Anti-inflammatory treatment of bipolar depression: promise and disappointment

Anti-inflammatory treatment of bipolar depression: promise and disappointmen

To the Editor

To the Edito

The interplay between oxidative stress and bioenergetic failure in neuropsychiatric illnesses: can we explain it and can we treat it?

Nitro-oxidative stress and lowered antioxidant defences play a key role in neuropsychiatric disorders such as major depression, bipolar disorder and schizophrenia. The first part of this paper details mitochondrial antioxidant mechanisms and their importance in reactive oxygen species (ROS) detoxification, including details of NO networks, the roles of H2O2 and the thioredoxin/peroxiredoxin system, and the relationship between mitochondrial respiration and NADPH production. The second part highlights and identifies the causes of the multiple pathological sequelae arising from self-amplifying increases in mitochondrial ROS production and bioenergetic failure. Particular attention is paid to NAD+ depletion as a core cause of pathology; detrimental effects of raised ROS and reactive nitrogen species on ATP and NADPH generation; detrimental effects of oxidative and nitrosative stress on the glutathione and thioredoxin systems; and the NAD+-induced signalling cascade, including the roles of SIRT1, SIRT3, PGC-1α, the FOXO family of transcription factors, Nrf1 and Nrf2. The third part discusses proposed therapeutic interventions aimed at mitigating such pathology, including the use of the NAD+ precursors nicotinamide mononucleotide and nicotinamide riboside, both of which rapidly elevate levels of NAD+ in the brain and periphery following oral administration; coenzyme Q10 which, when given with the aim of improving mitochondrial function and reducing nitro-oxidative stress in the brain, may be administered via the use of mitoquinone, which is in essence ubiquinone with an attached triphenylphosphonium cation; and N-acetylcysteine, which is associated with improved mitochondrial function in the brain and produces significant decreases in oxidative and nitrosative stress in a dose-dependent manner

The Association Between Use of Antidepressants and Bone Quality Using Quantitative Ultrasound.

The Association Between Use of Antidepressants and Bone Quality Using Quantitative Ultrasound

Early intervention in bipolar disorders: opportunities and pitfalls.

The early phases of bipolar disorders are difficult to diagnose and have specific treatment issues. The initial polarity of the illness is more commonly depressive, yet in counterpoint, mania is required for diagnosis; consequently, there is often a substantial delay in the initiation of appropriate therapy. There is good evidence that lithium in particular is most effective early in the illness course, and that its efficacy declines after multiple episodes. The notion of neuroprotection reflects this, and furthermore suggests that appropriate therapy may prevent the neurostructural and neurocognitive changes seen in the disorder. Inappropriate therapy may worsen the course of the illness. Patients with a first episode have specific psychosocial needs, and adherence to medication is relatively poor. There is a need for early identification, and to develop treatments and services applicable to the specific needs of this population

Depressive Symptoms and Gut Microbiota after Bowel Preparation and Colonoscopy: A Pre-post Intervention Study

Depressive Symptoms and Gut Microbiota after Bowel Preparation and Colonoscopy: A Pre-post Intervention Stud

Fiber intake and fiber intervention in depression and anxiety: a systematic review and meta-analysis of observational studies and randomized controlled trials

Abstract Context Dietary fibers hold potential to influence depressive and anxiety outcomes by modulating the microbiota–gut–brain axis, which is increasingly recognized as an underlying factor in mental health maintenance. Objective Evidence for the effects of fibers on depressive and anxiety outcomes remains unclear. To this end, a systematic literature review and a meta-analysis were conducted that included observational studies and randomized controlled trials (RCTs). Data sources The PubMed, Embase, CENTRAL, CINAHL, and PsychINFO databases were searched for eligible studies. Data extraction Study screening and risk-of-bias assessment were conducted by 2 independent reviewers. Data analysis Meta-analyses via random effects models were performed to examine the (1) association between fiber intake and depressive and anxiety outcomes in observational studies, and (2) effect of fiber intervention on depressive and anxiety outcomes compared with placebo in RCTs. A total of 181 405 participants were included in 23 observational studies. In cross-sectional studies, an inverse association was observed between fiber intake and depressive (Cohen’s d effect size [d]: −0.11; 95% confidence interval [CI]: −0.16, −0.05) and anxiety (d = −0.25; 95%CI, −0.38, −0.12) outcomes. In longitudinal studies, there was an inverse association between fiber intake and depressive outcomes (d = −0.07; 95%CI, −0.11, −0.04). In total, 740 participants were included in 10 RCTs, all of whom used fiber supplements. Of note, only 1 RCT included individuals with a clinical diagnosis of depression. No difference was found between fiber supplementation and placebo for depressive (d = −0.47; 95%CI, −1.26, 0.31) or anxiety (d = −0.30; 95%CI, −0.67, 0.07) outcomes. Conclusion Although observational data suggest a potential benefit for higher fiber intake for depressive and anxiety outcomes, evidence from current RCTs does not support fiber supplementation for improving depressive or anxiety outcomes. More research, including RCTs in clinical populations and using a broad range of fibers, is needed. Systematic Review Registration PROSPERO registration no. CRD42021274898

Lithium should be borne in mind: Five key reasons

Lithium should be borne in mind: Five key reason

Corrigendum to “A multi-national, multi-disciplinary Delphi consensus study on using omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the treatment of major depressive disorder”. [J Affect Disord. 15 (2020) 233-238] (Journal of Affective Disorders (2020) 15 (233-238) (S0165032719319299), (10.1016/j.jad.2020.01.050))

The authors regret in the article “A multi-national, multi-disciplinary Delphi consensus study on using omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the treatment of major depressive disorder” published in Journal of Affective Disorders on 15 March 2020, some information in the “6. Disclosure” section was omitted from the manuscript. This statement can now be found below. 6. Disclosures Dr. Guu has been a speaker and received speaker honorarium for Johnson & Johnson, Astra-Zeneca, Lundbeck and Hoan Pharmaceuticals, Standard Chem & Pharm, Pfizer, GSK Taiwan, ChenHua-Bio, Eli Lilly, Excelsior, Otsuka, EB Pharmaceutical and Servier – all unrelated to this work. Dr. Mischoulon has received research support from Nordic Naturals. He has provided unpaid consulting for Pharmavite LLC and Gnosis USA,Inc. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, Blackmores, Harvard Blog, and Peer Point Medical Education Institute, LLC. He has received royalties from Lippincott Williams & Wilkins for published book “Natural Medications for Psychiatric Disorders: Considering the Alternatives.” He also works with the MGH Clinical Trials Network and Institute (CTNI), which has received research funding from multiple pharmaceutical companies and NIMH. Dr. JR Hibbeln has received no honoraria and has no conflicts of interest. Dr. Sarris has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Integria Healthcare & MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Australian Natural Therapies Group, Fiji Kava, Taki Mai, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Grunbiotics, Australian Natural Therapeutics Group, Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, SanofiAventis, Omega-3 center, the National Health and Medical Research Council, CR Roper Fellowship. Dr. Mcnamara has received investigator-initiated grant support from manufacturers of omega-3 fatty acid products including Martek Biosciences Inc (2007-2009), Royal DSM Nutritional Products, LLC (2013-2015), and the Inflammation Research Foundation (2008-2010), investigator-initiated grant support from Ortho-McNeil Janssen, NARSAD, and the national institutes of health (NIH), and previously served on the scientific advisory board of the Inflammation Research Foundation (2011-2013). Dr. Hamazaki received a research grant from the First Bank of Toyama Scholarship Foundation, speaking honoraria from the DHA&EPA Association, Niigata Medical Association, Toyama Medical Association, and Toyama Occupational Health Promotion Center, and a supervision fee from Otsuka Pharmaceutical Factory. Dr. Freeman (past 12 months): Investigator Initiated Trials /Research: JayMac, Sage; Advisory boards: Otsuka, Alkermes, Sunovion; Independent Data Safety and Monitoring Committee: Janssen (Johnson& Johnson). Dr. Freeman is an employee of Massachusetts General Hospital, and works with the MGH National Pregnancy Registry [Current Registry Sponsors: Teva (2018- present), Alkermes, Inc. (2016-Present); Otsuka America Pharmaceutical, Inc. (2008-Present); Forest/Actavis (2016-Present), Sunovion Pharmaceuticals, Inc. (2011-Present)]. As an employee of MGH, Dr. Freeman works with the MGH CTNI, which has had research funding from multiple pharmaceutical companies and NIMH. Dr. Maes has no conflict of interest. Dr. Matsuoka has received speaker's honoraria from Suntory, Pfizer, Mochida, Eli Lilly, Morinaga Milk, and NTT Data, and donation from Morinaga Milk and is conducting collaborative research with SUSMED and has conducted collaborative research with Morinaga Milk. Dr. RH Belmaker has no conflict of interest. Dr. Marx is currently funded by an Alfred

N-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms

N-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptom