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May 24, 2011
12:51 AM
836 views

U.S. Tornado Deaths: Limits of Technology (Updated)

by William Yates, M.D. in Brain Posts

An earlier draft of this article first published as Tornado Deaths and the Limits of Tornado-Related Technologies onTechnorati.Deaths in the southeastern United States related to the April 27, 2011 tornadoes and the tornado deaths in Joplin, Missouri prompt an examination of tornado safety. A key question is whether modern tornado detection and warning technology significant reduces risk of tornado-related death.Storm and tornado tracking technology has exploded over the last 30 years. Doppler radar technology continues to improve and national and regional news channels trumpet their own systems with names such as SkyTraK DopplerMax, First Alert Mega Doppler Radar and Doppler 9000 HD. Local news stations in the the midwestern and southern U.S. regions frequently break into regular programming to alert viewers to potential dangerous storms and tornado watches.In 1982, The Weather Channel started broadcasting in the United States. This 24 hour channel monitors severe weather across the U.S. providing access to instant weather information.But what has been the effect of these tornado technologies in the trends for tornado-related deaths? The trends to do not appear to support these technologies in their ability to reduce tornado-related death. Below is a plot of the yearly number of tornado-related deaths in the U.S. between 1950 and 2011 (year-to-date) from data published by the U.S. National Oceanic and Atmospheric Administration. Tornado-related deaths have dropped dramatically in the United States but the biggest declines occurred between 1925 and 1980. Between 1875 and 1925, the U.S. averaged nearly two deaths per million residents. Since 1980, the U.S. death rate has averaged around .2 deaths per million people. This is around a 90 per cent decrease and a significant advance in publichealth safety. health safety.The problem for tornado technology advocates is the trend in tornado-related deaths between 1980 and 2011. The over 420 deaths in the recent southeastern U.S. tornado and the deadly tornado in Joplin, Missouri make 2011 already one of the top two years for tornado deaths in the U.S. since 1950. The number of deaths so far in 2011 is topped by only by 1953 . Yearly death rates vary significantly and should be corrected for total population to compare trends. Taking a look at the rates of tornado-related deaths per decade per million population finds the following results in the last six decades:Decade Total Deaths Deaths/Million1950s 1419 8.61960s 942 4.91970s 998 4.71980s 522 2.2... Read more »

Ashley, W. (2007) Spatial and Temporal Analysis of Tornado Fatalities in the United States: 1880–2005. Weather and Forecasting, 22(6), 1214-1228. DOI: 10.1175/2007WAF2007004.1

Simmons, K., & Sutter, D. (2005) WSR-88D Radar, Tornado Warnings, and Tornado Casualties. Weather and Forecasting, 20(3), 301-310. DOI: 10.1175/WAF857.1

Brooks, Harold E. (2002) Deaths in the 3 May 1999 Oklahoma City Tornado from a Historical Perspective. Weather and Forecasting. info:/

Eidson M, Lybarger JA, Parsons JE, MacCormack JN, & Freeman JI. (1990) Risk factors for tornado injuries. International journal of epidemiology, 19(4), 1051-6. PMID: 2083989

May 23, 2011
09:03 AM
1,053 views

Neuroethics: The Brain and Political Beliefs

by William Yates, M.D. in Brain Posts

Article first published as Brain Science and Political Belief on Technorati.Brain science is providing some important insights into the mechanisms involved in a variety of beliefs including political, religious and moral beliefs. Dr. Jordan Grafman, Ph.D. currently with the Kessler Foundation has led some of the key research initiatives in this area of brain research. He recently presented at the May, 2011 Warren Frontiers in Neuroscience lecture series in Tulsa, Oklahoma. I previously posted a summary of work relevant to the brain science and moral beliefs and a separate post on religious beliefs. Here are some of the key points from his presentation related to political beliefs and relevant published research manuscripts.A important starting point in understanding how the brain processes political beliefs is to discover key elements of these beliefs. The classical description of political beliefs defines individuals long a single criterion domain, conservative to liberal. But statistical modeling of large numbers of individuals demonstrates three key domains for political belief. These domains appear somewhat independent of each other and appear to engage different brain neural circuits. The three domains and localized areas the brain involved include:• individualism--medial prefrontal cortex and the temperoparietal junction• conservatism-dorsolateral prefrontal cortex• radicalism-ventral striatum and posterior cingulateSo how does brain circuitry differ between those who are interested in politics compared to those with little interest in the area? Grafman while at his previous NIH position and colleagues from Italy as well as George Mason University in the U.S. examined this question in a series of 25 subjects using functional magnetic imaging scanning technology.Subjects in the scanner were asked to agree or disagree with a variety of political opinions. Subjects who were interested in politics showed significantly more activation of the brains regions in the amygdala and ventral striatum. Subjects disinterested in politics showed limited activations in these regions regardless of the content of religious beliefs encountered.The amygdala has been demonstrated to be an important region for processing both positive and negative emotional stimuli. The ventral striatum appears to be a key region in processing reward and positive affect.The research suggests those with strong political interests, i.e. "political junkies" engage brain circuits involved in emotional and reward reinforcement. Similar circuits appear to be engaged in other individuals by chemical as well and specific environmental stimuli. For example, similar circuits may be activated by religious stimuli in those with strong religious beliefs.It is unknown exactly how the brain influences each individuals selection of an area of interest and engagement. We do not know why one individual is drawn to a field of technical interest, i.e. computer science rather than a field of social interest such as politics.... Read more »

Zamboni G, Gozzi M, Krueger F, Duhamel JR, Sirigu A, & Grafman J. (2009) Individualism, conservatism, and radicalism as criteria for processing political beliefs: a parametric fMRI study. Social neuroscience, 4(5), 367-83. PMID: 19562629

Gozzi M, Zamboni G, Krueger F, & Grafman J. (2010) Interest in politics modulates neural activity in the amygdala and ventral striatum. Human brain mapping, 31(11), 1763-71. PMID: 20162603

May 21, 2011
12:12 PM
1,064 views

Economic Distress and Suicide: Japan and U.S.

by William Yates, M.D. in Brain Posts

My colleagues and I are presenting a new research poster presentation this week at the 2011 American Psychiatric Association meeting in Honolulu. I wanted to use this post to summarize some of the current research related to our presentation as well as highlight the findings from our poster.Over the last few years, I have had the opportunity to meet yearly with a group of Japanese and American researchers and psychiatrists in a retreat setting in Itasca State Park in Minnesota. This group has recently been named the Itasca Brain and Behavior Association. The goal of the group is to promote international research collaboration in clinical neuroscience and areas of psychosomatic medicine.I learned from my Japanese colleagues last year that suicide rates in Japan increased significantly around 1998--a increase that has continued now for the last 12 years. The figure below documents the trend in suicide rates in Japan as well as the U.S. Suicide rates increased to a larger percent in males (47%) compared to females (23%) in this period. My Japanese colleagues reported that psychological autopsy information suggested unemployment and divorce as common factors felt to be contributing to this increased rate of suicide. Epidemiological work has now supported a link between regional unemployment in Japan and increased rates of suicides.Japan has experience a prolonged economic malaise since 1998. Several sources have suggested the U.S. and Japanese economic cycles may be similar with the U.S. trailing the pattern in Japan by 10 to 15 years. Unemployment began increasing in Japan in 1998 and jumped dramatically in the U.S. beginning in 2008. The housing bubble in Japan peaked in 1996 and in the U.S. peaked in 2008. The possibility that the U.S. is entering a prolonged economic downturn similar to Japan raises the question of the mental health and suicide rate response. Is the U.S. vulnerable to an increased rate of suicides similar to that found in Japan? If so, what would a similar response look like and could mental health clinicians and public health officials do anything to reduce of minimize this type of risk.Our research focused on looking at the age and gender distribution of increased rates of suicide in Japan and applying those rates to the U.S. population based on the 2010 Census. The baseline number of suicides in the U.S. average around 33,000 per year. If suicide rates were to increase to the magnitude found in Japan, the number of increased suicides in the U.S. would be about 14,000 per year. Interestingly, our model found that approximately 90% of the increased number of suicides would occur in men as men have higher baseline rates and experienced a greater increase in Japan after 1998.A recent manuscript published in the American Journal of Public Health looked at suicide rates in relation to economic cycles between 1929 and 2007. This analysis suggested that suicide rates in the U.S. do vary with economic cycles and need to be consider in public health planning.The presence of a primary psychiatric disorder (major depression, bipolar disorder, schizophrenia, substance dependence) is the primary determinant of risk for suicide. Our research does not predict a dramatic increase in suicide rates but rather is a warning to U.S. clinicians and public health officials. The take home messages from our collaborative research would be:The U.S. should be alert for the potential for economic crisis and unemployment to increase risk of suicide deathsElevated risk for suicide related to unemployment appears highest in middle to older aged men Adults with pre-existing mental disorders losing there job may also lose prescription benefits as well as re-imbursement for mental health services. Efforts should be made to identify these individuals and provide alternate pathways to mental health careEmployers should examine the support services provided those involved in layoffs with an effort to provide psychiatric and psychological services to these vulnerable populations Link to Copy of APA Poster is Here.Chang SS, Gunnell D, Sterne JA, Lu TH, & Cheng AT (2009). Was the economic crisis 1997-1998 responsible for rising suicide rates in East/Southeast Asia? A time-trend analysis for Japan, Hong Kong, South Korea, Taiwan, Singapore and Thailand. Social science & medicine (1982), 68 (7), 1322-31 PMID: 19200631... Read more »

Chang SS, Gunnell D, Sterne JA, Lu TH, & Cheng AT. (2009) Was the economic crisis 1997-1998 responsible for rising suicide rates in East/Southeast Asia? A time-trend analysis for Japan, Hong Kong, South Korea, Taiwan, Singapore and Thailand. Social science , 68(7), 1322-31. PMID: 19200631

Luo F, Florence C, Quispe-Agnoli M, Ouyang L, & Crosby A. (2011) Impact of Business Cycles on US Suicide Rates, 1928-2007. American journal of public health. PMID: 21493938

May 12, 2011
08:09 AM
1,300 views

Ecstasy Designer Drug 2C-E and a Death in Oklahoma

by William Yates, M.D. in Brain Posts

Chemical Structure 2C-EIf you are a parent of a teenager I hope you took chemistry in high school or college because you are going to need it. The reason you are going to need it is the emergence of designer drugs of abuse. Designer drugs typically have a parent compound that is chemically modified. There are two key reasons to modify existing illegal compounds: 1.) the new compound may not be illegal until state and federals laws can be modified and 2.) the new compound may have potent psychoactive effects.Unfortunately, some effects of the designer drugs may not be so beneficial. A young adult Oklahoma woman died recently after ingesting a designer drug known as 2C-E. Additionally, seven young adults at the same party were hospitalized for adverse effects. The number and type of designer drugs is pretty extensive. The parent compounds for some of these designer drugs include marijuana (tetrahydrocannabinol), ecstasy (MDMA), PCP and the opiate drug fentanyl. 2C-E is a designer drug derived from phenethylamine.Deaths due to ecstasy use are uncommon. Many deaths in ecstasy users occur in the context of alcohol and other drug use making the specific contribution from ecstasy unclear. MDMA may contribute to risk of death through seizure, cardiac arrhythmia, hyperthermia or water intoxication. MDMA may cause inappropriate release of the endogenous hormone ADH (antidiuretic hormone) that can cause low serum sodium, brain edema and death via water intoxication.Given the acute toxic effects on multiple users of 2C-E in Oklahoma, the potential for toxic contaminants will need to be explored. 2C-E is thought to block the 5-HT2A (serotonin) receptor. There is some evidence this effect is potentiated in those taking a selective serotonin reuptake inhibitory antidepressant drugs like Prozac. Some of these designer drugs can be ordered online. There is essentially no safety data so users are the defacto guinea pigs. Autopsy results in the Oklahoma death will not be known for weeks.Here is a listing of the compounds listed by parent compound type from a recent research review that explored the metabolism of these compounds.2C phenethylamine compounds(2C-B), 4-bromo-2,5-dimethoxy-beta-phenethylamine(2C-I), 4-iodo-2,5-dimethoxy-beta-phenethylamine(2C-D), 2,5-dimethoxy-4-methyl-beta-phenethylamine(2C-E), 4-ethyl-2,5-dimethoxy-beta-phenethylamine(2C-T-2), 4-ethylthio-2,5-dimethoxy-beta-phenethylamine and(2C-T-7) 2,5-dimethoxy-4-propylthio-beta-phenethylamineBeta-keto designer drugs (butylone, bk-MBDB), 2-methylamino-1-(3,4-methylenedioxyphenyl)butan(ethylone, bk-MDEA), 1-one2-ethylamino-1-(3,4-methylenedioxyphenyl)propan(methylone, bk-MDMA) 2-methylamino-1-(3,4-methylene notdioxy notphenyl)propanpyrrolidino notphenones(MPBP) 4-methyl-pyrrolidinobutyrophenone(PVP) alpha-pyrrolidinovalerophenone(PCPr) N (1 phenylcyclohexyl) propanaminephencyclidine (PCP)-derived drugs(PCEEA),N-(1-phenylcyclohexyl)-2-ethoxyethanaminePCMPA), N-(1-phenylcyclohexyl)-3-methoxypropanamine(PCMEA), (N-(1-phenylcyclohexyl)-2-methoxyethanamine... Read more »

Meyer MR, & Maurer HH. (2010) Metabolism of designer drugs of abuse: an updated review. Current drug metabolism, 11(5), 468-82. PMID: 20540700

May 11, 2011
10:48 AM
984 views

Women's Health: Illness and Prevention

by William Yates, M.D. in Brain Posts

A previous version of this article first published as Women's Health: Survey Highlights Illnesses, Care and Prevention onTechnorati.The Henry J. Kaiser Family Foundation recently published their Women's Health Care Chartbook--Key Findings from the Women's Health Survey. This report provides a snap shot of women's health in the U.S. Chapters in the Chartbook cover a Profile of Women's Health, Health Coverage, Delivery System, Prevention and Screening, Access and Affordability and Work, Family and Caregiving.Here are some of the highlights from the report:The most common chronic health conditions reported by women in the survey include: arthritis 22%, hypertension 22%, high cholesterol 20%, obesity 16%, asthma/other respiratory disorder 15%, thyroid disorders 11%, diabetes 9%, and heart disease 5%.Depression and anxiety problems are common. Twenty six percent of women in the survey report being diagnosed with depression or anxiety in the past five years by a physician. Depression and anxiety diagnosis is highest in women between 45 and 64, white women and women at less than 200% of the poverty income level. The leading causes of self-reported stress by women include: financial concerns 26%, job/career 23%, health problems of family member 16% and managing own health needs 13%.Rates of going without health insurance for at least the past four years rose to 27% of all women in 2008 compared to 20% in 2004.Use of mental health care in the last year was endorsed by 12% of all women in the survey. This rate increased to 21% in those who reported their health status as fair or poor.Seventy five percent of women reported receiving a mammogram in the past two years. Pap smear, blood pressure screening and blood cholesterol screening were also reported by a majority of women. However, only 40% of women over age 50 reported receiving colon cancer screening in the last two years.A recently published CDC survey of preventive health screening confirms low rates for colon cancer screening in women. The chart shows the percentage of women between 50 and 75 who were screened for colon cancer by one of three criteria: Fecal occult blood test in last year orFlexible sigmoidoscopy in last 5 years orColonoscopy in last 10 yearsThis lack of screening shows significant geographic variability. The chart shows the highest rates for colon cancer screening are in the northeast with the lowest rates in the south and western U.S.Percent of U.S. Women 50 to 75 Screened for Colon CancerWomen commonly reported delaying or going without care due to a variety of reasons. The most commonly reported reasons for delaying or going without care were: couldn't find the time 23%, couldn't take time off work 18%, no insurance 15%, child care problems 13%, and no doctor 13%.... Read more »

Henley SJ, King JB, German RR, Richardson LC, Plescia M, & Centers for Disease Control and Prevention (CDC). (2010) Surveillance of screening-detected cancers (colon and rectum, breast, and cervix) - United States, 2004-2006. MMWR. Surveillance summaries : Morbidity and mortality weekly report. Surveillance summaries / CDC, 59(9), 1-25. PMID: 21102407

May 5, 2011
08:52 AM
1,144 views

Neuroethics: The Brain and Religious Beliefs

by William Yates, M.D. in Brain Posts

This is the second in a series of three posts looking at how the brain processes complex beliefs in the domains of morality, religion and politics. Jordan Grafman, Ph.D. presented at the May 3, 2011 Warren Frontiers of Neuroscience lecture series in Tulsa, Oklahoma. Grafman summarized research he had conducted in these three domains. An fMRI study published in PNAS in 2009 outlined some of Grafman’s research team efforts related to brain processes and religion. In the introduction of this study manuscript, they cite work from the Baylor Institute of Religion survey on religious beliefs in the United States. This survey data appears to support three distinct elements of religious belief: God’s perceived level of involvement: a dimension ranging from a strong feeling of God’s (or a supernatural force) being involved in life to feeling that there is no purpose in life or God is far removed from the worldGod’s perceived emotion: whether one perceives a God or supernatural force as positive (forgiving, protecting) or negative emotionally (angry, punishing).Religious knowledge-a factor that can be sub-divided into doctrinal religious knowledge and experiential knowledge (i.e. personal experience with prayer or attending church) Participants in the fMRI study were recruited for having a wide range in the ratings on the three distinct elements of religious belief. They were then scanned while being asked whether they agreed or disagreed with a variety of statements related to the three elements. Statistical analysis examined brain region activation for each of the elements and these regions (and circuits) were then compared to already known cognitive and social networks in the brain.God’s perceived involvement appeared to activate brain circuits very similar to those activated in Theory of Mind tasks. Theory of Mind is the cognitive ability to comprehend others may have beliefs, desires, emotions and intentions that differ from one’s own. Theory of mind tasks (and in this experiment judging God’s perceived involvement) activated complex frontal, temporal and occipital cortex regions. In contrast God’s perceived emotion tasks activated fewer regions. Those with a perception that God was a loving being, activated a region in the right middle frontal gyrus while those with a perception of God as angry activated a region in the left middle temporal gyrus. These regions are known to be activated when processing emotional Theory of Mind information. The right middle frontal gyrus area is an area known to be linked to “positive emotional states and suppression of sadness”. Regions activated with religious knowledge statements differed between experiential versus doctrinal domains. The figure above shows regions activated by experiential religious knowledge in the top series of scans and that activated with doctrinal religious knowledge in the bottom two scans. Experiential religious knowledge statemenst activated a wide range of regions including the occipital cortex known to be key in high-imagery content. Doctrinal knowledge statements activated temporal lobe regions known involved in interpreting metaphorical meaning, abstractness and abstract linguistic content. These studies support religious beliefs being processed in regions already known to be important in the social cognition evolution of man’s brain. There is no specific “God Spot” in the brain. The authors note in the discussion “This study defines a psychological and neuroanatomical framework for the (predominately explicit) processing of religious belief.Within this framework, religious belief engages well-known brain networks performing abstract semantic processing, imagery, and intent-related and emotional ToM (Theory of Mind), processes known to occur at both implicit and explicit levels……The findings support the view that religiosity is integrated in cognitive processes and brain networks used in social cognition, rather than being sui generis.In the final post in this three part series, the focus will be on the brain processes involved in political beliefs. Kapogiannis, D., Barbey, A., Su, M., Zamboni, G., Krueger, F., & Grafman, J. (2009). Cognitive and neural foundations of religious belief Proceedings of the National Academy of Sciences, 106 (12), 4876-4881 DOI: 10.1073/pnas.0811717106... Read more »

Kapogiannis, D., Barbey, A., Su, M., Zamboni, G., Krueger, F., & Grafman, J. (2009) Cognitive and neural foundations of religious belief. Proceedings of the National Academy of Sciences, 106(12), 4876-4881. DOI: 10.1073/pnas.0811717106

May 4, 2011
11:19 AM
1,296 views

Neuroethics: The Brain and Moral Beliefs

by William Yates, M.D. in Brain Posts

Jerome Grafman, Ph.D. presented the May 2011 Warren Frontiers in Neuroscience lecture “Brain Regions Supporting the Establishment of Human Beliefs” in Tulsa, Oklahoma. I have typically summarized these lectures in a single Brain Posts blog posting. But given the broad character of this presentation, I will break my summary into three parts based on the sections in the presentation: moral beliefs, religious beliefs and political beliefs. Along with the lecture highlights, I will review relevant research manuscripts by Dr. Grafman and his research team.A first step in studying concepts as abstract as morality is to define key components or factors within moral beliefs. This is a common approach applicable to also religious and political beliefs. Dr. Grafman prefers a more data driven approach to this task, rather than coming from a theoretical perspective. The Moral Sentiment Task is a 98-item interview where subjects are given a scenario and asked to pick one of four responses that describes the feeling they would experience in that situation. Using large population survey data, responses in this interview can be assigned to one of two sentiments:Prosocial sentimentsembarrassment pityguiltCritical sentimentsangerdisgustIn a study with Jorge Moll and colleagues, Grafman examined a series of patients with frontotemporal dementia (FTD) using PET imaging and the Moral Sentiment Task. Patients with FTD commonly exhibit impairment in social behaviors such as acting inappropriately (misjudge the social appropriateness of a behavior). This socially inappropriate behavior commonly causes caregiver embarrassment and makes FTD often more difficult to manage than Alzheimer’s dementia. Since the frontal lobe is felt to contribute to moral beliefs and judgment, a disease variably affecting the frontal lobe is likely to provide information about the effect of deficits in specific regions.Patients with FTD were recruited for a study of the relationship between hypoactivation of specific brain regions with impairment in making accurate choices in the Moral Sentiment test. As expected FTD, patients showed widespread decreased frontal lobe glucose utilization compared to controls. In a correlational analysis, the following results were noted:Decreased glucose utilization in the medial frontopolar cortex correlated with reduced prosocial sentimentDecreased glucose utilization in the septum also correlated with impaired prosocial sentimentDecreased glucose utilization in the dorsal medial prefrontal cortex and the amygdala correlated with reduced critical sentiment scoresIn a review in the Annual Review of Neuroscience, Forbes and Grafman summarize the role of the prefrontal cortex in social cognition and moral judgment. They note that there is significant overlap between processes involved in social cognition and moral judgment. Social cognition has been described as the encoding, storage, retrieval and processing in the brain of information related to other members of the species. Elements of social cognition function can be implicit processes (occurring rapidly with little cognitive effort and outside conscious awareness) or explicit processes (deliberate, cognitively taxing and consciously accessible). Implicit social cognition appears to have evolved earlier and is linked to the posterior cortex and subcortical regions. Explicit social cognition evolved later and relies heavily on the prefrontal cortex (PFC). The prefrontal cortex appears to be a key area involved in making moral judgments. Using fMRI brain PFC regions activate with processing a moral challenge. Interestingly, the specific region of PFC involved in making a decision appears to be separate for making a decision on an impersonal moral dilemma (whether to flip a trolley track switch that will save five lives but lead to the death of one other person) or a personal moral dilemma (whether to smother your own crying baby if doing so would being detected by oppositional soldiers who will kill you and many other individuals). Forbes and Grafman note in the conclusion of their review that “social interactions and judgments of humans have been based on evolutionary pressures and environmental and social contingencies”. This evolution is continuing and they wonder if more impersonal world of advances such as Facebook and text messaging at a young age might drive the brain systems towards more “immediate results and gratification”. Nevertheless, the emerging field of social neuroscience is likely to play a key role in better understanding neuroanatomical, genetic and environmental influences that effect our social development and the moral judgment we make.Screen shot of prefrontal cortex from 3D Brain by Yates Photography.In the next post, I will summarize research related to the brain and religious beliefs. Dr. Grafman’s proposes an answer to the question “Is there a God spot in the brain?”... Read more »

Moll J, Zahn R, de Oliveira-Souza R, Bramati IE, Krueger F, Tura B, Cavanagh AL, & Grafman J. (2011) Impairment of prosocial sentiments is associated with frontopolar and septal damage in frontotemporal dementia. NeuroImage, 54(2), 1735-42. PMID: 20728544

Forbes, C., & Grafman, J. (2010) The Role of the Human Prefrontal Cortex in Social Cognition and Moral Judgment . Annual Review of Neuroscience, 33(1), 299-324. DOI: 10.1146/annurev-neuro-060909-153230

May 2, 2011
08:01 AM
1,080 views

Tornado Deaths: Limits of Current Technology

by William Yates, M.D. in Brain Posts

p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px Helvetica}p.p2 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px Helvetica; min-height: 14.0px} An earlier draft of this article first published as Tornado Deaths and the Limits of Tornado-Related Technologies onTechnorati.Deaths in the southeastern United States related to the April 27, 2011 tornadoes prompt an examination of tornado safety. A key question is whether modern tornado detection and warning technology significant reduces risk of tornado-related death.Storm and tornado tracking technology has exploded over the last 30 years. Doppler radar technology continues to improve and national and regional news channels trumpet their own systems with names such as SkyTraK DopplerMax, First Alert Mega Doppler Radar and Doppler 9000 HD. Local news stations in the the midwestern and southern U.S. regions frequently break into regular programming to alert viewers to potential dangerous storms and tornado watches.In 1982, The Weather Channel started broadcasting in the United States. This 24 hour channel monitors severe weather across the U.S. providing access to instant weather information.But what has been the effect of these tornado technologies in the trends for tornado-related deaths? The trends to do not appear to support these technologies in their ability to reduce tornado-related death. Below is a plot of the yearly number of tornado-related deaths in the U.S. between 1950 and 2011 (year-to-date) from data published by the U.S. National Oceanic and Atmospheric Administration. p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px Helvetica}p.p2 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px Helvetica; min-height: 14.0px}span.Apple-tab-span {white-space:pre} Tornado-related deaths have dropped dramatically in the United States but the biggest declines occurred between 1925 and 1980. Between 1875 and 1925, the U.S. averaged nearly two deaths per million residents. Since 1980, the U.S. death rate has averaged around .2 deaths per million people. This is around a 90 per cent decrease and a significant advance in public health safety.The problem for tornado technology advocates is the trend in tornado-related deaths between 1980 and 2011. The over 300 deaths in the recent southeastern U.S. tornado make 2011 already one of the top three years for tornado deaths in the U.S. since 1950. The number of deaths so far in 2011 is topped by only by 1953 with 519 deaths and 1974 with 366 tornado-related deaths . Yearly death rates vary significantly and should be corrected for total population to compare trends. Taking a look at the rates of tornado-related deaths per million population finds the following results in the last six decades:Decade Total Deaths Deaths/Million1950s 1419 8.61960s 942 4.91970s 998 4.71980s 522 2.21990s 579 2.22000s 556 1.9The decline in the 2000s to 1.9 deaths/million/decade is not statistically different than the rate for the decade of the 1980s or the rate for the 1990s decades. The 300 deaths in the recent U.S. tornado is about the number that could be expected over a six year span in the U.S. This suggests the decade of the 2010s is unlikely to show a decrease compared to the rates between 1980 and 2010.There is some data supporting regional tornado death decreases in the area surrounding new radar installations Additionally, there is some support for increased numbers of residents and mobile homes in the southeastern U.S. potentially contributing to the plateau in number of tornado deaths in the U.S. Nevertheless, it's hard to look at the raw data and feel like tornado detection technology has dramatically reduced the risk of tornado death.Technology has contributed to improvement in many areas of life. Tornado-related deaths in the U.S. have dropped significantly in th... Read more »

Ashley, W. (2007) Spatial and Temporal Analysis of Tornado Fatalities in the United States: 1880–2005. Weather and Forecasting, 22(6), 1214-1228. DOI: 10.1175/2007WAF2007004.1

Simmons, K., & Sutter, D. (2005) WSR-88D Radar, Tornado Warnings, and Tornado Casualties. Weather and Forecasting, 20(3), 301-310. DOI: 10.1175/WAF857.1

Brooks, Harold E. (2002) Deaths in the 3 May 1999 Oklahoma City Tornado from a Historical Perspective. Weather and Forecasting. info:/

April 27, 2011
09:23 AM
1,151 views

Getting Women with Fibromyalgia Moving

by William Yates, M.D. in Brain Posts

What is fibromyalgia and what exactly what does exercise have to do with the treatment and long-term outcome of the condition? A recent study published in Medicine & Science in Sports & Exercise is helpful in understanding the relationship between fibromyalgia and exercise and how clinicians (and patients) might find better strategies for treatment.Fibromyalgia is a clinically defined pain syndrome estimated to affect about 5 per cent of the general population with criteria for diagnosis defined by the American College of Rheumatology to include:Pain in all four quadrants of the bodyPain along the spinePresence of 11 of 18 specific tender pointsThe 18 specific tender points (or trigger points) are outlined in the accompanying public domain figure from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and Wikipedia.Women have higher prevalence rates for fibromyalgia. The reason for this gender discrepancy in unknown as is the cause of the disorder. Patients meeting criteria for this medical pain disorder commonly have significant cognitive and emotional symptoms as well. Endorsement rates for problems with cognitive impairment (poor concentration, memory problems, psychomotor speed problems and diminished attention span) are common in fibromyalgia. Additionally, rates of anxiety and mood symptoms and disorders appear high. The cause for this association is also unknown. Like many pain syndromes, exercise seems to be helpful in the long-term management of fibromyalgia. Although a natural response to pain is to reduce activity, this physical withdrawal can be counterproductive to a good long-term outcome. It is important for women with fibromyalgia and their physicians to assess and monitor response to exercise as a key component to treatment.McLoughlin and a research team from the University of Iowa and the University of Wisconsin studied the relationship between self-reported exercise and actual exercise in a group of women with fibromyalgia and a group of women without fibromyalgia. They utilized an accelerometer that was worn on the hip for 7 days to compare actual activity levels to what the women were reporting. The key findings from the study were:Fibromyalgia subjects reported less physical activity (confirmed by accelerometer data) than controlsBoth those with fibromyalgia and controls reported higher levels of activity than could be validated by accelerometer dataSelf-report activity levels were poorly correlated with accelerometer activity in fibromyalgia but not controlsHigh depression scores in fibromyalgia correlated with lower physical activityFor clinicians, the take home message here is you can’t rely only on your fibromyalgia patient’s self-report of exercise. I think we will be seeing more use of devices such as accelerometers in clinical practice to get a more objective measure of physical activity. Similar movement measurement capabilities (like those found in accelerometers) are available in the iPhone and iPod Touch. Such tools may also be used to monitor change in activity with a new intervention, i.e. attending Jazzercise on a regular basis. Targeting depression treatment in women with fibromyalgia may be one method to improve the chances of getting activity levels up.The need for implementing activity programs is not limited to the medical illness of fibromyalgia. Similar programs in obesity, heart disease, diabetes and lung disease are needed. Collecting activity levels in these and other medical conditions may give clinicians additional insight into the effects of inactivity on disease progression.Getting activity levels up in fibromyalgia can lead to significant improvement. A recent trial of exercise in fibromyalgia by Fontaine and colleagues found regular activity reduced pain and reduced functional impairment. This intervention paired education with a pedometer data that would be monitored by the research team. When accountability is incorporated in exercise trials, compliance and benefits go up.MCLOUGHLIN, M., COLBERT, L., STEGNER, A., & COOK, D. (2011). Are Women with Fibromyalgia Less Physically Active than Healthy Women? Medicine & Science in Sports & Exercise, 43 (5), 905-912 DOI: 10.1249/MSS.0b013e3181fca1eaFontaine KR, Conn L, & Clauw DJ (2010). Effects of lifestyle physical activity on perceived symptoms and physical function in adults with fibromyalgia: results of a randomized trial. Arthritis research & therapy, 12 (2) PMID: 20353551... Read more »

MCLOUGHLIN, M., COLBERT, L., STEGNER, A., & COOK, D. (2011) Are Women with Fibromyalgia Less Physically Active than Healthy Women?. Medicine , 43(5), 905-912. DOI: 10.1249/MSS.0b013e3181fca1ea

Fontaine KR, Conn L, & Clauw DJ. (2010) Effects of lifestyle physical activity on perceived symptoms and physical function in adults with fibromyalgia: results of a randomized trial. Arthritis research , 12(2). PMID: 20353551

April 26, 2011
11:04 AM
1,200 views

Pre-term Births Increase Risk of ADHD and Autism

by William Yates, M.D. in Brain Posts

Understanding the factors contributing to the prevalence of ADHD and autism requires examining the type and magnitude of risk factors for the disorders. One risk factors common to both disorders is early or pre-term birth. Advances in neonatal care dramatically increase survival in infants born as early as the fifth or sixth month of pregnancy.A recent study published in the journal Pediatrics provides some important new data about the risk of ADHD in pre-term birth infants. Scientists in Sweden examined the prevalence rates for ADHD in a group of children born pre-term and compared it to the rates in infants born at term or slightly later. Using several statistical models, they estimated the magnitude of effect of preterm birth on ADHD. They found a significant statistical effect--the earlier the birth in gestation the greater the likelihood of childhood ADHD. The magnitude of this effect is an approximate doubling of the risk for the earliest births. The data from the study (model 3) estimated the risk (odds ratio) of childhood ADHD at several stages of development at birth:23-28 weeks Odds ratio=2.129-32 weeks Odds ratio=1.633-34 weeks Odds ratio=1.435-36 weeks Odds ratio=1.337-38 weeks Odds ratio=1.1> 38 weeks Odds ratio=1.0Similar studies in autism and autism spectrum disorder estimated a similar magnitude of risk for autism and autism spectrum disorder in preterm birth. Infants born before 30 weeks appear to have approximately a doubled risk for autism and ASD.From a prevention viewpoint, these studies support efforts to reduce the risk of preterm birth. Although it is impossible to eliminate preterm births, the following measures can significantly reduce the risk:Smoking cessation during pregnancyEarly and regular prenatal careReducing the number of multiple birth pregnancies in infertility couplesProgesterone use in women with a previous history of preterm birthReducing the number of pregnancy inductions and C-sections in preterm pregnanciesIncreased number of viable preterm births may be contributing to a portion of the number of children with ADHD and autism/autism spectrum disorders. Improved neonatal care of preterm infants carries the potential for more children with special needs. Improving neonatal care for infants in the neonatal intensive care as well as public health efforts to reduce the number of preterm births are critical initiatives for prevention of ADHD and autism. The March of Dimes has an online resource site that provides professional education of the issue of reducing preterm births.Photo of St. Louis Cardinal Tony LaRussa hitting balls to outfielders in 2011 Spring TrainingLindstrom, K., Lindblad, F., & Hjern, A. (2011). Preterm Birth and Attention-Deficit/Hyperactivity Disorder in Schoolchildren PEDIATRICS DOI: 10.1542/peds.2010-1279Schendel D, & Bhasin TK (2008). Birth weight and gestational age characteristics of children with autism, including a comparison with other developmental disabilities. Pediatrics, 121 (6), 1155-64 PMID: 18519485... Read more »

Lindstrom, K., Lindblad, F., & Hjern, A. (2011) Preterm Birth and Attention-Deficit/Hyperactivity Disorder in Schoolchildren. PEDIATRICS. DOI: 10.1542/peds.2010-1279

Schendel D, & Bhasin TK. (2008) Birth weight and gestational age characteristics of children with autism, including a comparison with other developmental disabilities. Pediatrics, 121(6), 1155-64. PMID: 18519485

April 20, 2011
09:13 AM
1,174 views

Aerobic Exercise, Resistance Training and Mortality

by William Yates, M.D. in Brain Posts

The research support for regular exercise to be associated with reduced risk of death is growing. However, there is limited research that focuses on effects of aerobic versus strengthen (resistance) training. Additionally, there is limited data comparing mortality in those with and without a general medical condition. Schoenborn and Stommel recently published a study addressing these issues in teh American Journal of Preventive Medicine. They examined a large sample of U.S. adults and assessed whether they met the 2008 USDHHS Activity Guidelines for Americans:150 minutes per week of moderate intensity aerobic activityOR 75 minutes per week of high intensity aerobic activityEncourage two days per week of weight training of 7 large muscle groupsThe study examined exercise levels and mortality by linking data from the 1997-2004 National Health Interview Survey and death registry data from 1997-2006. Mortality examined in groups with no chronic medical conditions compared to those with one or more medical conditions including: diabetes, hypertension, vascular problems, lung disease (asthma/bronchitis), one or more functional limitations (any difficulty walking, climbing steps, standing, sitting, stooping, reaching, grasping, or lifting/pulling or pushing large objects).This study was informative because it looked at the effect of aerobic versus strength versus both aerobic and strength on mortality. Additionally, it examined the effect of exercise on mortality in four age categories: 18 and younger, 18 to 44 years of age, 45 to 64 years of age and 65 and older age groups. >The key findings from the study were:Strength training alone was not associated with decrease mortality riskAerobic exercise was linked to reduced mortality risk aerobic exercise with over 150 minutes per week somewhat better than less than 150 minutes per week ( although going above 300 minutes per week did not correlate with additional mortality reduction)Among those meeting aerobic exercise guidelines, adding strengthening showed a trend for correlation with an additional beneficial mortality effectOlder adults with one or more chronic conditions appeared to have the strongest association between exercise and lower mortality riskThe chart below summarizes the magnitude of association between exercise levels and lower mortality rates in those in the 45 to 64 age category and those aged 65 and older with one or more medical conditions. To aid in interpretation of the numbers the SMR for those 65 and older with one medical condition meeting both aerobic and strengthening exercise guidelines was .52. This means during follow up they were 48% (1-SMR) less likely to die than those not meeting exercise guidelines for either aerobic or strengthening types.This study is a correlational study and not a prospective controlled trial so the data need to be interpreted cautiously. It may be that individuals with chronic medical conditions die not because they don't exercise but because their illness is so severe they are unable to exercise. Nevertheless, this study adds to our knowledge of the relative correlation of aerobic and resistance training and mortality. Additionally, it suggests that exercise may have a significant beneficial role in older adults who have one or more medical conditions. Figure by author adapted from data provided in manuscript.Schoenborn, C., & Stommel, M. (2011). Adherence to the 2008 Adult Physical Activity Guidelines and Mortality Risk American Journal of Preventive Medicine, 40 (5), 514-521 DOI: 10.1016/j.amepre.2010.12.029... Read more »

Schoenborn, C., & Stommel, M. (2011) Adherence to the 2008 Adult Physical Activity Guidelines and Mortality Risk. American Journal of Preventive Medicine, 40(5), 514-521. DOI: 10.1016/j.amepre.2010.12.029

April 18, 2011
09:21 AM
1,108 views

Autism Twin Studies Point to Key Next Steps

by William Yates, M.D. in Brain Posts

p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px Helvetica}p.p2 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px Helvetica; min-height: 14.0px} Angelica Ronald and Rosa Hoekstra have written a nice review of recent twin studies in autism spectrum and autism traits. The review is online prior to print in the American Journal of Medical Genetics Neuropsychiatric Genetics.They note in the review that twin studies have evolved from a perspective of looking at narrowly defined autism, to the broader category of autism spectrum to an even broader phenotype, the dimensional character of autistic traits in the general population.I don't know much about autism traits in the general population but this twin studies review highlighted some current understanding.Relatives of individuals with autism spectrum disorder show elevated autistic traitsAutistic traits in the general population show a smooth distribution through the normal range to the clinical extreme--this suggests a biological continuum rather than a normal or disease clinical statusUnderstanding the cause of variation of autistic traits in the general population is likely to aid in the understanding of autismThe heritability of autistic traits in the population is very heritable (genetic) ranging from 40 to 60% in young twins but increasing to 60 to 90% in adolescence.Another insightful section of the manuscript dealt with the degree of genetic and environmental overlap between different autistic symptoms. Autism spectrum is made up of a triad of symptoms: social impairment, communication impairment and restrictive behaviors and interests. Twin studies suggest these different symptom clusters may be "fractionable", meaning they may have some independence from each of the other clusters. The authors note more genetic and twin studies should focus on one symptom cluster of the triad, rather than only studying those who have all three components.The authors note that twin studies have helped explain the relationship between autism and intellectual disability and low IQ. There appears to be some common genetic contribution to autism and intellectual disability. However, since some individuals with autism and ASD have relatively normal intelligence, the picture is complex. Studying ASD in those with normal intelligence may provide further insight into specific autism genetic influences. What needs to be done in the future?Need for twin studies to tease out genetic and environmental factors that explain the common co-occurence of autism, ASD and autism traits with conduct disorder, sleep disorders, antisocial behavior and depression.More attention needs to focus on genetic and environmental effects on developmental change in ASD and autistic traits in children (only two current studies published) and in adults (zero studies published).More research on age-appropriate measures of autism traits--measures appropriate for one developmental age may not be appropriate for other ages.More studies are necessary to look at cognitive phenotypes in autism and autism traits .Photo of St. Louis Cardinal Daniel Descalso Courtesy of Yates PhotographyRonald, A., & Hoekstra, R. (2011). Autism spectrum disorders and autistic traits: A decade of new twin studies American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 156 (3), 255-274 DOI: 10.1002/ajmg.b.31159... Read more »

Ronald, A., & Hoekstra, R. (2011) Autism spectrum disorders and autistic traits: A decade of new twin studies. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 156(3), 255-274. DOI: 10.1002/ajmg.b.31159

April 15, 2011
09:35 AM
1,177 views

Paranoia: Prevalence and Correlates

by William Yates, M.D. in Brain Posts

Clinicians dealing with psychiatric disorders commonly encounter patients with paranoia in their clinical practices. However, it is important for clinicians to understand the relatively frequency of paranoia endorsement by people in the general population. Whether paranoia is a pathological phenomenon commonly depends on the degree of paranoia, associated signs and symptoms and presence (or absence) of a formal psychiatric diagnosis. Freeman and colleagues from the Institute of Psychiatry other colleagues in London published an important paper to address this issue.Their data and research stems from a general population study of over 7,000 general population survey respondent in England. To assess paranoia in the general population, subjects were asked three questions where positive responses reflected increasing severity of paranoia. The three questions in the survery (and the general population rate of endorsement) were:Paranoia level 1. ‘Over the past year, have there been times when you felt that people were against you? (18.6%)Paranoia level 2. ‘In the past year, have there been times when you felt that people were deliberately acting to harm you or your interests ? (8.2%)Paranoia level 3. ‘In the past year, have there been times you felt that a group of people was plotting to cause you serious harm or injury? (1.8%)I found it interesting the relatively high rate of endorsement of paranoia level 1 in the general population. Nearly one in five endorsed feeling times in the last year when they felt that people were against them. As the severity of paranoia increased, the prevalence rates decreased to less than 2% of the population fealing a good of people was plotting to cause them harm or injury.The research also looked at some of the correlates of paranoia. Those endorsing each level of paranoia were compared to those with no endorsement of paranoia. The paper is packed with data but here are some of the things that stood out for me:Level 1 paranoia was more likely to be endorsed by women while level 3 paranoia was more likely to be endorsed by menParanoia rates were higher in populations with a variety of medical conditions including: diabetes, hearing or visual problems, recent heart attack/angina. There was a trend for increased level 3 paranoia in those with obesity (BMI greater than 30 kg/m2)Paranoia rates were higher in a variety variables indicating social isolation, i.e. separated, divorced or single marital status, fewer number of close family members or friends, fewer supportive relationshipsParanoia rates were higher along with a variety of other psychiatric symptoms/disorders, i.e. insomnia, depression,worry, anxiety, panic and PTSDParanoia rates were increased in those endorsing suicidal thoughts in past year, history of a suicide attempt, anxiolytic and antidepressant drug use and not surprisingly antipsychotic medication useParanoia rates were strongly and progressively associated with cannabis use and less strongly associated with heavy drinkingIn summary, this research manuscript provides a valuable overview of paranoia. Elements of paranoia are relatively common in the general population. Paranoia is a marker for many other psychiatric syndromes and cannabis abuse. Clinicians should include screening questions for paranoia in routine clinical assessment.Photo of Japanese Maple Courtesy of Yates PhotographyFreeman, D., McManus, S., Brugha, T., Meltzer, H., Jenkins, R., & Bebbington, P. (2010). Concomitants of paranoia in the general population Psychological Medicine, 41 (05), 923-936 DOI: 10.1017/S0033291710001546... Read more »

Freeman, D., McManus, S., Brugha, T., Meltzer, H., Jenkins, R., & Bebbington, P. (2010) Concomitants of paranoia in the general population. Psychological Medicine, 41(05), 923-936. DOI: 10.1017/S0033291710001546

April 14, 2011
09:09 AM
1,271 views

Nicotine Replacement in Schizophrenia

by William Yates, M.D. in Brain Posts

Inpatient psychiatric hospitals increasingly prohibit smoking by patients, staff and family in their units. Although the public health benefits of smoking restrictions are undeniable, there may be some situations where smoking restrictions have unintended consequences. One area is the emergency management of patients with serious psychiatric illnesses such as schizophrenia and bipolar affective disorder.Rates of smoking have been documented to be higher in both schizophrenia and bipolar affective disorder. The likelihood is high that acute psychiatric emergencies in schizophrenia and bipolar will be accompanied by nicotine dependence. Clinicians are left making a decision on how to manage nicotine dependence in the context of psychotic decompensation.Michael Allen and colleagues recently conducted a small study of nicotine dependence management in forty subjects with schizophrenia admitted to a psychiatric emergency service. Subjects were required to be smokers at the time of admission. Severity of smoking dependence was assessed using the Fagerstrom scale. Subjects received standard antipsychotic therapy without restriction but they were randomized to receive either nicotine replacement therapy (21 mg nicotine patch per day) or placebo patch. Here is a summary of the results of the study:Nicotine replacement reduced a measure of agitation by 33% in the first four hours and 23% at 24 hoursThis reduction was statistically significantly more than with antipsychotic alone and placeboSubjects with lower nicotine dependence scores tended to show the most response compared to placeboThe size of the effect of nicotine replacement on agitation reduction approached the level seen with standard antipsychotic therapySo the beneficial effects of replacing nicotine in the short term in this population is pretty dramatic and of signifcant magnitude. The authors note that it is possible the 21 mg nicotine patch is insufficient to address nicotine withdrawal in schizophrenics with more severe nicotine dependence. Since the nicotine patch typically takes several hours to provide significant blood levels, the authors suggest a combination of nicotine gum (with rapid onset) and a patch may be the best strategy. Encouraging patients with psychotic disorders and mood disorders to quit smoking is an important general health strategy. However, this study suggests that attempting this during an acute psychotic break is probably counter productive and may be inhumane. Acute nicotinie withdrawal may exacerbate the agitation of psychosis. Nicotine withdrawal attempts in this population is probably better suited for periods where psychotic symptoms are under control. It also makes sense to monitor patients with schizophrenia closely during attempts to stop smoking. This period may be one of increased risk of psychiatric decompensation.Photo of Nicotine Patch Courtesy of Wikipedia Creative Commons by RegBarcAllen MH, Debanné M, Lazignac C, Adam E, Dickinson LM, & Damsa C (2011). Effect of nicotine replacement therapy on agitation in smokers with schizophrenia: a double-blind, randomized, placebo-controlled study. The American journal of psychiatry, 168 (4), 395-9 PMID: 21245085... Read more »

Allen MH, Debanné M, Lazignac C, Adam E, Dickinson LM, & Damsa C. (2011) Effect of nicotine replacement therapy on agitation in smokers with schizophrenia: a double-blind, randomized, placebo-controlled study. The American journal of psychiatry, 168(4), 395-9. PMID: 21245085

April 13, 2011
10:44 AM
1,151 views

Ecstasy Acute Effects on Social Cognition

by William Yates, M.D. in Brain Posts

MDMA (Ecstasy) Chemical StructureAnecdotal reports suggest that some users of ecstasy (3,4-methlenedioxymethamphetamine-MDMA) experience increased feelings of empathy and are more social while under influence of the drug. Such effects may contribute to the timing and frequency of ecstasy use and may also contribute to risk of abuse or dependence. Understanding this phenomenon in more detail might provide clinicians with better strategies to reduce use and the associated complications of ecstasy use. Studying acute effects of illicit drugs is difficult under natural conditions. Users of ecstasy commonly also use alcohol, nictoine and other illicit drugs in the context of ecstasy use. Isolating psychological effects of one agent in this type of environment is difficult if not impossible. One alternative is to admiinster ecstasy in a laboratory setting with subjects blind to whether ecstasy or placebo is being administered. However, this approach poses significant ethical challenges. One approach, is to limit human study in the lab to those who have previously use ecstasy and intend to continue using. Although imperfect, this approach limits risk of exposing ecstasy naive individuals to an illicit drug that may have reinforcing effects and increase risk of future drug use.Chemical Structure of MethamphetamineA study in Biological Psychiatry took this approach when over four sessions, healthy ecstasy using volunteers received either a low or high dose of MDMA, a dose of methamphetamine (METH) or placebo. MDMA and methamphetamine share chemical (see chemical structures), pharmacological as well as psychological features. Methamphetamine is typically considered a compound that increases CNS dopamine and norepinephrine while MDMA is felt to also increase CNS serotonin. Ratings on a series of psychometric measures were obtained over a period of six hours after drug administration. Visual analog scales (VAS) rated subjective feelings in a variety of domains: stimulated, bored, sedated, anxious, insightful, nauseated, loving, dizzy, sociable, confused, lonely, elated, playful, blank and restless. Additionally, the rated themselves on the 72-item Profile of Mood States (POMS). Subjects also completed a facial affect recognition task where they were asked to identify four facial emotions: anger, fear, happiness, sadness.Here is a summary of the study findings for active agents compared to placebo:MDMA (high dose) increased subjective VAS ratings of feeling "loving" and "friendly"MDMA (low dose) increased subjective VAS ratings of "lonely"MDMA (high dose) and METH increased VAS ratings of "playful"METH alone increased VAS ratings of "sociability"MDMA (high dose) reduced the accuracy of recognizing angry facesSo there is some support in this study for the anecdotal reports of increased prosocial cognition with MDMA. The authors note their findings suggest MDMA increases social approach (sociability) rather thanThe authors note the study supports the possibility that increased social behavior with MDMA might be due to a reduced sensitivity to negative emotions of others rather than increasing recognition of positive emotions in others. There also might be danger with this effect as social risk taking might increase potential for adverse consequences (connecting with someone you would be unlikely to connect with when not under the influence of MDMA).Chemical structures of MDMA and methamphetamine from Wikipedia Creative Commons authored by Harbin.Bedi G, Hyman D, & de Wit H (2010). Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biological psychiatry, 68 (12), 1134-40 PMID: 20947066... Read more »

Bedi G, Hyman D, & de Wit H. (2010) Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biological psychiatry, 68(12), 1134-40. PMID: 20947066

April 12, 2011
12:54 PM
1,215 views

Phentermine/Topiramate Combo for Obesity

by William Yates, M.D. in Brain Posts

Molecular Model of TopiramatePrevious Brain Posts summarized some of the pharmacologic agents in the pipeline for weight loss as well as some drug combinations. A recent research study published in Lancet provides additional data on one of the drug combinations being studied: phentermine and topiramate.This new study is important because it looked at 56 weeks of treatment and target obese individuals with at least two obesity-related medical complications. Subjects were required to have significant obesity (BMI 27-45 kg/m2) and at least two of the following: hypertension, dyslipidemia, diabetes or prediabetes, abdominal obesity). Each of these factors increases the risk of mortality associated with being overweight.The key findings from the study--number of pounds lost at 56 weeks:placebo-- 3.1 pounds (1.4 kg)phentermine 7.5mg/topiramate 46 mg-- 17.8 pounds (8.1 kg)phentermine 15.0mg/topiramate 92 mg-- 22.4 pounds (10.2 kg)The weight loss outcome in the highest dose group was approximately 10% of body weight--a significantly positive result in light of previous single agent trials.One area of outcome caught my eye, the change in physiological and metabolic parameters over the course of the study. Waist circumference decreased about an inch (2.4 cm) in the control group but three (7.6 cm) to three and one half inches (9.2 cm) in the low dose and high dose treatment group. Blood lipid changes were also pretty impressive with LDL and triglycerides falling more in the treatment groups while good cholesterol values (HDL) increased more with the active drug combination. Fasting insulin levels dropped significantly more in the active groups also.Given historical problems with use of weight loss drugs, safety issues are important to monitor closely. The most common adverse events in the active agent groups with rates higher than placebo were dry mouth (21%), paresthesias (numbness and tingling) (21%), constipation (17%), dysguesia (10%), insomnia (10%), dizziness (10%), anxiety (4%) and irritability (3%). Although infrequent (1%) depression was noted in the high dose group more than placebo. One potential red flag with this combination was report of 11 cases of renolithiasis (kidney stones) in the high dose active agent group.Topiramate inhibits the action of carbonic anhydrase. This effect can cause decreases in serum bicarbonate and potassium as well as increasing risk of renolithiasis. The rate of renolithiasis was lower in the low dose group suggesting a dose-related effect. Additional, inhibitors of carbonic anhydrase have been noted to cause alterations in sensation (paresthesias) and in taste (dysguesia).The authors note several relevant areas of caution. Subjects with clinically relevant depression were excluded from the study due to concern about drug-induced depression. Also some subjects noted cognitive adverse events, attention or memory problems, and this needs to be monitored in those more prone to such effects. Additionally, the first application to approve this combination of phentermine and topiramate was turned down for lack of long-term cardiac safety data and data on risk of use during pregnancy. This additional data is likely being collected for analysis and possible re-application given the impressive level of weight loss associated with this combination.Molecular model of topiramate from Wikipedia Creative Commons, Author fvasconcellos.Kishore M Gadde, David B Allison, Donna H Ryan, Craig A Peterson, Barbara Troupin, Michael L Schwiers, Wesley W Day (2011). Eff ects of low-dose, controlled-release, phentermine plustopiramate combination on weight and associatedcomorbidities in overweight and obese adults (CONQUER):a randomised, placebo-controlled, phase 3 trial Lancet : 10.1016/S0140- 6736(11)60205-5... Read more »

Kishore M Gadde, David B Allison, Donna H Ryan, Craig A Peterson, Barbara Troupin, Michael L Schwiers, Wesley W Day. (2011) Eff ects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. info:/10.1016/S0140- 6736(11)60205-5

April 7, 2011
08:58 AM
1,155 views

Gabapentin Improves Outcome in Alcoholism

by William Yates, M.D. in Brain Posts

Molecular Model of GABAImproving abstinence rates in alcoholism continues to be a goal of treatment research. Several novel drug treatment strategies in alcoholism have targeted the neurotransmitter gamma-aminobutryic acid or GABA. GABA is the major inhibitor neurotransmitter in the brain. Alcohol has effects through the GABA receptor. Alcohol withdrawal is typically treated with the sedative drug class of benzodiazepines known to have effects on GABA receptors. There are two main types of CNS GABA receptors GABA(A) and GABA(B).Here is summary of drugs known to have effects through GABA and the GABA receptor:GABA analogues: gabapentin, pregabalinGABA(A) agonists (activators): alcohol, benzodiazepines, barbiturates,carisoprodol (SOMA), propofol, kava, valerianGABA (A) antagonists (inhibitors): flumazenilGABA(B) agonists: baclofenGABA(B) antagonists:phaclofenGABA reuptake inhibitors (activators): tiagabineNaltrexone (an opioid receptor antagonist) has an FDA indication for alcohol dependence in the United States. However, a significant number of patients taking naltrexone for alcohol dependence do relapse, so successful augmentation strategies are necessary. A recent randomized clinical has been published online at the American Journal of Psychiatry looking at augmentation of naltrexone with gabapentin in alcohol dependence. Here are the key elements of the study design:Molecular Model of GabapentinInclusion criteria: DSM-IV alcohol dependence, consuming 5 or more drinks per day (4 for women), able to enter study with a minimum of 4 days of abstinenceExclusion criteria: current suicidal or homicidal ideation, no drug dependence, use of illicit drugs in last 30 days, positive urine drug screen, psychotropic or anticonvulsant drug use, medical problems including elevated liver enzymesRandom drug assignments: placebo, naltrexone 50 mg, naltrexone 50 mg plus gabapentin up to 1200 mg dailyThe study found that the combined medication group was less likely to relapse to at least one heavy drinking day through six weeks (33% vs about 50% for both placebo and naltrexone alone). Biomarkers of drinking also favored the combined group suggesting validity to the self-reported drinking history finding. Interestingly, the combined gabapentin/naltrexone group reported the fewest complaints about sleep during the study. Sleep complaints correlated with number of heavy drinking days. Additionally, gabapentin augmentation appeared to also be most beneficial in subjects with a history of alcohol withdrawal.Gabapentin was withdrawn after six weeks and the drinking outcome improvement in the combined group waned in the ensuing 10 weeks of follow up. This suggests that longer term treatment with gabapentin may be necessary to sustain the original superior reponse.Although, this study is not large enough to change practice guidelines the results are encouraging and need replication. Gabapentin is currently available (and in generic form) and approved for the treatment of seizures. If confirmed effective in alcoholism gabapentin could provide clinicians with another safe medication option.Molecular Model of GABA From Creative Commons file--source Wikipedia author Ben MillsMolecular Model of Gabapentin From Creative Commons file--source Wikipedia, author FvasconellosAnton RF, Myrick H, Wright TM, Latham PK, Baros AM, Waid LR, & Randall PK (2011). Gabapentin Combined With Naltrexone for the Treatment of Alcohol Dependence. The American journal of psychiatry PMID: 21454917... Read more »

Anton RF, Myrick H, Wright TM, Latham PK, Baros AM, Waid LR, & Randall PK. (2011) Gabapentin Combined With Naltrexone for the Treatment of Alcohol Dependence. The American journal of psychiatry. PMID: 21454917

April 6, 2011
09:43 AM
1,281 views

Anxiety as a Gut Feeling: Understanding Interoception

by William Yates, M.D. in Brain Posts

Marcus Paulus presented the April 2011 Warren Neuroscience Frontiers in Neuroscience Lecture. The presentation was titled: Interoception and Anxiety. Interoception is the summation of a variety of bodily perceptions that make up the integrated sense of our own physiological state. Perceptions included in interoception include: pain, temperature, tickle, sensual touch, stomach discomfort to due acidity, air hunger and muscle tension. Here are my notes from Dr. Paulus' presentation and his research manuscript on this topic area.Anxiety proneness is a trait that can be measured and is associated with high risk of later development of an anxiety disorderAnxiety proneness linked to increased activation of the dorsal amygdala and the anterior insula in brain fMRI tasks such as the Emotion Face Assessment task of HaririPatients with anxiety also show insular hyperactivation in anticipation of negative cuesBenzodiazepines like Valium reduce activation of the insula as well as the amygdala in response to angry faces There is growing awareness the brain insular cortex plays a key role in interoception--receiving signals from the body and integrating these signals with emotional response and regulation (see a previous post summarizing the function of the insula and possible roles in clinical neuroscience disorders)The insula also connects to a central pathway important in anxiety involving the anterior cingulate cortex and the dorsolateral prefrontal cortex--these areas provide input to the insula for planning and acting in the face ofKey properties of the interoception include the signals from internal organs including the lungs, heart, gastrointestinal tract and genitourinary systemsMany of these signals provide awareness of body and help promote homeostasisThese signals also are involved in our sense of self and the passing of timeA new area of understanding is the important role of personal beliefs in emotional processing--personal beliefs may modulate interoception and the perception of emotional cuesA belief that a situation or cue is more dangerous than it really is, i.e. I will embarrass myself at the party, can modulate how emotion is processed, and can amplify a anxious response to the situationFuture research in the area of interoception and anxiety will target:Genetic influences on interoceptionHow cognitive interventions may influence dysfunctional beliefs related to anxietyHow interoception may help with more biological classification of types of anxietyCan people be trained to up or down regulate the insular cortex to reduce anxiety?How treatments for anxiety effect the elements of interoceptionBrain Tutor iPad Screenshot of Insular Cortex in Green Courtesy of AuthorPaulus MP, & Stein MB (2010). Interoception in anxiety and depression. Brain structure & function, 214 (5-6), 451-63 PMID: 20490545... Read more »

Paulus MP, & Stein MB. (2010) Interoception in anxiety and depression. Brain structure , 214(5-6), 451-63. PMID: 20490545

March 31, 2011
08:42 AM
1,050 views

Sleep and Cognition in Late-Life Depression

by William Yates, M.D. in Brain Posts

Depression commonly occurs with subjective as well as objective impairment in sleep and cognition. However, few studies have examined the interaction between sleep impairment, cognition and depression in elderly cohorts. Sleep disturbances predict increased risk for new onset depression and recurrence of depression in those with previous episodes. Impaired sleep appears to reduce memory function and possibly reduce neurogenesis. Naismith and colleagues recently examined the correlations between sleep parameter and cognition in a group of 44 subjects with a lifetime history of depression (minimum age >45 years, mean 63 years) and a group of similarly aged adults without depression. Neuropsychological testing in this study focused on domains felt to be impaired in mood disorders including: 1.) processing speed, 2.) attention, 3.)visual memory, 4.) verbal memory, 5.) language-as tested by counting number of animal names produced in one minute and 6.) executive function-planning, problem solving and response inhibition.Sleep function was measured using actigraphy and sleep diaries. Actigraphy typically involves using a wrist watch type device that measures movement during the night and provides an estimate of key sleep parameters including: 1.) total rest interval 2.) sleep latency—time from going to bed to falling asleep (in minutes), 3.) wake after sleep onset (WASO), 4.) arousals—number of periods during night where activity indicated being awake and 5.) sleep efficiency—the percent time asleep during the nightElderly subjects with a history of depression (current depression ratings suggest a relatively mild depression cohort at time of study) showed increased WASO and decreased sleep efficiency (two highly correlated sleep variables). WASO and sleep efficiency variables correlated with reduced cognitive function particularly in the domains of attention, memory (semantic and visual) and executive function. Of note, late onset of depression tended to be associated with poorer sleep quality than earlier age of onset. The authors controlled for depression severity in this study so the findings appear outside of this influence. The authors suggest greater cognitive impairment in late onset depression may relate to white matter changes due to cerebrovascular disease. White matter changes in frontal cortex-subcortical circuits have been associated with reduction in psychomotor speed and executive function.The authors also note this study is unable to identify the sequencing and causal pathway for these relationships. If impaired sleep directly impairs cognition, early identification of sleep abnormalities and treatment may limit associated cognitive impairment. Sleep apnea also needs to be considered in this population, although the authors found no association between measures of sleep apnea and cognitive impairment.The take home message from this study is that sleep impairment (poor efficiency) may be a marker for depression and cognitive impairment in those over 50. Clinicians caring for the older adult, should carefully assess the health of the sleep of their patients and keep the sleep, cognition and depression triad in mind. Sleep complaints in older adults need thorough assessment and should not be dismissed simply as age-related physiological in nature. Photo of Tiger Woods putting during practice for 2010 PGA championship courtesy of Yates Photography.Naismith SL, Rogers NL, Lewis SJ, Terpening Z, Ip T, Diamond K, Norrie L, & Hickie IB (2011). Sleep disturbance relates to neuropsychological functioning in late-life depression. Journal of affective disorders PMID: 21435728... Read more »

Naismith SL, Rogers NL, Lewis SJ, Terpening Z, Ip T, Diamond K, Norrie L, & Hickie IB. (2011) Sleep disturbance relates to neuropsychological functioning in late-life depression. Journal of affective disorders. PMID: 21435728

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