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May 1, 2012
11:36 AM
350 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
407 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
470 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
390 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
267 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
355 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
358 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
378 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
372 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
393 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
378 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
355 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
363 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
554 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
532 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

January 18, 2012
09:40 AM
502 views

Twin Study of Antisocial Personality Disorder

by William Yates, M.D. in Brain Posts

Twin studies provide a valuable method to explore the genetic and environmental contributions to a variety of clinical neuroscience disorders.Twin studies use a method where identical twins (monozygotic) sharing 100% of their genes are compared to non-identical twins (dizygotic) who share 50% of their genes.Disorders that are entirely environmental would be found at the same rates in non-identical twins and indentical twins. Disorders with a strong genetic contribution would be more likely to be found in monozygotic twin (where one twin is affected) than in a dizygotic twin (where one twin is affected).Antisocial personality disorder (ASPD) is an early-onset disorder characterized by aggressive behavior, frequent rule breaking and failure to consider the effect of one's behavior on other individuals. It represents one of the most valid of the personality disorder diagnoses as many defining characteristics are behavioral in nature. More common in men than in women, this condition contributes significantly to the burden of violent and non-violent crime, substance abuse and prison crowding.Kendler and colleagues recently published a twin study of the DSM-IV criteria for ASPD in a cohort of twins from the Virginia Adult Psychiatric and Substance Use Disorders. Data from 4291 twins were used in the analysis and included a factor analysis of the ASPD phenotype followed by twin analysis.The research group found two distinct ASPD phenotypes in the factor analysis with specific ASPD criteria loading on each factor:Factor 1: nonconformance, irritability/aggression and reckless disregard for othersFactor 2: deceitfulness, impulsivity/failure to plan, irresponsibility and lack of remorse for behaviorThe subsequent twin analysis confirmed two genetic factors in adult ASPD with a confirmation of the factor analysis criteria loading. Heritability (an estimate of genetic contribution) for individual ASPD criteria varied from .12 to .57.Additional support for these two factors came from a study of discriminant validity--the ability of the genetic factors to describe a unique clinical presentation. The clinical features found in each of the two factors were:Factor 1: presence of childhood conduct disorder, early age at first alcoholic drink, high number of maximum drinks consumed in 24 hours, treatment seeking for alcohol dependence and lower educational levelFactor 2: novelty seeking personality and history of major depressionThe authors note their study supports a view of two types of adult antisocial phenotypes. Factor one matches the general description of the psychopath with many traits persistent throughout adult life. Factor two matches primarily a deficit of disinhibition the may "reflect disturbances in anterior brain systems mediating affective and behavioral control".This is an important study the supports more vigorous phenotypic description of adults with antisocial personality. These subtype descriptions may play a key role in understanding cognitive, structural and functional imaging studies in adult ASPD.In the next few posts, I will review some of the emerging imaging research related to ASPD.Photo of olive sparrow from the author's file.Kendler KS, Aggen SH, & Patrick CJ (2012). A Multivariate Twin Study of the DSM-IV Criteria for Antisocial Personality Disorder. Biological psychiatry, 71 (3), 247-53 PMID: 21762879... Read more »

Kendler KS, Aggen SH, & Patrick CJ. (2012) A Multivariate Twin Study of the DSM-IV Criteria for Antisocial Personality Disorder. Biological psychiatry, 71(3), 247-53. PMID: 21762879

January 17, 2012
11:26 AM
499 views

The Economic Costs of Brain Disorders

by William Yates, M.D. in Brain Posts

Clinical disorders involving the brain are common and produce a variety of economic costs to society.Cost analyses provide an overview of the types of disorders and their relative contribution to the overall costs to society. Such types of analyses can aid public health officials in targeting strategies to reduce the burden of brain disorders.Andlin-Sobocki and colleagues recently published an analysis of the costs of brain disorder in Europe. This study included both neurological and mental disorders.This analysis included a comprehensive outline of the components of the costs related to brain disorders. The rank list of cost components (% of total costs) in the analysis were:Sick leave (33%)Hospitalization (20%)Social services (13%)Outpatient care (12%)Premature death (7%)Early retirement (7%)Pharmaceutical costs (3%)Informal care (3%)Other direct costs (2%)The authors estimated that the total costs related to brain disorders at 386 billion euro per year. The ranking for brain disorder total costs by disease area (and yearly costs in euro billions)Mood disorders (106 B €)Addictions (57 B €)Dementia (55 B €)Anxiety disorders (41 B €)Psychotic disorders (35 B €)Migraine/Headache (27 B €)Stroke (22 B €)Epilepsy (16 B €)Parkinson's disease (11 B €)Multiple sclerosis (9 B €)Brain tumor (8 B €)Brain trauma (3 B €)Total costs represent estimations of the prevalence for individual disorders multiplied by the yearly cost for each disorder. The authors estimate that brain tumors represent the highest cost component an nearly 40,000 € per year. Multiple sclerosis was estimated as the second most costly component at 25,000 € per year followed by stroke at about 16,000 € per year.The mental disorders (mood, addictions, dementia and anxiety disorders) have relatively lower cost per case estimates but their total cost contribution is high due to the higher prevalence rates for these disorders.The study reaffirms brain disorders as a key element in total direct and indirect health care costs. Indirect costs related to work function (sick leave and reduced productivity) are important areas for further study in the mental disorders.Economic costs represent only one aspect to the burden of disease. Individual pain and suffering and the effects on family members were not addressed in this analysis. This study supports the need for adequate research financing for the diagnosis, treatment and prevention of brain disorders.Photo of a pair of laughing gulls at sunrise from South Padre Island, Texas from the authors files.Olesen J, Gustavsson A, Svensson M, Wittchen HU, Jönsson B, on behalf of the CDBE2010 study group, & the European Brain Council (2012). The economic cost of brain disorders in Europe. European journal of neurology : the official journal of the European Federation of Neurological Societies, 19 (1), 155-162 PMID: 22175760... Read more »

Olesen J, Gustavsson A, Svensson M, Wittchen HU, Jönsson B, on behalf of the CDBE2010 study group, & the European Brain Council. (2012) The economic cost of brain disorders in Europe. European journal of neurology : the official journal of the European Federation of Neurological Societies, 19(1), 155-162. PMID: 22175760

January 16, 2012
10:06 AM
448 views

The Neuropsychology of Opioid Abuse

by William Yates, M.D. in Brain Posts

This is the last post in a series on prescription opioid abuse and dependence. Prescription opioid overdose fatalities is a growing public health problem in the United States. This problem varies by state of residence. There are effective pharmacological strategies for the treatment of opioid dependence, but relapse rates are high.With this growing problem, an important clinical question is "What are the cognitive effects of chronic opioid use/abuse/dependence?". One of the problems in studying the effects of chronic illicit drug use is finding the problems linked to specific drugs of abuse and separating the effects due to the drug itself from potential premorbid deficits typical in substance abuse populations.Individuals developing alcohol and drug dependence differ from the general population. Premorbid ADHD and learning disabilities occur in substance abusers more commonly in those without substance abuse. Premorbid anxiety disorders, mood disorders and psychotic disorders also are common in substance abuse populations.Fernando-Serrano and colleagues from the University of Granada in Spain recently published a summary of the effects of specific drugs of abuse on neuropsychological performance in the journal Neuroscience and Biobehavioral Reviews.The conducted a comprehensive review of neuropsychological performance from studies of primarily single drug class abuse "pure users" along with studies controlling for multiple drug use and found the following findings by drug class:Opioids: Impaired decision making, delayed time in making decisionsMethamphetamines: Increased impulsivity and impaired cognitive flexibilityMDMA: Impaired spatial processing, reduced perceptual speed and attentionCannabis: Impaired immediate and delayed episodic memory and reduced visual processing speedThe authors note the need for better designed research to study the effect of specific drugs on chronological cognitive functioning, i.e. subacute (24 to 48 hours), short-term (48 hours to 1 month), mid-term (1-6 months) and long term (6 months or more).Unfortunately, this research review found no studies in prescription opioid abusers as the only studies in opioid abuse/dependence were done in heroin or methadone users.There is a important need to conduct studies of neuropsychological effects in prescription opioid drug abuse populations. This population (and the effects of prescription opioid abuse/dependence) may differ significantly from results found in heroin and methadone clinical groups.Additionally, neuropsychological research is needed on the effect of substitution therapy, i.e. buprenorphine/naloxone (Suboxone) on neuropsychological performance. Does substitution therapy reduce cognitive effects of prescription opioid abuse? How do prescription opioid abusers placed on substitution therapy differ from controls without a history of prescription opioid abuse.Neuropsychological effects of prescription opioid abuse may contribute to social and occupational impairment, response to treatment and risk for opioid overdose fatality. The time is now to put more money and research into this emerging problem.Photo of great blue heron on South Padre Island, Texas from the author's files.Fernández-Serrano MJ, Pérez-García M, & Verdejo-García A (2011). What are the specific vs. generalized effects of drugs of abuse on neuropsychological performance? Neuroscience and biobehavioral reviews, 35 (3), 377-406 PMID: 20451551... Read more »

Fernández-Serrano MJ, Pérez-García M, & Verdejo-García A. (2011) What are the specific vs. generalized effects of drugs of abuse on neuropsychological performance?. Neuroscience and biobehavioral reviews, 35(3), 377-406. PMID: 20451551

January 13, 2012
09:56 AM
605 views

Suboxone Treatment for Prescription Opioid Abuse

by William Yates, M.D. in Brain Posts

Chemical Structures for Buprenorphine and NaloxoneIn three previous posts I have reviewed several aspects of prescription opioid abuse including posts on epidemiology, toxicology and clinical pathways to abuse.Given the growing numbers of individuals with prescription opioid abuse, safe and effective treatment options become increasingly important.Opioid withdrawal can be quite painful and often leads to resumption of opioid use. Treatment of opioid withdrawal can include non-opioid drugs or opiod drugs that target withdrawal symptoms. Symptomatic withdrawal treatment alone results in high relapse rates. This outcome has produced efforts to find more effective long-term treatments for prescription opioid abusers.Short or long-term opioid substitution treatment appears to produce an incremental improvement in outcomes. Methodone substitution or substitution with the combined drug buprenorphine and naloxone (Suboxone) provide two options for clinicians and patients.Buprenorphine is classified as a partial opioid agonist stimulating the opioid receptor with limited euphoric effect. Naloxone is felt to reduce the misuse of the combined drug compound by blocking/reducing euphoria with intravenous administration.A recent study examined the effectiveness of Suboxone in a group of 653 outpatients seeking treatment for prescription opioid dependence. The key elements of the design of this study included:Phase one: 2-week stablization on buprenorphine-naloxone, 2-week taper and 8-week follow-upPhase two: Individuals who relapsed after phase one entered a longer 12-week stabilization on buprenorphine-naloxone followed by a 4-week taper and 8-week follow-upAdjunctive counseling: Half the subjects received adjunctive counseling using a manual-based program emphasizing education, skills training and life-style modification.Outcome Assessment: During the follow-up period abstinence was measured by urine-test verified self reportOnly 7% of subjects achieved a successful outcome by the end of phase one. At the end of the treatment phase of phase 2, 49% of subjects were rated as having a successful outcome. However, after phase 2 tapering successful outcome rates dropped to 9%. Adjunctive counseling did not appear to improve outcomes in either phase.The authors note the study supports use of Suboxone with a primary medical management approach (without a formal substance abuse counseling component) in the clinician's office. Approximately 50% of users will experience a successful outcome during treatment with Suboxone.However, with the high relapse rates after the taper in phase 2 of the study, the study authors note: "What length of buprenorphine-naloxone treatment, if any, would lead to substantially better outcomes during a taper?" This study supports a longer term treatment trial using six months or a year of Suboxone treatment.Only a minority of clinicians are certified to give Suboxone in the U.S. It requires a specific 8 hour training course before certification. Suboxone costs about $10 per day and this may limit it's use. Nevertheless, it provided opioid prescription abusers and their clinicians an important treatment option.A resource to identify physicians certified to use Suboxone in the U.S. can be found here.Molecular structure of buprenorphine and naloxone from the PubChem Compound site.Weiss RD, Potter JS, Fiellin DA, Byrne M, Connery HS, Dickinson W, Gardin J, Griffin ML, Gourevitch MN, Haller DL, Hasson AL, Huang Z, Jacobs P, Kosinski AS, Lindblad R, McCance-Katz EF, Provost SE, Selzer J, Somoza EC, Sonne SC, & Ling W (2011). Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Archives of general psychiatry, 68 (12), 1238-46 PMID: 22065255... Read more »

Weiss RD, Potter JS, Fiellin DA, Byrne M, Connery HS, Dickinson W, Gardin J, Griffin ML, Gourevitch MN, Haller DL.... (2011) Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Archives of general psychiatry, 68(12), 1238-46. PMID: 22065255

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