Long Term Memories Can Be Selectively Erased

MedicalResearch.com Interview with:
Samuel Schacher, PhD and
Jiangyuan Hu, PhD,
Department of Neuroscience
Columbia University Medical Cente
New York State Psychiatric Institute
New York, NY 10032, USA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is well established that learning and memory requires changes in the properties of specific neural circuits in the brain activated by the experience. The long-term storage of the memory is encoded through changes in the function of the synapses within the circuit. Synapses are sites of communication between neurons, and the changes in their function come in two varieties: increases in strength and decreases in strength. The encoding of memories typically requires some combination of these synaptic changes, synaptic plasticity, which can last a long time to contribute to long-term memory. Thus the maintenance of a memory will require the persistent change (long-term synaptic memory) in the function of specific synapses.

But memories come in different flavors. In the original experiment by Pavlov, a neutral tone, which dogs ignore, came to predict the immediate appearance of a meal. After several of these pairings, the dogs would become happily excited just with the tone. The same type of conditioning could have a negative valence – the tone could proceed a shock to one of the dog’s paw. Now the neutral tone would predict a negative stimulus and the dog would express fearful behavior just with the tone (associative learning). A non-associative form of memory would be the same types of stimuli but without the preceding neutral stimulus. At random times the animal will be given a meal or a shock. The behavior of the animal for some time will take on the positive or negative features of its environment – a contented versus depressed condition.

Each of these forms of long-term memory would be maintained by increases in the strength of specific synapses.

The questions addressed in our study published in Current Biology, based on previous work in my lab and the lab of my colleague Wayne Sossin at McGill, were:

1) Do the same molecules maintain increases in synaptic strength in the neurons of the circuit after stimuli that produce long-term classical conditioning (associative learning) and long-term sensitization (non-associative learning)?
2) If different molecules maintain the different synaptic memories, is it possible to reverse or erase the different synaptic memories by interfering with the function of the different molecules?
3) If true, can we reverse the different synaptic memories expressed in the same neuron by interfering with the function of the different molecules.

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Pot Plus Alcohol Raises Fatal Traffic Accident Risk Over 500%

MedicalResearch.com Interview with:

Guohua Li DrPH, MD Professor and Director Center for Injury Epidemiology and Prevention Department of Epidemiology Mailman School of Public Health Columbia University

Dr. Li

Guohua Li DrPH, MD
Professor and Director
Center for Injury Epidemiology and Prevention
Department of Epidemiology
Mailman School of Public Health
Columbia University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Drugged driving has become a serious problem in the United States in the recent years due to increased consumption of marijuana and opioids. About 20% of fatally injured drivers used two or more substances, with alcohol-marijuana being the most commonly detected polydrug combination.

Our study of over 14000 fatal 2-car crashes indicates that drivers testing positive for alcohol, marijuana, or both are significantly more likely to be responsible for initiating these crashes than those using neither of the substances. Specifically, compared to drivers not using alcohol and marijuana, the risk of being responsible for initiating fatal crashes increases 62% for those testing positive for marijuana and negative for alcohol, 437% for those testing positive for alcohol and negative for marijuana, and 539% for those testing positive for both alcohol and marijuana. These results suggest that when used in combination, alcohol and marijuana have a positive interaction on the risk of fatal crash initiation.

The most common driver error leading to fatal 2-car crashes is failure to keep in proper lane, followed by failure to yield right of way and speeding.

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Frequent Marijuana Use Linked To Increased Risk of Severe Periodontal Disease

MedicalResearch.com Interview with:

Jaffer A Shariff DDS MPH cert.DPH Periodontal Resident | Research Scientist Division of Periodontics, Columbia University College of Dental Medicine New York

Dr. Shariff

Jaffer A Shariff DDS MPH cert.DPH
Periodontal Resident | Research Scientist
Division of Periodontics,
Columbia University College of Dental Medicine
New York

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Marijuana use for both medical and recreational purposes has become increasingly common in recent years; it is the most commonly used recreational drug in the United States. Subsequent increase in its legalization among countries including the United States for recreational purposes, poses an emergent oral and periodontal health concerns.

Our study revealed that frequent recreational marijuana users exhibited deeper periodontal probing depths, clinical attachment loss and higher odds of having severe periodontal disease than the non-frequent users, even after controlling for other risk factors linked to gum disease, such as cigarette smoking.

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Autism Increases Risk of Death From Injury, Especially Drowning

MedicalResearch.com Interview with:
Joseph Guan

MPH Candidate in Epidemiology, Certificate in Chronic Diseases Epidemiology
Columbia University Mailman School of Public Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The prevalence of autism has been increasing especially in the past two decades. With an estimate of more than 3.5 million people living with autism in the US, approximately 500,000 of them are children under 15 years old. Current studies show that males are approximately four times as likely than females to be diagnosed with autism. There is also evidence that people with autism are at a heightened risk of injury. However, the research on the relationship between autism and injury is understudied.

We found that 28% of deaths in individuals with autism were due to injury, compared to 7% of deaths in the general population. Injury deaths in individuals with autism occurred at a much younger age (29.1 years) on average compared to injury deaths in the general population (54.7 years). Our study show that drowning was the leading cause of injury death among individuals with autism, followed by suffocation and asphyxiation. Children under the age of 15 years were 160 times more likely to die from drowning.

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No Increased Health Consequences After Chinese Famine Except Schizophrenia

MedicalResearch.com Interview with:

L. H. Lumey, MD, PhD Professor of Epidemiology Mailman School of Public Health Columbia University

Dr. Lumey

L. H. Lumey, MD, PhD
Professor of Epidemiology
Mailman School of Public Health
Columbia University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Chinese Great Leap Forward Famine in 1959-1961 is the largest famine in human history. Earlier studies have reported that overweight, type 2 diabetes, hyperglycemia, the metabolic syndrome and schizophrenia were more common among adults who were exposed to the famine. Our re-analysis of all previous studies shows no increases in diabetes, high blood pressure and other chronic conditions among famine births except for schizophrenia.

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Ketamine Before Stressful Event May Reduce Risk of PTSD

MedicalResearch.com Interview with:

Christine Ann Denny, Ph.D. Assistant Professor Department of Psychiatry Columbia University Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. New York, NY 10032-2695

Dr. Christine Ann Denny

Christine Ann Denny, Ph.D.
Assistant Professor
Department of Psychiatry
Columbia University
Division of Integrative Neuroscience
Research Foundation for Mental Hygiene, Inc.
New York, NY 10032-2695

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Post-traumatic stress disorder (PTSD) is one of the most common psychiatric illnesses, affecting about 8 million adult Americans, and an annual prevalence of about 3.5% worldwide. At-risk populations such as soldiers and veterans are at a higher risk to develop PTSD. Stress exposure is one of the major risk factors for PTSD and major depressive disorder (MDD), a disorder which is often co-morbid with PTSD.

There are currently very limited treatments for PTSD and MDD. In addition, these disorders are treated in a symptom-suppression approach, which only mitigate symptoms and work in only a small fraction of patients. Prevention is rarely an approach considered except in the form of behavioral intervention. However, pharmacological approaches to preventing psychiatric diseases has not yet been developed.

Our laboratory has previously found that ketamine, a general anesthetic and rapid-acting antidepressant, administered sub-anesthetically prior to stress can prevent against stress-induced depressive-like behaviors. We decided to delve into the literature to determine whether ketamine has any effects on PTSD in the clinic. We found numerous reports linking ketamine to PTSD, but the results were varied. We realized that the main difference in all of these studies was the timing of administration. We decided to systematically test the efficacy of ketamine in mice at various time points relative to a stressor to determine when would be the most effective window to buffer against heightened fear expression.

We found that ketamine administered 1 week, but not 1 month or 1 day, prior to a stressor was the most effective time point to administer the drug to buffer fear. This is critical, as it suggests that a pharmacological approach to enhance resilience can be more effective at protecting against PTSD symptoms than attempting to mitigate symptoms after it has already affected an individual.

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PCSK9 Inhibition with Alirocumab Increases Removal of LDL Cholesterol

MedicalResearch.com Interview with:
Henry N. Ginsberg, MD

Irving Institute for Clinical and Translational Research
Columbia University
Columbia College of Physicians and Surgeons
New York, NY

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies in mice and cells have identified increased hepatic low density lipoprotein (LDL) receptors as the basis for LDL lowering by PCSK9 inhibitors, but there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism, particularly effects on very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) or LDL metabolism.

This study in 18 healthy subjects, found that alirocumab decreased the number of IDL and LDL particles in the circulation, and their associated cholesterol and apoB levels by increasing efficiency of the clearance of IDL and LDL. There were not effects on VLDL metabolism. The increased clearance of IDL meant that less LDL was produced from IDL, which is the precursor of LDL. Thus, the dramatic reductions in LDL cholesterol resulted from both less LDL being produced and more efficient clearance of LDL. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.

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AI plus Genetic Database Drives Personalized Cancer Treatment

MedicalResearch.com Interview with:

Dr. Kai Wang Zilkha Neurogenetic Institute, University of Southern California Institute for Genomic Medicine, Columbia University

Dr. Kai Wang

Dr. Kai Wang
Zilkha Neurogenetic Institute, University of Southern California
Institute for Genomic Medicine, Columbia University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cancer is a genetic disease caused by a small number of “driver mutations” in the cancer genome that drive disease initiation and progression. To understand such mechanism, there are increasing community efforts in interrogating cancer genomes, transcriptomes and proteomes by high-throughput technologies, generating huge amounts of data. For example, The Cancer Genome Atlas (TCGA) project has already made public 2.5 petabytes of data describing tumor and normal tissues from more than 11,000 patients. We were interested in using such publicly available genomics data to predict cancer driver genes/variants for individual patients, and design an “electronic brain” called iCAGES that learns from such information to provide personalized cancer diagnosis and treatment.

iCAGES is composed of three consecutive layers, to infer driver variants, driver genes and drug treatment, respectively. Unlike most other existing tools that infer driver genes from a cohort of patients with similar cancer, iCAGES attempts to predict drivers for individual patient based on his/her genomic profile.

What we have found is that iCAGES outperforms other tools in identifying driver variants and driver genes for individual patients. More importantly, a retrospective analysis on TCGA data shows that iCAGES predicts whether patients respond to drug treatment and predicts long-term survival. For example, we analyzed two groups of patients and found that using iCAGES recommend drugs can increase patients’ survival probability by 66%. These results suggest that whole-genome information, together with transcriptome and proteome information, may benefit patients in getting optimal and precise treatment. Continue reading

Fetal Structural Defects Detected Later in Pregnancy Than Chromosomal Abnormalities

MedicalResearch.com Interview with:
Sarah Horvath, MD
Paula M. Castaño, MD, MPH
Anne R. Davis, MD, MPH

Columbia University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Approximately 3% of pregnant women in the United States will receive a prenatal diagnosis of fetal aneuploidy (such as trisomy 21) or fetal structural abnormality (such as cardiac or CNS malformations). Many of these women will undergo abortion. Advances in screening over the past few decades have allowed earlier diagnosis of aneuploidy, but most structural abnormalities cannot be diagnosed until the anatomy ultrasound at 18-20 weeks gestational age because of fixed patterns of fetal development. Our analysis examines gestational age at time of abortion for these two types of fetal diagnosis from 2004-2014.

Our main finding was that median gestational age at time of abortion for fetal aneuploidy decreased from 19 weeks to 14 weeks. However, over the same 11 year period, median gestational age at time of abortion for fetal structural abnormalities remained unchanged and at or above 20 weeks gestation.

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Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis

MedicalResearch.com Interview with:

Dr. Jeri Nieves PhD Director of bone density testing New York's Helen Hayes Hospital

Dr. Jeri Nieves

Dr. Jeri Nieves PhD
Director of bone density testing
New York’s Helen Hayes Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Amyotrophic lateral sclerosis (ALS) is a devastating severe neurodegenerative disorder that causes progressive muscle atrophy, paralyses, and eventual respiratory failure.

Our objective was to evaluate the associations between nutrition and severity of ALS around the time of diagnosis. This was a cross-sectional analysis of data from a multicenter cohort of 302 patients with ALS. We assessed nutrient intake using a modified Block Food Frequency Questionnaire. The outcomes were respiratory function (measured using percentage forced vital capacity; FVC%) and functional performance measured by ALS Functional Rating Scale–Revised (ALSFRS-R), both considered important indicators of the severity of ALS. Results of the regression analysis were that higher intakes of antioxidants and carotenes from vegetable intake were associated with higher ALSFRS-R scores or better %FVC.

We used a novel analysis to evaluate the diet as a whole and found that higher intakes of antioxidants, fiber from grains, vegetables, fruit, eggs, fish, and poultry were all associated with higher function in patients with ALS. However, milk and lunch meats were associated with lower measures of function. These consistent results from two different statistical analyses indicate that diet may help minimize the severity of ALS. Perhaps these findings point to the role of oxidative stress in ALS severity.

In summary, increased consumption of antioxidant nutrients, foods high in carotenoids and fiber, vegetables and fruits, poultry and fish are associated with better function around the time of ALS diagnosis.

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