological disorders would be more likely to report childhood and adulthood traumatic life events, traumatic symptomatology, emotional dysregulation and symptoms of anxiety and depression, compared to those with organic neurological disorders. Sample consisted of a consecutive series of people with functional neurological disorders and with organic neurological disorders (n=82) recruited from a hospital in Scotland. Participants completed measures of life events, traumatic stress, emotional regulation, anxiety and depression. The two groups were found to significantly differ in relation to all measures, with the MUS group being more likely to report childhood and adulthood life events, more severe emotional dysregulation, traumatic stress and symptoms of anxiety and stress. Logistic regression analysis revealed that exposure to childhood traumatic life events, specifically childhood sexual abuse, and childhood physical neglect, were the only factors which were significantly associated with membership of the medically unexplained neurological symptoms group. Although further research is required to confirm our findings, our results suggest that identifying and addressing the impact of childhood trauma, may alleviate distress and aid recovery from functional neurological disorders.

16 Article Neuropsin Inactivation Has Protective Effects against Depressive-Like Behaviours and Memory Impairment Induced by Chronic Stress. 2016

Chang, Simon / Bok, Philane / Sun, Cheng-Pu / Edwards, Andrew / Huang, Guo-Jen. ·Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. · Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. · Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom. · Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan. ·PLoS Genet · Pubmed #27701413.

ABSTRACT: Mounting evidence suggests the interaction between stress and genetics contribute to the development of depressive symptoms. Currently, the molecular mechanisms mediating this process are poorly understood, hindering the development of new clinical interventions. Here, we investigate the interaction between neuropsin, a serine protease, and chronic stress on the development of depressive-like behaviours in mice. We found no difference in baseline behaviour between neuropsin knockout and wild-type mice. However, our results show that neuropsin knockout mice are protected against the development of depressive-like behaviours and memory impairment following chronic stress. We hypothesised that this difference in behaviour may be due to an interaction between neuropsin and elevated plasma corticosterone. To test this, we subjected mice to chronic corticosterone injections. These injections resulted in changes to hippocampal structure similar to that observed following chronic stress. We found that inactivation of neuropsin limits the extent of these anatomical changes in both the chronic stress and the corticosterone injection exposed cohorts. We next used viral vectors to knockdown or overexpress neuropsin in the hippocampus to confirm the results of the KO study. Additionally, we found that inactivation of neuropsin limited glutamate dysregulation, associated with increased generation of reactive oxygen species, resulting from prolonged elevated plasma corticosterone. In this study, we demonstrate that neuropsin inactivation protects against the impairment of hippocampal functions and the depressive-like behaviour induced by chronic stress or high levels of corticosterone. Consequently, we suggest neuropsin is a potential target for clinical interventions for the management of stress disorders.

17 Article Genetic and Environmental Risk for Chronic Pain and the Contribution of Risk Variants for Major Depressive Disorder: A Family-Based Mixed-Model Analysis. 2016

McIntosh, Andrew M / Hall, Lynsey S / Zeng, Yanni / Adams, Mark J / Gibson, Jude / Wigmore, Eleanor / Hagenaars, Saskia P / Davies, Gail / Fernandez-Pujals, Ana Maria / Campbell, Archie I / Clarke, Toni-Kim / Hayward, Caroline / Haley, Chris S / Porteous, David J / Deary, Ian J / Smith, Daniel J / Nicholl, Barbara I / Hinds, David A / Jones, Amy V / Scollen, Serena / Meng, Weihua / Smith, Blair H / Hocking, Lynne J. ·Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom. · Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom. · Institute for Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom. · Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. · 23andMe Inc., Mountain View, California, United States of America. · Pfizer WRD, Human Genetics and Computational Biomedicine, Granta Park, Cambridge, United Kingdom. · Division of Population Health Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom. · The Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom. ·PLoS Med · Pubmed #27529168.

ABSTRACT: BACKGROUND: Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study. METHODS AND FINDINGS: Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960), a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9%) that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%). Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68) and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, were associated with chronic pain in both GS:SFHS (maximum β = 6.18x10-2, 95% CI 2.84 x10-2 to 9.35 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 5.68 x 10-2, 95% CI 4.70x10-2 to 6.65x10-2, p < 3x10-4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum β = 6.62x10-2, 95% CI 2.82 x10-2 to 9.76 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 2.56x10-2, 95% CI 1.62x10-2 to 3.63x10-2, p < 3x10-4). Limitations of the current study include the possibility that spouse effects may be due to assortative mating and the relatively small polygenic risk score effect sizes. CONCLUSIONS: Genetic factors, as well as chronic pain in a partner or spouse, contribute substantially to the risk of chronic pain for an individual. Chronic pain is genetically correlated with MDD, has a polygenic architecture, and is associated with polygenic risk of MDD.

18 Article A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control. 2016

Tolomeo, Serenella / Christmas, David / Jentzsch, Ines / Johnston, Blair / Sprengelmeyer, Reiner / Matthews, Keith / Douglas Steele, J. ·School of Medicine (Neuroscience), Ninewells Hospital and Medical School, University of Dundee, UK. · Advanced Interventions Service, Area 7, Level 6, South Block, Ninewells Hospital and Medical School, UK. · School of Psychology and Neuroscience, University of St Andrews, St Andrews, UK. · School of Medicine (Neuroscience), Ninewells Hospital and Medical School, University of Dundee, UK Advanced Interventions Service, Area 7, Level 6, South Block, Ninewells Hospital and Medical School, UK. · School of Medicine (Neuroscience), Ninewells Hospital and Medical School, University of Dundee, UK Advanced Interventions Service, Area 7, Level 6, South Block, Ninewells Hospital and Medical School, UK d.steele@dundee.ac.uk. ·Brain · Pubmed #27190027.

ABSTRACT: Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. It has previously been proposed that this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral anterior cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy control subjects. Using the Ekman 60 faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received anterior cingulotomy were impaired in recognizing negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with this hypothesis, we found that larger volume lesions predicted more impairment in recognizing fear, disgust and anger, and no impairment in recognizing facial expressions of surprise or happiness. However, we found no impairment in recognizing expressions of sadness. Also consistent with the hypothesis, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman's meta-analysis-derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimizing behaviour in the presence of such stimuli, our findings support the assertion that this region has a causal role in these processes. While the clinical justification for cingulotomy is empirical and not theoretical, it is plausible that lesions within a brain region associated with the subjective experience of negative affect and pain may be therapeutic for patients with otherwise intractable mood, anxiety and pain syndromes.

19 Article Autobiographical memory specificity in response to verbal and pictorial cues in clinical depression. 2016

Ridout, Nathan / Dritschel, Barbara / Matthews, Keith / O'Carroll, Ronan. ·Department of Psychology, School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK. Electronic address: n.ridout@aston.ac.uk. · School of Psychology, University of St Andrews, St Andrews, KY16 9BU, UK. Electronic address: bd9@st-andrews.ac.uk. · Division of Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK. Electronic address: k.matthews@dundee.ac.uk. · Department of Psychology, University of Stirling, Stirling, FK9 4LA, UK. Electronic address: reo1@stir.ac.uk. ·J Behav Ther Exp Psychiatry · Pubmed #26808234.

ABSTRACT: BACKGROUND: Depressed individuals have been consistently shown to exhibit problems in accessing specific memories of events from their past and instead tend to retrieve categorical summaries of events. The majority of studies examining autobiographical memory changes associated with psychopathology have tended to use word cues, but only one study to date has used images (with PTSD patients). OBJECTIVE: to determine if using images to cue autobiographical memories would reduce the memory specificity deficit exhibited by patients with depression in comparison to healthy controls. METHODS: Twenty-five clinically depressed patients and twenty-five healthy controls were assessed on two versions of the autobiographical memory test; cued with emotional words and images. RESULTS: Depressed patients retrieved significantly fewer specific memories, and a greater number of categorical, than did the controls. Controls retrieved a greater proportion of specific memories to images compared to words, whereas depressed patients retrieved a similar proportion of specific memories to both images and words. LIMITATIONS: no information about the presence and severity of past trauma was collected. CONCLUSIONS: results suggest that the overgeneral memory style in depression generalises from verbal to pictorial cues. This is important because retrieval to images may provide a more ecologically valid test of everyday memory experiences than word-cued retrieval..

20 Article Neural correlates of social exchanges during the Prisoner's Dilemma game in depression. 2016

Gradin, V B / Pérez, A / Macfarlane, J A / Cavin, I / Waiter, G / Tone, E B / Dritschel, B / Maiche, A / Steele, J D. ·Faculty of Psychology,CIBPsi, Universidad de la República,Montevideo,Uruguay. · Medical Physics,NHS Tayside,University of Dundee,Dundee,UK. · Aberdeen Biomedical Imaging Centre,University of Aberdeen,Aberdeen,UK. · Department of Psychology,Georgia State University,Atlanta, GA,USA. · Department of Psychology,University of St Andrews,Fife,UK. · School of Medicine (Neuroscience),University of Dundee,Ninewells Hospital and Medical School,Dundee,UK. ·Psychol Med · Pubmed #26763141.

ABSTRACT: BACKGROUND: Depression is a disabling disorder that significantly impacts on the interpersonal functioning of individuals. However, little is known about the neural substrates of such difficulties. In the last few years neuroeconomics, which combines imaging with multiplayer behavioural economic paradigms, has been used to study the neural substrates of normal and abnormal interpersonal interactions. METHOD: This study used functional magnetic resonance imaging to investigate neural activity in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic game, the Prisoner's Dilemma. In this game, the participant and a co-player independently choose either to cooperate or not cooperate with each other. RESULTS: Depressed participants reported higher levels of negative feelings (betrayal, guilt) during the game than did controls. Neural activation was compared between 'imbalanced' events [when one of the players cooperated and the other defected ('CD' and 'DC')] and 'draw' events [when both players either cooperated or defected ('CC' and 'DD')]. Participants preferentially activated the anterior insula and the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and regulation of emotions. Importantly, compared to controls depressed participants showed reduced activation in the left DLPFC, with the extent of signal reduction correlating with increased self-report feelings of guilt associated with DC outcomes. CONCLUSIONS: Our findings suggest that depression is associated with reduced activation of the DLPFC during social events that involve unreciprocated cooperation. This abnormality may underlie anomalies in cognitive control and top-down regulation of emotions during challenging social exchanges.

21 Article Multidimensional apathy in ALS: validation of the Dimensional Apathy Scale. 2016

Radakovic, Ratko / Stephenson, Laura / Colville, Shuna / Swingler, Robert / Chandran, Siddharthan / Abrahams, Sharon. ·Department of Psychology, School of Philosophy, Psychology & Language Sciences, University of Edinburgh, Edinburgh, UK Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, UK. · Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK. · Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, UK Department of Neurology, Ninewells Hospital and Medical School, Dundee, UK. · Department of Psychology, School of Philosophy, Psychology & Language Sciences, University of Edinburgh, Edinburgh, UK Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, UK. ·J Neurol Neurosurg Psychiatry · Pubmed #26203157.

ABSTRACT: AIM: Apathy is a prominent symptom of amyotrophic lateral sclerosis (ALS), but measurement is confounded by physical disability. Furthermore, it has been traditionally measured as a unidimensional symptom despite research demonstrating a multifaceted construct. The new Dimensional Apathy Scale (DAS) has been specifically designed for patients with motor disability to measure 3 neurologically based subtypes of apathy: Executive, Emotional and Initiation. We aimed to explore this behavioural symptom by examining the substructure of apathy in ALS and to determine the reliability and validity of the DAS in patients and their carers. METHOD: Patients and carers were recruited through the national Scottish Motor Neurone Disease Register and were asked to complete the DAS, the standardised Apathy Evaluation Scale, and the Geriatric Depression Scale-Short Form. 83 patients with ALS, 75 carers and 83 sex-matched, age-matched and education-matched controls participated. RESULTS: When compared with healthy controls, patients showed a significant increase in apathy on the Initiation subscale, and were significantly less apathetic on the Emotional subscale. Scores on the DAS patient and carer versions did not significantly differ. Internal consistency reliability, convergent and discriminant validity were found to be good for the DAS subscales. There was no association between the DAS and functional disability using the ALS Functional Rating Scale. CONCLUSIONS: Apathy in ALS is characterised by a specific profile of increased initiation apathy and reduced emotional apathy. The DAS is a reliable and valid measure for the assessment of multidimensional apathy in ALS.

22 Article Structural MRI-Based Predictions in Patients with Treatment-Refractory Depression (TRD). 2015

Johnston, Blair A / Steele, J Douglas / Tolomeo, Serenella / Christmas, David / Matthews, Keith. ·Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom. · Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom; Advanced Interventions Service, Area 7, Level 6, South Block, Ninewells Hospital and Medical School, NHS Tayside, Dundee, United Kingdom. · Advanced Interventions Service, Area 7, Level 6, South Block, Ninewells Hospital and Medical School, NHS Tayside, Dundee, United Kingdom. ·PLoS One · Pubmed #26186455.

ABSTRACT: The application of machine learning techniques to psychiatric neuroimaging offers the possibility to identify robust, reliable and objective disease biomarkers both within and between contemporary syndromal diagnoses that could guide routine clinical practice. The use of quantitative methods to identify psychiatric biomarkers is consequently important, particularly with a view to making predictions relevant to individual patients, rather than at a group-level. Here, we describe predictions of treatment-refractory depression (TRD) diagnosis using structural T1-weighted brain scans obtained from twenty adult participants with TRD and 21 never depressed controls. We report 85% accuracy of individual subject diagnostic prediction. Using an automated feature selection method, the major brain regions supporting this significant classification were in the caudate, insula, habenula and periventricular grey matter. It was not, however, possible to predict the degree of 'treatment resistance' in individual patients, at least as quantified by the Massachusetts General Hospital (MGH-S) clinical staging method; but the insula was again identified as a region of interest. Structural brain imaging data alone can be used to predict diagnostic status, but not MGH-S staging, with a high degree of accuracy in patients with TRD.

23 Article Failure of hippocampal deactivation during loss events in treatment-resistant depression. 2015

Johnston, Blair A / Tolomeo, Serenella / Gradin, Victoria / Christmas, David / Matthews, Keith / Steele, J Douglas. ·1 Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, U.K, DD1 9SY. · 2 CIBPsi, Faculty of Psychology, Universidad de al República, Montevideo, Uruguay. · 3 Advanced Interventions Service, Area 7, Level 6, South Block, Ninewells Hospital and Medical School, Dundee, UK. · 1 Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, U.K, DD1 9SY 3 Advanced Interventions Service, Area 7, Level 6, South Block, Ninewells Hospital and Medical School, Dundee, UK. · 1 Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, U.K, DD1 9SY 3 Advanced Interventions Service, Area 7, Level 6, South Block, Ninewells Hospital and Medical School, Dundee, UK d.steele@dundee.co.uk. ·Brain · Pubmed #26133661.

ABSTRACT: Major depressive disorder is characterized by anhedonia, cognitive biases, ruminations, hopelessness and increased anxiety. Blunted responses to rewards have been reported in a number of recent neuroimaging and behavioural studies of major depressive disorder. In contrast, neural responses to aversive events remain an under-studied area. While selective serotonergic reuptake inhibitors are often effective in treating major depressive disorder, their mechanism of action remains unclear. Following a series of animal model investigations of depressive illness and serotonergic function, Deakin and Graeff predicted that brain activity in patients with major depressive disorder is associated with an overactive dorsal raphe nucleus with overactive projections to the amygdala, periaqueductal grey and striatum, and an underactive median raphe nucleus with underactive projections to the hippocampus. Here we describe an instrumental loss-avoidance and win-gain reinforcement learning functional magnetic resonance imaging study with 40 patients with highly treatment-resistant major depressive disorder and never-depressed controls. The dorsal raphe nucleus/ periaqueductal grey region of the midbrain and hippocampus were found to be overactive in major depressive disorder during unsuccessful loss-avoidance although the median raphe nucleus was not found to be underactive. Hippocampal overactivity was due to a failure to deactivate during loss events in comparison to controls, and hippocampal over-activity correlated with depression severity, self-report 'hopelessness' and anxiety. Deakin and Graeff argued that the median raphe nucleus normally acts to inhibit consolidation of aversive memories via the hippocampus and this system is underactive in major depressive disorder, facilitating the development of ruminations, while the dorsal raphe nucleus system is engaged by distal cues predictive of threats and is overactive in major depressive disorder. During win events the striatum was underactive in major depressive disorder. We tested individual patient consistency of these findings using within-study replication. Abnormal hippocampal activity correctly predicted individual patient diagnostic status in 97% (sensitivity 95%, specificity 100%) of subjects, and abnormal striatal activity predicted diagnostic status in 84% (sensitivity 79%, specificity 89%) of subjects. We conclude that the neuroimaging findings were largely consistent with Deaken and Graeff's predictions, abnormally increased hippocampal activity during loss events was an especially consistent abnormality, and brainstem serotonergic nuclei merit further study in depressive illness.

24 Article Management of Noncardiac Comorbidities in Chronic Heart Failure. 2015

Chong, Vun Heng / Singh, Jagdeep / Parry, Helen / Saunders, Jocelyn / Chowdhury, Farhad / Mancini, Donna M / Lang, Chim C. ·Department of Cardiology, Ninewells Hospital, Dundee, UK. · Division of Medicine and Therapeutics, University of Dundee, Dundee, UK. · Medical School, University of Dundee, Dundee, UK. · Department of Medicine, Columbia University, New York City, NY, USA. ·Cardiovasc Ther · Pubmed #26108139.

ABSTRACT: Prevalence of heart failure is increasing, especially in the elderly population. Noncardiac comorbidities complicate heart failure care and are increasingly common in elderly patients with reduced or preserved ejection fraction heart failure, owing to prolongation of patient's lives by advances in chronic heart failure (CHF) management. Common comorbidities include respiratory disease, renal dysfunction, anemia, arthritis, obesity, diabetes mellitus, cognitive dysfunction, and depression. These conditions contribute to the progression of the disease and may alter the response to treatment, partly as polypharmacy is inevitable in these patients. Cardiologists and other physicians caring for patients with CHF need to be vigilant to comorbid conditions that complicate the care of these patients. There is now more guidance on management of noncardiac comorbidities in heart failure, and this article contains a comprehensive review of the most recent updates on management of noncardiac comorbidities in CHF.

25 Article Putative transcriptomic biomarkers in the inflammatory cytokine pathway differentiate major depressive disorder patients from control subjects and bipolar disorder patients. 2014

Powell, Timothy R / McGuffin, Peter / D'Souza, Ursula M / Cohen-Woods, Sarah / Hosang, Georgina M / Martin, Charlotte / Matthews, Keith / Day, Richard K / Farmer, Anne E / Tansey, Katherine E / Schalkwyk, Leonard C. ·King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom. · King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom; Discipline of Psychiatry, University of Adelaide, Adelaide, Australia. · Division of Neuroscience, Ninewells Hospital and Medical School, Dundee, United Kingdom. ·PLoS One · Pubmed #24618828.

ABSTRACT: Mood disorders consist of two etiologically related, but distinctly treated illnesses, major depressive disorder (MDD) and bipolar disorder (BPD). These disorders share similarities in their clinical presentation, and thus show high rates of misdiagnosis. Recent research has revealed significant transcriptional differences within the inflammatory cytokine pathway between MDD patients and controls, and between BPD patients and controls, suggesting this pathway may possess important biomarker properties. This exploratory study attempts to identify disorder-specific transcriptional biomarkers within the inflammatory cytokine pathway, which can distinguish between control subjects, MDD patients and BPD patients. This is achieved using RNA extracted from subject blood and applying synthesized complementary DNA to quantitative PCR arrays containing primers for 87 inflammation-related genes. Initially, we use ANOVA to test for transcriptional differences in a 'discovery cohort' (total n = 90) and then we use t-tests to assess the reliability of any identified transcriptional differences in a 'validation cohort' (total n = 35). The two most robust and reliable biomarkers identified across both the discovery and validation cohort were Chemokine (C-C motif) ligand 24 (CCL24) which was consistently transcribed higher amongst MDD patients relative to controls and BPD patients, and C-C chemokine receptor type 6 (CCR6) which was consistently more lowly transcribed amongst MDD patients relative to controls. Results detailed here provide preliminary evidence that transcriptional measures within inflammation-related genes might be useful in aiding clinical diagnostic decision-making processes. Future research should aim to replicate findings detailed in this exploratory study in a larger medication-free sample and examine whether identified biomarkers could be used prospectively to aid clinical diagnosis.

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