Efficacy and safety of tocilizumab in treatment of Takayasu arteritis: A systematic review of randomized controlled trials.

BACKGROUND: Takayasu arteritis (TAK) is a chronic immune vasculitis in which Interleukin-6 (IL-6) receptors play a key role in pathogenesis. Tocilizumab (TCZ), an IL-6 receptor antagonist with a favorable safety and efficacy profile, has been tried as an option for patients with TAK. This systematic review analyzed the evidence from randomized control trials (RCT) assessing the safety and efficacy of TCZ in patients with TAK. METHODS: MEDLINE, Embase, the Cochrane Library, and clinical trial registries were searched from inception to July 2018. We included RCT assessing the efficacy and safety of TCZ versus placebo/other comparators for the treatment of patients with TAK. The risk of bias (RoB) was assessed using Cochrane RoB tool. RESULTS: 2799 identified articles were screened as per abstract and title; 42 selected full-texts articles were assessed for the potential inclusion. One trial, reported in two publications, comparing subcutaneous TCZ (162 mg/week) versus matching placebo in 36 patients with TAK was included. The relapse-free rate at 24 weeks was 50.6% and 22.9% in TCZ and placebo arm, respectively. The hazard ratio (HR) for time to first relapse was statistically significant in the per-protocol population (HR 0.34 [95.41% CI, 0.11-1.00]; p = .0345), while non-significant in the intention-to-treat population (HR 0.41 [95.41% CI, 0.15-1.10]; p = .0596). The serious adverse events were higher in the placebo arm. CONCLUSIONS: This systematic review finds the existing evidence from RCT on efficacy and safety profile of TCZ in TAK to be promising but limited. Additional evidence is required to draw a stronger conclusion.

New Media, Technology and Neurology Education.

The use of technology in neurology education has revolutionized many aspects of medical teaching, addressing some important challenges of modern education such as information overload and the unique needs of millennial learners. However, it also has inherent problems, such as depersonalization and high development costs. Due to the heterogeneity of different applications, it is difficult to establish general principles to guide front line educators, but it may be possible to describe "minimum" best practice elements. In this article, we examine commonalities of some of the most successful uses of technology in neurology education. We suggest the following for effective application of technology: (1) match technology to predetermined educational objectives, (2) characterize learners in relationship to technology, (3) optimize how technological components fit into the learning environment, (4) monitor and manage learner engagement with technology, (5) perform cost analyses, and (6) explore opportunities for educational scholarship and research.

Curriculum mapping as a tool to facilitate curriculum development: a new School of Medicine experience.

BACKGROUND: Every curriculum needs to be reviewed, implemented and evaluated; it must also comply with the regulatory standards. This report demonstrates the value of curriculum mapping (CM), which shows the spatial relationships of a curriculum, in developing and managing an integrated medical curriculum. METHODS: A new medical school developed a clinical presentation driven integrated curriculum that incorporates the active-learning pedagogical practices of many educational institutions worldwide while adhering to the mandated requirements of the accreditation bodies. A centralized CM process was run in parallel as the curriculum was being developed. A searchable database, created after the CM data was uploaded into an electronic curriculum management system, was used to ensure placing, integrating, evaluating and revising the curricular content appropriately. RESULTS: CM facilitated in a) appraising the content integration, b) identifying gaps and redundancies, c) linking learning outcomes across all educational levels (i.e. session to course to program), c) organizing the teaching schedules, instruction methods, and assessment tools and d) documenting compliance with accreditation standards. CONCLUSIONS: CM is an essential tool to develop, review, improve and refine any integrated curriculum however complex. Our experience, with appropriate modifications, should help other medical schools efficiently manage their curricula and fulfill the accreditation requirements at the same time.

Botulinum Toxin-A for Painful Diabetic Neuropathy: A Meta-Analysis.

OBJECTIVES: Painful diabetic neuropathy (PDN) is a debilitating complication of diabetes that greatly affects the quality of life of those afflicted. There are many treatment options for neuropathic pain. Recent studies show a promising analgesic effect using botulinum toxin-A (BTX-A) for neuropathic pain. METHODS: This article is a meta-analysis of two studies using BTX-A in the treatment of neuropathic pain. Electronic searches of MEDLINE/PubMed, EMBASE, and Cochrane Libraries using the terms "botulinum neurotoxin" and "neuropathic pain" were conducted. Only class I and class II therapeutic trials, as classified by the American Academy of Neurology were included. The primary outcome measured was the difference in visual analogue scale (VAS) from pre-intervention and post-intervention after 1 month. Data were analyzed for biases and heterogeneity following Cochrane and PRISMA guidelines. RESULTS: Two studies on PDN were analyzed in the meta-analysis showing improvement of 1.96 VAS points (95% CI, -3.09 to -0.84; Z score = 3.43, P < 0.001) following treatment with BTX-A. This corresponds to clinically significant improvement of "minimum change in pain." The adverse effects of infection at injection site was not statistically significant (P = 0.49). BTX-A may be effective for PDN. CONCLUSION: Tests for significance, low overall risk of bias, and almost no statistical heterogeneity suggests that there is a correlation between BTX-A and improvement of pain scores in PDN. Further large-scale controlled trials are needed.

Zingiberaceae extracts for pain: a systematic review and meta-analysis.

BACKGROUND: Members of the family Zingiberaceae including turmeric, ginger, Javanese ginger, and galangal have been used for centuries in traditional medicine. Preclinical studies of Zingiberaceae extracts have shown analgesic properties. This study aims to systematically review and meta-analyze whether extracts from Zingiberaceae are clinically effective hypoalgesic agents. METHODS: Literature was screened from electronic databases using the key words Zingiberaceae AND pain OR visual analogue score (VAS) to identify randomized trials. From this search, 18 studies were identified, and of these, 8 randomized, double-blinded, placebo-controlled trials were found that measured pain by VAS for inclusion in the meta-analysis. RESULTS: Findings indicated significant efficacy of Zingiberaceae extracts in reducing subjective chronic pain (SMD - 0.67; 95 % CI - 1.13 to - 0.21; P = 0.004). A linear dose-effect relationship was apparent between studies (R(2) = 0.71). All studies included in the systematic review reported a good safety profile for extracts, without the renal risks associated with non-steroidal anti-inflammatory drugs, and with similar effectiveness. CONCLUSION: Our findings indicated that Zingiberaceae extracts are clinically effective hypoalgesic agents and the available data show a better safety profile than non-steroidal anti-inflammatory drugs. However, both non-steroidal anti-inflammatory drugs and Zingiberaceae have been associated with a heightened bleeding risk, and there have been no comparator trials of this risk. Further clinical studies are recommended to identify the most effective type of Zingiberaceae extract and rigorously compare safety, including bleeding risk.

Development of a cost-effective high-throughput process of microsatellite analysis involving miniaturized multiplexed PCR amplification and automated allele identification.

BACKGROUND: Microsatellites are nucleotide sequences of tandem repeats occurring throughout the genome, which have been widely used in genetic linkage analysis, studies of loss of heterozygosity, determination of lineage and clonality, and the measurement of genome instability or the emergence of drug resistance reflective of mismatch repair deficiency. Such analyses may involve the parallel evaluation of many microsatellite loci, which are often limited by sample DNA, are labor intensive, and require large data processing. RESULTS: To overcome these challenges, we developed a cost-effective high-throughput approach of microsatellite analysis, in which the amplifications of microsatellites are performed in miniaturized, multiplexed polymerase chain reaction (PCR) adaptable to 96 or 384 well plates, and accurate automated allele identification has been optimized with a collective reference dataset of 5,508 alleles using the GeneMapper software. CONCLUSIONS: In this investigation, we have documented our experience with the optimization of multiplex PCR conditions and automated allele identification, and have generated a unique body of data that provide a starting point for a cost-effective, high-throughput process of microsatellite analysis using the studied markers.

Structural and functional neuroimaging in migraine: insights from 3 decades of research.

Modern imaging methods provide unprecedented insights into brain structure, perfusion, metabolism, and neurochemistry, both during and between migraine attacks. Neuroimaging investigations conducted in recent decades bring us closer to uncovering migraine as a multifaceted, primarily central nervous system disorder. Three main categories of structural and functional brain changes are described in this review, corresponding to the migrainous aura, ictal headache, and interictal states. These changes greatly advance our understanding of multiple pathophysiologic underpinnings of migraine, from central "migraine generating" loci, to cortical spreading depression, intimate mechanisms underlying activation of neuronal pain pathways in vulnerable patients, central sensitization, and chronification. Structural imaging begins to explain the complex connections between migraine and cerebral vascular events, white matter lesions, grey matter density alterations, iron deposition, and microstructural brain damage. Selected structural and functional alterations of brain structures, as identified with imaging methods, may represent the foundation of new diagnostic strategies and serve as markers of therapeutic efficacy.

The emerging role of dietary fructose in obesity and cognitive decline.

The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer's disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet.

Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Current antidepressants used to treat pediatric patients have the disadvantage of limited efficacy and potentially serious side effects. The purpose of this study was to assess the efficacy of vitamin C as an adjuvant agent in the treatment of pediatric major depressive disorder in a six-month, double-blind, placebo-controlled pilot trial. METHODS: The study group (n=12) was given fluoxetine (10-20 mg/day) plus vitamin C (1000 mg/day) and control group (n=12) administered fluoxetine (10-20 mg/day) plus placebo. The data were analyzed by ANOVA and t-test for independent samples. RESULTS: Both groups demonstrated significantly improved scores on the Children's Depression Rating Scale (CDRS), the Children's Depression Inventory (CDI), and the Clinical Global Impression (CGI). ANOVA was significantly different on all clinical measurements (group effect, time effect, and interaction), with the exception of group effect and interaction for CGI. Patients treated for six months with fluoxetine and vitamin C showed a significant decrease in depressive symptoms in comparison to the fluoxetine plus placebo group as measured by the CDRS (t=11.36, P<0.0001) and CDI (t=12.27, P<0.0001), but not CGI (t=0.13, P=0.90). No serious adverse effects were observed. CONCLUSIONS: These preliminary results suggest that vitamin C may be an effective adjuvant agent in the treatment of MDD in pediatric patients.

Innovative Technologies in CNS Trials: Promises and Pitfalls for Recruitment, Retention, and Representativeness.

Objective: Recruitment of a sufficiently large and representative patient sample and its retention during central nervous system (CNS) trials presents major challenges for study sponsors. Technological advances are reshaping clinical trial operations to meet these challenges, and the COVID-19 pandemic further accelerated this development. Method of Research: The International Society for CNS Clinical Trials and Methodology (ISCTM; www.isctm.org) Innovative Technologies for CNS Trials Working Group surveyed the state of technological innovations for improved recruitment and retention and assessed their promises and pitfalls. Results: Online advertisement and electronic patient registries can enhance recruitment, but challenges with sample representativeness, conversion rates from eligible prescreening to enrolled patients, data privacy and security, and patient identification remain hurdles for optimal use of these technologies. Electronic medical records (EMR) mining with artificial intelligence (AI)/machine learning (ML) methods is promising but awaits translation into trials. During the study treatment phase, technological innovations increasingly support participant retention, including adherence with the investigational treatment. Digital tools for adherence and retention support take many forms, including patient-centric communication channels between researchers and participants, real-time study reminders, and digital behavioral interventions to increase study compliance. However, such tools add technical complexities to trials, and their impact on the generalizability of results are largely unknown. Conclusion: Overall, the group found a scarcity of systematic data directly assessing the impact of technological innovations on study recruitment and retention in CNS trials, even for strategies with already high adoption, such as online recruitment. Given the added complexity and costs associated with most technological innovations, such data is needed to fully harness technologies for CNS trials and drive further adoption.

Appropriate controls for digital therapeutic clinical trials: A narrative review of control conditions in clinical trials of digital therapeutics (DTx) deploying psychosocial, cognitive, or behavioral content.

Digital therapeutics (DTx) are software programs that treat a disease or condition. Increasingly, DTx are part of medical care, and in the US healthcare system they are regulated by the FDA as Software as a Medical Device (SaMD). Randomized controlled trials (RCT) remain a key evidence generation step for most DTx. However, developing a unified approach to the design of appropriate control conditions has been a challenge for two main reasons: (1) inheriting control condition definitions from pharmacotherapy and medical device RCT that may not directly apply, and (2) challenges in establishing control conditions for psychosocial interventions that build the core of many DTx. In our critical review we summarize different approaches to control conditions and patient blinding in RCT evaluating DTx with psychosocial, cognitive or behavioral content. We identify control condition choices, ranging from very minimal digital controls to more complex and stringent digital applications that contain aspects of "fake" therapy, general wellness content or games. Our review of RCTs reveals room for improvement in describing and naming control conditions more consistently. We further discuss challenges in defining placebo controls for DTx and ways in which control choices may have a therapeutic effect. While no one-size-fits-all control conditions and study designs will apply to all DTx, we propose points to consider for defining appropriate digital control conditions. At the same time, given the rapid iterative development and optimization of DTx, treatments with low risk profile may be evaluated with minimal digital controls followed by extensive real-world effectiveness trials.

Pain management consultation for acute pancreatitis: impact on length of stay and opioid utilization.

Aim: The purpose of the study was to understand the impact of a pain management consult for acute pancreatitis patients on their inpatient length of stay, morphine milligram equivalences (MMEs) and pancreatitis severity. Materials & methods: Adult patient data were extracted from the electronic health records from 1 October 2016 to 31 December 2018. Results & conclusion: Of 277 patients with a single acute pancreatitis hospitalization, 23 had a pain consultation (treatment group), whereas 254 did not (control group). There were statistically significant differences in median length of stay, median MME total and median MME per day between the treatment and control groups with comparable severity and pain scores (6.8 vs 3.1 days, 196.5 vs 33.8 MMEs, 30.9 vs 12.1 MMEs, respectively, p < 0.0001). This study emphasizes the complexity of pain management and the importance of further research in the field.

Anti-inflammatory effects of nicotine in obesity and ulcerative colitis.

Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell.

Gut microbiota and sirtuins in obesity-related inflammation and bowel dysfunction.

Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS), which controls virtually all gut functions. Recent studies have revealed that the gut microbiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gut microbiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered.

A Virtual, Randomized, Control Trial of a Digital Therapeutic for Speech, Language, and Cognitive Intervention in Post-stroke Persons With Aphasia.

Background: Post-stroke aphasia is a chronic condition that impacts people's daily functioning and communication for many years after a stroke. Even though these individuals require sustained rehabilitation, they face extra burdens to access care due to shortages in qualified clinicians, insurance limitations and geographic access. There is a need to research alternative means to access intervention remotely, such as in the case of this study using a digital therapeutic. Objective: To assess the feasibility and clinical efficacy of a virtual speech, language, and cognitive digital therapeutic for individuals with post-stroke aphasia relative to standard of care. Methods: Thirty two participants completed the study (experimental: average age 59.8 years, 7 female, 10 male, average education: 15.8 years, time post-stroke: 53 months, 15 right handed, 2 left handed; control: average age 64.2 years, 7 female, 8 male, average education: 15.3 years, time post-stroke: 36.1 months, 14 right handed, 1 left handed). Patients in the experimental group received 10 weeks of treatment using a digital therapeutic, Constant Therapy-Research (CT-R), for speech, language, and cognitive therapy, which provides evidence-based, targeted therapy with immediate feedback for users that adjusts therapy difficulty based on their performance. Patients in the control group completed standard of care (SOC) speech-language pathology workbook pages. Results: This study provides Class II evidence that with the starting baseline WAB-AQ score, adjusted by -0.69 for every year of age, and by 0.122 for every month since stroke, participants in the CT-R group had WAB-AQ scores 6.43 higher than the workbook group at the end of treatment. Additionally, secondary outcome measures included the WAB-Language Quotient, WAB-Cognitive Quotient, Brief Test of Adult Cognition by Telephone (BTACT), and Stroke and Aphasia Quality of Life Scale 39 (SAQOL-39), with significant changes in BTACT verbal fluency subtest and the SAQOL-39 communication and energy scores for both groups. Conclusions: Overall, this study demonstrates the feasibility of a fully virtual trial for patients with post-stroke aphasia, especially given the ongoing COVID19 pandemic, as well as a safe, tolerable, and efficacious digital therapeutic for language/cognitive rehabilitation. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04488029.

Neuroinflammation in inflammatory bowel disease.

Inflammatory bowel disease is a chronic intestinal inflammatory condition, the pathology of which is incompletely understood. Gut inflammation causes significant changes in neurally controlled gut functions including cramping, abdominal pain, fecal urgency, and explosive diarrhea. These symptoms are caused, at least in part, by prolonged hyperexcitability of enteric neurons that can occur following the resolution of colitis. Mast, enterochromaffin and other immune cells are increased in the colonic mucosa in inflammatory bowel disease and signal the presence of inflammation to the enteric nervous system. Inflammatory mediators include 5-hydroxytryptamine and cytokines, as well as reactive oxygen species and the production of oxidative stress. This review will discuss the effects of inflammation on enteric neural activity and potential therapeutic strategies that target neuroinflammation in the enteric nervous system.

Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review.

BACKGROUND: Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal. METHODS: An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events. RESULTS: A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate. CONCLUSIONS: Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment.

Inflammatory mechanisms in ischemic stroke: therapeutic approaches.

Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours), complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies.

Endocytosis of glycosylphosphatidylinositol-anchored proteins.

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) represent an interesting amalgamation of the three basic kinds of cellular macromolecules viz. proteins, carbohydrates and lipids. An unusually hybrid moiety, the GPI-anchor is expressed in a diverse range of organisms from parasites to mammalian cells and serves to anchor a large number of functionally diverse proteins and has been the center of attention in scientific debate for some time now. Membrane organization of GPI-APs into laterally-organized cholesterol-sphingolipid ordered membrane domains or "rafts" and endocytosis of GPI-APs has been intensely debated. Inclusion into or exclusion from these membrane domains seems to be the critical factor in determining the endocytic mechanisms and intracellular destinations of GPI-APs. The intracellular signaling as well as endocytic trafficking of GPI-APs is critically dependent upon the cell surface organization of GPI-APs, and the associations with these lipid rafts play a vital role during these processes. The mechanism of endocytosis for GPI-APs may differ from other cellular endocytic pathways, such as those mediated by clathrin-coated pits (caveolae), and is necessary for unique biological functions. Numerous intracellular factors are involved in and regulate the endocytosis of GPI-APs, and these may be variably dependent on cell-type. The central focus of this article is to describe the significance of the endocytosis of GPI-APs on a multitude of biological processes, ranging from nutrient-uptake to more complex immune responses. Ultimately, a thorough elucidation of GPI-AP mediated signaling pathways and their regulatory elements will enhance our understanding of essential biological processes and benefit as components of disease intervention strategies.

Schizophrenia genomics and proteomics: are we any closer to biomarker discovery?

The field of proteomics has made leaps and bounds in the last 10 years particularly in the fields of oncology and cardiovascular medicine. In comparison, neuroproteomics is still playing catch up mainly due to the relative complexity of neurological disorders. Schizophrenia is one such disorder, believed to be the results of multiple factors both genetic and environmental. Affecting over 2 million people in the US alone, it has become a major clinical and public health concern worldwide. This paper gives an update of schizophrenia biomarker research as reviewed by Lakhan in 2006 and gives us a rundown of the progress made during the last two years. Several studies demonstrate the potential of cerebrospinal fluid as a source of neuro-specific biomarkers. Genetic association studies are making headway in identifying candidate genes for schizophrenia. In addition, metabonomics, bioinformatics, and neuroimaging techniques are aiming to complete the picture by filling in knowledge gaps. International cooperation in the form of genomics and protein databases and brain banks is facilitating research efforts. While none of the recent developments described here in qualifies as biomarker discovery, many are likely to be stepping stones towards that goal.