Global Neuroscience Initiative Foundation

Beverly Hills, CA, United States

Global Neuroscience Initiative Foundation

Beverly Hills, CA, United States
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Lakhan S.E.,Global Neuroscience Initiative Foundation | Kirchgessner A.,Global Neuroscience Initiative Foundation
Brain and Behavior | Year: 2012

Prescription stimulants are often used to treat attention deficit hyperactivity disorder (ADHD). Drugs like methylphenidate (Ritalin, Concerta), dextroamphetamine (Dexedrine), and dextroamphetamine-amphetamine (Adderall) help people with ADHD feel more focused. However, misuse of stimulants by ADHD and nonaffected individuals has dramatically increased over recent years based on students' misconceptions or simple lack of knowledge of associated risks. In this review, we discuss recent advances in the use and increasing misuse of prescription stimulants among high school and college students and athletes. Given the widespread belief that stimulants enhance performance, there are in fact only a few studies reporting the cognitive enhancing effects of stimulants in ADHD and nonaffected individuals. Student athletes should be apprised of the very serious consequences that can emerge when stimulants are used to improve sports performance. Moreover, misuse of stimulants is associated with dangers including psychosis, myocardial infarction, cardiomyopathy, and even sudden death. As ADHD medications are prescribed for long-term treatment, there is a need for long-term safety studies and education on the health risks associated with misuse is imperative. © 2012 The Authors. Published by Wiley Periodicals, Inc.


Lakhan S.E.,Global Neuroscience Initiative Foundation | Lakhan S.E.,Cleveland Clinic | Caro M.,Cleveland Clinic | Hadzimichalis N.,Global Neuroscience Initiative Foundation
Frontiers in Psychiatry | Year: 2013

N-Methyl-D-aspartate (NMDA) receptors play a variety of physiologic roles andtheir proper signaling is essential for cellular homeostasis. Any disruption in this pathway, leading to either enhanced or decreased activity, may result in the manifestation of neuropsychiatric pathologies such as schizophrenia, mood disorders,substance induced psychosis, Huntington's disease, Alzheimer's disease, and neuropsychiatric systemic lupus erythematosus. Here, we explore the notion that the overlap in activity of at least one biochemical pathway, the NMDA receptor pathway, may be the link to understanding the overlap in psychotic symptoms between diseases.This review intends to present a broad overview of those neuropsychiatric disorders for which alternations in NMDA receptor activity is prominent thus suggesting that continued direction of pharmaceutical intervention to this pathway may present a viable option for managing symptoms.© 2013 Lakhan, Caro and Hadzimichalis.


Lakhan S.E.,Global Neuroscience Initiative Foundation | Vieira K.F.,Global Neuroscience Initiative Foundation
Nutrition Journal | Year: 2010

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. © 2010 Lakhan and Vieira; licensee BioMed Central Ltd.


Lakhan S.E.,Global Neuroscience Initiative Foundation | Callaway E.,Global Neuroscience Initiative Foundation
BMC Research Notes | Year: 2010

Background: In spite of advances in psychotherapy and pharmacotherapy, there are still a significant number of patients with depression and obsessive-compulsive disorder that are not aided by either intervention. Although still in the experimental stage, deep brain stimulation (DBS) offers many advantages over other physically-invasive procedures as a treatment for these psychiatric disorders. The purpose of this study is to systematically review reports on clinical trials of DBS for obsessive-compulsive disorder (OCD) and treatment-resistant depression (TRD). Locations for stimulation, success rates and effects of the stimulation on brain metabolism are noted when available. The first observation of the effects of DBS on OCD and TRD came in the course of using DBS to treat movement disorders. Reports of changes in OCD and depression during such studies are reviewed with particular attention to electrode locations and associated adverse events; although these reports were adventitious observations rather than planned. Subsequent studies have been guided by more precise theories of structures involved in DBS and OICD. This study suggests stimulation sites and prognostic indicators for DBS. We also briefly review tractography, a relatively new procedure that holds great promise for the further development of DBS. Methods. Articles were retrieved from MEDLINE via PubMed. Relevant references in retrieved articles were followed up. We included all articles reporting on studies of patients selected for having OCD or TRD. Adequacy of the selected studies was evaluated by the Jadad scale. Evaluation criteria included: number of patients, use of recognized psychiatric rating scales, and use of brain blood flow measurements. Success rates classified as "improved" or "recovered" were recorded. Studies of DBS for movement disorders were included if they reported coincidental relief of depression or reduction in OCD. Most of the studies involved small numbers of subjects so individual studies were reviewed. Results: While the number of cases was small, these were extremely treatment-resistant patients. While not everyone responded, about half the patients did show dramatic improvement. Associated adverse events were generally trivial in younger psychiatric patients but often severe in older movement disorder patients. The procedures differed from study to study, and the numbers of patients was usually too small to do meaningful statistics or make valid inferences as to who will respond to treatment. Conclusions: DBS is considered a promising technique for OCD and TRD. Outstanding questions about patient selection and electrode placement can probably be resolved by (a) larger studies, (b) genetic studies and (c) imaging studies (MRI, fMRI, PET, and tractography). © 2010Lakhan et al; licensee BioMed Central Ltd.


Lakhan S.E.,Global Neuroscience Initiative Foundation | Avramut M.,Global Neuroscience Initiative Foundation
Pain Research and Treatment | Year: 2012

Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent endopeptidases that mediate extracellular matrix turnover and associated processes, such as cell survival, growth, and differentiation. This paper discusses important functions of MMP in the normal and injured nervous system, focusing on the role played by these proteases in neurological pain syndromes, most prominently in neuropathic pain and migraine headaches. In the past decade, metalloproteinases emerged as key modulators of neuropathic pain, with MMP-9 acting as an initiator of the neuropathic cascade. Increased MMP activity was detected in migraine patients, independent of aura, in tight association with metabolic derangements. The therapeutic implications of MMP inhibition are considered in the context of neurogenic pain regulation. © 2012 Shaheen E. Lakhan and Mihaela Avramut.


Lakhan S.E.,Global Neuroscience Initiative Foundation | Kirchgessner A.,Global Neuroscience Initiative Foundation
Nutrition and Metabolism | Year: 2010

Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder's pathogenesis. Studies examining the microecology of the gastrointestinal (GI) tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut. If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients. © 2010 Lakhan and Kirchgessner; licensee BioMed Central Ltd.


Lakhan S.E.,Global Neuroscience Initiative Foundation | Vieira K.,Global Neuroscience Initiative Foundation | Hamlat E.,Global Neuroscience Initiative Foundation
International Archives of Medicine | Year: 2010

For more than 20 years, researchers have attempted to identify diagnostic and prognostic biomarkers for psychiatric disorders including schizophrenia, major (unipolar) depression, and bipolar disorder. Advocates of this research contend that identifying such biomarkers will aid in the diagnosis of these disorders, as well as the possible development of effective psychiatric medications to treat them. Currently, there are no diagnostic tests available. This is largely due to the multi-factorial nature of psychiatric disorders. Biomarker testing of individuals is also prohibitively expensive because significant expertise is required to conduct tests and follow-up counseling for the patient is often necessary. It is cautioned that widespread biomarker testing could lead to negative consequences such as discrimination in health insurance and employment, as well as selective abortion. © 2010 Lakhan et al; licensee BioMed Central Ltd.


Lakhan S.E.,Global Neuroscience Initiative Foundation | Schofield K.L.,Global Neuroscience Initiative Foundation
PLoS ONE | Year: 2013

Background:Mindfulness-based therapy (MBT) has been used effectively to treat a variety of physical and psychological disorders, including depression, anxiety, and chronic pain. Recently, several lines of research have explored the potential for mindfulness-therapy in treating somatization disorders, including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome.Methods:Thirteen studies were identified as fulfilling the present criteria of employing randomized controlled trials to determine the efficacy of any form of MBT in treating somatization disorders. A meta-analysis of the effects of mindfulness-based therapy on pain, symptom severity, quality of life, depression, and anxiety was performed to determine the potential of this form of treatment.Findings:While limited in power, the meta-analysis indicated a small to moderate positive effect of MBT (compared to wait-list or support group controls) in reducing pain (SMD = -0.21, 95% CI: -0.37, -0.03; p<0.05), symptom severity (SMD = -0.40, 95% CI: -0.54, -0.26; p<0.001), depression (SMD = -0.23, 95% CI: -0.40, -0.07, p<0.01), and anxiety (SMD = -0.20, 95% CI: -0.42, 0.02, p = 0.07) associated with somatization disorders, and improving quality of life (SMD = 0.39, 95% CI: 0.19, 0.59; p<0.001) in patients with this disorder. Subgroup analyses indicated that the efficacy of MBT was most consistent for irritable bowel syndrome (p<0.001 for pain, symptom severity, and quality of life), and that mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MCBT) were more effective than eclectic/unspecified MBT.Conclusions:Preliminary evidence suggests that MBT may be effective in treating at least some aspects of somatization disorders. Further research is warranted. © 2013 Lakhan, Schofield.


Lakhan S.E.,Global Neuroscience Initiative Foundation | Pamplona F.,Global Neuroscience Initiative Foundation
Stroke Research and Treatment | Year: 2012

Background. Stroke occurs due to an interruption in cerebral blood supply affecting neuronal function. Body temperature on hospital admission is an important predictor of clinical outcome. Therapeutic hypothermia is promising in clinical settings for stroke neuroprotection. Methods. MEDLINE/PubMed, CENTRAL, Stroke Center, and ClinicalTrials.gov were systematically searched for hypothermia intervention induced by external or endovascular cooling for acute stroke. NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were the main stroke scales used, and mortality was also reported. A meta-analysis was carried out on stroke severity and mortality. Results. Seven parallel-controlled clinical trials were included in the meta-analysis. Sample sizes ranged from 18 to 62 patients, yielding a total of 288. Target temperature (∼33°C) was reached within 3-4 hours. Stroke severity (Cohen's d=-0.17, 95% CI: -0.42 to 0.08, P=0.32; I 2=73%; Chi 2 = 21.89, P=0.0001) and mortality (RR=1.60, 95% CI: 0.93 to 2.78, P=0.11; I 2 = 0%; Chi 2 = 2.88, P=0.72) were not significantly affected by hypothermia. Discussion. Hypothermia does not significantly improve stroke severity; however, this finding should be taken with caution due to the high heterogeneity and limited number of included studies. No impact on mortality was observed. © 2012 Shaheen E. Lakhan and Fabricio Pamplona.


Lakhan S.E.,Cleveland Clinic | Lakhan S.E.,Global Neuroscience Initiative Foundation | Avramut M.,Global Neuroscience Initiative Foundation | Tepper S.J.,Cleveland Clinic
Headache | Year: 2013

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. © 2012 American Headache Society.

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