245 posts · 139,037 views
I am a physician interested in clinical neuroscience research. I will use this blog to post more detailed analysis of recent studies in addition to my @WRY999 Twitter scientific reading log. I will also post some of my wildlife/sports photography. Aim to educate and amuse. Not selling anything.
William Yates, M.D.
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- May 21, 2012
- 11:52 AM
- 9 views
First Panic Attack and Agoraphobia
by William Yates, M.D. in Brain Posts
Panic disorder commonly presents acutely with a first severe panic attack. Many patients can distinctly remember their first attack even years after the onset of the disorder.Agoraphobia may complicate panic disorder. The word agoraphobia stems from the Greek word "agora" meaning gathering place. The Greek agora was the common area for public assembly. People with agoraphobia commonly fear situations where they may be in a crowd of people. They often fear that in such situations a panic attack may occur and they will be unable to escape. In the modern world, common settings for agoraphobia are crowded buses, airplanes or motor vehicles.Not all individuals with panic disorder develop agoraphobia. It is unclear why this pattern exists. Agoraphobia does tend to occur with more severe and chronic panic disorder. Individuals with relative few and mild panic attacks are less likely to develop agoraphobia.A recent clinical research study from Japan suggests that the place where the first panic attack occurs may play a role in the risk of developing panic disorder. Hara and colleagues studied a large group (n=830) of individuals with panic disorder and classified them into 5 groups based on the site of their first panic attack. These five sites were:homeschool or officedriving a carpublic transportationoutside of homeIndividuals experiencing their first panic attack while driving or using public transportation had higher rates of agoraphobia. The rank order for agoraphobia rates by site of first panic attack were: public transportation (61%), driving a car (56%), outside of home (49%), school or office (41%) and home (37%).Although individuals experiencing their first panic attack at home had lower rates of agoraphobia they exhibited other markers of severity. They had higher rates of endorsement of the symptom of "fear of dying". Additionally, individuals experiencing their first panic attack at home rated the severity of their first panic attack higher than the other 4 groups.This study supports exploration of the setting and severity of the first panic attack in the assessment of panic disorder. First panic attack setting may contribute to the pattern clinical symptoms and risk of agoraphobia.Photo of black bear and yearling cub from Itasca State Park from the author's files.Hara N, Nishimura Y, Yokoyama C, Inoue K, Nishida A, Tanii H, Okada M, Kaiya H, & Okazaki Y (2012). The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack. BioPsychoSocial medicine, 6 (1) PMID: 22494552... Read more »
Hara N, Nishimura Y, Yokoyama C, Inoue K, Nishida A, Tanii H, Okada M, Kaiya H, & Okazaki Y. (2012) The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack. BioPsychoSocial medicine, 6(1), 12. PMID: 22494552
- May 17, 2012
- 11:33 AM
- 42 views
Modafinil for Shift Work Sleep Disorder
by William Yates, M.D. in Brain Posts
In a recent post, I reviewed a summary of the research status of jet lag and shift work sleep disorder. Shift work sleep disorder may affect up to 20% of U.S. workers and few FDA-approved medications target this problem.Modafinil and its derivative armodafinil are two stimulant compounds that have FDA approval for shift work sleep disorders. These compounds are also approved for the treatment of narcolepsy and obstructive sleep apnea.A recent study from India compares the efficacy of these two compounds in the treatment of shift sleep disorder. The comparison is important since modafinil is an older drug with generic forms becoming available making the per unit cost lower than brand name armodafinil (Nuvigil).In this Indian study, 211 subjects received either modafinil (200 mg) or armodanil (150 mg) one hour prior to beginning a night shift of work. Subjects and investigators were blind to drug assignment. The key outcome measure in the study was the change in the Stanford Sleepiness Score.Subjects participating in the study averaged 32 years of age with men outnumbering women by about a four to one ratio. An improvement by two or more points in the Stanford Sleepiness Scale was identified as evidence of response in the study. The efficacy rates did not did differ between the two compounds with 74% of the modafinal subjects responding compared to 72% of the armodafinil subjects.Physician and patient ratings of tolerability for the two compounds were also not different. The most common adverse effects reported were headache, dry mouth and nausea.This study confirms the benefit of modafinil and armodafinil in the treatment of shift work sleep disorder. For individuals working night shifts, these agents may provide improvement in alertness and work productivity. This study does not find any superiority to the newer armodafinil compared to modafinil.Other treatment interventions may also be helpful for shift work sleep disorder including use of melatonin or hypnotics for sleep after work as well as behavioral therapy. Treatment options are best considered in the context of a comprehensive assessment and treatment plan by a physician.Canada geese gosling photo from the author's files.Tembe, D., Dhavale, A., Desai, H., Mane, D., Raut, S., Dhingra, G., Sardesai, U., Saoji, S., Rohra, M., Shinde, V., Padsalge, M., Paliwal, A., Abbasi, K., Devnani, P., Papinwar, S., Phadke, S., Mehta, H., & Bhailume, V. (2011). Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial Neurology Research International, 2011, 1-6 DOI: 10.1155/2011/514351... Read more »
Tembe, D., Dhavale, A., Desai, H., Mane, D., Raut, S., Dhingra, G., Sardesai, U., Saoji, S., Rohra, M., Shinde, V.... (2011) Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial. Neurology Research International, 1-6. DOI: 10.1155/2011/514351
- May 16, 2012
- 12:37 PM
- 54 views
Jet Lag and Shift Work Sleep Disorder
by William Yates, M.D. in Brain Posts
Transcontinental air travel and shifting work cycles present two of the most common challenges to circadian rhythm and sleep adjustment. For individuals who travel frequently or have many shifts in their work schedule, adjusting sleep patterns effectively can increase alertness and work performance.Kolla and Auger from the Mayo Clinic recently published an excellent review of the current knowledge of jet lag and shift work disorders. Here are some of the key findings and recommendations from their clinical and research summary:BackgroundSleep and wakefulness are driven by two processes: process S and process CProcess S is the drive to sleep and is directly related to how long you have been awake--it becomes highest at 40 hoursProcess C is the drive for wakefulness and is related to circadian rhythmsWhen your internal clock is out of synchronization with the sun, individuals experience symptoms of loss of energy, insomnia, hypersomnia and physical symptoms that can include emotional (i.e. irritability) and gastrointestinal distressCircadian rhythm abnormalities can be assessed using clinical history, sleep diaries, activity monitors (actigraphy) as well as understanding whether individuals prefer early morning of evening night Jet LagTraveling west by jet is typically easier than travelling eastIt is unclear whether age affects ability to accomodate circadian rhythms to jet travelManipulating exposure to light and dark can help with adjusting to jet travel and a nice summary chart shows how an individual might gradually adjust dark and light exposure over eight days when traveling from Chicago to RomePharmacotherapy may be helpful in managing jet lagMelatonin may be helpful and regimens using pre-flight synchronization of darkness and melatonin dosing as well as initiation on arrival have been describedStandard hypnotics such as zolpidem (Ambien) or eszopiclone (Lunesta) appear to help with changing sleep schedules but may not aid daytime sleepinessStimulants such as caffeine and the drug modafanil may reduce daytime drowsiness when taken around 8 am local time in the city of arrivalShift Work Sleep DisorderShift work sleep disorder is defined as "chronic insomnia or sleepiness at times that are not conducive to the externally demanded sleep-wake schedule despite the opportunity for sufficient daytime sleep"Approximately 20% of workers in the U.S. work on-call, rotating or permanent night shiftsOlder workers appear to have more difficulty adjusting their circadian rhythms to shift work changesMelatonin demonstrates mixed results in research trials for this conditionHypnotics appear safe and may improve sleep quality and alertnessModafanil is the only FDA-approved drug approved for shift work sleep disorder and improves measures of workplace sleepiness and neuropsychological tests of alertness such as reaction timeThe physiological optimum schedule for changing work shift cycles is unknownWorkers who work the night shift are encouraged to continue day time sleep during periods off work if possibleThis review presents an excellent introduction to the topic of jet lag and shift work sleep disorder. The review is free to access in the citation below. In my next post I will review a recent clinical trial of modafanil and a newer derivative drug armodafanil in the treatment of shift work sleep disorder.Photo of great blue heron from Hunter Park in Tulsa, Oklahoma from the author's files. KOLLA, B., & AUGER, R. (2011). Jet lag and shift work sleep disorders: How to help reset the internal clock Cleveland Clinic Journal of Medicine, 78 (10), 675-684 DOI: 10.3949/ccjm.78a.10083... Read more »
KOLLA, B., & AUGER, R. (2011) Jet lag and shift work sleep disorders: How to help reset the internal clock. Cleveland Clinic Journal of Medicine, 78(10), 675-684. DOI: 10.3949/ccjm.78a.10083
- May 15, 2012
- 12:16 PM
- 63 views
Doxepin For Chronic Primary Insomnia
by William Yates, M.D. in Brain Posts
I have previously posted a summary and commentary on the use of low-dose doxepin in the treatment of insomnia. The first post summarized the results of two studies supporting the safety and efficacy of this compound including it's efficacy in elderly individuals.In a second post a randomized placebo controlled trial demonstrated safety and efficacy in a group of elderly subjects over a 12-week period.Another study of the efficacy and safety of doxepin has been recently published. This study focused on individuals with chronic primary insomnia. Chronic primary insomnia is defined in DSM-IV as a primary complaint of difficulty falling asleep, staying asleep or not feeling rested after sleep. The primary complaint must have been present for at least one month. The diagnosis requires that the insomnia not be due to a primary medical or mental disorder. Additionally, it must not be better explained by substance use, i.e. heavy chronic alcohol use.The key elements of the study design of chronic primary insomnia were:Trial characteristics: Randomized, double-blind, parallel-group placebo controlled trialSubjects: All met criteria for chronic primary insomnia and the study group included 229 subjects divided evenly between the three assignments (73% of subjects were women with an average age for the total sample being 44.5 years of age)Drug assignment: Doxepin 3 mg, Doxepin 6 mg or placebo nightly for 35 nightsKey outcome measures: Wake time after sleep onset, latency to persistent sleep and total sleep timeMeasurement technique: Sleep laboratory polysomnography on nights 1, 15 and 29 of the trialStatistical analysis: Analysis of covariance (ANCOVA) and calculation of effect size on primary outcome variables using Cohen's d statisticAs in previous studies, doxepin at both 3 mg and 6 mg significantly reduced wake time after sleep onset as well as total sleep time and sleep efficacy (sleep time divided by total time in bed). These positive effects were present on the first night of treatment and appeared to persist for the duration of the study. The study findings suggest no tolerance to the effects of doxepin on these sleep parameters over time.Of note, there did appear to be some tolerance to the time it took to fall asleep with doxepin (latency to persistent sleep). This measure was improved on the first night of treatment but no different than baseline on night 15 and night 29.Doxepin treatment increased the duration of time in stage 2 sleep but not in the other stages of sleep including stage 1, stage 3/4 and REM sleep.The study subjects generally tolerated both doses of doxepin although there were more reports of nausea (9% of doxepin subjects) and sedation (5% of subjects) in the doxepin groups compared to controls.The authors of the study compare the results of their subjects with results of trials with common sleep aids such as zolidem (Ambien) and eszopiclone (Lunesta). They note in some ways that doxepin is a unique sleep aid with better effects on the last hour of sleep and lower carry over sedation during the day.I think this study adds additional support to the use of low dose doxepin in primary insomnia. In addition to drug treatment options, it is important to consider non-drug therapies with proven efficacy in the treatment of insomnia such as cognitive behavioral therapy.Photo of Canada geese and goslings from the author's files.Krystal, A., Lankford, A., Durrence, H., Ludington, E., Jochelson, P., Rogowski, R., & Roth, T. (2011). Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia SLEEP DOI: 10.5665/SLEEP.1294... Read more »
Krystal, A., Lankford, A., Durrence, H., Ludington, E., Jochelson, P., Rogowski, R., & Roth, T. (2011) Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia. SLEEP. DOI: 10.5665/SLEEP.1294
- May 4, 2012
- 11:50 AM
- 122 views
Naltrexone Implants for Polydrug Dependence
by William Yates, M.D. in Brain Posts
One of the challenges in the treatment of drug dependence is the common clinical feature of polydrug dependence. Those with serious drug dependence problems typically use multiple substances including alcohol.Pharmacological interventions that address one specific drug may not influence craving or use of another substance. For example, methadone clinics for heroin dependence commonly find continued use of cocaine and other stimulants despite significant reduction in heroin use. Obviously, reduction in drug use across all the drugs of abuse categories is a better clinical outcome.A clinical trial recently published in the American Journal of Psychiatry suggests that naltrexone implants may provide one strategy in drug dependence across more than one drug class. Here are the key components in the design of this clinical trial:Overview: Double-blind randomized controlled clinical trial of 10 weeks durationSubjects: 100 subjects with combined opioid and amphetamine dependence ages 18 to 50 years oldIntervention: Implantation (beneath the skin) of a device with 1000 mg of naltrexone sufficient to block opioid effects for 8 to 10 weeks or implantation of a similar device containing placeboOutcome: Primary outcome variables including compliance in follow up (retention in the study), percentage of urine drug screens negative for both opioids and amphetamines and a clinician rated global assessment of clinical statusStatistical analysis: Intention to treat model using Chi-square analysis for categorical variables and Mann-Whitney U test between groups for continuous measuresThe clinical trial demonstrated a significant improvement in all three outcome measures (nalrexone vs control rates)Study retention: 52% vs 28%Proportion of drug free samples: 38% vs 16%Improvement in global clinical status rating: 56% vs 14%Polydrug dependence clinical trials typically show low rates of response in previous clinical research studies. The relative low percentage of urine drug samples clean for both opioids and amphetamine in this study shows further work to be done in designing more effective treatment approaches. But the outcome for naltrexone implants in this study is a step in the right direction.Naltrexone implants reduce problems of drug compliance found in many drug dependence populations. The authors note the subjects in the study tolerated the implants well with no increase in liver enzymes that has been noted in some studies of oral naltrexone. No deaths due to drug overdose or natural causes occurred during the course of the study.This is one of the first studies to show improvement across drug classes using a pharmacological interventions. The study was conducted in Russia, a country with limited research publications in the clinical neuroscience domain. I hope we see more research from Russian sources in the years to come.Photo of Canadian goose goslings from the author's files.Tiihonen, J. (2012). Naltrexone Implant for the Treatment of Polydrug Dependence: A Randomized Controlled Trial American Journal of Psychiatry DOI: 10.1176/appi.ajp.2011.11071121... Read more »
Tiihonen, J. (2012) Naltrexone Implant for the Treatment of Polydrug Dependence: A Randomized Controlled Trial. American Journal of Psychiatry. DOI: 10.1176/appi.ajp.2011.11071121
- May 1, 2012
- 11:36 AM
- 102 views
Bipolar Disorder, Lithium and Hippocampal Volume
by William Yates, M.D. in Brain Posts
Brain neuroimaging studies continue to outline the structural and functional abnormalities in disorders of mood. A relatively consistent finding has been a reduced volume of the brain hippocampus in major depressive disorder. Studies of hippocampal volume in the less common bipolar disorder have been inconsistent--some studies have found reduced hippocampal volumes while others have not.The hippocampus is an important brain region to understand in the mood disorders. The hippocampus has a key role in memory. Patients with mood disorders commonly display impairments in mood including deficitis in autobiographical memory. Unipolar depression appears to increase risk for later development of Alzheimer's disease. Hippocampal volume reduction is a common finding in Alzheimer's disease.In an attempt to explain the discrepant findings of hippocampal volume in bipolar disorder, Hajek and colleagues completed a meta-analysis of 16 previous studies. They hypothesized that lithium pharmacotherapy status may be a confounder in studies of hippocampal volume in this disorder.Lithium is noted to have significant neuroprotective effects. The authors of this study note the neuroprotective effects of lithium have been demonstrated in tissue culture and animal models involving neurons. It is possible that bipolar patients treated with lithium may experience less hippocampal atrophy than those not treated with lithium.The key elements of the design of this study were:Study inclusion: MEDLINE and other online journal studies of hippocampal volumes in bipolar disorder were included if subjects current lithium treatment status was notedStatistical analysis: Comprehensive Meta-Analysis software was used to calculate a Cohens d (a standardized measure of effect size) of right and left hippocampal volume in three groups: bipolar disorder on lithium (n=101), bipolar disorder not on lithium (n=245) and controls (n=456) without bipolar disorderThe key results from the study were:Bipolar subjects not on lithium: smaller hippocampal volumes were noted compared to controls for both the left hippocampus (effect size= -0.36) and the right hippocampus (effect size= -0.38)Bipolar subjects on lithium: larger hippocampal volumes were noted compared to bipolar subjects not on lithium for the left hippocampus (effect size=0.93) and the right hippocampus (effect size=1.07). Additionally, the bipolar subjects on lithium had larger hippocampal volumes than controls for the left hippocampus (effect size =0.51) and right hippocampus (effect size=0.53).The authors note their study had significant limitations. Current lithium status is a dichotomous variable and does not reflect historical duration and dose exposure to lithium in the subjects. The study does not example include any neuropsychological data that might inform whether volume preservation with lithium results in memory preservation in the disorder.However, this study does provide an important contribution to the research in brain structure in bipolar disorder. Future studies in bipolar subjects will need to examine historical and current exposure to lithium and other psychotropics in structural and functional imaging results.Photo of macaw from Palm Beach zoo from the author's files.Hajek T, Kopecek M, Höschl C, & Alda M (2012). Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis. Journal of psychiatry & neuroscience : JPN, 37 (3) PMID: 22498078... Read more »
Hajek T, Kopecek M, Höschl C, & Alda M. (2012) Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis. Journal of psychiatry , 37(3), 110143. PMID: 22498078
- April 30, 2012
- 12:08 PM
- 126 views
Ten Steps to Reduce Your Risk of Alzheimer's Disease
by William Yates, M.D. in Brain Posts
Alzheimer's disease (AD) presents one of the greatest public health challenges of the 21st century. The risk for Alzheimer's is most strongly linked to advancing age. As heart disease and cancer treatment improves, more individuals are reaching the age of risk for AD. Prevention is an important topic in AD as effective treatments are yet to be discovered. Although several AD drugs are available, these agents appear only to slow progression rather than reverse or cure the disorder.Genetic factors play a key role in risk for AD. However, environmental and behavioral factors also contribute to risk and are modifiable. Identifiable risk factors are known for AD. The U.S. Agency for Healthcare Research and Quality has recently published a comprehensive summary of the risk factors in AD and cognitive decline. A second recent review suggests that population-based prevention strategies may reduce the rates of AD by up to 25%. Links to these two references and a summary of prevention research at the Alzheimer's Association website are listed at the bottom of this post.Based on what we currently know, I will outline ten steps individuals might consider in their own personal lives to reduce their risk of AD.1. Build and maintain cognitive reserve. Cognitive decline occurs with the aging process. AD represents a specific more rapid decline in memory and other cognitive functions with age. Several studies demonstrate the protective effect of early cognitive development and lifelong engagement in intellectual stimulation. By "banking" a high level of cognitive reserve, individuals may prolong the period of time they function at a higher level.2. Engage in vigorous exercise on a regular basis. Aerobic exercise appears to contribute to prolonged brain vascular health. Vascular factors appear to contribute to components of cognitive decline and AD. Aerobic exercise for 30 minutes a day on most days of the week may reduce or delay the risk for AD.3. Protect against risk for traumatic brain injury. Traumatic brain injury can result in an increased risk for later AD. This effect may be primarily found in men as some studies fail to find an association in women with traumatic brain injury. The best interventions for reducing risk of traumatic brain injury include reducing exposure to high risk activities (i.e. football), wearing protective helmets when biking or riding a motorcycle, using seat belts in automobiles and driving automobiles with advanced airbag technology and safety design.4. Don't smoke cigarettes. Regular heavy smoking increases risk for brain vascular abnormalities including stroke and AD. If you smoke quit. If you don't smoke, don't start. Smoking cessations options are increasing and past failed attempts should not discourage additional cessation attempts.5. Maintain a normal body weight. Recent research studies are finding increased AD in individuals with obesity. The mechanism for this association is unclear, but may be related to the effects of obesity on vascular health, insulin function or a link to systemic inflammation. Reduce your weight if your are overweight. If you are in the normal weight range, maintain this weight over your lifespan.6. Consider the Mediterranean diet. The Mediterranean diet appears to reduce the rate of cognitive decline with age and may reduce risk of developing AD. This diet is high in content of fruits and vegetables with reduced consumption of red meat and full fat dairy products. Limited alcohol consumption also is included in the diet. High consumption of foods with protective omega three fatty acids may contribute to the diet's effect on cognitive function. I have previously posted on the potential benefits of the Mediterranean diet here and here.7. Maintain normal serum cholesterol and lipids. High serum cholesterol appears to affect the brain as well as the heart. There is some evidence the use of cholesterol lowering agents such as statins may reduce the process of amyloid development in the brain--a key pathological feature in AD.8. Treat depression if it is present. Depression is also a brain disease and appears to be associated with an increased risk for later AD. It is unclear whether late-onset depression is a possible symptom of early AD or whether depression specifically leads to an increased AD risk. Depression may contribute to behaviors that increase AD risk, i.e. higher smoking rates and reduced physical activity. Treatment of depression may reduce symptoms of depression as well as reduce risk of later AD.9. Treat diabetes if it is present. The potential role of insulin in AD is receiving increased research attention. Insulin resistance, a common feature of diabetes, appears to have a variety of deleterious effects on the brain and brain vasculature. Early identification and treatment of diabetes (both type I and type II) may reduce risk for AD.10. Build and maintain social support and social engagement. Social factors appear to contribute to the risk of AD. AD rates are higher in unmarried individuals living alone. Social interaction may be a cognitive enhancing activity that promotes learning and general cognitive engagement. Friends and family can challenge individuals to maintain intellectual interaction and stimulation.Definitive prospective research clinical trials linking these ten interventions to reduced AD risk are limited or non-existent. Association research studies cannot prove causality. Nevertheless, these ten steps are generally consistent with leading a healthy lifestyle. The chance that they may also reduce AD risk should provide added incentive forPhoto of a macaw from the Palm Beach Zoo from the author's files.Alzheimer's Association Prevention WebsiteAgency for Healthcare Research and Quality Report on Preventing Alzheimer's Disease and Cognitive DeclineBarnes DE, & Yaffe K (2011). The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet neurology, 10 (9), 819-28 PMID: 21775213... Read more »
Barnes DE, & Yaffe K. (2011) The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet neurology, 10(9), 819-28. PMID: 21775213
- April 27, 2012
- 02:06 PM
- 106 views
Alzheimer's and Brain Imaging: Part II
by William Yates, M.D. in Brain Posts
This is the second post on a review of the status of brain imaging research in Alzheimer's disease (AD). The source article for this post is a recent manuscript published in Cold Spring Harbor Perspectives in Medicine.My first post on this review summarized structural magnetic resonance imaging and functional magnetic imaging. That post can be found here.Two additional methods of imaging provide clinical and research opportunities in AD. These include fluorodeoxyglucose (FDG) positron emission tomography and imaging techniques that target a brain pathological marker for AD--deposition of the protein amyloid.Here is a summary of for each of these areas starting with FDG PET imaging:FDG PET imaging targets brain glucose metabolism--this is a marker for brain synaptic signaling reflecting predominantly the glutamate neurotransmitter systemAD typically shows decreased glucose metabolism in specific brain regions: posterior and medial parietal cortex, lateral parietal cortex, lateral temporal cortex and medial temporal cortexThe brain regions found affected in AD by FDG PET are part of the brain default mode networkSeverity of glucose hypometabolism by PET correlates with severity of clinical symptoms in ADFDG PET abnormalities are seen in those with the AD gene APOE episilon 4FDG PET can differentiate AD from other types of dementia such as frontotemporal dementiaFDG PET shows promise as a method of monitoring effectiveness of new AD drugs and may reduce the number of individual needed to participate using current psychometric outcome measuresThis imaging method has limitations of being relatively more expensive and may be affected by other non-AD brain pathological processes such as brain ischemia or inflammationAmyloid PET imaging in AD:Amyloid imaging represents a technique that directly images the distribution and amount of deposition of the amyloid protein in the brainSeveral tracer drugs for amyloid are available or in the process of developmentPooled research studies found 96% of AD patients demonstrated amyloid PET imaging abnormalitiesPooled research studies of individuals with mild cognitive impairment (MCI) found 59% had amyloid PET imaging abnormalities93% of MCI subjects who progressed to dementia on follow up had amyloid PET abnormalitiesAmyloid PET provides a quantitative measure of general and region specific brain amyloid burden that provides valuable research leverageAmyloid PET imaging is limited by cost and some tracers require an on site cyclotronAmyloid PET is an early measure of AD but does not allow for monitoring of progression of the disease--MRI and FDG PET are more appropriate for this functionThe authors of this review note additional research imaging applications in AD are being developed including diffusion tensor imaging, neurofibrillary tangle tracers and cholinergic neurotransmitter system markers. From a clinical standpoint, structural brain imaging (CT or MRI) can provide valuable information in the clinical assessment of cognitive decline. FDG PET appears clinically indicated when a presumed diagnosis of AD needs to be confirmed.Future research that combines several imaging techniques may provide additional insight into the diagnosis and progression of AD. Such types of combined imaging studies may also aid in clinical drug trials for AD by measuring brain response and monitoring for adverse effects of new drugs.Photo of sunrise in Juno Beach, Florida from the author's files.Johnson KA, Fox NC, Sperling RA, & Klunk WE (2012). Brain imaging in Alzheimer disease. Cold Spring Harbor perspectives in medicine, 2 (4) PMID: 22474610... Read more »
Johnson KA, Fox NC, Sperling RA, & Klunk WE. (2012) Brain imaging in Alzheimer disease. Cold Spring Harbor perspectives in medicine, 2(4). PMID: 22474610
- April 24, 2012
- 12:34 PM
- 85 views
Alzheimer's and Brain Imaging: Part I
by William Yates, M.D. in Brain Posts
Brain imaging research in Alzheimer's disease (AD) is advancing rapidly. Well written reviews of key current research findings and future directions are sometimes difficult to find. A recent review published in Cold Spring Harbor Perspectives in Medicine fills this gap with a summary of this topic. I will provide some commentary and key elements of their review.The imaging research related to AD can be separated into four areas: structural magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging and amyloid PET imaging. I will highlight some of the manuscript from each area. In this post, I will cover MRI and in the next post I will cover PET imaging.Structural MRI:An important tool for assessing the progressive cerebral atrophy seen in AD and other neurogenerative disordersMRI research has helped define the typical sites and sequencing of cerebral atrophy in AD: medial temporal lobe (entorhinal cortex), then hippocampus, amygdala and parahippocampusMRI can detect AD cerebral atrophy (medial temporal) before the onset of clinical symptoms allowing for it to be a proposed pre-dementia biomarker The extent of cerebral atrophy correlates highly with the severity of AD symptomsLongitudinal monitoring of cerebral atrophy by MRI may be one method to measure AD progressionMRI is widely available in clinical settings and clinical guidelines recommend MRI as one of two structural imaging tests for individuals with cognitive decline (the other option being computed tomography)The limitations of MRI in AD include nonspecificity as cerebral atrophy can occur in a variety of disorders and MRI lacks the ability to measure brain function or detect specific histopathological characteristics of ADMRI typically tasks longer to complete than a more rapid CT scan--for agitated noncompliant subjects it may be technically difficult to complete the scanFunctional MRI:Provides the ability to assess brain function on specific tasksEarly fMRI studies have documented decreased medial temporal lobe activation during memory encoding tasks in ADParadoxically, AD at-risk individuals and those with mild cognitive impairment have shown increased medial temporal lobe activation with memory tasks suggesting a brain function compensation prior to significant neuronal lossfMRI provides the ability to study brain networks including resting or default networks--research has documented abnormalities in the default network with ADStudies of brain network function in AD have demonstrated impaired connectivity between the hippocampus and the posterior cingulate/precuneusConnectivity deficits in AD have correlated with areas known to be affected by the amyloid plaques in ADA key limitation to fMRI is the technical requirement for very limited head motion during scanning--this may limit its use in AD patients with more severe cognitive impairmentfMRI is not currently clinically indicated in AD, more research will be needed to determine the clinical utility of this imaging techniqueThe authors note that MRI and fMRI will be important resources in future development of AD assessment and more importantly in monitoring progression and potential response to new treatment in AD. In the next post, I will review the research status in AD with FDG PET and amyloid marker PET imaging.Photo of seven pelicans flying at sunrise at Juno Beach, Florida from the author's files. Johnson KA, Fox NC, Sperling RA, & Klunk WE (2012). Brain imaging in Alzheimer disease. Cold Spring Harbor perspectives in medicine, 2 (4) PMID: 22474610... Read more »
Johnson KA, Fox NC, Sperling RA, & Klunk WE. (2012) Brain imaging in Alzheimer disease. Cold Spring Harbor perspectives in medicine, 2(4). PMID: 22474610
- April 23, 2012
- 12:01 PM
- 74 views
Prevention of Anxiety and Depression in Childhood
by William Yates, M.D. in Brain Posts
Strategies to prevent the development of mental disorders such as anxiety disorders and mood disorders are urgently needed. Prevention of mental disorders is important for a variety of reasons. First, these disorders cause significant psychological distress and emotional pain. Second, mental disorders impair academic, occupational and interpersonal function. Finally, many individuals with anxiety and mood disorders does not respond adequately to current pharmacological and psychotherapeutic interventions.Now a group from the Netherlands describes a new ongoing clinical trial designed to examine the effect of cognitive behavioral therapy (CBT) in a group of children at high-risk for anxiety and mood disorders. CBT is a relatively intense and costly intervention and probably impractical on a general population basis. Identifying high-risk individuals allows for targeting those most likely to need prevention interventions and those most likely to show a response.The Netherlands research team published an outline of the design of their prevention study in the journal BMC Psychiatry. To meet eligibility criteria for "ultra high-risk" children and adolescents need to meet one of two pathways to entry.Scoring at or above the 80th percentile on a psychometric measure of depression or anxietyMeeting two out of three of the following criteriaFemale genderBoth parents affected by a mood or anxiety disorderOne parent with a suicide attempt or completed suicideThe study seeks to enroll 554 children and adolescents between the ages of 8 and 17 with at least 204 receiving the CBT active intervention. The CBT active interventions includes:10 sessions with the child or adolescent that focus on "family functioning and social network, being proud of strengths, focus on positive emotions and events, problem solving, and breaking the cycle of avoidance behaviour"2 sessions with the parents that include how to discuss their own mood or anxiety disorder with their child, positive parenting behaviors and how to use the family social network to support the childA group of control children and adolescents not receiving the CBT intervention will be identified. After 24 months, the CBT group and the control groups will be compared on the rate of development of an anxiety or mood disorder diagnosis us structured psychiatric interviews.The study is currently ongoing and with a two year follow-up period there will be several years before the results will be known. This is an important study and other studies of prevention interventions in high risk children and adolescents need to be designed and completed.Photo of wood stork from Palm Beach Gardens, Florida from the author's files.Nauta MH, Festen H, Reichart CG, Nolen WA, Stant AD, Bockting CL, van der Wee NJ, Beekman A, Doreleijers TA, Hartman CA, de Jong PJ, & de Vries SO (2012). Preventing mood and anxiety disorders in youth: a multi-centre RCT in the high risk offspring of depressed and anxious patients. BMC psychiatry, 12 (1) PMID: 22510426... Read more »
Nauta MH, Festen H, Reichart CG, Nolen WA, Stant AD, Bockting CL, van der Wee NJ, Beekman A, Doreleijers TA, Hartman CA.... (2012) Preventing mood and anxiety disorders in youth: a multi-centre RCT in the high risk offspring of depressed and anxious patients. BMC psychiatry, 12(1), 31. PMID: 22510426
- April 20, 2012
- 12:07 PM
- 47 views
ADHD Symptoms and Brain Volume in Adults
by William Yates, M.D. in Brain Posts
Inattention is a core feature of attention deficit-hyperactivity disorder (ADHD). For a diagnosis of ADHD, inattention or hyperactivity symptoms must begin during childhood. Many children and adolescents with ADHD demonstrate improvement of symptoms during maturation. However, a significant number of individuals will continue with significant ADHD symptoms into adulthood.The imaging correlates of ADHD and attention symptoms is a research area of significant interest. Understanding the brain correlates of ADHD may provide insight into the pathophysiology and treatment of this disorder.Hoogman and colleagues from the Netherlands recently examined the association of attention symptoms in adults with a measure of brain structure known as total brain volume. The key elements of the design of their study included:Study sample: 652 adults aged 18-35 years self-reported as in good healthPsychometrics: Rating of 23 ADHD symptoms as outlined in DSM-IV-TRImaging: Magnetic brain imaging using 1.5 and 3.0 Tesla scannersKey outcome variable: Total brain volume (sum of white and grey matter volumes) calculated by computerized algorithmStatistical analysis: Comparison of inattention and hyperactivity and total ADHD symptom scores on brain volume measurements using linear regression analysisThe research team demonstrated an association between total ADHD symptoms and reduced total brain volume. The strongest association was noted between inattention symptoms and reduced total brain volume. Those with four or more inattention symptoms (the threshold for impairment in DSM-IV ADHD) were noted to have the smallest total brain volumes.Inattention in adulthood is a non-specific symptom and may be related to a variety of underlying conditions including anxiety and mood disorders. Cross-sectional study designs used in this study are unable to tease out longitudinal effects of symptoms or disorders on measures such as brain volumes.The authors noted this sample was a very highly educated group. Seventy percent of the subjects were graduates or students in masters or doctoral education programs. Such a highly educated subgroup may not be representative of the association of ADHD symptoms and total brain volumes in the general population.The authors also noted prior research links total brain volumes with genetic influences. They note total brain volume may be helpful as an intermediate phenotype helpful in identification of genes increasing risk for ADHD.Longitudinal brain imaging studies in ADHD and normal individuals will be needed to better understand the brain structural and functional correlates in ADHD.Photo of squirrel from Juno Beach, Florida from the authors files.Hoogman, M., Rijpkema, M., Janss, L., Brunner, H., Fernandez, G., Buitelaar, J., Franke, B., & Arias-Vásquez, A. (2012). Current Self-Reported Symptoms of Attention Deficit/Hyperactivity Disorder Are Associated with Total Brain Volume in Healthy Adults PLoS ONE, 7 (2) DOI: 10.1371/journal.pone.0031273... Read more »
Hoogman, M., Rijpkema, M., Janss, L., Brunner, H., Fernandez, G., Buitelaar, J., Franke, B., & Arias-Vásquez, A. (2012) Current Self-Reported Symptoms of Attention Deficit/Hyperactivity Disorder Are Associated with Total Brain Volume in Healthy Adults. PLoS ONE, 7(2). DOI: 10.1371/journal.pone.0031273
- April 19, 2012
- 11:18 AM
- 50 views
Frailty as a Risk Factor for Alzheimer's Dementia
by William Yates, M.D. in Brain Posts
Several traditional risk factors have been identified for the future development of Alzheimer's dementia. These include age, lower premorbid educational level, history of head trauma and family history of Alzheimer's. However, despite discovery of these risk factors they fail to completely explain the risk of developing Alzheimer's.A group of researchers from Dalhousie University in Halifax, Canada recently published a study exploring novel non-traditional factors that might influence risk of dementia and death. They constructed a roster of 19 variables linked to frailty but not previously linked to dementia. These variables included items such as:vision problemshearing problemsarthritisdental problemsbladder or bowel control problemsstomach problemsA group of over 7,000 elderly Canadian subjects with normal cognitive function at baseline were rated on these 19 frailty variables and were followed for ten years. Risk for death and dementia in the sample were analyzed with attention to the association with the frailty variables.Individual frailty variables had limited association with risk for death or dementia. However, when combined to produce a frailty index important associations were found. Subjects with higher scores on the frailty index were much more likely to die in the ten-year followup period (65% risk of death in the high index score group compared to only 25% in the low index score group). Additionally, the risk of developing Alzheimer's disease in the ten-year followup period was elevated by higher frailty index scores (50% risk for higher frailty versus 15% for lower index subjects).The research group controlled for possible confounding effects of variables noted to be related to dementia, i.e. age and educational status. The effect of a higher frailty index on Alzheimer's dementia risk persisted after controlling for these variables.The authors note the potential important clinical and public health implications of their findings. Efforts to identify and treat general medical health conditions in the elderly may reduce the risk for incident Alzheimer's disease. Future research in the epidemiology of dementia will need to assess and examine the effect of general medical status.Photo of osprey from the author's files.Song, X., Mitnitski, A., & Rockwood, K. (2011). Nontraditional risk factors combine to predict Alzheimer disease and dementia Neurology, 77 (3), 227-234 DOI: 10.1212/WNL.0b013e318225c6bc... Read more »
Song, X., Mitnitski, A., & Rockwood, K. (2011) Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology, 77(3), 227-234. DOI: 10.1212/WNL.0b013e318225c6bc
- March 21, 2012
- 04:06 PM
- 165 views
Risk Factors for Pathological Gambling
by William Yates, M.D. in Brain Posts
The risk for developing pathological gambling appears to vary among individuals in the population. Risk factors that have been identified include male gender, a substance use disorder including alcohol, drug or nicotine dependence, and a proneness to other impulsive behaviors. Individuals who seek novelty and exposure to risk appear to be more likely to get into pathological gambling behaviors.There may also be some protective factors in risk for pathological gambling. Strong belief in a religion that proscribes gambling may play a role in reducing such behavior.Neuroscience is just beginning to understand the mechanisms of risk assessment in decision making. One recently published study examined the role of risk aversion in both conscious and non-conscious decision making.Shou Wang at California Institute of Technology along with colleagues in Switzerland, Japan and Australia studies a series of individuals using a variant of the Iowa Gambling Task. The Iowa Gambling Task is a neuropsychological task that examines decision making including unconscious components to decision making.The task in this study examines how likely individuals are to risk a monetary wager in a perceived game of chance similar to the task in many gambling games. The authors of the study came to the following conclusion about risk aversion as it affects decision making:Individuals can make optimal choices without being fully aware of the basis for their choicesRisk aversion may have two components: a cognitive/explicit component that individuals are conscious of and a second component that may be unconscious and based on an emotional feeling of riskThe authors note that many pathological gamblers can cognitively identify the risk/reward ratio in gambling games but fail to be able to act in this manner in real life possibly due to an "inability to implement risk mechanisms based on emotional feelings."The authors note the brain circuits controlling emotional learning and decision making appear to be located in the brain insula and in portions of the basal ganglia. This study suggests a risk factor for pathological gambling may be an abnormal reduction in the ability to process unconscious emotional cues in the assessment of risk.In the next to posts, I will examine a recent brain imaging study in pathological gambling as well as a clinical trial for treatment of the disorder.Photo of sand hill crane captured at Busch Wildlife Refuge center in Jupiter, Florida from the author's files.Wang, S., Krajbich, I., Adolphs, R., & Tsuchiya, N. (2012). The Role of Risk Aversion in Non-Conscious Decision Making Frontiers in Psychology, 3 DOI: 10.3389/fpsyg.2012.00050... Read more »
Wang, S., Krajbich, I., Adolphs, R., & Tsuchiya, N. (2012) The Role of Risk Aversion in Non-Conscious Decision Making. Frontiers in Psychology. DOI: 10.3389/fpsyg.2012.00050
- February 27, 2012
- 08:23 AM
- 151 views
Risk Factors for Accidental Overdose Death
by William Yates, M.D. in Brain Posts
The recent accidental overdose deaths of Whitney Houston and other celebrities highlights the growing problem of prescription drug abuse. I have previous highlighted some recent important clinical research studies in prescription drug abuse including:The Epidemiology of Prescription Opioid AbusePathways to Prescription Opioid OverdosePrescription Opioid Overdose ToxicologyNow there is a recent study that examines some of the risk factors for accidental overdose death. This study by Bohnert and colleagues at the University of Michigan focused on a sample of U.S. veterans. The key elements of the design of their study included:Subject selection: All veterans accessing the VA health care system during a one year period from October 1, 1998 to September 30, 1999.Case identification: Using the U.S. National Death Index, all subjects were queried for evidence of an accidental overdose death from their death certificates from fiscal year 2000 through fiscal year 2006.Risk factor data: The risk factor information was collected from centralized VA health data bases and the charts. Data included sociodemographic information and coded psychiatric and substance dependence diagnoses.Data analysis: Cox proportional hazards statistical modeling adjusting for age, gender, VA priority status (service connected disabled individuals have higher priority status), and the medical illness severity using a measure known as the Charlson comorbidity score.The study yielded some important results for understanding the risk factors for accidental overdose deaths. There were 4, 485 accidental overdose deaths in this veterans population of over 3,000,000 individuals (.13%). Men were approximately twice as likely as women to suffer an accidental overdose death. The risk peaked in individuals in the 40-49 year age group and declined in those in older age cohorts. The diagnoses associated with the highest non-adjusted risks (hazard ratios) were:Opioid use disorders (22.0)Stimulant use disorders (12.5)Cannabis use disorders (7.9)Alcohol use disorders (7.8)Bipolar disorder (5.1)Major depression (4.3)PTSD (3.9)Schizophrenia (3.6)Alcohol and substance use disorders are more common in mental disorders so it is important to control for this is looking for risk with individual mental disorder diagnoses. After controlling for this substance abuse comorbidity, the psychiatric disorders continued to contribute approximately a 20-80% increase in accidental overdose death. The authors review some of the potential mechanism for higher rates of accidental overdose deaths in those with a mental disorder. These include more wreckless use of medication with lower fear of adverse consequences, misclassification of a suicide as an accidental overdose death, and simply that psychiatric disorders are treated with medications that can contribute to an accidental overdose death.This study has important implications as it suggests those with mental disorders need assessment for risk accidental overdose death as well as assessment of risk for suicide. In addition, the study supports the need for education about the risk of combining pain medication with antianxiety and antidepressant drugs as well as the increased risk of drinking and intoxication with psychotropic drugs.Photo of Siamung from the Palm Beach Zoo from the author's files.Bohnert, A., Ilgen, M., Ignacio, R., McCarthy, J., Valenstein, M., & Blow, F. (2011). Risk of Death From Accidental Overdose Associated With Psychiatric and Substance Use Disorders American Journal of Psychiatry DOI: 10.1176/appi.ajp.2011.10101476... Read more »
Bohnert, A., Ilgen, M., Ignacio, R., McCarthy, J., Valenstein, M., & Blow, F. (2011) Risk of Death From Accidental Overdose Associated With Psychiatric and Substance Use Disorders. American Journal of Psychiatry. DOI: 10.1176/appi.ajp.2011.10101476
- February 24, 2012
- 11:34 AM
- 195 views
Genetic Variants and Risk of ADHD
by William Yates, M.D. in Brain Posts
The search for specific genes contributing to the risk for attention deficit-hyperactivity has failed to demonstrate a consistent result. Genetic factors do appear to be important given the results of family, adoption and twin studies. The failure to find specific gene effects suggest the genetic contribution to ADHD risk is more complex and will require larger samples and more complex genetic research designs.Stergiakouli and colleagues recently published a novel study examining the genetics of ADHD. In this study, the combined an approach looking at copy number variations (CNVs) with more specific gene effects using the technique known as single-nucleotide polymorphisms (SNPs). CNVs are genetic variations that represent not a specific genetic mutation, but rather a variation in the number of copies of specific genes. CNVs appear to produce abnormalities in gene function and contribute to the risk of a variety of clinical disorders.In this combined CNV and SNP study, 727 children with ADHD were compared to 5081 comparison subjects. Using a genome-wide association approach, the authors noted the following key findings:No SNP reached statistically significant levels in the sampleRare CNVs were more common in the ADHD sample than controlsThere were 13 biological pathways (linked with SNPs) that overlapped with the rare CNVsThese pathways included pathways for cholesterol metabolism and central nervous system developmentAt the specific gene level, the gene CHRNA7 (a nicotinic receptor subunit) was found in six CNV duplication subjectsThe authors conclude their study demonstrates a "highly significant overlap of biological pathways hit by both CNVs and SNPs". They note this finding indicates a need to continue the search for both CNV and SNPs in further understanding the genetics of ADHD. Additionally, they conclude that "CHRNA7 is a promising candidate" gene.The authors the gene CHRNA7 is widely expressed in the hippocampus and other brain regions and has been implicated in rapid synaptic transmission, cognitive deficits, schizophrenia and nicotine dependence. The findings support the potential importance of this gene in ADHD.In summary, the search for a single gene in ADHD appears to be unlikely to yield a final answer in the genetics of ADHD. However, more complex genetic effects are being found and further study of CNVs in conjunction with genome-wide association studies may produce important results in this common clinical neuroscience disorder.Phote of green heron from the Busch Wildlife Refuge Center in Juno Beach, Florida for the authors files.Stergiakouli, E. (2012). Investigating the Contribution of Common Genetic Variants to the Risk and Pathogenesis of ADHD American Journal of Psychiatry, 169 (2) DOI: 10.1176/appi.ajp.2011.11040551... Read more »
Stergiakouli, E. (2012) Investigating the Contribution of Common Genetic Variants to the Risk and Pathogenesis of ADHD. American Journal of Psychiatry, 169(2), 186. DOI: 10.1176/appi.ajp.2011.11040551
- February 12, 2012
- 01:21 PM
- 188 views
Cell Phone Use and Risk of Brain Cancer
by William Yates, M.D. in Brain Posts
In my last post I examined the epidemiology of brain tumors using a summary of the latest data from the United States. The summary noted the slight decline in the number of malignant brain cancers over the last twenty years.One area of concern that is receiving increased attention is the potential for cell phone risk to raise the risk of brain cancers.Obviously if cell phone use was a very large effect one might have expected an increase in the rates of brain tumors and cancer over the last twenty years. This corresponding to the time when cell phone use has increased dramatically in the U.S. and around the world. Multiple case control studies have been completed examining this possible association and the majority of studies have not demonstrated a significant effect. One recent study from Frei in Denmark along with colleagues in France and Switzerland adds to the apparent safety of cell phones.The key design elements of the Frei study included:Study type: Cohort study using all individuals born in Denmark from April 1, 1968Study groups: Cell phone subscribers status (subscribers versus non-subscribers) was identified via phone records and linked to centralized health records containing health registry information including presence or central nervous system tumors.Confounding variables controlled: age, gender, education level, incomeOutcome variable: incidence rates ratio with 95% confidence interalThis data set included over 300,000 individuals with a cell phone subscription and a larger group of control individuals. The researchers grouped brain tumors into malignant gliomas, meningiomas (largely benign brain tumors) and a residual group of other brain tumor and cancer types.The analysis showed the incidence rates for cell phones subscribers did not statistically differ from those who did not differ from those without cell phone subscriptions in any brain tumor or cancer group.This is an important study. It represents a very large data set with comprehensive registry data that would be difficult to replicate in the United States health care system. The authors noted no specific increase in temporal lobe gliomas in the cell phone user group. This region of the brain would be the closest region to cell phone placement during calls and theoretically most likely to be affected if an association was present.The authors concluded: "a small to moderate increase in risk for subgroups of heavy users or after even longer induction periods than 10-15 years cannot be ruled out". Nevertheless, this study should reduce worry that cell phones users are significantly increasing their risk for brain tumors or cancer.Photo of male and female chachalaca pair from Bentsen Birding Center in Texas from the author's files.Frei, P., Poulsen, A., Johansen, C., Olsen, J., Steding-Jessen, M., & Schuz, J. (2011). Use of mobile phones and risk of brain tumours: update of Danish cohort study BMJ, 343 (oct19 4) DOI: 10.1136/bmj.d6387... Read more »
Frei, P., Poulsen, A., Johansen, C., Olsen, J., Steding-Jessen, M., & Schuz, J. (2011) Use of mobile phones and risk of brain tumours: update of Danish cohort study. BMJ, 343(oct19 4). DOI: 10.1136/bmj.d6387
- January 28, 2012
- 05:38 PM
- 140 views
Epidemiology of Brain Cancer
by William Yates, M.D. in Brain Posts
A recent summary of the trends in cancer highlighted the epidemiology of brain and other nervous system tumors. In the United States, 213,500 brain and other nervous system tumors were diagnosed during the four year period from 2004 through 2007.Brain and other nervous systems (ONS) tumors rank fourteenth in the top 15 cancers for men and fifteenth in the top 15 cancers for women in the United States.Overall rates for brain and ONS tumors during this period were 22.37 per 100,000 for men and slightly higher at 26.55 per 100,000 for women.In adults, the majority (66.3%) of brain and ONS tumors were benign. Although brain and ONS tumors are less common in children, when they occur they are less likely (34.8%) to be benign.The most common histological types of brain and ONS tumors in the most recent analysis were (rate per 100,000):Meningioma (9.2)Glioblastoma (4.4)Tumors of the sella turcica region (3.6)Acoustic neuroma (1.5)Astrocytomas (1.2)Glioblastomas and astrocytomas are malignant brain cancers while the other three types of tumors are overwhelmingly benign with less than 3% classified as malignant.Five year survival rates for the malignant brain cancers have improved over the last approximately twenty year periods. Here are the most recent five year survival rates group by age:19 and younger (75.3%)20-39 (65.1%)40-64 years (26.6%)65 and older (<5%)The five year survival rates demonstrate a significant trend for a poorer prognosis with older age groups. This represents a trend for brain cancer in older populations to be of a more aggressive type with poorer response to surgery, radiation and chemotherapy interventions.The rates of brain cancer are relatively similar throughout the geographic regions of the United States and throughout the world. This supports a predominant genetic role for brain cancer risk. Known risk factors for brain cancer are:Family history of brain cancerCaucasian raceAdvanced ageExposure to ionizing radiationExposure to toxic chemicalsSeveral studies have demonstrated that individuals with atopic diseases such as eczema, seasonal allergies and asthma have a reduced risk of malignant gliomas. The mechanism for this protective effect is unclear.In the next two posts, I will summarize some of the recent research related to cell phone use and brain cancer rates. Additionally, I will review an interesting study suggesting the antiseizure drug valproic acid may contribute to increased survival duration in brain cancer.Photo of bird known as the plain chachalaca from the author's files.Kohler, B., Ward, E., McCarthy, B., Schymura, M., Ries, L., Eheman, C., Jemal, A., Anderson, R., Ajani, U., & Edwards, B. (2011). Annual Report to the Nation on the Status of Cancer, 1975-2007, Featuring Tumors of the Brain and Other Nervous System JNCI Journal of the National Cancer Institute, 103 (9), 714-736 DOI: 10.1093/jnci/djr077... Read more »
Kohler, B., Ward, E., McCarthy, B., Schymura, M., Ries, L., Eheman, C., Jemal, A., Anderson, R., Ajani, U., & Edwards, B. (2011) Annual Report to the Nation on the Status of Cancer, 1975-2007, Featuring Tumors of the Brain and Other Nervous System. JNCI Journal of the National Cancer Institute, 103(9), 714-736. DOI: 10.1093/jnci/djr077
- January 23, 2012
- 03:18 PM
- 149 views
Parent Training and Conduct Disorder Outcome
by William Yates, M.D. in Brain Posts
Three previous posts examined the clinical neuroscience disorder antisocial personality disorder (ASPD). This condition results in high societal costs for crime and incarceration for individuals with ASPD.ASPD appears to have significant genetic contributions and brain imaging studies show abnormal brain maturational patterns in the premotor cortex area as well as impaired processing of facial emotional expression.Antisocial personality is an early age of onset disorder with conduct disorder symptoms emerging during childhood and adolescence. Their is no evidence-based consensus on pharmacological treatment options in conduct disorder and ASPD.This leaves psychological and behavioral interventions as the current primary treatment option. But do these types of interventions work and do they produce lasting changes in the longitudinal trajectory of ASPD.Drugli and colleagues from Norway published an outcome study of conduct disorder following a randomized controlled trial of a parental training intervention known as "The Incredible Years".The Incredible Years parent training program emphasized developing parental skills to improve the child's social and behavioral development. Key features include instruction on how to play with other children, social and emotional skills training, establishment of routines and rules to promote responsibility, strategies to manage misbehavior and teaching problem solving. More information about The Incredible Years program can be found here.Drugli and colleagues followed a subgroup of children in their initial randomized trial. This follow up lasted five to six years. Control children in the original study were on a wait list for six months and then received The Incredible Years intervention so no controlled group outcome can be made. However, in the follow up analysis the research team found only one third of children enrolled with an initial diagnosis of oppositional defiant disorder or conduct continued to meet diagnostic criteria for the disorder.Predictors for persistence of a clinical diagnosis at outcome included:female genderliving with mother onlya baseline diagnosis of conduct disorder rather than oppositional defiant disorderhigher levels of conduct disorder symptomshigher baseline levels of internalizing symptoms such as anxiety or depressionmaternal depressive symptoms after treatment interventionmaternal stress rating of parentingThe predictor findings suggest that parental factors play a key role in the effectiveness of the parental training intervention. Single mothers and those with higher stress and depression symptoms may have more trouble in continuing to use the skills learned with the intervention.Additionally, this intervention may not be as effective for children with more severe conduct disorders. Parental training in childhood behavioral disorders provides a reasonable first step for early treatment of those at risk of antisocial personality. However, such an intervention strategy is limited by frequent parental emotional and behavioral problems found in the families of high-risk children.Increased research targeting the secondary prevention of aggressive behaviors and ASPD in children with conduct disorder should be a priority. Photo of a flicker searching for food from the author's file.Drugli MB, Larsson B, Fossum S, & Mørch WT (2010). Five- to six-year outcome and its prediction for children with ODD/CD treated with parent training. Journal of child psychology and psychiatry, and allied disciplines, 51 (5), 559-66 PMID: 20015193 ... Read more »
Drugli MB, Larsson B, Fossum S, & Mørch WT. (2010) Five- to six-year outcome and its prediction for children with ODD/CD treated with parent training. Journal of child psychology and psychiatry, and allied disciplines, 51(5), 559-66. PMID: 20015193
- January 20, 2012
- 11:40 AM
- 308 views
Brain Imaging in Antisocial Personality: II
by William Yates, M.D. in Brain Posts
This is the second in a series of posts looking at recent imaging findings in antisocial personality. In the first post, I reviewed an fMRI study that found deficits in connectivity maturation involving the premotor cortex in a sample of incarcerated juveniles.In this post, I will review a study looking a emotional face processing. Accurately assessing the emotions of others and adjusting ones own behavior is a key component to social development and appropriate social behavior.Individuals with antisocial personality disorder commonly display childhood and adolescent forms of the disorder. These child and adolescent behaviors often meet the criteria for conduct disorder. About 75% of children with conduct disorder will go on to develop adult antisocial personality disorder.Passamonti and colleagues from the University of Cambridge in England recently completed and published a study of emotional face processing in a series of male adolescents with conduct disorder and control adolescents without conduct disorder.Conduct disorder adolescents were divided into those with an earlier age of onset (at least one significant conduct disorder symptoms prior to age 10) and those whose first significant symptom developed at 10 or later. This classification is considered valid as adolescents with later emerging conduct disorder problems are felt to be more influenced by peer group behaviors. Subjects completed a series of face emotion tasks while being imaged using functional magnetic resonance imaging. Emotional images presented fell into one of three emotions--angry faces, sad faces or a neutral facial expression.The key findings from the study related to amygdala responses were:Both groups of adolescents with conduct disorder demonstrated a reduced responses in brain regions felt to be linked to antisocial behaviorEarly onset conduct disorder adolescents showed reduced amygdala activation for sad versus neutral facesEarly onset conduct disorder adolescents showed reduced amygdala activation for sad faces relative to the control fixation taskThe conduct disorder groups also demonstrated abnormal responses to facial emotions in ventromedial prefrontal cortex, orbitofrontal cortex and the insula. The authors note their study provides some support for the distinction between early and late onset conduct disorder. Although these groups share some features in emotional processing, early onset conduct disorder appears to be associated with more severe deficits in accurately processing sad faces.This study suggests emotional processing deficits may contribute to some of the behaviors of antisocial personality. Such individuals are typically seen to lack empathy and to behave without regard for the effect of their behavior on others. Part of this pattern may be a reduced ability to recognize emotional expression in others. A part of their behavior may represent a partial "blindness" to sad emotional states of those around them including family members and peers.The authors note their study my provide a impetus to describing a phenotype with a poor prognosis and likely continuation of antisocial behavior into adulthood. Functional MRI studies of neural markers may aid in defining high-risk groups for more intensive secondary prevention intervention.Photo of great blue heron at sunrise in South Padre Island, Texas from the author's files.Passamonti L, Fairchild G, Goodyer IM, Hurford G, Hagan CC, Rowe JB, & Calder AJ (2010). Neural abnormalities in early-onset and adolescence-onset conduct disorder. Archives of general psychiatry, 67 (7), 729-38 PMID: 20603454... Read more »
Passamonti L, Fairchild G, Goodyer IM, Hurford G, Hagan CC, Rowe JB, & Calder AJ. (2010) Neural abnormalities in early-onset and adolescence-onset conduct disorder. Archives of general psychiatry, 67(7), 729-38. PMID: 20603454
- January 19, 2012
- 09:22 AM
- 268 views
Brain Imaging in Antisocial Personality: I
by William Yates, M.D. in Brain Posts
Antisocial personality disorder (ASPD) is linked to a variety of emotional and behavioral abnormalities with significant public health implications.Key components of antisocial personality disorder include irritability with anger dysregulation. Individuals with ASPD are quick tempered with anger outbursts commonly leading to physical or emotional aggressiveness towards others.The emotional and behavioral abnormalities in ASPD may provide a model for studying specific brain regions controlling these functions. In the next few posts, I will review some of the brain imaging abnormalities that have been linked to ASPD. I will first begin by looking at a study of functional connectivity in juvenile offenders.Shannon from Washington University in Saint Louis and colleagues from the Oregon Health and Science University and the University of New Mexico have published a study of the default network in a group of juvenile offenders. The authors of this study note functional connectivity is a developmental process. Children's brain show different functional connectivity patterns than that of adults--children have strong short-distant connections while adults have stronger long-distant connections. They note that abnormal maturation patterns in functional connectivity have been linked to several clinical neuroscience disorders including ADHD, autism, schizophrenia, Alzheimer's disease and Parkinson's disease. These finding support the potential for abnormal maturation patterns in conduct disorder and antisocial personality disorder.The key elements in the design of their study were:Subjects: 122 juveniles incarcerated for a variety of crimes including physical and sexual assault contrasted with 95 control individualsScanning method: Mobile fMRI 1.5T scanner (cases) and 3.0T scanner (controls)Scanning analysis: Resting state connectivity among brain systemsPsychometric assessment: Hare Psychopathy Checklist (PCL-YV) consisting of a empathy subfactor and an impulsivity/need for stimulation factorNo resting connectivity abnormalities were linked to the empathy factor from the PCL-YV. However, some interesting findings were noted in the impulsivity domain. The found differences linked to impulsivity in the motor planning region of the cortex (premotor cortex).High impulsivity scores common in the juvenile offender group was associated with connections between the motor planning region and regions linked to spontaneous behavior and self-referential cogniton.In contrast, low impulsivity offenders and controls showed associations between this motor planning region with spatial attention and executive function and control.Interestingly, the high impulsivity pattern of connectivity appeared common in the youngest controls. Older controls showed the typical motor planning-executive functioning connectivity.The authors propose that "impulsivity in the offender population is a consequence of delay in typical development rather than a distinct abnormality".The authors note that their finding raises the possibility that specific intervention strategies to modify functional maturation connectivity may promising. The relatively focal nature of deficits in this study support the potential for specific therapeutic remediation.This finding in juvenile populations needs to be replicated in adult offender populations. Impulsivity and aggressiveness abnormalities in ASPD have an early age of onset and is persistent into adulthood for many individuals.Nevertheless, designing specific impulsivity remediation treatments with serial functional connectivity maturation analysis holds promise for new secondary prevention strategies in ASPD.Filtered image of a pair of laughing gulls from the author's file. Original photo can be found here.Shannon BJ, Raichle ME, Snyder AZ, Fair DA, Mills KL, Zhang D, Bache K, Calhoun VD, Nigg JT, Nagel BJ, Stevens AA, & Kiehl KA (2011). Premotor functional connectivity predicts impulsivity in juvenile offenders. Proceedings of the National Academy of Sciences of the United States of America, 108 (27), 11241-5 PMID: 2170923621709236... Read more »
Shannon BJ, Raichle ME, Snyder AZ, Fair DA, Mills KL, Zhang D, Bache K, Calhoun VD, Nigg JT, Nagel BJ.... (2011) Premotor functional connectivity predicts impulsivity in juvenile offenders. Proceedings of the National Academy of Sciences of the United States of America, 108(27), 11241-5. PMID: 21709236
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