Author Interviews, JAMA, NYU, PTSD / 24.07.2015

Charles R. Marmar, MD The Lucius Littauer Professor and Chair, Department of Psychiatry, NYU Langone Medical Center and Director of the Steven and Alexandra Cohen Veterans Center at NYU LangonMedicalResearch.com Interview with: Charles R. Marmar, MD The Lucius Littauer Professor and Chair, Department of Psychiatry, NYU Langone Medical Center and Director of the Steven and Alexandra Cohen Veterans Center at NYU Langone MedicalResearch: What is the background for this study? What are the main findings? Dr. Marmar: Approximately 2.7 million men and women served in Vietnam, and, for those who returned, many have suffered for decades from a variety of psychological problems resulting from their experiences and other injuries such as traumatic brain injury (TBI). The 25-year National Vietnam Veterans Longitudinal Study (NVVLS) was a way we could determine at various points in time how veterans were faring emotionally four decades after their service. While the vast majority are resilient, there are still over 270,000 Vietnam veterans who still have some form of post-traumatic stress disorder (PTSD) and one-third of these veterans have depression. We followed up with veterans who participated in the National Vietnam Veterans Readjustment Study (NVVRS) from 1984 to 1988 who were evaluated for PTSD. The NVVRS group represented a probability sample of those who served in Vietnam. Of the 1,839 participants still alive, 1,409 participated in at least one phase of the NVVLS, which involved a health questionnaire, health interview and clinical interview. The results showed that between 4.5 percent and 11.2 percent of male Vietnam veterans and 6.1 and 8.7 percent of the female veterans are currently experiencing some level of PTSD. About 16 percent of veterans in the study reported an increase of more than 20 points on a PTSD symptom scale compared to 7.6 percent who reported a decrease of greater than 20 points.
Author Interviews, Brain Injury, JAMA, Outcomes & Safety, UCLA / 23.07.2015

Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research, University of California Los Angeles Los Angeles, CA 90024MedicalResearch.com Interview with: Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research, University of California Los Angeles Los Angeles, CA 90024 Medical Research: What is the background for this study? What are the main findings? Dr. Dawes: In the fall of 2013, we formed the Los Angeles County Trauma Consortium, building upon a prior administrative relationship between LA County’s 14 trauma centers. We added health research researchers from UCLA and USC, and shifted the focus of the group from logistical issues to quality improvement. As a first project, our hospitals wanted to know if there was any variation in how traumatic brain injury patients are cared for across the county. Traumatic brain injury accounts for over 1/3 of all injury-related deaths in the U.S. and is the number one reason for ambulance transport to a trauma center in LA County. When we looked at the data, we found widespread variation in both how these patients were cared for at different hospitals and what happened to them as a result of that care. After adjusting for important differences in patient mix, we found that mortality rates varied by hospital from roughly 25% to 55%. As we tried to explain this variation, we looked into how often hospitals complied with two evidence-based guidelines from the Brain Trauma Foundation, hoping that we could eventually develop an intervention to boost compliance with these recommended care practices. While compliance rates varied even more widely than mortality—from 10 to 65% for intracranial pressure monitoring and 7 to 76% for craniotomy—they did not appear to be associated with risk-adjusted mortality rates. Put simply, we found no connection between how often hospitals complied with the guidelines and how likely their patients were to survive.
Alzheimer's - Dementia, Author Interviews, NYU / 21.07.2015

Fernando Goni, PhD MS Adjunct associate professor Department of Neurology, Center for Cognitive Neurology NYU School of Medicine NYU Langone Medical CenterMedicalResearch.com Interview with: Fernando Goni, PhD MS Adjunct associate professor Department of Neurology, Center for Cognitive Neurology NYU School of Medicine NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Goni: It has been established that most neurodegenerative diseases including Alzheimer's, Lewy Body and other dementias, Parkinson's and prion diseases develop and progress along similar paths. In each disease, a particular protein undergoes a change in its shape from a soluble, physiologically functional protein to a protein that has lost the ability to perform its required tasks in the brain, starting off a chain reaction of binding to each other with little control. These aggregates become toxic to brain cells. We raised antibodies in mice against the common beta-sheet structures present in toxic oligomers of many neurodegenerative diseases including amyloid and tau in Alzheimer's; oligomeric forms of prions and oligomerized alpha-synuclein in Parkinson's. From that response, we produced monoclonal antibodies of the same characteristics. At least three of the monoclonals recognize pathological structures in histological samples of human brains from Alzheimer's disease, Parkinson's disease and GSS (human prionosis). They also recognized in vitro the oligomeric forms particular for each disease. In old animals of a mouse model of Alzheimer's, that already had pathology, the monoclonal antibodies could rescue behavior and reduced significantly the oligomers of Tau and Abeta.
Author Interviews, Memory, Occupational Health, Sleep Disorders / 14.07.2015

MedicalResearch.com Interview with: Jonathan Cedernaes M.D., Ph.D. Department of Neuroscience Uppsala University SwedenJonathan Cedernaes M.D., Ph.D. Department of Neuroscience Uppsala University Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Cedernaes: Sleep is known to facilitate the formation of long-term memory in humans, by transferring newly learned memories from short-term to long-term memory stores. Studies however indicate that even shorter periods of sleep - including naps - can ensure access to different types of memories under normal restful conditions. Furthermore, while some studies have shown that acute sleep loss can exacerbate e.g. physiological responses to acute stress, it it has not been studied whether shortened sleep in combination with acute cognitive stress can have a negative impact on the retrieval of newly learned memories. With this background in mind, we conducted a study where we aimed to investigate how nocturnal sleep duration impacts this memory transfer, and to what extent long-term memories formed by sleep remain accessible after acute cognitive stress. We recruited 15 participants who in each of two sessions first underwent a learning session in the evening, during which they learned 15 card pair locations on a computer screen. Then, in one of the two experimental session, subjects slept for half a night (4-hr), instead being able to sleep for a full night (8-hr) in the other session. On the morning after each sleep condition, we had the subjects try to recall as many card pair locations as possible. We found that following half a night of sleep (4-hr), participants were equally able to recall memories for the learned card pair locations, as after a full night of sleep (8-hr). However, we also showed that the ability to retrieve memories following 30 minutes of acute stress, in the morning after these two sleep conditions, was different depending on whether the participants had slept for 8 or 4 hours. Following short sleep, the 30-min long stress exposure reduced the participants' ability to recall the card pair locations that the participants had learned the previous night by around 10%. In contrast, no such stress-induced memory impairment was observed when the same men were allowed to sleep for a full night.
Author Interviews, PTSD / 14.07.2015

MedicalResearch.com interview with Dr. Ella James, Post-Doctoral Investigator Scientist Medical Research Council Cognition and Brain Sciences Unit Cambridge, UK. MedicalResearch: What is the background for this study? Dr. James: Post-traumatic stress disorder (PTSD) is experienced by some people after a traumatic event. While many people who’ve been involved in traumatic events don’t experience PTSD, those who do typically have repeated visual intrusive memories of certain moments in vivid detail that pop back into mind, seemingly out of the blue. For example, with PTSD after a car crash might repeatedly ‘see’ the moment the other car crashed into them. The recommended treatment for PTSD is cognitive behaviour therapy, a talking therapy that has been demonstrated to work well. But it is only delivered once intrusive memories have become established and PTSD is diagnosable – i.e. at least one month after the traumatic event occurred. At present, there is nothing readily available for use soon after trauma that has been shown to prevent symptoms building up and PTSD becoming established. In previous laboratory work our research team showed that playing Tetris shortly after viewing events with traumatic content (e.g. film footage of road safety campaigns – what we call an experimental trauma) could reduce intrusive memories of those events in healthy volunteers over the following week [2, 3] when played in a 4-hour time window after viewing. We reasoned that this was because having to follow and track the shapes, colour and movement of the coloured blocks in Tetris soon after seeing the experimental trauma (the film) disrupted aspects of the visual memory of that event from being ‘laid down’ in the sensory part of the brain, whilst leaving memory for the narrative and meaning of the events unaffected. However, it is hard to reach people so soon after a traumatic event in the real world and memories for events become ‘fixed’ in mind within hours after an event making them difficult to change. Therefore it was important to show whether we can change older, established memories of trauma.
Author Interviews, Cancer Research, Cognitive Issues, Radiation Therapy / 13.07.2015

MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UKMedicalResearch.com Interview with: MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UK Medical Research: What is the background for this study? Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months. The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions. Medical Research: What are the main findings? Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors. For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response. For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking. Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted.
Author Interviews, Cognitive Issues, Diabetes, JCEM / 11.07.2015

MedicalResearch.com Interview with: Wei-Che Chiu, MD, PhD National Taiwan University College of Public Health, Cathay General Hospital and Fu Jen Catholic University Taipei, Taiwan Medical Research: What is the background for this study? Response: Diabetes mellitus is a common risk factor for dementia and accounts for 6–8% of all cases of dementia in older populations. Cognitive impairment is associated with the presence of diabetic complications and diabetic severity, but the effects of diabetic severity on dementia are unclear. Our study was to investigate the association between the severity and progress of diabetes and the risk of dementia. Medical Research: What are the main findings? Response: The diabetic severity and progression reflected the risk of dementia, and the early progress in diabetic severity could predict the risk of dementia in new-onset diabetic patients.
Author Interviews, Beth Israel Deaconess, Cognitive Issues, Diabetes, Neurology / 11.07.2015

Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MAMedicalResearch.com Interview with: Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MA MedicalResearch: What is the background for this study? Dr. Novak: Diabetes mellitus (DM) is a major contributor to morbidity and mortality. Type 2 diabetes mellitus affects more than 44 million people in the U.S., and its numbers are growing rapidly, affecting up to 27% of older adults. Diabetes mellitus accelerates brain aging by about 5 years1, manifests as a widespread generalized atrophy2, and promotes earlier onset of vascular dementia and Alzheimer’s disease (AD).3,4 Diabetes mellitus -related atrophy manifests as worse cognitive function, memory, and gait, especially during a dual task, 5,6 and even a tight glycemic control did not improve cognitive function in participants of the large clinical trials 7. MedicalResearch: What are the main findings? Dr. Novak: Sixty-five participants (aged 66± 9.2 years) 35 with T2DM and 30 non-diabetic controls participated in this study. After 2 years of follow-up, participants with T2 Diabetes mellitus had diminished vascular reactivity in the brain (an ability to increase blood flow in responses to a task or metabolic demands) and performed worse on multiple cognitive tasks (in particular verbal learning and memory). In T2DM group, lower cerebral vasoreactivity correlated with worse performance on daily living activities. Specifically, the lower vasodilatation (ability to increase blood flow) was associated with worse mental functions. In addition, those with higher markers of inflammation had greater decline in vascular function in the brain.
Author Interviews, Depression, Mental Health Research, Pediatrics / 10.07.2015

MedicalResearch.com Interview with: Katie Burkhouse, Graduate Student and Dr. Brandon Gibb Ph.D Professor of Psychology Director of the Mood Disorders Institute and Center for Affective Science Binghamton University Medical Research: What is the background for this study? What are the main findings? Dr. Gibb:  One of the strongest risk factors for depression is a family history of the disorder.  However, even among this at-risk group, the majority of children of depressed parents do not develop depression themselves.  For those who do become depressed, the depression can severely and negatively affect their social and academic functioning, become chronic or recurrent over the lifespan, and increase risk for suicide.  What is needed therefore, is a good indicator of which children may be at greatest risk for depression so that interventions can be targeted to these individuals.  We believe that pupil dilation may represent one such marker.  Changes in pupil dilation are associated with activity in the brain’s emotional circuits and have been linked in previous research to the presence of depression.  What my graduate student Katie Burkhouse found is that, even among children who are not currently experiencing symptoms of depression, the degree to which their pupil dilates when they look at pictures of sad faces predicts their risk for developing clinically significant episodes of depression over the next two years.  The findings were specific to pupil responses to sad faces and were not observed when children looked at happy or angry faces suggesting that there is something specific to how the children were processing sad images.
Author Interviews, Insomnia, JAMA, Mental Health Research / 07.07.2015

Jason Ong, Ph.D., CBSM Associate Professor, Department of Behavioral Sciences Director, Behavioral Sleep Medicine Training Program Rush University Medical CenterMedicalResearch.com Interview with: Jason Ong, Ph.D., CBSM Associate Professor, Department of Behavioral Sciences Director, Behavioral Sleep Medicine Training Program Rush University Medical Center Medical Research: What is the background for this study? What are the main findings? Response: Insomnia is a very common sleep problem that was previously thought to be related to another medical or psychiatric condition.  Evidence now supports the notion that insomnia can emerge as a disorder distinct from the comorbid condition.  In this study, we evaluated the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), the most widely used nonpharmacologic treatment for insomnia, in the context of medical and psychiatric comorbidities. We conducted a systematic review and meta-analysis of 37 studies and found that 36% of patients who received cognitive behavioral therapy for insomnia were in remission at post-treatment compared to 17% who received a control or comparison condition.  CBT-I had medium to large effects for improving sleep quality and reducing the amount of time awake in bed.  Positive findings were also found on the comorbid condition, with greater improvements in psychiatric conditions compared to medical conditions.
Author Interviews, Cognitive Issues, FASEB / 05.07.2015

Milan Fiala, M.D. Research Professor, UCLA Department of Surgery Los Angeles, CAMedicalResearch.com Interview with: Milan Fiala, M.D. Research Professor, UCLA Department of Surgery Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Fiala: Omega-3 fatty acid supplementation is well-known to public for its health benefits in cardiovascular diseases and putative benefits against “Minor Cognitive Impairment” reported in other studies . This study shows that omega-3 protected against oxidation and resveratrol improves the immune system against amyloid-beta in the brain,  probably by increasing its clearance from the brain by the immune system. Overall the patients taking the drink seemed to preserve their memory better for up to 2 years than expected based on previous studies. However, our study was small and not controlled by a placebo, which may present a bias.  
Author Interviews, Depression, Sexual Health, Testosterone / 03.07.2015

Michael S. Irwig MD Division of Endocrinology Medical Faculty Associates George Washington UniversityMedicalResearch.com Interview with: Michael S. Irwig MD Division of Endocrinology Medical Faculty Associates George Washington University Medical Research: What is the background for this study? What are the main findings? Response: Many factors are associated with lower testosterone levels and many men who have their testosterone levels checked have non-specific depressive symptoms. The main finding is a remarkably high rate of depression and depressive symptoms (56%) in men who are referred for borderline testosterone levels. Other significant findings include a prevalence of overweight and obesity higher than the general population.
Author Interviews, Columbia, JACC, PTSD, Women's Heart Health / 30.06.2015

Jennifer A. Sumner, Ph.D.MedicalResearch.com Interview with: Jennifer A. Sumner, Ph.D. Columbia University Mailman School of Public Health New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Dr. Sumner: Cardiovascular disease, which includes conditions like heart attack and stroke, is the leading cause of death worldwide. Stress has long been thought to increase risk of cardiovascular disease, and posttraumatic stress disorder (PTSD) is the quintessential stress-related mental disorder. Some individuals who are exposed to traumatic events, such as unwanted sexual contact, the sudden unexpected death of a loved one, and physical assault, develop PTSD, which is characterized by symptoms of re-experiencing the trauma (e.g., nightmares), avoidance of trauma reminders (e.g., avoiding thinking about the trauma), changes in how one thinks and feels (e.g., feeling emotionally numb), and increased physiological arousal and reactivity (e.g., being easily startled). PTSD is twice as common in women as in men; approximately 1 in 10 women will develop PTSD in their lifetime. Research has begun to suggest that rates of cardiovascular disease are higher in people with PTSD. However, almost all research has been done in men. My colleagues and I wanted to see whether PTSD was associated with the development of cardiovascular disease in a large sample of women from the general public. We looked at associations between PTSD symptoms and new onsets of heart attack and stroke among nearly 50,000 women in the Nurses’ Health Study II over 20 years, beginning in 1989. Women with the highest number of PTSD symptoms (those reporting 4+ symptoms on a 7-item screening questionnaire) had 60% higher rates of developing cardiovascular disease (both heart attack and stroke) compared to women who were not exposed to traumatic events. Unhealthy behaviors, including lack of exercise and obesity, and medical risk factors, including hypertension and hormone replacement use, accounted for almost 50% of the association between elevated PTSD symptoms and cardiovascular disease. We also found that trauma exposure alone (reporting no PTSD symptoms on the screening questionnaire) was associated with elevated cardiovascular disease risk compared to no trauma exposure. Our study is the first to look at trauma exposure and PTSD symptoms and new cases of cardiovascular disease in a general population sample of women. These results add to a growing body of evidence suggesting that trauma and PTSD have profound effects on physical health as well as mental health.
Author Interviews, Mental Health Research / 25.06.2015

MedicalResearch.com Interview with: Ezequiel Morsella, Ph.D. Associate Professor of Neuroscience Department of Psychology San Francisco State University Assistant Adjunct Professor Department of Neurology University of California, San Francisco Boardmember, Scientific Advisory Board Institute of Cognitive Neurology (INECO), Buenos Aires Medical Research: What is the background for this study? What are the main findings? Dr. Morsella: The theoretical framework, Passive Frame Theory, builds on an action-based, theoretical project that first appeared in Psychological Review, in 2015. The framework is a synthesis of hypotheses from disparate fields. It reveals that consciousness serves as a frame that constrains and directs skeletal muscle output, thereby yielding adaptive behavior.  From this unique, action-based perspective, consciousness is in the service of the somatic nervous system. How consciousness achieves this is more counterintuitive, ‘low level,’ and passive than the kinds of functions that theorists have attributed to consciousness.
Author Interviews, Autism, JAMA, OBGYNE / 25.06.2015

MedicalResearch.com Interview with: Ali S. Khashan, Ph.D. Irish Centre for Fetal and Neonatal Translational Research (INFANT) Cork, Ireland Medical Research: What is the background for this study? What are the main findings? Dr. Khashan: The Caesarean section rate is increasing worldwide reaching 30% in some western countries and 50% in China and Brazil. As a result, it is becoming increasingly important to understand the long-term effects this procedure may have on both mother and child. Previously, our group conducted a systematic review and meta-analysis of published literature and found birth by Caesarean to be associated with approximately 20% increased risk of autism spectrum disorder (ASD), compared to birth by vaginal delivery. This means if the risk of ASD in children born by vaginal delivery were 1%, and the association was causal, the risk of autism spectrum disorder in children born by Caesarean section is 1.2% i.e. two additional ASD cases per 1000 births. However, studies were limited, and we were unable to determine what was driving this association. In our new study, now published in JAMA Psychiatry, we investigated this issue further with the largest study on this subject to date, including all children born in Sweden between 1982 and 2010. Our study included data on over 2.9 million people and accounted for variety of factors known to be associated with both Caesarean section and autism spectrum disorder. After controlling for known confounders, such as maternal age and psychiatric history as well as various other perinatal and socio-demographic factors, we confirmed our previous findings that birth by Caesarean was associated with approximately 20% increased risk of autism spectrum disorder, compared to birth by vaginal delivery. However, with this analysis it remained unclear whether the increased risk was due to the Caesarean section itself, or some genetic or environmental factor that we were unable to measure. To determine if it was birth by Caesarean section or another unknown factor which led to an increased risk of ASD, we compared children with autism spectrum disorder to their non-diagnosed brothers and sisters. In other words, we analysed pairs of siblings in which one was diagnosed with ASD and one was not, to determine if birth by Caesarean was associated with increased risk of ASD within families. In this way, we attempted to indirectly account for genetic and family environment factors that are shared by siblings but we were unable to measure in the general population. In this analysis, which included data on over 13,000 sibling pairs, there was no longer any association between birth by Caesarean section and ASD. Overall, these results indicate that though birth by Caesarean section may be associated with an increased risk of ASD, it is likely due to family factors such as genetics or environment, rather than the Caesarean section itself. These findings are more informative than many previous studies as we had the largest sample size on this topic to date and estimated the association between Caesarean section and the risk of autism spectrum disorder while comparing siblings born by different methods of delivery. This allowed us to control for many factors that other studies did not.
Author Interviews, Brain Injury, Pediatrics, Sleep Disorders / 14.06.2015

MedicalResearch.com Interview with: Kimberly Allen PhD, RN Assistant Professor Center dr-kimberly-allenfor Narcolepsy, Sleep and Health Research Department Women Children and Family Health Science Chicago, IL 60612 Medical Research: What is the background for this study? Dr. Allen: Pediatric traumatic brain injuries (TBI) are a leading cause of morbidity and mortality worldwide.Each year in the United States over 1Ž2 million children are admitted to the hospital for traumatic brain injuries (TBIs). Depending on the severity of the injury and how the individual child responds to the primary injury, a range of medical care may be necessary from an overnight hospital admission for observation to admission in the intensive care unit (ICU) and inpatient rehabilitation facility to re-teach and help to recover skills children once knew. The short- and long-term consequences of traumatic brain injuries include: motor and sensory impairments; cognitive, emotional, psychosocial impairments; headaches, and sleep disruptions. Medical Research: What are the main findings? Dr. Allen: The main finding from this pilot study with two groups with 15 children in each group: one of children with traumatic brain injuries and one of typically, developing healthy children was that children with traumatic brain injuries have significantly more daytime sleepiness and worse sleep quality compared to the control group. Additionally, children with TBI also had lower overall  functional scores (e.g, school, social) compared to the controlled children. All of the surveys were completed by the child’s parent.
Author Interviews, Cognitive Issues / 12.06.2015

Dr. Li-Huei Tsai Ph.D. Professor and Director - Picower Institute For Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge, MA MedicalResearch.com Interview with: Dr. Li-Huei Tsai Ph.D. Professor and Director - Picower Institute For Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Medical Research: What is the background for this study? What are the main findings? Dr. Tsai: For a while now, we have been interested in observations made by many labs, including our own, that the accumulation of DNA lesions is a hallmark of the aging brain, and that mutations in DNA repair factors manifest in congenital and neurodegenerative disorders. However, the precise contribution of unrepaired DNA lesions to the development of neurological disorders remains poorly understood. A major confounding factor is that the sources that generate DNA lesions in the brain are not well characterized, and it is not known whether damage accumulates non-specifically throughout the genome, or whether there are certain regions that are more prone to accumulate DNA damage. In this regard, our study reports three major findings: (1) Physiological neuronal activity itself results in the formation of DNA breaks; (2) Neuronal activity-induced DNA breaks form at highly specific locations, including within the promoters of a subset of immediate early genes, including Fos, Npas4, and Egr1. These genes are also rapidly expressed in response to neuronal stimulation, and play crucial roles in experience-driven changes to synapses, and learning and memory; (3) Neuronal activity-induced breaks are generated by a topoisomerase, Topo IIβ, and Topo IIβ-generated DNA breaks facilitate the rapid expression of these immediate early genes following neuronal stimulation.
Author Interviews, Autism, Education / 10.06.2015

Annette Estes, Ph.D. Research Associate Professor of Speech and Hearing Sciences Adjunct Research Associate Professor of Psychology Director, University of Washington Autism Center Susan & Richard Fade Endowed Chair Center on Human Development and Disability University of WashingtonMedicalResearch.com Interview with: Annette Estes, Ph.D. Research Associate Professor of Speech and Hearing Sciences Adjunct Research Associate Professor of Psychology Director, University of Washington Autism Center Susan & Richard Fade Endowed Chair Center on Human Development and Disability University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Estes: Although a number of studies have shown the positive effects of early intervention on children’s abilities during the preschool period, there have been few studies to date that have followed children longitudinally to find out if these gains are sustained.  We found that two years after completing the intervention, children maintained their gains in cognitive and adaptive behavior skills and also showed a reduction in autism symptoms.  The results suggest that early intervention results in long term benefits for children across a wide range of skills.  Children who received the ESDM intervention as toddlers later showed fewer autism symptoms at school age. Medical Research: What should clinicians and patients take away from your report? Dr. Estes: Early intensive behavioral intervention has been found to be efficacious in improving developmental outcomes for young children with autism spectrum disorder. Children were able to maintain the developmental gains that they made in early, intensive, in-home intervention over a 2-year follow-up period. These children did not exhibit developmental regression or lose skills, even after substantial reductions in services. Intellectual, language, and adaptive functioning gains made as a result of early intervention may generalize to new domains of functioning, such as reduced Autism Spectrum Disorder symptom severity, 2 years later.
Author Interviews, Depression, Diabetes, Heart Disease, Pharmacology, Women's Heart Health / 08.06.2015

Dr. Karin Rådholm MD Ph.D. Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Department of Local Care West, County Council of Östergötland, Linköping, SwedenMedicalResearch.com Interview with Dr. Karin Rådholm MD Ph.D. student Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University Department of Local Care West, County Council of Östergötland, Linköping, Sweden MedicalResearch: What is the background for this study? Dr. Rådholm: Psychosocial risk factors and depressive disorders often co-occur with general medical comorbidities, such as myocardial infarction. Depression is more common in patients with diabetes than in patients without diabetes. About 10-30% of patients with diabetes have a comorbid depressive disorder, which is double the estimated prevalence of depression in individuals without diabetes. There is an association between comorbid depressive symptoms and diabetes complications. This is believed to be mainly due to poor adherence to treatment recommendations and diabetes self-management activities, but could also possibly be due to biological and behavioural causes that could predispose for both metabolic and affective disorders. The general risk of myocardial infarction is strongly dependent on age and sex, where men have an earlier disease onset compared to women. In the general population women are at much lower risk for ischemic heart disease mortality than men are. However, women with diabetes are at especially high risk for coronary heart disease, relatively more so than men with type 2 diabetes, meaning that the impact of diabetes on the risk of coronary death is significantly greater for women than men. The age- and gender-specific risk for myocardial infarction due to diabetes with coexistent depression has not previously been described. Data on all dispensed drug prescriptions in Sweden are available in the Swedish Prescribed Drug Register and all myocardial infarctions are registered in the Myocardial Infarction Statistics. These registers are population-based and have a total national coverage and high validity, which has been previously shown. Prescribed and dispensed antidiabetics and antidepressants were used as markers of disease. Our objective was to prospectively explore the gender- and age-specific risk of first myocardial infarction in people treated with antidiabetic and/or antidepressant drugs compared to participants with no pharmaceutical treatment for diabetes or depression in a nationwide register study.
Author Interviews, BMJ, Depression, Pediatrics / 03.06.2015

Dr. Lucy Bowes Ph.D Leverhulme Early Career Research Fellow Fellow of Magdalen College Department of Experimental Psychology University of Oxford OxfordMedicalResearch.com Interview with: Dr. Lucy Bowes Ph.D Leverhulme Early Career Research Fellow Fellow of Magdalen College Department of Experimental Psychology University of Oxford Oxford Medical Research: What is the background for this study? What are the main findings? Response: Major depression is a severe mental illness, and a leading contributor to the global burden of disease. Rates of depression begin to rise in the teenage years, though the reasons for this remain unclear. Peers become particularly important during this time, and victimisation by peers or “bullying” has been proposed as one potentially modifiable risk factor for depression. There are robust findings that peer victimisation in childhood is associated with short-term internalizing symptoms, however it remains unclear whether victimization in the teenage years is associated with major depression. Only a relatively small number of longitudinal studies have prospectively investigated victimisation in relation to depression meeting diagnostic criteria in late adolescence or adulthood. Limitations of these studies include poor measures of bullying, lack of adjustment for key confounders such as baseline emotional and behavioral difficulties and child maltreatment. Our prospective cohort observational study, published in The BMJ, used detailed self-report data on peer victimisation at 13 years from 6,719 participants of the ALSPAC or ‘Children of the 90s’ study. The outcome was depression at 18 years, measured using a self-administered computerised version of the Clinical Interview Schedule Revised, CIS-R (data available for 3,898 participants). We adjusted for a range of confounders including baseline emotional and behavioral problems, family background and other risk factors. Of the 683 children who reported frequent victimisation at 13 years, 101 (14.8%) were depressed at 18 years. Of the 1,446 children reporting some victimisation, 103 (7.1%) were depressed, and of the 1,769 children reporting no victimisation at 13 years, 98 (5.5%) were depressed. Children who were frequently victimized had over a two-fold increase in odds of depression compared with children who were not victimized by peers. This association was slightly reduced when adjusting for key confounders. The population attributable fraction suggested that 29% of depression at 18 could be explained by peer victimisation if this were a causal relationship.
Author Interviews, Cognitive Issues, Endocrinology, OBGYNE / 03.06.2015

Dr.Carey Gleason Ph.D School of Medicine and Public Health, University of Wisconsin Geriatric Research, Education and Clinical Center William S. Middleton Memorial Veterans Hospital Wisconsin Alzheimer's Disease Research Center, Madison, WisconsinMedicalResearch.com Interview with: Dr.Carey Gleason Ph.D School of Medicine and Public Health, University of Wisconsin Geriatric Research, Education and Clinical Center William S. Middleton Memorial Veterans Hospital Wisconsin Alzheimer's Disease Research Center, Madison, Wisconsin Dr. Gleason: In this response I refer to hormone therapy (HT), which was formally called hormone "replacement" therapy. In particular, we examined menopausal HT, i.e., the use of HT during the menopausal transition to address menopausal symptoms. Medical Research: What is the background for this study? What are the main findings? Dr. Gleason: The WHI Memory Study (WHIMS) suggested that HT was associated with cognitive harm for women age 65 and older. In contrast, we found that the cognitive performance of women randomized to receive menopausal hormone therapy did not differ from that of women randomized to receive the placebo. On a measure of mood states, women treated with conjugated equine estrogens showed improvements compared to those on placebo.
Author Interviews, Depression, End of Life Care, JAMA / 28.05.2015

Katherine Ornstein, PhD MPH Assistant Professor Brookdale Department of Geriatrics and Palliative Medicine Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1070 New York, NY 10029MedicalResearch.co Interview with: Katherine Ornstein, PhD MPH Assistant Professor Brookdale Department of Geriatrics and Palliative Medicine Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai New York, NY 10029 Medical Research: What is the background for this study? What are the main findings? Dr. Ornstein: There is an increased focus on the need to support caregivers and families, particularly at the End of Life (EOL). They play a critical role in the care process and decision making, yet this can be a very high stress role with an increased risk for negative consequences. Hospice services, which are increasing, are focused on palliative rather than curative care and include medical services, symptom management, spiritual counseling, social services and bereavement counseling delivered by an interdisciplinary team of professionals for dying patients.  An important part of the hospice service is the provision of support to families during illness and after death.  Prior research suggests that hospice (which is cost saving, has benefits to patients), may also  be beneficial to families. Yet these studies have been largely limited to patients with cancer, have failed to adequately control for differences between patients who do or do not use hospice. Overall, there was an increase in depressive symptoms after death.  However, surviving spouses of those who used hospice were more likely to have a decrease in depressive symptoms. We found that the positive benefit of hospice was much stronger when we looked at least 1 year after death.
Author Interviews, Cognitive Issues, Infections, PLoS / 24.05.2015

Dr. Michael Eriksen Benrós Mental Health Centre Copenhagen University of Copenhagen Faculty of Health Sciences Copenhagen NV, Denmark, National Centre for Register-based Research Aarhus University DenmarkMedicalResearch.com Interview with: Dr. Michael Eriksen Benrós Mental Health Centre Copenhagen University of Copenhagen Faculty of Health Sciences Copenhagen NV, Denmark, National Centre for Register-based Research Aarhus University Denmark Medical Research: What is the background for this study? Response: It is increasingly recognized that infections and immune responses can affect the brain and activate immunocompetent cells within the brain, influencing on neuronal signal transduction and possibly cognition. Impaired cognition has been observed in association with several infections and with elevated levels of CRP in smaller studies. Furthermore, experimental activation of inflammatory reactions in healthy volunteers has been shown to induce short-term reduced cognitive performance. Moreover, particularly patients with infection in the brain or sepsis have been shown to have affected cognition in long time periods after the infection has been cleared, thus infections might also have a longer lasting effect on cognition. However, large-scale longitudinal studies had been lacking on the association between infections and cognitive ability in the general population. Medical Research: What are the main findings? Response: Our study is the first large-scale study utilizing the extensive Danish registers to follow 190,000 males that had their IQ assessed at conscription, out of which 35% had a previous hospital contact with infection before the IQ testing was conducted. Our research shows a correlation between severe infections with a hospital contact and subsequent impaired cognition corresponding to an IQ score of 1.76 lower than the average. People with five or more hospital contacts with infections had an IQ score of 9.44 lower than the average. The study thus shows a clear dose-response relationship between the number of infections. Furthermore the effect on cognitive ability increased with the temporal proximity of the last infection and with the severity of the infection. Infections in the brain affected the cognitive ability the most, but many other types of infections severe enough to require a hospital contact where also associated with impairment of the cognitive ability.
Author Interviews, CDC, Mental Health Research, Occupational Health / 21.05.2015

Dr. Hope M. Tiesman MSPH, PhD CDC, AtlantaMedicalResearch.com Interview with: Dr. Hope M. Tiesman MSPH, PhD CDC, Atlanta Medical Research: What is the background for this study? What are the main findings? Dr. Tiesman: The authors regularly monitor non-occupational injury trends, including the recent and significant increase in suicide rates. This finding led the authors to consider how these non-occupational trends impacted the workplace. We used data for two large national surveillance systems.  We obtained data on workplace suicides from the Bureau of Labor Statistics' Census of Fatal Occupational Injury (CFOI) which compiles data on all fatal work-related injuries in the US.  We obtained data on non-workplace suicides from the CDC's Web-Based Injury Statistics Query and Reporting System or WISQARS. WISQARS data are compiled using national death certificate data.  From here we calculated suicide rates and compared trends across workplace and non-workplace suicides as well as examined the socio-demographics and occupational characteristics of those who chose suicide in the workplace. Several important findings to highlight.  Across the 8-yr timeframe, we found that workplace suicide rates remained relatively stable, even somewhat decreasing that it is until 2007 when a large and significant jump in rates was found.  This was in contrast with non-workplace suicide rates which increased over the entire study period.  Men had signifıcantly higher workplace suicide rates compared to women and generally, as age increased, so did workplace suicide rates.  Those aged between 65 and 74 years had the highest suicide rate of all workers which was also a bit different from non-workplace suicide rates.  Finally, we found that those in protective service occupations, such as police and firefighters, had the highest workplace suicide rates, followed closely by those in farming/fishing/and forestry occupations.  These occupations have been associated with higher overall suicide rates in prior studies.  A somewhat novel finding was that those in automotive maintenance and repair occupations also had significantly higher workplace suicide rates.
Alzheimer's - Dementia, Author Interviews, JAMA, Medical Imaging, UCSF / 20.05.2015

Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging CenterMedicalResearch.com Interview with: Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging Center MedicalResearch: What is the background for this study? Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database. MedicalResearch: What are the main findings? Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of 1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype), 2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and 3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”). The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials. In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect 1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or 2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander.
Author Interviews, Mental Health Research, Pediatrics, Race/Ethnic Diversity / 20.05.2015

Jeff Bridge, Ph.D Center for Innovation in Pediatric Practice Principal Investigator The Research Institute at Nationwide Children's HospitalMedicalResearch.com Interview with: Jeff Bridge, Ph.D Center for Innovation in Pediatric Practice Principal Investigator The Research Institute at Nationwide Children's Hospital Medical Research: What is the background for this study? Dr. Bridge: Suicide is a leading cause of death among children younger than 12 years. Suicide rates in this age group have remained steady overall for the past 20 years, but this is the first national study to observe higher suicide rates among black children compared to white children. Little is known about the epidemiology of suicide in this age group, as prior research has typically excluded children younger than 10 years old and investigated trends only within specific older age groups. Medical Research: What are the main findings? Dr. Bridge: We found that suicide ranked 14th as a cause of death among 5- to 11-year old black children in 1993-97 but rose to 9th in 2008-12. For white children, suicide ranked 12th in 1993-97 and 11th in 2008-12. Rates have remained stable in Hispanic and non-Hispanic children. The findings in this study highlight an emerging racial disparity in the epidemiology of childhood suicide.
Author Interviews, Brain Injury, JAMA, UT Southwestern / 18.05.2015

C. Munro Cullum, PhD, ABPP Professor of Psychiatry and Neurology & Neurotherapeutics Pamela Blumenthal Distinguished Professor of Clinical Psychology Chief of Psychology Director of Neuropsychology Univ. of Texas Southwestern Medical Center Dallas, TX 75390-9044 MedicalResearch.com Interview with: C. Munro Cullum, PhD, ABPP Professor of Psychiatry and Neurology & Neurotherapeutics Pamela Blumenthal Distinguished Professor of Clinical Psychology Chief of Psychology , Director of Neuropsychology Univ. of Texas Southwestern Medical Center Dallas, TX Medical Research: What is the background for this study? What are the main findings? Dr. Cullum: My colleague and principal investigator of the study, Dr. John Hart and I have been interested in the acute and longer-term effects of traumatic brain injury for years, and because of my roles in the Alzheimer’s Disease Center and the Texas Institute for Brain Injury and Repair at the University of Texas Southwestern Medical Center, it seemed like a natural to begin studying older individuals with and without cognitive disorder who have a history of traumatic brain injury.  Our main findings are two-fold: First, we demonstrated that a history of concussion with loss of consciousness (which make up only about 10% of all concussions) was associated with smaller memory centers in the brain (the hippocampus) and lower memory results in our sample of retired professional football players. Concussions that did not result in loss of consciousness did not show that same strong association. Second, our data suggest that patients with a clinical diagnosis of mild cognitive impairment (ie a memory disorder that does not grossly impair overall functioning but may lead to dementia) who also have a history of concussion with loss of consciousness show worse memory results and more brain atrophy than similar individuals diagnosed with mild cognitive impairment in the absence of a history of concussion.
Author Interviews, Bipolar Disorder, Depression, JAMA / 18.05.2015

MedicalResearch.com Interview with: Maaike M. M. Rive Program for mood disorders AMC/De Meren, Department of Psychiatry PA3.221 Amsterdam  The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: For clinicians, it can be difficult to distinguish whether a depressed patient suffers from major depressive disorder (characterized by depressive episodes only) or bipolar disorder (characterized by both depressive and (hypo)manic episodes). Differentiation between the two disorders is important because e.g. the treatment approaches are different. Although we know that both types of mood disorders are characterized by emotion regulation disturbances, little is known about differences in emotion regulation between the two disorders. Better insight in these differences would be helpful for differentiation between uni- and bipolar disorder. However, previous studies comparing these disorders often allowed medication use, and this may have influenced results. Furthermore, much is unknown about the effect of mood state on emotion regulation differences. We therefore investigated emotion regulation by showing happy, sad and fearful pictures to patients and healthy controls. Participants were instructed to either passively view the pictures, or to distance themselves from their feelings, by thoughts like: ‘this is only a picture’, ‘this will never happen to me’, etc. Emotion regulation success was measured by the difference between subjective ratings of emotional intensity after passive viewing versus distancing. Brain activity was measured with fMRI. The results of our study indicate that emotion regulation does indeed differ between medication-free major depressive or bipolar patients, and that specific differences depend on mood state. During remission, bipolar patients showed impaired emotion regulation across different types of emotions. In contrast, patients with major depressive disorder did not how such impairments during remission. During depression, patients differed regarding happy and sad emotion regulation: bipolar patients showed impaired sad, but unexpectedly normal happy emotion regulation, whereas in major depressive disorder, both sad and happy emotion regulation were compromised. These emotion regulation difficulties were associated with differences in brain activity in the dorsolateral prefrontal cortex (involved in effortful emotion regulation) and the rostral anterior cingulate cortex (connecting emotional and cognitive brain areas).