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September 7, 2010
03:29 PM
1,511 views

Perfectionism as a Risk Factor for Anorexia Nervosa

by William Yates, M.D. in Brain Posts

Temperament is generally defined as innate early emotional and behavioral characteristics that precede puberty and adult development. Felt to have significant genetic components, temperament is also potentially influenced by environmental factors. There are a variety of temperament domains that have received significant attention in childhood, adolescent and adult populations. Some of the most commonly studied domains include:neuroticismharm avoidancenovelty seekingreward dependenceperfectionism (subdomains have included: concern about mistakes, personal standards, doubts about actions, organizationThe temperament of perfectionism has been noted to be elevated in clinical samples of women with anorexia nervosa (AN). AN has been conceptualized as an overvalued importance of being in control over eating and weight. Control is a key element of perfectionism as it relates to reducing risk of mistakes and maintaining organization). Previous studies looking at perfectionism in AN have had limited potential to understand the direction of the relationship between temperament and the diagnosis of AN. Perfectionism could develop after the illness in response to weight loss or other factors. Wade, et al. published a study using the Australian twin registry that helps address the issue of direction of effect as well as the potential mechanism for perfectionism to increased AN risk. In this study, the classic twin genetic methodology was used. Perfectionism was evaluated as a risk factor along with a variety of of other temperament domains. The key findings from the study included:Anorexia nervosa subjects showed increased concerns about personal standards, making mistakes and doubts about actionsAnorexia nervosa temperament factors linked to genetic mechanism include perfectionism subdomain of personal standards Significant argument had occurred about how perfectionism might be involved in contributing to risk of AN. High standards typically has been considered a benign component of perfectionism. But experimental studies that manipulated personal standards in nonclinical populations have shown this to lead to increases in dietary restraint and regret after eating. The authors conclude: "Results of the current study would suggest that it is the setting of high standards and goals, rather than self-criticism when goals are not obtained that predisposes people to AN." Perfectionism acts as risk factor for AN only in presence of other risk factors (i.e. low self-esteem, body dissatisfaction).So setting high personal standards (i.e. academic goals, athletic achievement, low body weight) is not independently a problem. But when high personal standards are accompanied by other psychological vulnerabilities, problems can develop. Personal standards can be benign (and productive in many ways) but they can not be considered benign for all. Better understanding of the personal standards temperament (and cofactors for dysfunctional behavior) that precede AN may provide pathways for prevention as well as treatment. Photo of Phil Mickelsen at 2010 PGA Championship Courtesy of Yates PhotographyWade TD, Tiggemann M, Bulik CM, Fairburn CG, Wray NR, & Martin NG (2008). Shared temperament risk factors for anorexia nervosa: a twin study. Psychosomatic medicine, 70 (2), 239-44 PMID: 18158375... Read more »

Wade TD, Tiggemann M, Bulik CM, Fairburn CG, Wray NR, & Martin NG. (2008) Shared temperament risk factors for anorexia nervosa: a twin study. Psychosomatic medicine, 70(2), 239-44. PMID: 18158375

May 31, 2011
07:49 AM
1,369 views

Brief Behavioral Therapy for Insomnia in Older Adults

by William Yates, M.D. in Brain Posts

Insomnia is a common complaint in the general population and among patients treated by primary care physicians. This is particularly true for older adults who experience physiological changes in sleep with aging. Clinicians commonly prescribe hypnotics for insomnia and the use of these types of drugs is increasing in the United States and elsewhere. Behavioral and psychological interventions may be overlooked or bypassed in the sequencing of interventions for complaints of insomnia. I had previously posted on the promise of cognitive behavioral therapy for insomnia. This therapy appears to be effective across a variety of patient groups including those with an underlying psychiatric diagnosis. Now, a recent study in elderly subjects finds support for an even briefer intervention for those with primary insomnia.Buysse and colleagues from the University of Pittsburgh and the Cleveland Clinic have recently published a randomized control trial of brief behavioral therapy intervention (BBTI) for primary insomnia in a group of adults averaging 71-72 years of age. The brief intervention included direct contact with a single masters level nurse practitioner for an initial 45 to 60 minute session followed by a 20 minute direct contact session in 2 weeks. Two 20-minute phone sessions were scheduled at one and three weeks following the initial contact session. The authors note the sessions focused on customizing for each subject the four key elements of sleep education and stimulus control:reduce the total amount of time in bedget up at the same time daily regardless of sleep durationdo not go to bed unless feeling sleepydo not stay in bed unless asleepThe control group was provided educational material that included information related to behavioral treatment of insomnia but did not include personalized contact session with the nurse practitioner. Outcome was measured by whether subjects continued to meet criteria for insomnia as well as other secondary measures.The BBTI group demonstrated a 67% response rate compared to only 25% response in the control group. Remission of an insomnia diagnosis was noted in 55% of the BBTI group compared to only 13% of the control. Most psychometric, sleep diary and actigraphy measures improved more in the BBTI group more than the control group. Interestingly, there were no differences between the groups in polysomnography sleep lab measures including sleep latency, total sleep time and sleep efficiency.The authors note attractive features of BBTI including:it is easily taught to nurse practitioners and other cliniciansit includes a workbook that allows patients to follow exercises aimed at reducing insomniathe strict behavioral approach limits some of the stigma associated with psychological treatment approaches in primary careThis study supports a stepped care approach for older adults with primary insomnia. Following careful assessment to rule out another sleep disorder, i.e. sleep apnea or an untreated psychiatric disorder, i.e. depression or anxiety disorder, a trial of brief behavioral therapy may be a good first step. Patients who fail to respond to this step may be candidates for consideration of hypnotic or other pharmacological interventions.Photo of Lilly Pad Flower Bloom from Maui Courtesy of Yates PhotographyBuysse, D., Germain, A., Moul, D., Franzen, P., Brar, L., Fletcher, M., Begley, A., Houck, P., Mazumdar, S., Reynolds, C., & Monk, T. (2011). Efficacy of Brief Behavioral Treatment for Chronic Insomnia in Older Adults Archives of Internal Medicine, 171 (10), 887-895 DOI: 10.1001/archinternmed.2010.535... Read more »

Buysse, D., Germain, A., Moul, D., Franzen, P., Brar, L., Fletcher, M., Begley, A., Houck, P., Mazumdar, S., Reynolds, C.... (2011) Efficacy of Brief Behavioral Treatment for Chronic Insomnia in Older Adults. Archives of Internal Medicine, 171(10), 887-895. DOI: 10.1001/archinternmed.2010.535

December 13, 2011
01:01 PM
1,249 views

Weight Suppression and Bulimia Recovery

by William Yates, M.D. in Brain Posts

Weight suppression is a variable that is defined as highest ever historical weight minus current weight. It represents a measure of the level of weight lost since being at the highest weight over a lifetime.Although many individuals with bulimia nervosa are within normal weight ranges, these individuals tend to have higher levels of weight suppression than those without an eating disorder.Weight loss in bulimia may increase drive for binge eating. Weight suppression may similarly be a marker for drive for binge eating among those with a diagnosis of bulimia.Lowe and colleagues recently published a study of the correlation between weight suppression and the time to remission in a group of women. If weight suppression is a valid prognostic variable, higher levels of weight suppression should predict a poorer prognosis and a longer time to remission.Here are the key elements of design of the study:Sample: 110 women with DSM-IV bulimia nervosa recruited from treatment centersWeight suppression groups: lowest third group less than 9 pounds, medium third group 9 to 25 pounds and high weight suppression group over 25 poundsFollow-up: In person or telephone interviews every 6 to twelve months for approximately 9 yearsDefinition of recovery: Full remission of bulimia nervosa: absence of bulimia symptoms or only residual symptoms for a period of 8 consecutive weeksStatistical analysis: Cox proportional hazard modeling of the effect of baseline weight suppression on time to first recoveryWeight suppression was statistically related to time to recovery. The highest tertile (1/3) group in weight suppression took nearly three times as long to recovery (see chart above). The highest tertile group took over three years for 50% of the group to meet recovery. This was significantly longer that the low weight suppression group that took only about 12 months for 50% of the group to recover.This study supports collecting weight suppression data on women in treatment for bulimia nervosa. Those weighing 25 pounds less than their maximum weight appear to represent a poor prognosis group. Individuals with bulimia and high weight suppression may require more intense psychological therapy than those with lower weight suppression scores. Additionally, they may need combination therapy with behavior therapy paired with a pharmacological intervention. Fluoxetine is an FDA approved drug for the treatment of bulimia nervosa. Topiramate appears to be a promising drug for the reduction of binge eating.Figure is original chart by author from data presented in manuscript.Lowe, M., Berner, L., Swanson, S., Clark, V., Eddy, K., Franko, D., Shaw, J., Ross, S., & Herzog, D. (2011). Weight suppression predicts time to remission from bulimia nervosa. Journal of Consulting and Clinical Psychology, 79 (6), 772-776 DOI: 10.1037/a0025714... Read more »

Lowe, M., Berner, L., Swanson, S., Clark, V., Eddy, K., Franko, D., Shaw, J., Ross, S., & Herzog, D. (2011) Weight suppression predicts time to remission from bulimia nervosa. Journal of Consulting and Clinical Psychology, 79(6), 772-776. DOI: 10.1037/a0025714

December 12, 2011
12:16 PM
1,173 views

Best Test for Diagnosing Alzheimer's Dementia

by William Yates, M.D. in Brain Posts

PET Image Normal Definitive diagnosis of Alzheimer's disease (AD) from other forms of dementia is a complex clinical challenge. Positron imaging tomography (PET) scans are widely available in the United States. A more recent approach has used the estimation of brain amyloid levels using an amyloid ligand Pittsburgh Compound B (PiB). PiB imaging is primarily a research tool at the present.I have previously summarized some of the research related to PiB imaging from a lecture presented by Dr. Chet Mathis here. Now a study comparing the sensitivity and specificity of the PiB imaging method with PET imaging using fluorodeoxyglucose has been published.Rabinovici and colleagues from the University of California, San Francisco, the University of California, Berkeley and the University of Pennsylvania used both scans in a group of 62 subjects with AD and a group of 45 subjects with frontotemporal dementia (FTD). An additional group of 25 age-matched normal controls participated in the study.The two dementia groups had similar levels of cognitive impairment scoring around 22 on the 30 item Mini-mental status exam. This indicates a relatively mild level of dementia.PET Image in Alzheimers-Temporal DeficitsThe assignment of a diagnosis of AD or FTD was done by clinical diagnosis that included MRI information but was blind to PET imaging results. Additionally, genetic testing for the APOE genotype, progranulin mutations, tau protein and mutations in presenilin-1 and presenilin 2 were obtained. A subset of 11 subjects died after completion of scanning and ten underwent brain autopsy providing histopathology information for group assignment.Two raters blinded to clinical diagnosis reviewed the scans and assigned a qualitative diagnosis of AD, FTD or normal. Additionally, quantitative scoring of the scans was completed using an quantitative thresholds for assignment of AD or FTD.Key sensitivity and specificity for the correct diagnosis in the study were (mean rater scores followed by quantitative scoring)PET-FDG: sensitivity 78%, 73%, specificity 84%, 98%PiB: sensitivity 90%, 89%, specificity 83%, 83%Tests with the highest sensitivity and specificity provide the best diagnostic tool. This study comparison supports the current clinical use of PET-FDG for testing for AD. The PiB imaging in this study showed better sensitivity for diagnosis compared to the PET-FDG. The authors note their study supports the use of PiB for a biomarker for differentiating AD from FTD.Quantitative scoring in PET-FDG proved superior to visual ratings by experts in specificity. This suggest the value of incorporating quantitative score in clinical settings where PET is used to test for AD.The results of the study suggest that rather than one test being superior, they appear to be complementary.The authors note PiB is unlikely to become widely used due to the short half-life of the amyloid tracer (20 minutes). However, newer amyloid tracers are in development that would make use of this imaging method more clinically feasible.In summary, amyloid tracer imaging appears to be a promising method for improving accurate diagnosis of Alzheimer's and other dementias. Until this method becomes available, PET-FDG is a sensitive and accurate tool, particularly when quantitative methods are used to assist in assignment of the diagnosis.PET images from Wikipedia Creative Commons files authored by Jens Langner (normal) and U.S. National Institute of Aging, Alzheimer's Disease Education and Referral Center (AD).Rabinovici GD, Rosen HJ, Alkalay A, Kornak J, Furst AJ, Agarwal N, Mormino EC, O'Neil JP, Janabi M, Karydas A, Growdon ME, Jang JY, Huang EJ, Dearmond SJ, Trojanowski JQ, Grinberg LT, Gorno-Tempini ML, Seeley WW, Miller BL, & Jagust WJ (2011). Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology, 77 (23), 2034-42 PMID: 22131541... Read more »

Rabinovici GD, Rosen HJ, Alkalay A, Kornak J, Furst AJ, Agarwal N, Mormino EC, O'Neil JP, Janabi M, Karydas A.... (2011) Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology, 77(23), 2034-42. PMID: 22131541

December 14, 2011
12:44 PM
1,159 views

Brain and Gut in Processing Emotion

by William Yates, M.D. in Brain Posts

Ventrolateral Prefrontal Cortex in BlueIntense emotional experiences frequently occur with bodily sensations such as a rapid heart rate or gastrointestinal distress.It appears that bodily sensation (interoception) can be an important source of information when judging one's emotional. How the brain processes interoception is becoming better understood. However, how the brain integrates interoceptive signals with other brain emotional processing circuits is less well understood.Terasawa and colleagues from Japan recently presented results of their research on this interaction of interoception and emotion.Eighteen graduate and undergraduate students were scanned using a 3T fMRI scanner.Stimulus cues were separated into those in the interoceptive domain using the Body Perception Questionnaire and the emotional domain using the Positive and Negative Affect scale.Interoceptive cues included cues such as "I have a fast pulse" while a typical emotional cue was "I am happy". Each cue was compared to a control possession cue such as "I have money".The authors then contrasted brain regions activated by interoceptive, emotional or both interoceptive and emotional cues.Brain regions identified as being activated during interoceptive cues included:Interoception only: supplementary motor area (Brodmann area 6), inferior parietal gyrusInteroception and emotional cues: right insular cortex (Brodmann area 13), ventromedial prefrontal cortex (Brodmann area 11) and the bilateral lingual cortex (Brodmann area 17).The authors propose these finding support the role of the insula and ventromedial prefrontal cortex in the integration of interoception and central brain emotional signaling. They conclude "Our findings indicate that activation in these areas (ventromedial prefrontal cortex and right insula) and precuneus are functionally associated for subjective awareness of the emotional state".Some may argue that in making important decisions you should "Go with your gut feeling".The findings from this study suggest a more informed approach might be "Use your gut and other bodily signals (interoception) integrated with central brain signals in accurately judging your emotional state for making decisions"This study suggests the brain has allocated specific regions to aid in the integration of body and brain signals to accurately judge and assess one's own emotional state.Figure of ventrolateral prefrontal cortex from a screen shot of the iPad app Brain Tutor HD.Terasawa, Y., Fukushima, H., & Umeda, S. (2011). How does interoceptive awareness interact with the subjective experience of emotion? An fMRI Study Human Brain Mapping DOI: 10.1002/hbm.21458... Read more »

Terasawa, Y., Fukushima, H., & Umeda, S. (2011) How does interoceptive awareness interact with the subjective experience of emotion? An fMRI Study. Human Brain Mapping. DOI: 10.1002/hbm.21458

March 2, 2011
10:19 AM
1,012 views

Decoding the Faces of Depression: Anhedonia and Dopamine

by William Yates, M.D. in Brain Posts

Diego Pizzagalli presented the March 2011 Warren Frontiers in Neuroscience Series lecture in Tulsa, Oklahoma on March 1, 2011. Dr. Pizzagalli works at the Harvard Medical School affiliated Center for Depression, Anxiety and Stress Research & Neuroimaging Center at McLean Hospital in Boston. He has been involved in research related to brain abnormalities in major depression as well as predictors of treatment response. I will highlight some of the key points from his lecture and incorporate three recent research manuscripts related to this topic:There are over 100 symptom combinations to diagnosis major depression (5 of 9 symptoms required)Distinct depressive phenotypes (clinical presentations) are difficult to define--but the phenotype defined by anhedonia (pervasive lack of ability to experience pleasure) has significant research supportDepression with anhedonia also has a biological component--the brain reward pathways involving dopamine and the striatum.Anhedonia has been linked to impaired dopamine function in these brain reward pathwaysAnhedonia appears more heritable than depression and may be related to abnormalities in genes controlling dopamine neurotransmissionThe dopamine reward pathway (substantia nigra-striatum-cingulate/prefrontal cortex) is vulnerable to stress (acute stress increases dopamine, chronic stress reduces it in the rat model)He and colleagues developed a heuristic model of the functional neuroanatomy of anhedonia: both environmental and biological factors influence risk of depression: depression includes a decrease in the brains reward response, exaggerated stress responsivity and eventually a blunted mesolimbic dopamine system (and anhedonia)Laboratory models and psychometric measures of anhedonia have been developed--studies suggest the ventral striatum (nucleus accumbens) is involved in hedonic coding while the dorsal striatum (caudate) is involved in positive re-inforcementDecreased activation of cingulate and caudate with monetary incentive delay task is seen in untreated depressionUntreated depression (and anhedonia) also linked to decreased size of the caudateEarly life stress (abuse) may increase depression risk through dysregulation of mesolimbic pathways including left putamen and left pallidumStress even in healthy individuals impairs brains reward processing pathwaySome genes related to anhedonia may work through stress pathways, i.e. mineralcorticoids, corticotrophin hormone (CRH)Future research will focus on further parsing of the heterogeneity associated with depression, developing animal models of reward tasks, using PET to better understand the role of dopamine in depression, using dopaminergic drugs (i.e. pramipexole) in stimulation models of depression and further study of the neurobiology of stress-induced anhedoniaI agree that evaluating the role of dopaminergic drugs in depression accompanied by anhedonia is worthy of basic and clinical research study. Among typical antidepressants, only bupropion appears to have dopaminergic effects. Other compounds such as psychostimulants also increase dopamine but carry the risk for abuse. Several of the dopaminergic drugs used for Parkinson disease are beginning to see more use off-label for the treatment of depression. I will look at this issue in a future Brain Post. Photo of Blake Griffin shooting free throw against Oklahoma City Thunder in 2011 NBA game courtesy of Tim Yates.... Read more »

Pizzagalli DA. (2011) Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 36(1), 183-206. PMID: 20861828

Pizzagalli DA, Holmes AJ, Dillon DG, Goetz EL, Birk JL, Bogdan R, Dougherty DD, Iosifescu DV, Rauch SL, & Fava M. (2009) Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. The American journal of psychiatry, 166(6), 702-10. PMID: 19411368

Wacker J, Dillon DG, & Pizzagalli DA. (2009) The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: integration of resting EEG, fMRI, and volumetric techniques. NeuroImage, 46(1), 327-37. PMID: 19457367

February 20, 2011
11:46 PM
997 views

Did the Red Fox Predate the Dog as Man's Best Friend?

by William Yates, M.D. in Brain Posts

Pets have longed played a role in human companionship. Wild animals were primarily a source of food (and danger) in early human development. Later in evolution, animals began to serve a more complex role. Domestication of a variety of animals served a more utilitarian role. For example, domestication of horses allowed for extended travel, improved efficiency of hunting and provided a strategic advantage in battle.The domestications of wild wolves has been felt to be one of the earliest examples of using animals for companionship and the development of a human/mammal pet relationship. Now some recent archaelogical research suggests that the red fox may have predated the domesticated wolf as the original canine domesticated by humans.Mather and colleagues present the case for the red fox predating domesticated wolves in a recent research summary in Plos One. This research team includes members from the University of Cambridge in the UK as well as the University of Toronto. Using findings from burial grounds in what is now northern Jordan, they lay out the evidence that the red fox predates the wolf as man's domesticated canine.Seven human grave sites have been examined in the Uyun al-Hamman region between the Transjordanian Highlands and the Jordan valley. The key elements from these findings include:Red fox skulls and bones are noted in several burial sites in proximity to human remainsThe proximity and manner of red fox bones suggest intentional placement rather than coincidenceSome human bones were re-interred with movement and replacement of red fox bones in the new graveThis re-burial process suggests a personal relationship between the deceased human and a specific red fox--the transfer may have indicated an attempt that "the dead person would continue to have the fox with him or her in the afterlife"The pattern of remains are not consistent with some secondary process such as use the red fox as a pelt or as part of consumption of the animalThe carbon dating data suggest this area and this burial site pre-dated by thousands of years the earliest known burial sites that include domesticated wolvesLater grave sites show humans being buried with dogs supporting an emotional tie with social, ideological or symbolic significanceIn summary, the research team feels these recent findings support an earlier "non-economic connections between people and animals".I admit this post is outside my area of expertise. However, we are becoming more aware of the potential importance of pet relationships in reducing loneliness, stress reduction and social psychology. I do have to note that I took the photo of the red fox in this post in the winter of 2009-2010 in my back yard in Tulsa Oklahoma. After a prolonged period of very low temperatures and frozen water sources, this red fox jumped a fence into my back yard and drank from our pool. This research study suggests the red fox was one of man's earliest pets. I'm happy to do whatever I can to aid this beautiful animal.Photo of Red Fox Courtesy of Yates PhotographyMaher, L., Stock, J., Finney, S., Heywood, J., Miracle, P., & Banning, E. (2011). A Unique Human-Fox Burial from a Pre-Natufian Cemetery in the Levant (Jordan) PLoS ONE, 6 (1) DOI: 10.1371/journal.pone.0015815... Read more »

Maher, L., Stock, J., Finney, S., Heywood, J., Miracle, P., & Banning, E. (2011) A Unique Human-Fox Burial from a Pre-Natufian Cemetery in the Levant (Jordan). PLoS ONE, 6(1). DOI: 10.1371/journal.pone.0015815

March 4, 2011
09:37 AM
943 views

Fluoxetine (Prozac) Boosts Motor Recovery After Stroke

by William Yates, M.D. in Brain Posts

Antidepressant drugs are being used for multiple non-depression indications including chronic pain, peripheral neuropathy, migraine prophylaxis, irritable bowel syndrome, hot flashes, premature ejaculation and insomnia (list not inclusive). I had previously posted results of research looking at the effect of antidepressants after stroke on cognitive recovery. This study from the University of Iowa College of Medicine, Department of Psychiatry found that escitalopram was linked to improved cognitive recovery following stroke compared to placebo.Now on a related note, a study has been randomized placebo controlled study of fluoxetine has been published looking at recovery of motor function following acute ischemic stroke. Here are the key elements of the design of this study:Subjects: 113 patients with acute ischemic stroke ages 18-85 suffering hemiplegia or hemiparesisBaseline motor deficit: Fugl-Meyer motor scale (FMMS) score of 55 or lessIntervention: Fluoxetine 20 mg daily for 3 months or placeboKey outcome measure: FMMS score at day 90The raters on the key outcome measure were blinded to the assigned treatment. The findings from the study were impressive—mean (standard deviation) FMSS scores for the fluoxetine group was 54(28) compared to only 35.1 (22) in the placebo group. As might be expected, rates of post-stroke depression were lower in the fluoxetine group (7% vs 29%). Adverse events included nausea and diarrhea in the fluoxetine group—a typical selective serotonin reuptake inhibitor side effect. One subject in each group died during the follow up period. More patients in the fluoxetine group were more independent suggesting that motor recovery is an important contributor to global function after stroke. The motor recovery effect appeared independent of lower depression rates in the fluoxetine group.So why would a drug used typically for depression potentially have a role in post-stroke motor recovery? The authors note animal studies have shown that drugs affecting brain neurotransmitters can modulate the rate and extent of recovery following brain injury. Rats given fluoxetine after ischemic brain injury appear to have enhanced hippocampal neurogenesis. These studies support a potential role for selective serotonin reuptake inhibitors like fluoxetine to have a neuroplasticity effect that may aid brain healing from a variety of insults. This is not a magic bullet—it appears necessary to pair the drug treatment with active rehabilitation efforts. But when used together, the combination appears to result in a better motor recovery after stroke. I think we are likely to see more active research in this area and search for novel neuroprotective compounds that my provide better outcomes for stroke and other brain injury patients. Molecular model of fluoxetine molecule from Wikipedia Creative Commons, author Benjah-bmmj27.Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, Guillon B, Moulin T, Marque P, Pariente J, Arnaud C, & Loubinoux I (2011). Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet neurology, 10 (2), 123-30 PMID: 21216670... Read more »

Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P.... (2011) Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet neurology, 10(2), 123-30. PMID: 21216670

May 4, 2011
11:19 AM
917 views

Neuroethics: The Brain and Moral Beliefs

by William Yates, M.D. in Brain Posts

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

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

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

October 13, 2010
04:50 PM
915 views

The Brain Insula: Function and Disease

by William Yates, M.D. in Brain Posts

Nature Reviews Neuroscience is a scientific journal dedicated to neuroscience topics that recently celebrated it’s ten year anniversary. To commemorate the accomplishment, the most highly cited articles from each of the last 10 years was identified. This method provides a good proxy for the most important publication each year. The 2009 most cited article was Dr. A.D. Craig’s article entitled: “How do you feel—now? The anterior insula and human awareness”.Dr. Craig’s article highlights the converging fields of knowledge about the brain cortex region known as the insula. This region lays hidden inside the brain in close proximity to the anterior cingulate gyrus (ACC). The ACC is receiving increased attention as an important area for emotional processing. The insula and the ACC have significant numbers of connections supporting a role for their mutual role in a variety of brain functions. The insula has been long identified as a sensory region for the gut and body. New anatomical and imaging research has identified significant expanded domains related to the insular cortex including:Interoception (sensing state of gut, heart, pain etc)Body movementSelf-recognitionVocalizationand musicEmotional awarenessRisk, uncertainty and anticipationVisual and auditory awareness of movementTime perceptionAttentionPerceptual decision-makingCognitive control and performance monitoringDr. Craig provides a summary of the research supporting the expanded role of the insula in each of these additional domains. He notes that the expanding role of the insula is supportive of the James-Lang theory of emotion. The James-Lang theory of emotion denotes a theory developed independently by William James and Carl Lange in the 19th century. Their theory states that emotions follow rather than precede the autonomic nervous system changes to environmental stimuli. So instead of the sequence 1.) see bear, 2.) experience fear, 3.) heart races, the James-Lang theory states the correct sequence is 1.) see bear, 2.) heart races, 3.) experience fear. The James-Lang theory. The evolving research on insular cortex function also supports the somatic marker hypothesis of Antonio Damasio from the University of Iowa. Damasio proposes that decision making is influenced by somatic/emotional processes that can guide or bias our behaviors. These somatic/emotional processes are thought to be stored in the ventromedial prefrontal cortex regions.There are going to be significant discoveries related to a variety of clinical neuroscience disorders that are likely to involve the insular cortex. There is already evidence of it playing a key role in such diverse disorders as:AutismADHDAddictions including nicotine dependenceAnorexia nervosaMajor depressionPain disordersAlzheimer’s disease (in nonfluent primary progressive aphasia) I highly recommend both the 10 year anniversary manuscript as well as the 2009 summary of research on the insula. They are both packed with data and commentary that I found quite revealing and intriquing.Craig AD (2009). How do you feel--now? The anterior insula and human awareness. Nature reviews. Neuroscience, 10 (1), 59-70 PMID: 19096369Luo L, Rodriguez E, Jerbi K, Lachaux JP, Martinerie J, Corbetta M, Shulman GL, Piomelli D, Turrigiano GG, Nelson SB, Joëls M, de Kloet ER, Holsboer F, Amodio DM, Frith CD, Block ML, Zecca L, Hong JS, Dantzer R, Kelley KW, & Bud Craig AD (2010). Ten years of Nature Reviews Neuroscience: insights from the highly cited. Nature reviews. Neuroscience, 11 (10), 718-26 PMID: 20852655... Read more »

Craig AD. (2009) How do you feel--now? The anterior insula and human awareness. Nature reviews. Neuroscience, 10(1), 59-70. PMID: 19096369

Luo L, Rodriguez E, Jerbi K, Lachaux JP, Martinerie J, Corbetta M, Shulman GL, Piomelli D, Turrigiano GG, Nelson SB.... (2010) Ten years of Nature Reviews Neuroscience: insights from the highly cited. Nature reviews. Neuroscience, 11(10), 718-26. PMID: 20852655

February 22, 2011
02:27 PM
883 views

Naps Boost Cognitive Performance in Seniors

by William Yates, M.D. in Brain Posts

Insomnia is a common complaint among elderly individuals. With aging, there is a pattern of decreased number of total sleep time and reduced time in deep sleep. Deep sleep is considered restorative sleep, an important component of feeling rested and alert the following day.Sleep hygiene recommendations commonly warn against napping during the day time as it is felt to reduce the quantity and quality of sleep at night. However, many individuals report that napping during the day is helpful for them in getting sufficient sleep on a regular basis. Now there is some limited data that supports a role for regular napping for increasing total sleep time as well as some parameters of cognitive function.Campbell and colleagues studied the effects of a month-long napping regimen in a series of individuals between the ages of 50 and 88 years of age. Key elements of the research design included:Inclusion criteria: age over 50 with self-reported good physical health, subjective insomnia complaints allowed but subjects had to score less than 5 on the Pittsburgh Sleep Quality Index and 2 or less on the sleep latency item from this scale, no regular sleeping medications, not taking psychotropic meds or other medications known to affect sleep, minor but not major medical problems, no periodic limb movements on baseline polysomnographyStudy variables/procedures: Sleep diaries and actigraphy at home 1 to 2 weeks before baseline laboratory examination, 3 consecutive nights and 2 days spent in sleep lab with polysomnography and neuropsychological testing including a test of logical reasoning, mathematical processing, letter memory search and reaction time test.Intervention: Randomization to either directed 45 minute nap or 2 hour nap, at least 5 times per week but recommended daily, to be completed in single setting before 6 pm to include daily sleep logsOutcome measures: Subjects returned for sleep lab evaluation for 2 nights at 2 and 4 weeks after randomizationThe key elements of the outcome of the study:Napping did not change any of the night time sleep parameter: sleep onset latency, sleep efficiency or total nocturnal sleep timeIn 24 hour assessment of sleep both groups increased their total sleep time although as expected the long nap group had a longer total sleep time than the short nap groupNeuropsychological performance improved in both groups at 2 and 4 weeks on three of the four neuropsychological measures (all but reaction time). The improvement was not statistically significant but the longer nap group tended to show greater improvementAdherence to recommended nap assignment: (9/11) in the short nap group met defined adherence while 5/10 in the long nap group met adherence—this difference was not significantAlthough a small sample study, this research finding seems allay some concerns about a regular nap regimen for those over age 55 years of age. There does not appear to be evidence that napping impairs nocturnal sleep in duration or quality. The added sleep during the day with a nap in this study was accompanied by improvement in some elements of cognitive function. This improvement appeared to continue through 4 weeks and may not have reached its peak by that time. The authors note that none of the subjects were regular nappers before entering the study. So the take home message from the study is that for those 50 or older if you are taking a daily nap and feel it helps you, keep doing it. If you are not taking a daily nap and would like to consider adding one, it does not appear to be a risk for disrupting nocturnal sleep and you may get some cognitive boost from a daily napping regimen.Photo of napping kittens courtesy of Wikepedia Commons author Tilman Piesk.Campbell, S., Stanchina, M., Schlang, J., & Murphy, P. (2011). Effects of a Month-Long Napping Regimen in Older Individuals Journal of the American Geriatrics Society, 59 (2), 224-232 DOI: 10.1111/j.1532-5415.2010.03264.x... Read more »

Campbell, S., Stanchina, M., Schlang, J., & Murphy, P. (2011) Effects of a Month-Long Napping Regimen in Older Individuals. Journal of the American Geriatrics Society, 59(2), 224-232. DOI: 10.1111/j.1532-5415.2010.03264.x

May 21, 2010
10:30 AM
879 views

Physical Features in Autism

by William Yates, M.D. in Brain Posts

Social and language issues dominate most of the discussion about the features of autism spectrum disorder (ASD). A neglected area of study are the physical feature characteristics that have been known to be associated with ASD. Unlike some of the diagnostic physical changes in disorders such as Down Syndrome, physical features found in ASD are often subtle and missed by most clinicians.Ozgen and colleagues from the Netherlands, UCLA and the UK recently published a case-control study of physical features in children with autism. They compared 224 children with ASD and normal intelligence to a matched pair child without ASD. A portion of the assessment was completed by raters blind to the diagnosis of the child.The assessment included a variety of quantitative and qualitative assessments. For example, in the quantitative assessment category, boys (but not girls) with ASD had a smaller BMI indicating a lower weight to height ratio.The most common structural (morphological) features found in the ASD children included:Sandal gap toes (59%)Facial asymmetry (46%)Abnormal non-frontal hair whorl (39%)High narrow palate (37%)Attached ear lobes (35%)Hypermobile joints (33%)Some morphological features were found in the ASD that were absent in the 224 controls including:Brachycephaly Mouth asymmetry Eyes asymmetryEar lobe crease Macrostomia (large mouth)Limited facial expressionOpen mouth appearanceAbnormal whorlProminent lower jawThe authors note these minor physical characteristics were more common among the boys than girls in the study. These types of features have been described in other populations with copy number variations (CNVs). CNVs are an alteration of the genome with a complete loss of a gene copy, gain of a copy or disruption of a dosage-sensitive gene.The authors note that these physical characteristics are unlikely to be incorporated into diagnostic features. However, they note that the features might be helpful in identifying relevant subgroups for further study. It is important to not bring too much attention to these features in individual children. Some features may add a level of social scrutiny to an already challenging clinical problem. Photo of Blue Jay Courtesy of Yates PhotographyOzgen, H., Hellemann, G., Stellato, R., Lahuis, B., Daalen, E., Staal, W., Rozendal, M., Hennekam, R., Beemer, F., & Engeland, H. (2010). Morphological Features in Children with Autism Spectrum Disorders: A Matched Case–Control Study Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-010-1018-7... Read more »

Ozgen, H., Hellemann, G., Stellato, R., Lahuis, B., Daalen, E., Staal, W., Rozendal, M., Hennekam, R., Beemer, F., & Engeland, H. (2010) Morphological Features in Children with Autism Spectrum Disorders: A Matched Case–Control Study. Journal of Autism and Developmental Disorders. DOI: 10.1007/s10803-010-1018-7

April 6, 2011
09:43 AM
869 views

Anxiety as a Gut Feeling: Understanding Interoception

by William Yates, M.D. in Brain Posts

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

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

September 14, 2010
04:46 PM
857 views

The Neurocircuitry of Anorexia Nervosa

by William Yates, M.D. in Brain Posts

Walter Kaye, M.D., Director of the Eating Disorders Treatment and Research Program at the University of California, San Diego presented a Frontiers in Neuroscience lecture on September, 14, 2010. The presentation was titled: “ Is anorexia nervosa an eating disorder? New insights into puzzling symptoms”. The presentation highlighted some his recent research that has been summarized in the manuscript cited at the end of this blog post.Dr. Kaye noted that eating disorders characterized by a phenotype of several continuous behavioral traits that appear to have some genetic contributions. Childhood temperamental and characterological traits associated with anorexia nervosa include:Drive for thinnessPerfectionismHarm avoidanceNegative emotionalityAltered interoceptive awarenessInhibitionObsessive-compulsive personality traitsInteroreceptive awareness includes a variety of body sensations such as gastric fullness, hunger and satiety. The insular brain cortex is being recognized as a crucial brain structure in interoceptive awareness and it's integration with other brain functions. Some of the imaging research in anorexia nervosa focuses on abnormalities involving appetite. Underweight patients with anorexia nervosa appear to have altered appetite or an ability to suppress appetite to an unusually large degree. Appetite dysregulation in anorexia nervosa includes a dislike for high-fat foods, failure to rate food as positive when hungry and a reduced aversive response to sucrose during satiation. Several brain circuits appear to contribution to appetite and food consumption regulation including the hypothalamus, the ventral (limbic) neurocircuit and the dorsal neurocircuit. Dr. Kaye and colleagues have performed a series of imaging studies examining appetite in those with anorexia nervosa. He feels the anterior insula cortex might play a key role in anorexia nervosa. This brain structure integrates with the cortex region involved in taste. The insula also projects and interacts with key limbic structures including the amygdale, the anterior cingulated cortex and the orbitofrontal cortex. These regions may interpret taste in a manner that integrates affective relevance, conflict monitoring and incentive learning. Kaye summarized that dysregulation in both the dorsal and ventral neurocircuits may contribute to anorexia nervosa. Cortical circuits (top-down) are overengaged in anorexia nervosa resulting in high anticipatory reactivity, behavioral rigidity, and excessive worry. This top-down overengagement is implemented through the interoceptive pathways, insular cortex amydala and anterior cingulated cortex. The neural information converges in the straitum where food delay receives priority over eating. Dr. Kaye summarizes “..future imaging studies should focus on characterizing neural circuits, their functions and their relationship to anorexia nervosa. Genetic studies might shed light on the complex interaction of molecules within these neural circuits.”Dr. Kaye’s Eating Disorders Treatment and Research Program website is here.Link to full pdf of the citation noted below and other UCSD publications is here. This has several excellent figures explaining issues in neurocircuitry in anorexia nervosa.Photo above of limbic system with cingulate cortex in pink, amygdala in blue, and hippocampus in green from 3D Brain iPad screen shot. Courtesy of Yates PhotographyKaye WH, Fudge JL, & Paulus M (2009). New insights into symptoms and neurocircuit function of anorexia nervosa. Nature reviews. Neuroscience, 10 (8), 573-84 PMID: 19603056... Read more »

Kaye WH, Fudge JL, & Paulus M. (2009) New insights into symptoms and neurocircuit function of anorexia nervosa. Nature reviews. Neuroscience, 10(8), 573-84. PMID: 19603056

February 23, 2011
04:17 PM
855 views

Brain Circuit Tied to Gambling Risk in Parkinson Disease Identified

by William Yates, M.D. in Brain Posts

Some of the drugs used to treat Parkinson disease (PD) increase the risk for pathological gambling. This can have a significant economic adverse effect on some individuals. I have previous posted on the use of amantadine in reducing pathological gambling in PD. Although some medications may reduce the risk of pathological gambling, there is a need to further understand the mechanism of drug-related gambling behavior.Cilia and colleagues from the University of Toronto as well as Italy recently published a study examining the neural network in a series of patients with PD and pathological gambling. The research team used a brain imaging technique called SPECT. SPECT is an earlier technology that measures brain anatomical blood flow. In contrast to functional MRI, SPECT requires an intravenous injection of contrast agent. In this study, the authors conducted a correlational analysis between regional cerebral blood flow and a measure of gambling severity from a psychometric instrument called the South Oaks Gambling Screen. A series of subjects with PD with pathological gambling were compared to a matched PD group without pathological gambling and a matched group without PD. Using a complicated statistical analysis strategy called path analysis, they estimated effective brain connectivity (circuitry) associated with pathological gambling behavior.High pathological gambling scores were associated with the reduced blood flow in the following brain regions (inpartial list):Right ventrolateral prefrontal cortex (VLPFC)Right anterior cingulate cortex (ACC)Right posterior cingulate cortex (PCC)Right medial frontopolar cortex (mPFC)Bilateral anterior insulaLeft striatumThe authors summarize why these specific regions and connections could affect the risk for development of pathological gambling behaviors.Right VLPC: this brain region is involved with behavioral response inhibition, impulsivity and “risk-taking choices during decision making under conflict”. Studies of damage to this region produces a “blunted reaction to aversive outcome and risk-taking behavior. ACC and striatum: In healthy individuals, the authors note the ACC in a region involved in monitoring and processing negative outcomes. The ACC regulates behavioral adjustments in scenarios where outcome predictability is low. The ACC becomes activated in detecting errors after inhibition fails. The striatum has previously been shown to be dysfunctional in problem gamblers without PD. Dopamine (a neurotransmitter target of many PD drugs) is rich in the striatum and dopamine signaling mediates the “computation of reward prediction error and outcome expectation from future choices”.The authors suggest that in PD gamblers, a disconnection develops between the ACC and striatum. This may explain why they have difficulty with perserveration of behavior (continued gambling) despite continued monetary losses.The authors note a weakness of their study is a reliance on correlational resting data. A more powerful design would be to activate the brain regions involved in gambling with a task and study the anatomical and connectivity changes in those with PD associated with gambling and controls. I suspect we will see such a study in the near future. Image of Anterior Cingulate Cortex (ACC) Brain Region from 3D Brain Screen Shot Courtesy of Yates Photography.Cilia R, Cho SS, van Eimeren T, Marotta G, Siri C, Ko JH, Pellecchia G, Pezzoli G, Antonini A, & Strafella AP (2011). Pathological gambling in patients with Parkinson's disease is associated with fronto-striatal disconnection: A path modeling analysis. Movement disorders : official journal of the Movement Disorder Society PMID: 21284039... Read more »

Cilia R, Cho SS, van Eimeren T, Marotta G, Siri C, Ko JH, Pellecchia G, Pezzoli G, Antonini A, & Strafella AP. (2011) Pathological gambling in patients with Parkinson's disease is associated with fronto-striatal disconnection: A path modeling analysis. Movement disorders : official journal of the Movement Disorder Society. PMID: 21284039

September 21, 2010
02:17 PM
844 views

The Neurobiology of Anxiety Disorders

by William Yates, M.D. in Brain Posts

A key question in the classification of anxiety disorders is whether the DSM-IV classification system describes distinct useful categories. There is a great deal of overlap in clinical populations. You do not find many individual who have one unique disorder. Typically, someone with say panic disorder is likely to have one or more additional anxiety disorder such as social phobia or PTSD. A key question is whether there is a broader anxiety disorder phenotype that might include a variety of symptoms found in specific anxiety disorders.If specific anxiety disorders describe specific phenotypes, there should be evidence from what we know about the neurobiology of these disorders. A recent comprehensive review of this issue has been published in the 2009 September issue of Psychiatric Clinics of North America and has been republished in Clinical and Laboratory Medicine. The authors of this review make the argument that “there exist many distinguishing features that support the continued classification of individual anxiety disorders that are distinct from each other and from major depression.” I will summarize some of their highlights for several of the individual anxiety, disorders. The authors group their findings into anatomical and functional imaging findings, neuroendocrine and neurotransmitter, and genetic domains. I will focus on the anatomical and functional imaging domains and refer the reader to the original manuscript for the other domains. Panic DisorderDecreased glucose metabolism in parietal lobe and overall decreased cerebral blood flowElevated glucose metabolism in amygdale, hippocampus, thalamus, midbrain and cerebellumElevations normalize with successful treatment with behavioral or pharmacotherapyPanic attacks are linked with hyperactivity burst in right amygdaleAnxious visual stimuli provoke increased activity in inferior frontal cortex, hippocampus, anterior and posterior cingulated cortex and orbitofrontal cortexPosttraumatic Stress DisorderSeverity of PTSD linked to greater activation of amygdale in response to fearful facesVentral activation of anterior cingulate cortex with fearful faces predicts poor response to cognitive behavioral therapyPTSD patients activate the executive function network with combat-related images—this network is typically not activated in normals for emotional/affective processing tasksPTSD patients anxiety overwhelms brain inhibitory network producing more errors with cognitive tasksSocial PhobiaAnticipation of public speaking tasks excessively elevates activation of subcortical, limbic and lateral paralimbic regionsResponse to trazodone in social phobia linked to decreased blood flow to ventral and dorsl anterior cingulate cortex and prefrontal cortex and increased cerebral blood flow to middle cingulated cortex, left hippocampus and parahippocampal gyrusMisinterpretation of social cues due to dysfunction of the cortico-striato-thalamic networkGeneralized Anxiety DisorderPediatric patients with generalized anxiety show enlargement of amygdaleElevated prefrontal cortex resting activity felt to be an anxiety compensatory responseElevated amygdala and insular cortex activation with angry facesVenlafaxine drug response tied to lower pretreatment amygdala activity and higher anterior cingulated activityOne of the methodological problems with imaging, neurotransmitter and genetic studies in anxiety disorders is the issue of identifying individuals with a unique anxiety disorder. Even this strategy may be problematic. Studying a young adult patient with a unique panic disorder diagnosis does not account for the possibility of later development another anxiety disorder such as social phobia or PTSD.Although a great deal of progress has been made in the neurobiology of anxiety disorders, the challenge of understanding the best classification strategies remain. Clinicians are typically, left with a implementing a trial of a selective serotonin re-uptake inhibitor or cognitive behavior therapy in patients with a single or multiple anxiety disorder diagnoses. The jury is out whether neurobiology can lead to improved and more specific treatments. Photo of Tiger Woods Chipping at 2010 PGA Championship Courtesy of Yates PhotographyMartin EI, Ressler KJ, Binder E, & Nemeroff CB (2009). The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. The Psychiatric clinics of North America, 32 (3), 549-75 PMID: 19716990... Read more »

Martin EI, Ressler KJ, Binder E, & Nemeroff CB. (2009) The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. The Psychiatric clinics of North America, 32(3), 549-75. PMID: 19716990

April 14, 2010
04:35 PM
843 views

Brain Neurocircuitry in Depression

by William Yates, M.D. in Brain Posts

This is the second in a series of three posts from my notes at the NARSAD Healthy Minds Across American 2010 symposium in Tulsa, Oklahoma. The University of Oklahoma-Tulsa and OU-Tulsa President Dr. Gerry Clancy served as host for the event. Following a presentation by Dr. Helen Mayberg from Emory University (notes here), Dr. Wayne Drevets presented a review of neurocircuitry in depression.Dr. Drevets has been a leader in neuroimaging research in mood disorders. His studies have included using both positron emission tomography, MRI and functional MRI. Dr. Drevets played a key role in identifying potential brain stimulation sites in the treatment of depression.The key points from Dr. Drevets' presentation and a recent publication covering the presentation topic:Mood disorders affect multiple domains: affect, sleep, attention, reward behavior, memory, autonomic regulation to name a few. It is possible that neurocircuitry imaging can elucidate circuit dysfunction tied to specific domains. Patients with mood disorders show structural abnormalities in the medial prefrontal network and limbic structuresImaging has informed neuropathology in mood disorders--areas identified as involved in mood disorders by imaging have now been show to have neuropathological changesBrain gray matter volume and brain cell counts/markers are decreased in medial prefrontal cortex and the anterior cingulate cortex in depressed versus control subjectsDepressed bipolar disorder subjects have reduced cell counts in the parahippocampal cortex and hippocampusGlucose metabolism and cerebral blood flow have been shown to be increased in depression in many of these same regionsMedial prefrontal cortex and amygdala have projections to the hypothalamus and other regions affection endocrine, autonomic and behavior responses to stress and emotional stimuliThese projects may explain some of the role of depression in increasing risk of death in heart diseaseDysfunction in the medial prefrontal network may contribute to the features of anhedonia, lack of motivation and inattention common in depressionDopamine circuitry may play a role in these symptoms. The anterior cingulate receives extensive dopamine projections from the ventral segmental area VTAThis area influences dopamine reward response in the nucleus accumbensLess dopamine in depression might reduce motivated behavior and learning In the cited paper below, the authors note: "From a clinical viewpoint, elucidation of the functional relationships between various components of the neurocircuits underlying emotional processing is needed to establish a nosology for mood disorders that is based upon pathophysiology".Dr. Drevets is now the president and director of the Laureate Institute of Brain Research in Tulsa, Oklahoma. He is planning to continue his work in understanding the neurocircuitry of mood disorders. Disclosure: The author is a part-time employee of the Laureate Institute for Brain Research. Photo of Female Cardinal Courtesy of Yates PhotographyPrice JL, & Drevets WC (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 35 (1), 192-216 PMID: 19693001... Read more »

Price JL, & Drevets WC. (2010) Neurocircuitry of mood disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 35(1), 192-216. PMID: 19693001

April 26, 2011
11:04 AM
836 views

Pre-term Births Increase Risk of ADHD and Autism

by William Yates, M.D. in Brain Posts

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

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

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

February 16, 2011
05:35 PM
827 views

Brain Stimulation for Parkinson Disease: Expert Opinion

by William Yates, M.D. in Brain Posts

Parkinson disease is a chronic progressive disease with significant impairment and distress. A host of pharmacological options are available. Unfortunately, drug treatment often is only partially successful in reducing symptoms and can produce problematic adverse events. Deep brain stimulation (DBS) has emerged as a potential therapeutic option for those with severe Parkinson disease. DBS involves a neurosurgical procedure that places an electrode or electrodes into the brain with a device to modulate an electric current. The brain subthalamic nuclei has become the most common site for DBS electrode placement.Many questions remain unanswered in DBS therapy for Parkinson disease. A recent consensus conference assembled 49 experts in the use and care of patients receiving DBS therapy. They have published their recommendations in a recent manuscript published in Archives of Neurology. I will summarize some of their recommendations:Surgical Selection: Expert selection of candidates for DBS is viewed as the most important variable in getting a good DBS outcome. Best candidates for DBS include those with the following features:Excellent response to the drug levodopaYounger ageNo or few axial motor symptoms that do not respond to levodopaLimited cognitive impairmentLimited or well-controlled psychiatric diseaseSurgical Complications: Surgical complications are not common but are not trivial and need to be taken into account when considering DBS surgery. Complications can include intracranial hemorrhage (bleeding), stroke, infection, erosion of DBS leads, and death. Advanced age and medical comorbidities appear to increase the risks for surgical complications but should not be absolute contraindications. Surgical team experience is important and patients and their families should select centers with extensive experience with the procedure. There is a need for a standardized system of reporting DBS complications to allow for comparison across treatment sites.Parkinson Disease Outcome: If a patient has improvement in gait and speech with levodopa, they are more likely to have improvement in these domains with DBS. Initial improvement in gait and speech with DBS may later fade as the disease progresses. Some patients experience increase in depression after DBS and this may be related to the site of the electrodes. Patients need to have depression, anxiety, apathy, psychosis and impulsivity levels assessed before surgery as these parameters may complicate outcome. Improvement in some aspects of Parkinson disease has been demonstrated for up to 5 years. Nevertheless, progression of disease commonly occurs in good DBS repsonders and DBS does not prevent the late stages of Parkinson disease including freezing of gait, postural instability and cognitive decline.This expert consensus guideline will aid clinicians, patients and family members in considering DBS as a therapeutic option. A patient resource for those with Parkinson disease considering DBS can be found here (DBS-STN.org-an affiliate of the Parkinson Alliance).Figure of coronal section of brain showing subthalamic nuclei (STN in yellow)--common electrode placement site in DBS for Parkinson disease. Figure courtesy of Creative Commons from Wikipedia, author Andrew Gillies.Bronstein, J., Tagliati, M., Alterman, R., Lozano, A., Volkmann, J., Stefani, A., Horak, F., Okun, M., Foote, K., Krack, P., Pahwa, R., Henderson, J., Hariz, M., Bakay, R., Rezai, A., Marks, W., Moro, E., Vitek, J., Weaver, F., Gross, R., & DeLong, M. (2010). Deep Brain Stimulation for Parkinson Disease: An Expert Consensus and Review of Key Issues Archives of Neurology, 68 (2), 165-165 DOI: 10.1001/archneurol.2010.260... Read more »

Bronstein, J., Tagliati, M., Alterman, R., Lozano, A., Volkmann, J., Stefani, A., Horak, F., Okun, M., Foote, K., Krack, P.... (2010) Deep Brain Stimulation for Parkinson Disease: An Expert Consensus and Review of Key Issues. Archives of Neurology, 68(2), 165-165. DOI: 10.1001/archneurol.2010.260

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William Yates, M.D.

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