Assessing regional cerebral blood flow in depression using 320-slice computed tomography

While there is evidence that the development and course of major depressive disorder (MDD) symptomatology is associated with vascular disease, and that there are changes in energy utilization in the disorder, the extent to which cerebral blood flow is changed in this condition is not clear. This study utilized a novel imaging technique previously used in coronary and stroke patients, 320-slice Computed-Tomography (CT), to assess regional cerebral blood flow (rCBF) in those with MDD and examine the pattern of regional cerebral perfusion. Thirty nine participants with depressive symptoms (Hamilton Depression Rating Scale 24 (HAMD24) score >20, and Self-Rating Depression Scale (SDS) score >53) and 41 healthy volunteers were studied. For all subjects, 3 ml of venous blood was collected to assess hematological parameters. Trancranial Doppler (TCD) ultrasound was utilized to measure parameters of cerebral artery rCBFV and analyse the Pulsatility Index (PI). 16 subjects (8 =  MDD; 8 =  healthy) also had rCBF measured in different cerebral artery regions using 320-slice CT. Differences among groups were analyzed using ANOVA and Pearson\u27s tests were employed in our statistical analyses. Compared with the control group, whole blood viscosity (including high\middle\low shear rate)and hematocrit (HCT) were significantly increased in the MDD group. PI values in different cerebral artery regions and parameters of rCBFV in the cerebral arteries were decreased in depressive participants, and there was a positive relationship between rCBFV and the corresponding vascular rCBF in both gray and white matter. rCBF of the left gray matter was lower than that of the right in MDD. Major depression is characterized by a wide range of CBF impairments and prominent changes in gray matter blood flow. 320-slice CT appears to be a valid and promising tool for measuring rCBF, and could thus be employed in psychiatric settings for biomarker and treatment response purposes

Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression

Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. Conclusion: This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression

Group cognitive behavioural therapy for stroke survivors with depression and their carers

Background: Depression in stroke survivors is common, leads to poorer outcomes and often not treated. A group cognitive behavioural therapy (CBT) program (Brainstorm) for stroke survivors with depression, and their carers has been running as part of usual care since 2007. Objective: To evaluate the implementation and acceptability of Brainstorm, a closed group intervention consisting of up to 10 sessions of education, activity planning, problem solving and thought challenging. Methods: Participating stroke survivors and their carers complete assessment measures at baseline, post-treatment and 1-month and 6-months follow-up. A mixed models for repeated measures data was conducted with depression and anxiety scores for stroke survivors (Beck Depression Inventory-II; Hospital Anxiety and Depression Scale) and the assessment of depression, anxiety and carer burden for carers. Acceptability was assessed by session attendance and written and open participant feedback upon completion of the program. Results: Forty-eight community dwelling stroke survivors and 34 carers attended Brainstorm, with a median attendance of 88% of sessions. Follow-up assessments were completed by 77% (post-treatment), 46% (1-month) and 38% (6-month) of stroke survivors. Stroke survivors’ depression scores decreased from baseline to post-treatment (p<.001); maintained at 1-month (p<.001) but not at 6-month (p=.056). Anxiety scores decreased between baseline and 1-month (p=.013). Carer burden, depression and anxiety scores at 1-month and 6-month follow-up, for carers, were all reduced when compared with baseline (p<.05). Conclusion: The Brainstorm group intervention for depression in stroke survivors appears to have been effectively implemented and is acceptable to stroke survivors and carers

An online intervention for improving stroke survivors' health-related quality of life : study protocol for a randomised controlled trial

Background: Recurrent stroke is a major contributor to stroke-related disability and costs. Improving health-risk behaviours and mental health has the potential to significantly improve recovery, enhance health-related quality of life (HRQoL), independent living, and lower the risk of recurrent stroke. The primary aim will be to test the effectiveness of an online intervention to improve HRQoL among stroke survivors at 6 months' follow-up. Programme effectiveness on four health behaviours, anxiety and depression, cost-effectiveness, and impact on other hospital admissions will also be assessed. Methods/design: An open-label randomised controlled trial is planned. A total of 530 adults will be recruited across one national and one regional stroke registry and block randomised to the intervention or minimal care control group. The intervention group will receive access to the online programme Prevent 2nd Stroke (P2S); the minimal care control group will receive an email with Internet addresses of generic health sites designed for the general population. The primary outcome, HRQoL, will be measured using the EuroQol-5D. A full analysis plan will compare between groups from baseline to follow-up. Discussion: A low-cost per user option to supplement current care, such as P2S, has the potential to increase HRQoL for stroke survivors, and reduce the risk of second stroke

The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial

BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting.METHODS AND DESIGN: This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress.DISCUSSION: The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial

A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo

A phasic dysregulation of mitochondrial bioenergetics may operate in bipolar disorder, increased in mania and decreased in depression. We aimed to examine efficacy of two add-on treatments in bipolar depression: N-acetylcysteine (NAC) and NAC with a combination of nutraceutical agents that may increase mitochondrial biogenesis. A three-arm 16-week, double-blind, randomised, placebo-controlled trial, adjunctive to usual treatment, was conducted. Participants (n = 181) with bipolar disorder and current depressive symptoms were randomised to 2000 mg/day NAC (n = 59), 2000 mg/day NAC with the combination nutraceutical treatment (CT, n = 61), or placebo (n = 61). The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 16. Young Mania Rating Scale, Clinical Global Impression (CGI)-Improvement and CGI-Severity scales, Patient Global Impression scale, Social and Occupational Functioning Assessment Scale (SOFAS), Longitudinal Interval Follow-Up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT), and Quality of Life Enjoyment, and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) were secondary outcomes. One hundred forty-eight participants had post-randomisation data and were analysed (NAC = 52, CT = 47, Placebo = 49). No between-group differences were found for the rate of change between baseline and 16 weeks on any of the clinical and functioning variables. Improvements in MADRS, BDRS, SOFAS, and LIFE-RIFT scores from baseline to the week 20 post-discontinuation visit were significantly greater in the CT group compared to those in the placebo. At week 20, the CGI-I was significantly lower in the CT group versus placebo. Gastrointestinal symptoms were significantly greater in the NAC than in the placebo group. These overall negative results, with no significant differences between groups detected at the primary outcome but some positive secondary signals, suggest either delayed benefit of the combination or an improvement of symptoms on withdrawal which warrants further exploration regarding the composition, mechanisms, and application of mitochondrial agents in illnesses characterised by mitochondrial dysfunction. ANZCTR ( ACTRN12612000830897 )

Altered cardiac autonomic nervous function in depression

Background:Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia.Methods:Individuals (n&thinsp;=&thinsp;53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score &ge;20 and a Zung Self-Rating Depression Scale score&thinsp;&gt;&thinsp;53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals&thinsp;&gt;&thinsp;50 ms different from preceding interval (pNN50). Pearson&rsquo;s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)).Results:The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P&lt;.05). The mean value of the LF in the depression group was higher than the in control group (P&lt;.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P&lt;.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P&lt;.05), particularly supraventricular arrhythmias.Conclusions:Our findings suggest that depression is accompanied by dysfunction of the cardiac autonomic nervous system, and further, that depression severity is linked to severity of this dysfunction. Individuals with depression appear to be susceptible to premature atrial and/or ventricular disease

The Therapeutic Potential of Mangosteen Pericarp as an Adjunctive Therapy for Bipolar Disorder and Schizophrenia

New treatments are urgently needed for serious mental illnesses including bipolar disorder and schizophrenia. This review proposes that Garcinia mangostana Linn. (mangosteen) pericarp is a possible adjunctive therapeutic agent for these disorders. Research to date demonstrates that neurobiological properties of the mangosteen pericarp are well aligned with the current understanding of the pathophysiology of bipolar disorder and schizophrenia. Mangosteen pericarp has antioxidant, putative neuroprotective, anti-inflammatory, and putative mitochondrial enhancing properties, with animal studies demonstrating favorable pharmacotherapeutic benefits with respect to these disorders. This review summarizes evidence of its properties and supports the case for future studies to assess the utility of mangosteen pericarp as an adjunctive treatment option for mood and psychotic disorders

Depression prevalence using the HADS-D compared to SCID major depression classification:An individual participant data meta-analysis

Objectives: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale – depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. Methods: We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. Results: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was −21.1% to 19.5%. Conclusions: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.This study was funded by the Canadian Institutes of Health Research (CIHR, KRS-144045 & PCG 155468). Ms. Neupane was supported by a G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University. Drs. Levis and Wu were supported by Fonds de recherche du Québec - Santé (FRQS) Postdoctoral Training Fellowships. Mr. Bhandari was supported by a studentship from the Research Institute of the McGill University Health Centre. Ms. Rice was supported by a Vanier Canada Graduate Scholarship. Dr. Patten was supported by a Senior Health Scholar award from Alberta Innovates, Health Solutions. The primary study by Scott et al. was supported by the Cumming School of Medicine and Alberta Health Services through the Calgary Health Trust, and funding from the Hotchkiss Brain Institute. The primary study by Amoozegar et al. was supported by the Alberta Health Services, the University of Calgary Faculty of Medicine, and the Hotchkiss Brain Institute. The primary study by Cheung et al. was supported by the Waikato Clinical School, University of Auckland, the Waikato Medical Research Foundation and the Waikato Respiratory Research Fund. The primary study by Cukor et al. was supported in part by a Promoting Psychological Research and Training on Health-Disparities Issues at Ethnic Minority Serving Institutions Grants (ProDIGs) awarded to Dr. Cukor from the American Psychological Association. The primary study by De Souza et al. was supported by Birmingham and Solihull Mental Health Foundation Trust. The primary study by Honarmand et al. was supported by a grant from the Multiple Sclerosis Society of Canada. The primary study by Fischer et al. was supported as part of the RECODEHF study by the German Federal Ministry of Education and Research (01GY1150). The primary study by Gagnon et al. was supported by the Drummond Foundation and the Department of Psychiatry, University Health Network. The primary study by Akechi et al. was supported in part by a Grant-in-Aid for Cancer Research (11−2) from the Japanese Ministry of Health, Labour and Welfare and a Grant-in-Aid for Young Scientists (B) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The primary study by Kugaya et al. was supported in part by a Grant-in-Aid for Cancer Research (9–31) and the Second-Term Comprehensive 10-year Strategy for Cancer Control from the Japanese Ministry of Health, Labour and Welfare. The primary study Ryan et al. was supported by the Irish Cancer Society (Grant CRP08GAL). The primary study by Keller et al. was supported by the Medical Faculty of the University of Heidelberg (grant no. 175/2000). The primary study by Love et al. (2004) was supported by the Kathleen Cuningham Foundation (National Breast Cancer Foundation), the Cancer Council of Victoria and the National Health and Medical Research Council. The primary study by Love et al. (2002) was supported by a grant from the Bethlehem Griffiths Research Foundation. The primary study by Löwe et al. was supported by the medical faculty of the University of Heidelberg, Germany (Project 121/2000). The primary study by Navines et al. was supported in part by the Spanish grants from the Fondo de Investigación en Salud, Instituto de Salud Carlos III (EO PI08/90869 and PSIGEN-VHC Study: FIS-E08/00268) and the support of FEDER (one way to make Europe). The primary study by O'Rourke et al. was supported by the Scottish Home and Health Department, Stroke Association, and Medical Research Council. The primary study by Sanchez-Gistau et al. was supported by a grant from the Ministry of Health of Spain (PI040418) and in part by Catalonia Government, DURSI 2009SGR1119. The primary study by Gould et al. was supported by the Transport Accident Commission Grant. The primary study by Rooney et al. was supported by the NHS Lothian Neuro-Oncology Endowment Fund. The primary study by Schwarzbold et al. was supported by PRONEX Program (NENASC Project) and PPSUS Program of Fundaçao de Amparo a esquisa e Inovacao do Estado de Santa Catarina (FAPESC) and the National Science and Technology Institute for Translational Medicine (INCT-TM). The primary study by Simard et al. was supported by IDEA grants from the Canadian Prostate Cancer Research Initiative and the Canadian Breast Cancer Research Alliance, as well as a studentship from the Canadian Institutes of Health Research. The primary study by Singer et al. (2009) was supported by a grant from the German Federal Ministry for Education and Research (no. 01ZZ0106). The primary study by Singer et al. (2008) was supported by grants from the German Federal Ministry for Education and Research (# 7DZAIQTX) and of the University of Leipzig (# formel. 1–57). The primary study by Meyer et al. was supported by the Federal Ministry of Education and Research (BMBF). The primary study by Stone et al. was supported by the Medical Research Council, UK and Chest Heart and Stroke, Scotland. The primary study by Turner et al. was supported by a bequest from Jennie Thomas through Hunter Medical Research Institute. The primary study by Walterfang et al. was supported by Melbourne Health. Drs. Benedetti and Thombs were supported by FRQS researcher salary awards. No other authors reported funding for primary studies or for their work on this study. No funder had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication