Author Interviews, JAMA, Mental Health Research, MRI, Neurological Disorders / 12.12.2015
Brains of Troubled Youth Demonstrate Key Grey Matter Changes
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Dr. De Brito[/caption]
MedicalResearch.com Interview with:
Stephane De Brito, PhD
Birmingham Fellow
School of Psychology
Robert Aitken Building, Room 337a
University of Birmingham UK
Medical Research: What is the background for this study? What are the main findings?
Dr. De Brito: In the last decade, an increasing number of neuroimaging studies have used structural magnetic resonance imaging (sMRI) to examine the brains of youths who show behavioural problems that include antisocial and aggressive behaviour. Those studies have mostly relied on a method called voxel-based morphometry (or VBM), which is a whole-brain and automated technique that allows researchers to objectively assess the local composition of brain tissue, such as grey matter volume. The main problem is that the findings from those sMRI studies have been quite disparate and few have been replicated, partly due to differences in sample sizes and characteristics across studies. Therefore, we set out to carry out a meta-analysis of the available data to provide a clearer account of the literature on this topic. A particular strength of our meta-analysis is that we used the original brain imaging maps (also referred to as statistical parametric maps) from 11 of the 13 studies, which makes our analysis more accurate and reliable. The final sample comprised of 394 youths with behavioural problems and 350 typically developing youths, making it the largest study on this topic to date.
Our results showed that, compared to typically developing youths, those with behavioural problems show reduced grey matter volume in the amygdala, the insula, and the prefrontal cortex. These brain areas have been shown to be important for decision-making, empathic responses, processing facial expressions and emotion regulation; key cognitive and affective processes that are shown to be deficient in youths with behavioural problems.
Dr. De Brito[/caption]
MedicalResearch.com Interview with:
Stephane De Brito, PhD
Birmingham Fellow
School of Psychology
Robert Aitken Building, Room 337a
University of Birmingham UK
Medical Research: What is the background for this study? What are the main findings?
Dr. De Brito: In the last decade, an increasing number of neuroimaging studies have used structural magnetic resonance imaging (sMRI) to examine the brains of youths who show behavioural problems that include antisocial and aggressive behaviour. Those studies have mostly relied on a method called voxel-based morphometry (or VBM), which is a whole-brain and automated technique that allows researchers to objectively assess the local composition of brain tissue, such as grey matter volume. The main problem is that the findings from those sMRI studies have been quite disparate and few have been replicated, partly due to differences in sample sizes and characteristics across studies. Therefore, we set out to carry out a meta-analysis of the available data to provide a clearer account of the literature on this topic. A particular strength of our meta-analysis is that we used the original brain imaging maps (also referred to as statistical parametric maps) from 11 of the 13 studies, which makes our analysis more accurate and reliable. The final sample comprised of 394 youths with behavioural problems and 350 typically developing youths, making it the largest study on this topic to date.
Our results showed that, compared to typically developing youths, those with behavioural problems show reduced grey matter volume in the amygdala, the insula, and the prefrontal cortex. These brain areas have been shown to be important for decision-making, empathic responses, processing facial expressions and emotion regulation; key cognitive and affective processes that are shown to be deficient in youths with behavioural problems.
Dr. Eileen Shinn[/caption]
MedicalResearch.com Interview with:
Dr. Eileen H. Shinn PhD
Assistant Professor, Department of Behavioral Science
Cancer Prevention and Population Sciences
MD Anderson Cancer Center
The University of Texas
Houston, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Shinn: Recent studies with leukemia, breast, lung, renal and liver cancer patients have shown that patients with depression have worsened survival. These effect sizes are small, but independent of any of the traditional factors that are known to impact survival, such as extent of cancer, types of treatment administered and baseline health and age of the patient. The current thinking is that cancer patients who are depressed have chronically heightened responses to stress; the constant release of stress hormones trigger changes in the tumor itself (such as noradrenergically-driven tumor angiogenesis) or may weakens the body’s immune function and ability to resist tumor growth.
When we measured depression in newly diagnosed patients with oropharyngeal cancer (cancer of the base of tongue and tonsil), we found that those patients who scored as depressed were 3.5 times more likely to have died within the five year period after their diagnosis, compared to nondepressed patients. We also found that patients who were depressed were also 3.8 times more likely to have their cancer recur within the first five years after diagnosis. We also found that patients who continued to smoke after diagnosis were more likely to recur within the first five years. These effect sizes were larger than those typically found in recent studies. We believe that the larger effect size may be due to the tight eligibility criteria ( e.g., we did not include patients who already had recurrent disease, we only included patients with one specific type of head and neck cancer, oropharyngeal) and also due to controlling other known factors (all patients completed individualized treatment regimens of radiation/ chemoradiation at a comprehensive cancer center and patients with more advanced disease stage were more likely to have received treatment intensification compared to patients with early stage disease). In all, we had 130 patients, one of the largest prospective studies with oropharyngeal cancer to examine the effect of depression on cancer outcome.
Dr. Frans Boch Waldorff[/caption]
Dr. Kevin Nead[/caption]
MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil
Dept. of Radiation Oncology
Perelman School of Medicine
University of Pennsylvania
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Nead: There are a growing number of studies suggesting that the use of Androgen Deprivation Therapy (ADT) may be associated with cognitive changes and some of these changes overlap with characteristic features of Alzheimer’s disease. In addition, low testosterone levels have been associated with Alzheimer’s disease risk and ADT lowers testosterone levels. Despite these findings, we could not identify any studies examining the association between ADT and Alzheimer’s disease risk. We therefore felt this study could make an important contribution in guiding future research to fully understand the relative risks and benefits of ADT.
We examined electronic medical record data from Stanford University and Mt. Sinai hospitals to identify a cohort of 16,888 patients with prostate cancer. We found that men with prostate cancer who received Androgen Deprivation Therapy were more likely to develop Alzheimer’s disease than men who did not receive
Dr. Douglas A. Mata Harvard Medical School[/caption]
Douglas A. Mata, M.D., M.P.H.
Anatomic and Clinical Pathology
Resident Physician, Brigham & Women’s Hospital
Clinical Fellow, Harvard Medical School
Boston, MA 02115
Marco A. Ramos, M.Phil., M.S.Ed.
History of Science and Medicine
M.D./Ph.D. Candidate, Yale School of Medicine
New Haven, CT 06511
Medical Research: What is the background for your study?
Dr. Mata: Training to be a doctor is clearly stressful, but the prevalence of depression among trainees is not well known. They may get especially depressed during their grueling years of residency, when young physicians are learning their craft by working long hours and taking care of critically ill patients. Coming up with a reliable estimate of the prevalence of depression among graduate medical trainees would help us identify causes of resident depression and begin to treat or prevent it. We thus aimed to find answers to two questions:
Halle Amick[/caption]
MedicalResearch.com Interview with:
Halle Amick, research associate
Sheps Center for Health Services Research
University of North Carolina at Chapel Hill
Chapel Hill, NC
Medical Research: What is the background for this study? What are the main findings?
Response: Major depressive disorder (MDD) affects more than 32 million Americans and millions more worldwide. Many patients first seek care from a primary care provider, and the most common treatment initiated in that setting is medication. Although there is an evidence base that shows certain psychotherapies to be effective treatments, primary care providers may not be familiar enough with psychotherapy to present it as a treatment option. We conducted a full review of clinical trials that compared antidepressant medication—specifically second-generation antidepressants (SGAs)—with cognitive behavioral therapy (CBT).
We found that symptom improvement and rate of remission were similar between SGAs and CBT, whether they were used alone or in combination with each other. We also found no difference in the rates of withdrawal from the clinical trials either overall or due to adverse events.
Dr. Jamie Stagl[/caption]
MedicalResearch.com Interview with:
Dr. Jamie Stagl, PhD
Was a Ph.D. student in Psychology at University of Miami during the research period
Currently, a post-doctoral fellow in Psychiatric Oncology
Massachusetts General Hospital Cancer Center in Boston
Medical Research: What is the background for this study? What are the main findings?
Dr. Stagl: This is a newly published finding from a randomized trial funded by the National Cancer Institute that showed that women with breast cancer who received stress management skills early on in their treatment had longer survival and longer time without breast cancer recurrence at eight to 15 years after their initial diagnosis. This secondary analysis is published online and in the November 2015 issue of Breast Cancer Research and Treatment.
The study was conducted by senior investigator, Michael Antoni, Ph.D., Survivorship Theme Leader of the Cancer Control research program at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and Professor of Psychology and Psychiatry and Behavioral Sciences, and his research team, including lead author Jamie Stagl, Ph.D., currently a postdoctoral fellow at Massachusetts General Hospital Cancer Center in Psychiatric Oncology and Behavioral Sciences.
In this trial, women received an intervention called Cognitive-Behavioral Stress Management, which was created by Dr. Michael Antoni at the University of Miami. After surgery for breast cancer, women received 10 weekly, group-based sessions of skills to manage stress based in
Dr. Elsa Suberbielle[/caption]
MedicalResearch.com Interview with:
Elsa Suberbielle, DVM, PhD
Research Scientist
Gladstone Institute of Neurological Diseases
San Francisco, CA 94158
Medical Research: What is the background for this study?
Dr. Suberbielle: BRCA1 is a key protein involved in DNA repair, and mutations that impair its function increase the risk for breast and ovarian cancer. Research into DNA repair mechanisms in dividing cells recently was recently rewarded by the Nobel Prize in Chemistry. In such cells, BRCA1 helps repair a type of DNA damage known as double-strand breaks that can occur when cells are injured. In neurons, though, such breaks can occur even under normal circumstances, for example, after increased brain activity, as shown by the team of Gladstone scientists in an
Dr. Haque[/caption]
MedicalResearch.com Interview with:
Reina Haque, PhD, MPH
Research scientist
Department of Research & Evaluation
Kaiser Permanente Southern California
Pasadena Calif
Medical Research: What is the background for this study? What are the main findings?
Dr. Haque: Tamoxifen is a commonly prescribed generic drug taken by women with breast cancer to reduce their chances of developing a recurrence. Tamoxifen is recommended for five years, but has notable side effects, including hot flashes, night sweats and depression. Since hormone replacement therapy is not recommended to alleviate these symptoms in breast-cancer survivors, antidepressants have been increasingly prescribed for relief. Almost half of the 2.4 million breast-cancer survivors in the U.S. take antidepressants.
However, previous studies have suggested that antidepressants reduce tamoxifen's effectiveness in lowering subsequent breast-cancer risk. This study was conducted to determine whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer.
Kevin Bieniek[/caption]
MedicalResearch.com Interview with:
Kevin Bieniek B.Sc.
Biology and Psychology
Neuroscience researcher
Mayo Clinic’s campus in Florida.
Medical Research: What is the background for this study? What are the main findings?
Response: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury often sustained through contact sports and military blast exposure. While CTE was first described in boxers in the 1920s, to date many descriptions of CTE have been made in high-profile professional athletes, but the frequency of Chronic traumatic encephalopathy pathology in athletes with more modest contact sports participation is unknown. For this study, researchers at the Mayo Clinic in Jacksonville, FL examined the Mayo Clinic Brain Bank, one of the largest brain banks of neurodegenerative diseases. In searching through medical records of over 1,700 patients, 66 individuals with clinically-documented contact sports participation were identified. Of these 66 former athletes, 21 or 32% had pathologic changes in their brains consistent with CTE. By comparison, none of 198 control individuals that did not have contact sports documentation in their medical records (including 66 women) had CTE pathology. These results have been recently published in the December issue of the journal Acta Neuropathologica <<hyperlink:
Dr. Storebø[/caption]
MedicalResearch.com Interview with:
Dr. Ole Jakob Storebø
Region Zealand, Child and Adolescent Psychiatric Department, Roskilde
Region Zealand Psychiatry
Psychiatric Research Unit, Slagelse
University of Southern Denmark
Department of Psychology
Faculty of Health Science,
Odense Denmark
Medical Research: What is the background for this study? What are the main findings?
Dr. Storebø: Despite widespread use of methylphenidate for the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD), a comprehensive systematic review of its benefits and harms has not yet been conducted. Over the past 15 years, several reviews investigating the efficacy of methylphenidate for ADHD (with or without meta-analyses) have been published. Each of these reviews, however, has several shortcomings and these are described in detail in the review. The most important concerns are that none of these reviews are based on a pre-published protocol, and most assessed neither the risk of bias (systematic errors) of included trials nor adverse events. Moreover, none of these reviews considered the risk of random errors. Therefore, their interpretation of findings is unlikely to have taken into account the poor reporting of adverse events, the impact of combining data from small trial samples, or the impact of risk of bias on their analyses; information about adverse events is also missing from several RCTs. Because of this it is our opinion that these previous reviews might have overestimated the true treatment effect.
We found that Methylphenidate may improve ADHD symptoms, general behaviour and quality of life in children and adolescents aged 18 years and younger with ADHD. We rated the evidence to be of very low quality and, as a result, we cannot be certain about the magnitude of the effects from the meta-analyses. The evidence is limited by serious risk of bias in the included trials, under-reporting of relevant outcome data, and a high level of statistical variation between the results. We found no evidence for serious adverse events, but a lot of non-serious adverse events. Most of these are well known but the number of adverse events might even be higher than the number we found due to underreporting of adverse events. We know very little about the long term effects or harms as most of the trials in our review did not measure outcomes beyond 6 months. The risk of rare, serious adverse events seem low over the short duration of follow-up of the trials that reported on harms, but in general there was inadequate reporting of adverse events in many trials.
Ms. Mewborn[/caption]
MedicalResearch.com Interview with:
Catherine Mewborn, B.A.
Neuropsychology and Memory Assessment Laboratory
Department of Psychology
University of Georgia
Medical Research: What is the background for this study?
Response: Vision and cognitive functioning both tend to decline as individuals age. Processing speed, or the speed at which an individual can process information, is particularly vulnerable to age-related declines. In previous studies, cognition has typically been measured using traditional paper-and-pencil tests; however, these tests can be quite complex and recruit many different abilities. We wanted to use a simpler test to assess processing speed in the hopes of tapping into the more basic abilities that underlie performance on more complex cognitive tasks. For this study, we chose a measure of visual processing speed called critical flicker fusion, or CFF. We tested how well CFF could predict cognition in both younger and older adults.
Medical Research: What are the main findings?
Response: As expected, younger adults had better visual processing speed than older adults. Interestingly, in both age groups, CFF significantly predicted performance on a test of executive functioning, which assess abilities such as problem-solving and shifting attention between different tasks.
Dr. Nesper[/caption]
MedicalResearch.com Interview with:
Arica Nesper, MD, MAS
Resident Physician
Stanford/Kaiser Emergency Medicine Residency
Stanford University Medical Center
Department of Emergency Medicine
Stanford
Medical Research: What is the background for this study? What are the main findings?
Dr. Nesper: Patients with severe mental illness are a distinct demographic in the emergency department. Unfortunately, resources to help these vulnerable patients are frequently the target of funding cuts. We aimed to describe the effect of these cuts on our emergency department and the care provided to our patients. In this study we evaluated data from before our county mental health facility cut its inpatient capacity by half and closed its outpatient unit, and compared this data with data collected after this closure. We found that the mean number of daily psychiatric consultations in our emergency department more than tripled and that the average length of stay for these patients increased by nearly eight hours. These two data combined demonstrate a five-fold increase in daily emergency department bed hours for psychiatric patients, placing a significant strain on the emergency department and demonstrating a delay in definitive care provided to these vulnerable patients.
Dr. Kenworthy[/caption]
MedicalResearch.com Interview with:
Lauren Kenworthy, PhD
Associate professor of Neurology, Pediatrics, and Psychiatry
George Washington University School of Medicine
Director of the Center for Autism Spectrum Disorders
Children’s National Health System
Medical Research: What is the background for this study? What are the main findings?
Dr. Kenworthy: Connectivity among brain regions may account for variability in autism outcomes not explained by age or behavioral measures, according to a study. We have previously shown that behavioral assessments of intelligence, baseline adaptive behavior and executive functions in people with autism can explain some of the variation in outcomes and function, but we have not been able to explain all of the variance in outcome (e.g. Pugliese et al 2015a, 2015b).
In this study, we found that 44% of the study group experienced significant change in scores on adaptive behavior between the initial scan and follow-up. Connectivity between three resting-state networks, including the salience network, the default-mode network, and the frontoparietal task control network, was linked not only to future autistic behaviors but also to changes in autistic and adaptive behaviors over the post-scan period. Further, connectivity involving the salience network and associated brain regions was associated with improvement in adaptive behaviors, with 100% sensitivity and around 71% precision.
Dr. Raymond Lam[/caption]
MedicalResearch.com Interview with:
Raymond W. Lam, MD, FRCPC
Professor and Associate Head for Research
Department of Psychiatry, University of British Columbia
Director, Mood Disorders Centre, Djavad Mowafaghian Centre for Brain Health
Executive Chair, Canadian Network for Mood and Anxiety Treatments (CANMAT)
Vancouver, BC, Canada
Medical Research: What is the background for this study?
Dr. Lam: Our multicentre team studied the effects of bright light therapy for nonseasonal depression. Light therapy is a non-pharmacological approach that has been studied as a treatment for seasonal affective disorder (SAD, or "winter depression"), but only a small number of studies has explored the use of light therapy in treating nonseasonal depression.
Clinical depression, known formally as Major Depressive Disorder (MDD) is the most common psychiatric disorder and one of the most common medical conditions worldwide. At any given time, at least 1 person in 20 (5% of the general population) is experiencing MDD, which will become the second-leading cause of disability worldwide by 2020, according to the World Health Organization.
MedicalResearch.com Interview with:
Claudia van Borkulo, MSc
University of Groningen, University Medical Center Groningen
Department of Psychiatry,
Research School of Behavioural and Cognitive Neurosciences,
Interdisciplinary Center for Psychopathology and Emotion Regulation,
Groningen, the Netherlands
Medical Research: What is the background for this study? What are the main findings?
Response: We consider psychiatric disorders as complex dynamical systems in which symptoms can interact with each other. This novel network approach to psychopathology – that is new to psychiatry – implies that a more densely connected network of symptoms of a disorder might be indicative of worse prognosis. Having one symptom can easily lead to developing more symptoms in a densely connected network, in which more symptoms reinforce each other. Reversely, a symptom in a less densely connected network will rarely turn on other symptoms. A densely connected network can theoretically be related to an increased vulnerability; because of the high level of mutual reinforcement, a small external stressor can induce a quicker transition from a healthy state to a depressed state for people with a more densely connected network.
In our study, we investigated the association between baseline network structure of
Dr. Chui[/caption]
MedicalResearch.com Interview with:
Helena Chui, Ph.D.
CPsychol Lecturer Division of Psychology
University of Bradford
Bradford England
Medical Research: What is the background for this study? What are the main findings?
Dr. Chui: It is debatable whether psychological well-being improves or declines with age. Findings of the age-related changes in psychological well-being, life satisfaction, and depressive symptoms, are not unequivocal. Some studies have found that people stay pretty stable in terms psychological well-being until late life. Other studies have found otherwise. My recent publication reports the findings using a 15-year longitudinal study from Australia. Results showed that as people get older, depressive symptoms increase. Both men and women reported increasingly more
MedicalResearch.com Interview with:
Shahrzad Mavandadi, PhD
Research Health Science Specialist and Investigator
Veterans Integrated Services Network 4 Mental Illness Research,
Education, and Clinical Center
Corporal Michael J. Crescenz Veterans Affairs Medical Center
Philadelphia, Pennsylvania
Medical Research: What is the background for this study?
Dr. Mavandadi: Mental health (MH) conditions are underidentified and undertreated in later life. This is particularly true among subgroups of older adults who are more vulnerable to developing mental health issues, have poor access to specialty care, and are less responsive to treatment and therapy. Thus, we sought to evaluate longitudinal MH outcomes among low-income, community-dwelling older adults enrolled in an evidence-based, collaborative mental health care management service (i.e., the SUpporting Seniors Receiving Treatment And INtervention (SUSTAIN) program). The SUSTAIN program integrates mental health with primary care (which is where the majority of behavioral health conditions in later life are managed) and provides standardized, measurement-based, software-aided MH assessment and connection to community resources to older adults by telephone.
While there is a strong evidence base for the efficacy of collaborative care models for me conditions, little is known about the amount or level of patient and provider support that is needed to achieve optimal behavioral health outcomes. Thus, we specifically examined outcomes among older adults randomized to one of two program arms of varying intensity: MH symptom monitoring alone or
Dr. Gulden[/caption]
MedicalResearch.com Interview with:
Dr. Mai-Britt Guldin PhD
Department of Public Health
Aarhus University
Medical Research: What is the background for this study?
Dr. Guldin: The background for this study is that death of a parent in childhood is experienced by 3-4% of children in Western societies, and we know such a loss is one of the most stressful and potentially harmful events in childhood. Therefore, we aimed to investigate how parental death may influence the long-term risk of suicide and how this risk differes by cause of parental death, age at loss, sex of child, socioeconomic factors and parental history of psychiatric illness.The sample size in this study is unparalleled by other studies on risk of suicide.
Medical Research: What are the main findings?
Dr. Guldin: The main findings were that in a population of 7.302,033 (in three Scandinavian countries), we identified 189,094 persons who lost a parent before the age of 18. Of these bereaved persons, 265 died from suicide. Compared to a control group of persons matched by age and sex, but who did not lose a parent before the age of 18, suicide was twice as common in the bereaved cohort (IRR = 2.02; 95% CI, 1.67-2.44). The risk remained high for at least 25 years of follow-up. The risk was particularly high for children who lost a parent due to suicide, but was also high for children who lost a parent due to other causes. The risk tended to be particularly high for boys who lost a mother and children losing a parent before the age of six.
Dr. Vonberg[/caption]
MedicalResearch.com Interview with:
Frederick W. Vonberg, MA, MBBS
Research Fellow in Neurocritical Care
Boston Children's Hospital and Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Response: An association between schizophrenia and epilepsy has long been suspected, ever since people noticed similarities in some aspects of the presentation of the two conditions, and in their epidemiology. For example, people with epilepsy are thought to be more at risk of developing schizophrenia. Furthermore, a psychosis resembling schizophrenia can characterize some forms of
Dr. Molnar[/caption]
MedicalResearch.com Interview with:
Miklos Z Molnar, MD, PhD, FEBTM, FERA, FASN
Associate Professor of Medicine
Division of Nephrology, Department of Medicine
University of Tennessee Health Science Center
Memphis, TN, 38163
Medical Research: What is the background for this study? What are the main findings?
Dr. Molnar: We examine the association between presence of depression and all-cause mortality; incident Coronary Heart Disease (CHD) (new onset AMI, CABG or PCI), incident ischemic stroke, slopes of eGFR (OLS, <-5 vs ≥-5 ml/min/1.73m2/yr) in 933,211 diabetic (based on ICD9, medication and HbA1c ≥ 6.5%) US Veterans with eGFR ≥ 60 ml/min/1.73m2 at baseline. We adjusted for independent covariates, collected from VA databases, such as age, gender, race, BMI, marital status, income, service connection, comorbid conditions (ICD9), baseline eGFR, serum albumin.
Mean age was 64±11 years, 97% were male and 18% African-American. Depression was present in 340,806 (37%) patients at enrollment. During a median follow-up of 7.3 years, 180,343 patients (19%) developed Chronic Kidney Disease (CKD).AS (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: 1.20 (1.19-1.21)). Similarly, depression was associated with 35% higher risk of incident stroke (aHR and 95% CI: 1.35 (1.32-1.39), 24% higher risk of incident CHD (aHR and 95% CI: 1.24 (1.22-1.27) and 25% higher risk of all cause mortality (aHR and 95% CI: 1.25 (1.24-1.26) during the follow-up.



