It is well-known that approximately 20% of patients who underwent Roux-en-Y gastric bypass (RYGB) and 11% of patients who undertook laparoscopic adjustable gastric banding acquired AUD within five years of surgery. Notably, decreases in BMI following RYGB have decreased food addiction symptoms (as measured by the Yale Food Addiction Scale) and increased alcohol intake 24 months post-operation. After many years of successful bariatric (weight-loss) surgeries targeted at the obesity epidemic, clinicians report that some patients replace compulsive overeating with newly acquired compulsive disorders such as alcoholism, gambling, drugs, and other addictions like compulsive shopping and exercise. Our laboratory previously coined the term Reward Deficiency Syndrome (RDS) for common genetic determinants in predicting addictive disorders and reported that the Bayesian predictive value for future RDS behaviors in subjects carrying the DRD2 Taq A1 allele was 74% [1]. Transfer potential, data from our laboratory has shown that in an obese cohort undergoing bariatric surgery based on genetic addiction risk testing showed that these individuals carried a high risk for illicit drug abuse as well as Alcohol Use Disorder (AUD) suggestive of addiction transfer potential. Arterburn, et al. summarized the literature on bariatric surgery benefits and risks. Obesity and associated health largest public health causing preventable et examined the current epidemiology of obesity and surgical and the beneficial effects on numerous obesity-related comorbidities type
Pioneering work reported by Anton, et al. [1] in this journal may be an important step in the treatment algorithm of patients with alcohol use disorder (AUD). Identifying patients who need and would benefit from treatment with naltrexone [2] might help to change clinicians’ hesitancy to utilize these medications in AUD where twelve step treatment programs have renewed interest and support [3]. Modern therapeutics and personalized medication are predicated on the basis of tests or measures that can provide potential matching of safe and effective medications with the population of patients who are most likely to benefit from these therapeutic interventions. Anton’s work might help to improve the utilization of medications in not only in classical AUD but also in a wider spectrum of alcohol misusing patients. The importance of genetic testing to predict Medical Assistance Treatment (MAT) response came to prominence by the initial discovery of the DRD2 Taq A1 allele and its relationship to alcoholism [4]. In addition, it also seems essential to analyze genetic polymorphisms related to opioid and dopaminergic genes as antecedent polymorphic predictors of clinical responses to naltrexone [5]. We also applaud the efforts of Anton’s team in evaluating whether response to naltrexone depends on or is predicted by potential interactions of the OPRM1 SNP rs1799971 with the dopamine transporter gene DAT1/SLC6A3
This study aimed to identify strengths and weaknesses in a cognitive profile of children with Autism Spectrum Disorders (ASD) and to study relationship between the triad of impairments in ASD, delayed achievement of speech milestones and cognitive abilities.Our sample consisted of 30 children, male-to-female ratio 5:1, diagnosed with ASD using the Autism Diagnostic Interview -Revised and the Autism Diagnostic Observation Schedule.Results showed significant variations in their cognitive abilities as measured the Woodcock-Johnson International Editions.Cognitive efficiency, consisting of Processing speed and working memory, has been significantly reduced, yet individuals with ASD performed well on fluid intelligence, suggesting possible underestimation of their performance assessed with tests standardized for neurotypical population.We also identified three negative predictors of their overall IQ: inflexible adherence to specific non-functional routines or rituals, persistent preoccupation with parts of objects or non-functional elements of play materials and a delayed use of sentences.
The Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA) has completed its review of your de novo request for classification of the Neuropsychiatric EEG-Based Assessment Aid for Attention Deficit Hyperactivity Disorder (ADHD), referred to as the NEBA System, a prescription device under 21 CFR Part 801.109 that is indicated as follows:The Neuropsychiatric EEG-Based ADHD Assessment Aid (NEBA) uses the theta/beta ratio of the EEG measured at electrode CZ on a patient 6-17 years of age combined with a clinician's evaluation to aid in the diagnosis of ADHD.NEBA should only be used by a clinician as confirmatory support for a completed clinical evaluation or as support for the clinician's decision to pursue further testing following a clinical evaluation.The device is NOT to be used as a stand-alone in the evaluation or diagnosis of ADHD.FDA concludes that this device, and substantially equivalent devices of this generic type, should be classified into class II.This order, therefore, classifies the Neuropsychiatric EEG-Based Assessment Aid for ADHD (NEBA) System, and substantially equivalent devices of this generic type, into class II under the generic name, Neuropsychiatric Interpretive Electroencephalograph Assessment Aid.FDA identifies this generic type of device as:Neuropsychiatric Interpretive Electroencephalograph Assessment Aid.The Neuropsychiatric Interpretive Electroencephalograph Assessment Aid is a prescription device that uses a patient's electroencephalograph (EEG) to provide an interpretation of the patient's neuropsychiatric condition.The Neuropsychiatric Interpretive EEG
The unpredictable chronic mild stress (UCMS) mouse model of depression causes a variety of neuronal structural alterations ranging from dendritic spines loss and dendrite arbor retraction to spine proliferation in brain regions involved in the control of mood.Based on data showing that the plant stress hormone methyl jasmonate (MJ: methyl acetate-2,2-d2) mimics the effect of imipramine in rescuing the UCMS-induced depressive behavioral phenotype, here we examine whether the UCMS protocol used to demonstrate the antidepressant action of the compound triggers structural alterations in basolateral amygdala, hippocampus and prefrontal cortex which can be rescued by MJ treatment.Male C57BL/6 mice were injected with MJ (50 mg/kg) or saline (SAL) before each of the two daily exposures to UCMS administered over a 10-day period.Home cage, daily manipulated, SAL-injected mice served as controls (CTRL).On day 11, mice were sacrificed for Golgi-staining.Results show that in comparison with CTRL mice, SAL+UCMS mice exhibit a massive reduction in spine density and dendritic arbor extension/complexity in the three regions examined.Remarkably, MJ+UCMS mice show an alleviation of neuronal structural alterations in the three regions, with a more complete recovery observed in the prefrontal cortex.Our data provide further validation of the antidepressant action of the compound by revealing its efficacy in globally preventing the collapse in synaptic density and neuronal connectivity identified as key nodes of the mood circuitry.
In genetically predisposed WAG/Rij rats and healthy Wistar rats, we studied functioning of the paralemniscal region of the thalamo-cortical system. The responses of neurons of the somatosensory cortex to single electrical stimulation of the posterior nucleus of the thalamus were recorded in two- to three-monthold rats within the period when the epileptic activity was not developed. We revealed lower number of shortterm inhibitory responses in WAG/Rij rats as compared to Wistar rats. This may create preconditions for the spreading of spike-wave activity in the somatosensory cortex, which is an electrophysiological sign of absence epilepsy.
In face of an American opioid/psychostimulant crisis with overdose fatalities, due, in part, to the COVOD 19 pandemic, we are proposing a paradigm shift in response. Currently, The FDA has approved pharmaceuticals for the treatment of opioids, alcohol, and nicotine but not for psychostimulants or even cannabis.
A recent information processing model of two-choice RT situations (Servant et al., 2015), suggests that conditions which reduce the duration of peripheral motor processes, should also reduce the efficiency of the action monitoring system, because letting no time enough for correction of partial errors (i.e. subthreshold transient muscle activity of the agonists of the incorrect response preceding the correct response). A physiological situation, namely sustained physical exercise, has repeatedly been reported to reduce the duration of response execution. Therefore, in order to test the prediction of the model, we compared action monitoring efficiency between a sustained exercise (59.42% of MAP) and a control (15 W) condition in the same subjects while they were performing a Simon task. Electromyographic (EMG) recordings of muscles implicated in the response allowed to measure premotor time (time interval between the stimulus and the onset of the EMG burst) and motor time (MT, time interval between the onset of the EMG burst and the mechanical response, which gives access to response execution processes). Electromyogram further permitted to unmask partial errors. Correction ratio was calculated by dividing the number of partial errors by the number of incorrect activations (partial errors + errors). As expected, exercise decreased MT. In addition, exercise reduced the correction ratio. Furthermore, there was a positive inter-subject correlation between these two dependent variables. In line with Servant et al.'s model (2015), we propose that the drop in the efficiency of cognitive control was due to insufficient MT available for action monitoring to operate when incorrect activations were produced.
Among the different cognitive training approaches tested in healthy older adults, multifactorial programs, which target higher-order processes such as memory and attention, best promote the transfer of learning to untrained cognitive processes.Objective: In the present study, we investigated the effects of a multifactorial cognitive training program on executive functions in older adults. Method:This training was developed to embed the processing of executive information in memory and attention training tasks, and mnemonic and executive strategies were implemented progressively throughout training. Results:The results showed that this training program (24 sessions, 2 sessions per week) improved executive functions in older adults (n=15; mean age=74.5±2.1).Significant improvements were found for the switching and inhibition of irrelevant stimuli.We also report enhanced performance in the efficiency of a dual-task activity.Additionally, we report that these benefits were present at the 6-month follow-up without any additional training. Conclusion:Taken together with previous results obtained with the same training protocol, the present results showed that the multifactorial training program we developed is an efficient tool to positively act on memory-related and executive aspects of the cognitive decline found in normal aging.
A previous behavioural study on healthy subjects and callosotomized patients showed that subjects imitated mainly in mirror mode when free to choose the imitation mode, using the right limb to copy a left limb gesture of the facing model; when asked to use the same limb as the model, patients still perform in mirror mode, but controls imitated in anatomical mode, using the right limb for imitating a right limb gesture. These data suggest that the anatomical mode of imitation recruites both hemispheres, being linked to the integrity of the corpus callosum. The present study aims at investigating with fMRI the neural correlates of imitative perspective-taking, specially the anatomical mode. Functional MRI was performed in 10 control subjects of the previously tested groups, asked to Observe or Imagine-to-Imitate-with-the-same-limb , in separete runs, intransitive gestures. Different cortical activation in the two conditions were observed: opercular part of left inferior frontal gyrus, left inferior parietal lobule, right temporo-parietal junction and bilateral parietal opercular cortices were activated in Imagine-to-Imitate condition only. Present data confirm previous behavioural observations and indicate that neural circuitry underpinning the anatomical imitation of intransitive gesture likely requires the cooperation of both hemispheres, and therefore the integrity of the corpus callosum.
Alzheimer's disease (AD) is a presently incurable disease with a significant health burden, with a prevalence of 5.8 million Americans as of2019.Prognosis as well as more effective treatment regimens could be greatly augmented by reliable means of diagnosis in the earlier stages of development.Efforts to characterize impairments in memory in pre Clinical AD and mild cognitive impairment (MCI) range from the domain involved (episodic, semantic, working, perceptual, or visuospatial), to storage (sensory, long-term, short-term, explicit, implicit, autobiographical and morpheus), to memory processing including working memory or information processing (encoding, storage, and retrieval).An emerging area of research aims to determine whether detectable impairments in encoding, storage or retrieval have the ability to serve as hallmarks of pre Clinical Alzheimer's and early MCI giving both clinicians and patients a window of opportunity to halt or reverse progression to AD via early treatment options.For the identification of event related potential (ERP) markers, the P300 has shown promise as a state-of-the-art new device.While prolonged P300 latency recorded via electroencephalograph's (EEG) like BrainView NeuralScan is seen in normal aging, individuals with AD exhibit more prolonged P300 latencies and frontal-dominant P300 distribution when compared to normal individuals of the same age.Key questions now remaining include whether identification of these EEG hallmarks identified with the assistance of devices such as the P300 may provide us with an earlier timeframe in the diagnosis, prognosis and early treatment for AD, as well as providing crucial insights into mechanisms of its early pathogenesis.
An estimated 14.5 million United States (U.S.) citizens ages 12 and older consume enough alcohol to meet the diagnosis for alcohol use disorder (AUD), as reported by the Center for Behavioral Health Statistics and Quality in 2018. A National Survey on Drug Use and Health (NSDUH) conducted in 2019, revealed that 85.6 percent of adults admit to consuming alcohol at some point during their life, 69.5 percent of adults admit to having consumed alcohol within the past year, and 54.9 percent (51.0 percent of adult females and 59.1 percent of adult males) self-report to have consumed alcohol within the past month. The survey also reported that among adults, 25.8 percent (22.2 percent of adult females and 29.7 percent of adult males) reported engaging in binge drinking within the past 30 days. The survey also revealed the 6.3 percent of adults (4.5 percent of adult females and 8.3 percent of adult males) reported to engage in heavy alcohol use within the past 30 days [1]
Background: In face of an American opioid/psychostimulant crisis with overdose fatalities, due, in part, to the COVOD 19 pandemic, we are proposing a paradigm shift in response. Currently, The FDA has approved pharmaceuticals for the treatment of opioids, alcohol, and nicotine but not for psychostimulants or even cannabis. Proposition: To respond to the deadly overdose issue globally, we are proposing that the FDA embrace, for the treatment and prophylaxis of opioid and psychostimulant abuse, induction of DNA-guided, dopamine homeostasis. We refer to this novel therapeutic target as the Anti-Reward Deficiency Restoration Solution (ARDS). Expert opinion: This futuristic proposal regarding the FDA will provide important information that may ultimately lead to significant improvement in the recovery of individuals with opioid/psychostimulant and polydrug abuse issues, especially, those with genetically-induced dopamine deficiency. Conclusion: With large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, the neuroscience and neurological community may eventually have the clinical ability to classify addiction severity, according to genotype and possession of risk alleles. A promising goal is the identification of high risk vulnerability, along with the provision of a safe, non-addicting ARDS natural nutrigenomic, involving a therapeutic model that potentially up-regulates instead of down-regulates dopaminergic receptors, preferably, the D2 subtype, is one laudable goal.
Kenneth Blum1,2,3,4,5,6,*, David Baron1, Rehan Jalali6, Edward J Modestino7, Bruce Steinberg7, Igor Elman8, Rajendra D Badgaiyan9,10, Mark S Gold11 1Western University Health Sciences, Pomona, CA, USA 2Institute of Psychology, ELTE Eotvos Lorand University, Budapest, Hungary 3Division of Nutrigenomics, Genomic Testing Center Geneus Health, LLC, San Antonio, TX, USA 4Department of Psychiatry, University of Vermont, VT, USA 5Department of Psychiatry, Wright University Boonshoff School of Medicine, Dayton, OH., USA 6The Kenneth Blum Behavioral Neurogenetic Institute (Division of iVitalize Inc.), Austin, Tx, USA 7Department of Psychology, Curry College, Milton, MA, USA 8Department of Psychiatry, Harvard School of Medicine, Cambridge, MA, USA 9Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA 10Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy I Memorial VA Hospital, San Antonio, TX. and Long School of Medicine, University of Texas Medical Center, San Antonio TX, USA
Suprasellar arachnoid cysts (SAC), due to their location, are a separate group, regarding clinical symptoms and therapeutic approach, compared to AC in other locations.For this reason they are more similar to other benign suprasellar lesions.SACs are most often diagnosed in children.Symptoms of SAC depend on the age in which they occurred.The treatment needs the engagement of consultant doctors from many fields: neurosurgery, neurology, ophthalmology, endocrinology and radiology and should be also supported by psychologists.
In the face of the global pandemic of COVID 19, approaching 1.75 Million infected worldwide (4/12/2020) and associated mortality (over 108, 000 as of 4/12/2020) as well-as other catastrophic events including the opioid crisis, a focus on brain health seems prudent [1] (https://www.coronavirus.gov). This manuscript reports on the systemic benefits of restoring and achieving dopamine homeostasis to reverse and normalize thoughts and behaviors of Reward Deficiency Syndrome (RDS) dysfunctional conditions and their effects on behavioral physiology; function of reward genes; and focuses on digestive, immune, eye health, and the constellation of symptomatic behaviors. The role of nutrigenomic interventions on restoring normal brain functions and its benefits on these systems will be discussed. We demonstrate that modulation of dopamine homeostasis using nutrigenomic dopamine agonists, instead of pharmaceutical interventions, is achievable. The allied interlinking with diverse chronic diseases and disorders, roles of free radicals and incidence of anaerobic events have been extensively highlighted. In conjunction, the role of dopamine in aspects of sleep, rapid eye movement and waking are extensively discussed. The integral aspects of food indulgence, the influence of taste sensations, and gut-brain signaling are also discussed along with a special emphasis on ocular health. The detailed mechanistic insight of dopamine, immune competence and the allied aspects of autoimmune disorders are also highlighted. Finally, the integration of dopamine homeostasis utilizing a patented gene test and a research-validated nutrigenomic intervention are presented. Overall, a cutting-edge nutrigenomic intervention could prove to be a technological paradigm shift in our understanding of the extent to which achieving dopamine homeostasis will benefit overall health.
A recent analysis from Stanford University suggested that without any changes in currently available treatment, prevention, and public health approaches, we should expect to have 510,000 deaths from prescription opioids and street heroin from 2016 to 2025 in the US. In a recent review, Mayo Clinic Proceedings (October 2019), Gold and colleagues at Mayo Clinic reviewed the available medications used in opioid use disorders and concluded that in private and community practice adherence is more important as a limiting factor to retention, relapse, and repeat overdose. It is agreed that the primary utilization of known opioid agonists like methadone, buprenorphine and naloxone combinations, while useful as a way of reducing societal harm, is limited by 50% of more discontinuing treatment within 6 months, their diversion, and addiction liability. Opioid agonists may have other unintended consequences, like continuing the down regulation of dopamine systems. While naltrexone would be expected to have opposite effects, adherence is also low even after detoxification and long acting naltrexone injections. Recent studies have shown Naltrexone is beneficial by attenuation of craving via "psychological extinction" and reducing relapse. Buprenorphine is the MAT of choice currently but injectable Naltrexone plus an agent to improve dopaminergic function and tone may renew interest amongst addiction physicians and patients. Understanding this dilemma there is increasing movement to opt for the non-addicting narcotic antagonist Naltrexone. Even with extended injectable option there is still poor compliance. As such, we describe an open label investigation in humans showing improvement of naltrexone compliance and outcomes with dopamine augmentation with the pro- dopamine regulator KB220 (262 days) compared to naltrexone alone (37days). This well studied complex consists of amino-acid neurotransmitter precursors and enkephalinase inhibitor therapy compared to treatment as usual. Consideration of this novel paradigm shift may assist in not only addressing the current opioid epidemic but the broader question of reward deficiency in general.
Enteric nervous system (ENS) cells respond to the intestinal extracellular matrix (ECM) signals changing their proliferation rate, migration and differentiation.In this study, we explored in vitro the adaptive response of primary ENS cell cultures to the stimulation of gut acellular matrix (AM) defining the gene expression profile of neuronal functionality markers.Scanning electron microscopy was used to detect the acquisition of specific morphological features.Intestinal AM was prepared using an enzyme-detergent treatment.Primary rat enteric cells were isolated from the myenteric plexus of postnatal rats using an enzymatic method and seeded on intestinal AM in the presence of exogenous neurotrophic factors.The morphological properties and the expression of specific differentiation markers were evaluated by Scanning Electron Microscopy (SEM) and wholemount fluorescent staining.In order to verify the synergic activity of soluble factors and AM, the gene expression of neurotransmitter receptors was evaluated by qPCR in ENS cells cultured in SM conditions in the presence or not of AM.The development of interconnected ganglion-like structures and the expression of neurotransmitter receptors suggested that gut matrix engineered with ENS cells could be useful for medical applications of regenerative medicine or for the in vitro assessment of tridimensional culture system of ENS.
