Similar Signaling Pathways Trigger Anxiety In Variety of Species

MedicalResearch.com Interview with:

Yuanyuan Xie, PhD Postdoctoral Researcher Department of Neuroscience University of Pennsylvania Philadelphia, PA 19104

Dr.Yuanyuan Xie

Yuanyuan Xie, PhD
Postdoctoral Researcher
Department of Neuroscience
University of Pennsylvania
Philadelphia, PA 19104

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

Response: I joined Dr. Richard Dorsky’s lab in mid 2013 after a lab switch toward the end of the fourth year in my PhD. By then, the Dorsky lab at the University of Utah had published zebrafish lef1 mutants with a hypothalamic neurogenesis phenotype. I was asked to perform an RNA-sequencing (RNA-seq) experiment to identify Lef1-dependent genes. In doing so, I also characterized the cellular phenotype in the hypothalamus of our zebrafish mutants in a greater detail.

The first transition of this project happened when I proposed in late 2013 to test whether Lef1’s function was conserved in the mouse hypothalamus. Dr. Dorsky liked that idea, but told me that I could only pursue that idea if there was a Lef1-flox mouse strain available, because he did not want me to delay my graduation after a lab switch by making a new mouse line. Fortunately, a quick google search located the right mouse line published from the group of Dr. Hai-Hui Xue, who was generous enough to share some mice with us. Because the Dorsky lab was a zebrafish lab by then, we collaborated with Dr. Edward Levine to maintain our mice under his animal protocol. I was initially trained by Dr. Levine and his lab specialist Anna Clark for general mouse colony management. After Dr. Levine moved to Vanderbilt University in early 2016, we began to maintain our mice under Dr. Camille Fung’s animal protocol. Dr. Dorsky also supported me in attending a 3-week Cold Spring Harbor Laboratory Course on Mouse Development, Stem Cells & Cancer in mid 2015, which made me much more confident in handling mouse work afterwards.

Continue reading

Gene Helps Explain Why More Women Than Men Have Alzheimer’s

MedicalResearch.com Interview with:

Arthur W. Toga PhD Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences, Radiology and Engineering Ghada Irani Chair in Neuroscience Director, USC Mark and Mary Stevens Neuroimaging and informatics institute USC Institute for Neuroimaging and Informatics Keck School of Medicine of USC University of Southern California Los Angeles, CA  90032

Dr. Toga

Arthur W. Toga PhD
Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences,
Radiology and Engineering
Ghada Irani Chair in Neuroscience
Director, USC Mark and Mary Stevens Neuroimaging and informatics institute
USC Institute for Neuroimaging and Informatics
Keck School of Medicine of USC
University of Southern California
Los Angeles, CA  90032 

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

Response: The ε4 allele of the Apolipoprotein E (APOE) gene is the main genetic risk factor for late-onset Alzheimer’s disease.  This study reexamines and corrects the sex-dependent risks that white men and women with one copy of the ε4 allele face for developing Alzheimer’s disease using a very large data set of 57,979 North Americans and Europeans from the Global Alzheimer’s Association Interactive Network (GAAIN).

The study results show that these men and women between the ages of 55 and 85 have the same odds of developing Alzheimer’s disease, with the exception that women face significantly higher risks than men between the ages of 65 and 75.  Further, these women showed increased risk over men between the ages of 55 and 70 for mild cognitive impairment (MCI), which is often a transitional phase to dementia.

Continue reading

Serotonin Receptors Tied To Weight Gain From Atypical Antipsychotic Medications

MedicalResearch.com Interview with:

Chen Liu, Ph.D. Assistant Professor Departments of Internal Medicine and Neuroscience Division of Hypothalamic Research The University of Texas Southwestern Medical Center Dallas, Texas 75390-9077

Dr. Chen Liu

Chen Liu, Ph.D.
Assistant Professor
Departments of Internal Medicine and Neuroscience
Division of Hypothalamic Research
The University of Texas Southwestern Medical Center
Dallas, Texas 75390-9077 

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

Response: Atypical antipsychotics are second-generation antipsychotics (SGAs) that have been increasingly used to treat a variety of neuropsychiatric conditions such as schizophrenia, depression, and autism. Many patients taking these medications, however, are left in an agonizing dilemma.

On one hand, they rely on these drugs’ psychotropic effect for normal functioning in daily life. On the other, many SGAs, including the most widely prescribed olanzapine and clozapine, can cause a metabolic syndrome that is known for excessive weight gain, dyslipidemia, and type-2 diabetes_ENREF_2. Notably, while full-blown type 2 diabetes and morbid obesity typically take years to unfold in the general population, these conditions progress at a much faster pace (within months) following second-generation antipsychotics treatment. Other factors such as ethnicity, age, and sex can also aggravate SGA-induced metabolic syndrome. Together, these peculiar features strongly suggest a distinct etiology underlying SGA-induced metabolic syndrome that has yet been fully elucidated. Currently, there is no medication specifically targeting SGA-induced metabolic syndrome. For many youths and adults taking second-generation antipsychotics, metabolic complications are difficult to manage as lifestyle changes, nutritional consulting, and commonly used anti-diabetic medications only provide limited relief.

Continue reading

Weakening Neural Connections Can Eliminate Fearful Memories

MedicalResearch.com Interview with:

Jun-Hyeong Cho MD PhD Department of Molecular, Cell and Systems Biology University of California, Riverside Riverside, CA 92521

Dr. Jun-Hyeong Cho

Jun-Hyeong Cho MD PhD
Department of Molecular, Cell and Systems Biology
University of California, Riverside
Riverside, CA 92521

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

Response: To survive in a dynamic environment, animals develop fear responses to dangerous situations. For these adaptive fear responses to be developed, the brain must discriminate between different sensory cues and associate only relevant stimuli with aversive events.

In our current study, we investigated the neural mechanism how the brain does this, using a mouse model of fear learning and memory. Our study demonstrates that the formation of fear memory associated with an auditory cue requires selective synaptic strengthening in neural pathways that convey the auditory signals to the amygdala, an essential brain area for fear learning and memory.

Continue reading

Alzheimer’s: Antidepressants Increase Risk of Head and Traumatic Brain Injuries

MedicalResearch.com Interview with:

Heidi Taipale, PhD Pharm Senior Researcher School of Pharmacy, University of Eastern Finland; and Department of Clinical Neuroscience Karolinska Institutet 

Dr. Taipale

Heidi Taipale, PhD Pharm
Senior Researcher
School of Pharmacy, University of Eastern Finland; and
Department of Clinical Neuroscience
Karolinska Institutet 

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

Response: Antidepressant use among older persons has been associated with an increased risk of falling and fall-related events, such as hip fractures, in previous studies. Our previous study identified risk of hip fractures in antidepressant among persons with Alzheimer’s disease. As falling is the main causal factor for head traumas and traumatic brain injuries among older persons, we hypothesized that antidepressant use could also be associated with these injuries.

We utilized a nationwide cohort of 70,718 persons newly diagnosed with Alzheimer’s disease, identified from the Finnish registers. The risk of head injuries and traumatic brain injuries was compared between persons initiating antidepressant use and comparison persons of the same age, gender and time since they received diagnoses of Alzheimer’s disease but not using antidepressants. We found a 40-percent increased risk of head injuries and 30-percent increased risk of traumatic brain injuries associated with antidepressant use. Antidepressant use was associated with a higher risk of head injuries especially at the beginning of use – during the first 30 days – but the risk persisted even longer, up to two years. The association was also confirmed in a study design comparing time periods within the same person, thus eliminating selective factors. Continue reading

Schizophrenia: Impaired White Matter Linked To Deficits in Cognitive Processing Speed

MedicalResearch.com Interview with:

Peter Kochunov PhD Professor Maryland Psychiatric Research Center

Dr. Kochunov

Peter Kochunov PhD
Professor
Maryland Psychiatric Research Center 

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

Response: Schizophrenia is a debilitating disorder that strikes young people at the point of entering adulthood. In the past, we and others demonstrated that patients with schizophrenia are characterized by deficits in the white matter of the brain. White matter is the part of the brain that serves the backbone of cerebral networks transmitting information and interconnecting brain regions.

In this report, we link the impaired white matter of the brain in schizophrenia patients with the disorder-related deficits in the processing speed. We also showed that mental processing speed is a fundamental cognitive construct that partially supports other functions like working memory in patients, where processing speed acting as the intermediate between white matter deficits and reduced working memory. This interesting relationship between processing speed, working memory, and white matter is most obvious in white matter regions most vulnerable to schizophrenia. That was the main finding of the study.

Continue reading

New Biomarker Has Potential For Sideline Diagnosis of Traumatic Brain Injury

MedicalResearch.com Interview with:

Dr-Adrian-Harel.jpg

Dr. Adrian Harel

Dr. Adrian Harel, PhD
Chief Executive Officer
Medicortex Finland

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

Response: Every 15 seconds, someone in the United States suffers a new head injury. Of the 2.5M people treated in hospital emergency rooms each year, 80,000 become permanently disabled because of TBI. Currently, there are no reliable diagnostic tests to assess the presence or severity of an injury on-site, nor are there any pharmaceutical therapies that could stop the secondary injury from spreading. Accurate diagnostics would benefit especially mild cases of TBI (concussions), which, if occurring repeatedly, may cause neurodegenerative conditions such as Chronic Traumatic Encephalopathy (which is typical for athletes in NFL and Ice-hockey).

We have performed extensive preclinical research comparing fluid biopsies from normal and injured lab animals. The results showed some unique biomarkers released as a biodegradation products after head injury. The data served as the basis and confirmation for our patent applications to protect the biomarker concept.

Medicortex has completed a clinical proof-of-concept trial in collaboration with Turku University Hospital (Tyks). Samples from 12 TBI patients and 12 healthy volunteers were collected and analyzed for the presence and for the level of the biomarker in state-of-the-art laboratories. The study demonstrated the diagnostic potential of the new biomarker in humans and it confirmed the prior preclinical findings. This was a significant milestone for Medicortex.

Continue reading

MRI Biomarkers Track Cognitive Impairment Due to Head Trauma

MedicalResearch.com Interview with:

Virendra Mishra, Ph.D. Department of Imaging Research Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas

Dr. Virendra Mishra

Virendra Mishra, Ph.D.
Department of Imaging Research
Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas

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

Response: Repetitive head trauma has been shown to be a risk factor for various neurodegenerative disorders, mood swings, depression and chronic traumatic encephalopathy. There has been a significant amount of research into identifying an imaging biomarker of mild traumatic brain injury (mTBI) due to repetitive head trauma. Unfortunately, most of the biomarkers have not been able to find a successful translation to clinics. Additionally, the quest for the mTBI imaging biomarker especially using Magnetic Resonance Imaging (MRI) techniques has been done by looking at either the gray matter (T1-weighted) or the white matter (Diffusion Tensor Imaging) independently; and both have shown changes that are associated with repetitive head trauma.

Hence in this study, we wanted to investigate if combining gray matter and white matter information enables us to better predict the fighters who are more vulnerable to cognitive decline due to repetitive head trauma. Our method found seven imaging biomarkers that when combined together in a multivariate sense were able to predict with greater than 73% accuracy those fighters who are vulnerable to cognitive decline both at baseline and follow-up. The imaging biomarkers were indeed a combination of gray and white matter measures of regions reported previously in the literature. A key point in our study was we found the regions predicting cognitive decline without enforcing any assumptions on the regions previously reported.

Continue reading

Drug-Related Deaths Among Whites Soar But Alcohol and Suicide Mortality Stable

MedicalResearch.com Interview with:
Andrea M. Tilstra
Doctoral Student, Department of Sociology
Population Program, Institute of Behavioral Science
University of Colorado Boulder and
Ryan K. Masters
Assistant Professor, Department of Sociology
Faculty Associate, Population Program and Health & Society Program
Institute of Behavioral Science
University of Colorado Boulder

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

Response:  “Despair” deaths – deaths from suicides, alcohol poisonings, and drug overdoses – have been a topic of interest in recent mortality research. For instance, existing findings suggest that mortality among white Americans has increased as a result of middle-aged whites experiencing elevated levels of despair and distress. These factors supposedly are driving white Americans to cope in unhealthy ways – excessive drinking, drug use, and suicides.

However, there were two major problems with the existing research that supported this narrative. First, men and women were analyzed together, despite the knowledge that overall mortality levels and trends differ significantly by gender. Second, all three of the aforementioned causes of death were pooled together and analyzed as one group. This is highly problematic if deaths from suicides, alcohol use, and drug use are not, in fact, moving in conjunction with one another. We addressed these issues and expanded previous analyses by analyzing cause-specific death rates for men and women separately, for years 1980-2014, and decomposing the trends into period- and cohort- based analyses.

We find that there are huge gender differences in U.S. white mortality rates and that trends in mortality from the three causes of death are quite distinct from one another. Recent increases in U.S. white mortality are largely driven by period-based increases in drug poisoning deaths and cohort-based increases in metabolic disease deaths.

Continue reading

Disadvantaged Neighborhoods Help Explain Some Of Alzheimer’s Disease Racial Disparities

MedicalResearch.com Interview with:

Amy Kind, M.D., Ph.D. Associate Professor, Division of Geriatrics Director, Department of Medicine Health Services and Care Research Program University of Wisconsin School of Medicine and Public Health and Associate Director- Clinical Geriatrics Research, Education and Clinical Center (GRECC) William S. Middleton Veteran’s Affairs Hospital

Dr. Amy Kind

Amy Kind, M.D., Ph.D.
Associate Professor, Division of Geriatrics
Director, Department of Medicine Health Services and Care Research Program
University of Wisconsin School of Medicine and Public Health and
Associate Director- Clinical
Geriatrics Research, Education and Clinical Center (GRECC)
William S. Middleton Veteran’s Affairs Hospital

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

Background: Dementia due to Alzheimer’s Disease (AD) disproportionately impacts racial/ethnic minorities and the socioeconomically disadvantaged—populations often exposed to neighborhood disadvantage. Neighborhood disadvantage is associated with education, health behaviors and mortality. Health improves with moving to less disadvantaged neighborhoods (Ludwig, Science 2012). Although studies have linked neighborhood disadvantage to diseases like diabetes and cancer, little is known about its effect on development of dementia.

Objective:  To examine the association between neighborhood disadvantage, baseline cognition, and CSF biomarkers of Alzheimer’s Disease among participants in the WRAP study, comprising a cohort of late-middle-aged adults enriched for parental family history of AD.

Methods:  We created and validated neighborhood-level quantifications of socioeconomic contextual disadvantage for the full US—over 34 million Zip+4 codes—employing the latest American Community Survey and Census data. This metric–the Area Deprivation Index (ADI)–incorporates poverty, education, housing and employment indicators; predicts disparity-related health outcomes; and is employed by Maryland and Medicare through our provision. We used standard techniques to geocode all WRAP subjects with a documented address (N= 1479). WRAP participants were ranked into deciles of neighborhood disadvantage, by ADI. Baseline cognitive function (indexed by factor scores) and CSF biomarker outcomes for levels of Aβ42 and P-tau181 (n=153 with CSF samples) were examined by neighborhood disadvantage decile.

Continue reading