516 posts · 446,688 views

I am a physician interested in clinical neuroscience research. I will use this blog to post more detailed analysis of recent studies in addition to my @WRY999 Twitter scientific reading log. I will also post some of my wildlife/sports photography. Aim to educate and amuse. Not selling anything.

William Yates, M.D.
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January 14, 2015
10:51 AM
335 views

Obesity, Inflammation and the Brain

by William Yates, M.D. in Brain Posts

Brain inflammation produces a variety of emotional, behavior and cognitive symptoms.I remember clearly a patient I cared for with central nervous system lupus erythrematosis (SLE). With SLE flairs she developed flagrant psychotic symptoms including hallucinations requiring inpatient psychiatric care.Between flares she had no significant psychiatric symptoms.Nicole Castanon and two colleagues from France have published a review of the role of obesity-associated inflammation and brain dysfunction.Obesity is linked to a variety of blood markers of inflammation including proinflammatory cytokines, IL-6, interleuking and TNF. These inflammatory markers diminish with weight loss accomplished by either diet restriction or bariatric surgery.The authors note evidence obesity is associated with the following:Depression (not all studies and not confirmed in animal models)AnxietyMemory and other cognitive impairmentIncreased age-related cognitive declineSo how could primarily a peripheral body condition impact the brain?Figure from Castonon et alThe authors summarize potential mechanisms in a nice figure that I have reproduced here as it is open-access under the Creative Common Attribution License. See the citation below for the source of this figure.Increased adipose (fat) tissue is known to promote local inflammation including recruitment of microphages and secretion of inflammatory chemicals. This peripheral adipose inflammation can transfer to the brain through the vagus nerve, hormones or other blood inflammtory chemicals and cellular pathways.Brain evidence for this transfer has been noted via inflammation in the hippocampus, basal ganglia and prefrontal cortex.Additional obesity-related brain inflammatory effect has been noted through dysruption of the hypothalamic/pituitary/adrenal (HPA) axis and changes in brain serotonin and dopamine metabolism.A second potential pathway is described as working through changes in the gut in obesity. Obesity is linked to changes in gut bacteria composition, a change that results in increased gut permeability. This permeability change potentially promotes increased gut-blood absorption of endotoxins that can promote a systemic anti-inflammatory response. The authors note their review of this topic supports weight management approaches to limit the effect of obesity on the brain. Additionally, there may be some evidence to investigate anti-inflammatory diet and drug interventions for those with combined obesity and brain disorders. Readers with more interest in this topic can access the free full-text manuscript by clicking on the link below.Photo of blue jay in the snow is from the author's files.Figure of obesity-brain interaction is from Castanon, Lasselin and Capuron, citation below.Follow the author on Twitter WRY999Castanon N, Lasselin J, & Capuron L (2014). Neuropsychiatric comorbidity in obesity: role of inflammatory processes. Frontiers in endocrinology, 5 PMID: 24860551... Read more »

Castanon N, Lasselin J, & Capuron L. (2014) Neuropsychiatric comorbidity in obesity: role of inflammatory processes. Frontiers in endocrinology, 74. PMID: 24860551

January 12, 2015
10:56 AM
325 views

Dietary Grains and Heart/Stroke Mortality

by William Yates, M.D. in Brain Posts

Dietary intake of whole grains and fiber shows consistent beneficial effects on a variety of health and mortality measures.In a post in 2011, I reviewed study results from the NIH-AARP cohort. That study reported reduced cardiovascular disease but not cancer in men and women with the highest fiber intake.A recent Harvard University study examined mortality risk in a group of U.S. health professionals grouped by level of whole grain intake.Participants in this study were over 118,000 men and women from the Health Professionals Follow-Up Study and the Nurses' Health Study.Participants completed dietary questionnaires every two to four years over the course of the study. Each participant had an estimated daily grain consumption level calculated from dry weight whole grain intake of rice, bread, pasta and breakfast cereals.Participants were grouped into quintiles (5 groups each containing 20% of the sample) from lowest to highest whole grain intake. Mean levels of whole grain daily intake in three of the five quintiles for women/women were reported:Lowest (g/day): 4.2/5.9Low: 9.7/14.4Middle: 14.7/22.1High: 21.1/31.3Highest: 33.0/47.8The study team follow participants for death using next of kin, postal information and the National Death Index.Death certificate and medical record information was used to assign deaths into cardiovascular deaths (including myocardial infarction and stroke), cancer or other categories.During the follow-up period of 26 years, 15,106 deaths were identified with 2989 assigned to the cardiovascular disease death group, 5964 assigned to cancer and 6,153 assigned to other causes.Analysis of the rates of heart/stroke death rates by whole grain intake showed a consistent finding in men and women.Those in the highest whole grain intake group had about a 15% reduction in rates of heart/stroke deaths during the follow-up period (see chart left).Additionally, total mortality was about 8% over the follow-up period in the highest whole grain intake group.This estimate controlled for potential confounding variables such as age, BMI, smoking status, physical activity and aspirin use.Getting to the high or higher quintile group status takes between two and three daily servings of whole wheat, whole oats, whole cornmeal, whole rye, brown rice, popcorn or bran additive.One concern with whole grains is the carbohydrate levels. Individuals on a low carbohydrate diet may find a big portion of their daily carbohydrate limit is taken up with two or three portions of whole grain. Using bran additives, like All-Bran Buds may reduce the carbohydrate load associated with whole grains.The authors note their findings are consistent with several other studies linking whole grain intake to lower heart/stroke death risk. Additionally they note their findings support federal guidelines urging daily whole grain intake.This is an important study due to the large sample size, ability to examine effects in both men and women and the quality of dietary and mortality data.Photo of blue jay is from the author's files.Chart was an original chart made by author using data from the manuscript.Follow the author on Twitter WRY999.Wu H, Flint AJ, Qi Q, van Dam RM, Sampson LA, Rimm EB, Holmes MD, Willett WC, Hu FB, & Sun Q (2015). Association Between Dietary Whole Grain Intake and Risk of Mortality: Two Large Prospective Studies in US Men and Women. JAMA internal medicine PMID: ... Read more »

Wu H, Flint AJ, Qi Q, van Dam RM, Sampson LA, Rimm EB, Holmes MD, Willett WC, Hu FB, & Sun Q. (2015) Association Between Dietary Whole Grain Intake and Risk of Mortality: Two Large Prospective Studies in US Men and Women. JAMA internal medicine. PMID: 25559238

December 15, 2014
08:42 AM
408 views

Who is Getting High in Europe (and Where)?

by William Yates, M.D. in Brain Posts

My research training is in psychiatric epidemiology. Alcohol and drug dependence have been two of my topic areas of research.So I found a recent novel study of the epidemiology of illicit drug use in Europe intriguing.Typical methods of looking for the prevalence of drug use in populations are direct diagnostic interviews and studies of emergency room attendees or autopsy cases with medical complications of drug use.However, Christopher Ort from Switzerland along with a host of European colleagues took an interesting approach to studying illicit drug use in European populations.They conducted population wastewater illicit drug concentration analyses using liquid chromatography. They examined changes in illicit drug concentrations over time and across a number of cities and regions in Europe.This approach is slightly messy (pun intended) but logically follows a reasonable argument: high illicit drug concentrations in waste water reflects high drug use in the population producing the waste.Their full text manuscript can be accessed by clicking on the PMID link below. But for the few lazy readers of my blog here are the five highest ranked European cities by the five illicit drug classes. This list is produced by me through the precise method known as "eyeballing" from charts in the manuscript. Countries are listed after municipalities where waste water was sampled when city first makes a list.CannabisAmsterdam, NetherlandsParis, FranceNovisad, SerbiaAntwerp, BelgiumUtrecht, NetherlandsAmphetaminesEindhoven, NetherlandsAntwerpGothenburg, SwedenNinove, BelgiumHelsinki, FinlandMethamphetaminePrague, Czech RepublicBudweis, Czech RepublicOslo, NorwayBratislava, SlovakiaDresden, GermanyCocaineAntwerpLondon, EnglandZurich, SwitzerlandAmsterdamBarcelona, SpainMDMA (Ecstasy)EindhovenUtrechtAmsterdamAntwerpZurich/Barcelona (Eyeball tie)The authors note their findings for the prevalence of illicit drugs in wastewater generally match regional prevalence estimates for drug use using other methods.They note wastewater samples can be done by day of the week to follow chronological patterns of drug use (no surprise levels of drugs in wastewater samples are higher on the weekend). Additionally, this approach may be a valuable secondary source of trends in regional drug use over longer periods such as years. I found the differences in metabolite rankings for amphetamine versus methamphetamine interesting. The methamphetamine rank list is made up of more cities with lower per capita incomes. This suggests possible local production of methamphetamine while amphetamine is more likely diverted from pharmaceutical grade manufacture.This study did not include samples from the U.S., South America, Japan, China or Russia so it only reflects the cities listed in the methods section of the paper. Again, click on the citation PMID link below if you are interested in getting into more detail of this study. I would be interested in any comments from readers in Europe on whether these results seem valid.Image is from a Wikipedia Commons file showing tablets of ecstasy (MDMA) from a public domain file produced by the U.S. DEA.Follow the author on Twitter WRY999Ort C, van Nuijs AL, Berset JD, Bijlsma L, Castiglioni S,... Read more »

Ort C, van Nuijs AL, Berset JD, Bijlsma L, Castiglioni S, Covaci A, de Voogt P, Emke E, Fatta-Kassinos D, Griffiths P.... (2014) Spatial differences and temporal changes in illicit drug use in Europe quantified by wastewater analysis. Addiction (Abingdon, England), 109(8), 1338-52. PMID: 24861844

December 10, 2014
11:46 AM
328 views

Prescription Opiate Abuse: High-Risk Populations

by William Yates, M.D. in Brain Posts

Prescription opiate abuse is a significant problem in the United States.I have previously written about this issue in several previous posts.One important factor for clinicians and patients is the need to identify high-risk populations that may be more vulnerable to opiate abuse and dependence.One obvious group would be those with alcohol or another non-opiate abuse diagnosis. Additionally, some psychiatric disorders are associated with increased risk for substance abuse including opiate abuse.Given these high-risk markers, it would be encouraging if there would be evidence prescription opiate use is limited in those with substance abuse or a primary psychiatric disorder.Unfortunately, there is not much evidence for restriction of opiate prescribing in high-risk populations.Daniel Hackman and colleagues found the opposite finding in a study of patients with a substance abuse or primary psychiatric diagnosis in a dual diagnosis clinic.Patients (N=201) in this clinic had prescription drug use reviewed for a period of 12 months and found the following key findings:Subjects received an average of 4.0 prescriptions for an opiate by medical personnel not associated with the dual diagnosis clinicThese prescriptions resulted in the dispensing of an average of 213 opioid pillsConcurrent benzodiazepine prescriptions were also common in this populationMedicare or Medicaid coverage was associated with higher rates of opiate prescription compared to patients without insurance coverageThere are several take-home messages from this study.First, some high-risk populations for opiate abuse seem to be more likely to get prescription opiates from a medical provider. From the current study, it does not appear clinicians are restricting prescription opiates to those most likely to misuse or abuse these drugs.Second, concurrent benzodiazepine and opiate prescription use is common in this dual diagnosis group. This is important because accidental overdose deaths commonly find the combination of opiates and benzodiazepines in toxicology analysis.I am not suggesting that no legitimate reasons exist for careful opiate prescription use for the treatment of pain in those with a dual diagnosis. However, this population needs to be carefully assessed and monitored when prescribing opiates in the clinical setting.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of a tiger from the San Antonio zoo is from the author's files.Follow the author on Twitter WRY999Hackman DT, Greene MS, Fernandes TJ, Brown AM, Wright ER, & Chambers RA (2014). Prescription drug monitoring program inquiry in psychiatric assessment: detection of high rates of opioid prescribing to a dual diagnosis population. The Journal of clinical psychiatry, 75 (7), 750-6 PMID: 25093472... Read more »

Hackman DT, Greene MS, Fernandes TJ, Brown AM, Wright ER, & Chambers RA. (2014) Prescription drug monitoring program inquiry in psychiatric assessment: detection of high rates of opioid prescribing to a dual diagnosis population. The Journal of clinical psychiatry, 75(7), 750-6. PMID: 25093472

December 10, 2014
11:06 AM
340 views

Incentives in the Treatment of Cocaine Dependence

by William Yates, M.D. in Brain Posts

Relapse rates are high in treatment samples of adults with cocaine dependence.Cognitive behavioral therapy (CBT) is a common standard of care for cocaine dependence.A recent clinical trial from Switzerland examined the use of financial prize incentives to augment standard CBT in the treatment of cocaine dependence.Sixty subjects participated in this trial with the following inclusion criteria: least 18 years of age, had a DSM-IV diagnosis of cocaine dependence with at least one positive cocaine urine drug screen at baseline.Exclusion criteria included: current psychotic disorder, current severe alcohol or benzodiazepine dependence, serious medical illness, pathological gambling, language impairment, methylphenidate use and active homelessness.All subjects received 18 manual-based CBT sessions over 24 weeks targeted towards a goal of cocaine abstinence.Half of the subjects received an additional treatment intervention labelled prize-based contingency management: Subjects with cocaine negative urine samples (taken twice weekly in weeks 1-12 and weekly during weeks 13-24) were eligible to earn prizesPrizes were determined from a patient drawing from 500 chips in a bowl250 chips were non-winners219 had a value of $2 traded for food or hygiene rewards30 had a value of $20 with a voucher for prizes in this price rangeOne jumbo prize valued at $500 was present and could be traded for a television or vacation prizeInterestingly, the number of chips that was drawn started at one with the first cocaine free drug sample and increased by one with each consecutive negative sample up to a maximum of 15 chips.Subjects relapsing after a period of abstinence returned to a one chip reward restart with the next clean urine sample.The study failed to find a large statistically significant effect for the addition of prize-based contingency management.However, those in the prize-based contingency management group had higher rates of clean urine samples beginning at weeks 8, 9 and 10 as well as several other later time points.Additionally, the prize group had higher cocaine clean urine rates at 6 months follow up (66% vs 45%) although this did not reach statistical significance.One issue with this study is the small sample size with limited power to detect clinically significant differences between treatment. The trend for improvement with adding the prize intervention suggests the potential merit of conducting a similar study using larger samples, possibly in several settings and nations.The authors note the cost for the incentives in their design averaged $576 over the 24 week study. This additional cost is non-trivial and will need to be examined in larger samples.Readers with more interest in this clinical trial can access the free full-text manuscript by clicking on the free full-text link in the PMID link below.Photo of fall foliage is from the author's files and includes Google plus enhancement.Follow the author on Twitter WRY999.Petitjean SA, Dürsteler-MacFarland KM, Krokar MC, Strasser J, Mueller SE, Degen B, Trombini MV, Vogel M, Walter M, Wiesbeck GA, & Farronato NS (2014). A randomized, controlled trial of combined cognitive-behavioral therapy plus prize-based contingency management for cocaine dependence. Drug and alcohol dependence, 145C, 94-100 PMID: 25456571... Read more »

Petitjean SA, Dürsteler-MacFarland KM, Krokar MC, Strasser J, Mueller SE, Degen B, Trombini MV, Vogel M, Walter M, Wiesbeck GA.... (2014) A randomized, controlled trial of combined cognitive-behavioral therapy plus prize-based contingency management for cocaine dependence. Drug and alcohol dependence, 94-100. PMID: 25456571

December 1, 2014
12:09 PM
376 views

Common Genes in Neuropsychiatric Disorders

by William Yates, M.D. in Brain Posts

Finding a specific genes linked to specific neuropsychiatric disorders has been a key research strategy.However, this strategy has not been entirely successful.One problem with this unitary approach is the diagnostic overlap and comorbidity common to neuropsychiatric disorders such as mood disorders and autism.A promising alternative strategy is to focus on genes that share risk with more than one neuropsychiatric condition.Amit Lotan from Israel along with colleagues from the Netherlands, Germany and the U.S. recently published a study of common and distinct genetic components in six major neuropsychiatric disorders.Their study used large genome wide association databases mined from the National Human Genome Research Institute linked to the following six neuropsychiatric disorders:Anxiety disordersAttention deficit/hyperactivity disorderAutism/autism spectrum disordersBipolar disorderMajor depression Schizophrenia Using a variety of genetic and molecular biology strategies, the research team examined human and mouse genes common to more than one neuropsychiatric disorder as well as genes unique to only one of the six disorders.The key findings of the study including identification of 15 genes common to five of the six disorders. The genes identified in this analysis shared known activity in neuronal function known as postsynaptic density. Additionally, these shared genes are known to influence immune as well as brain function.Additionally, the research identified two genetic components shared by all six of the disorders. These two components were involved in neuronal projection, synaptic activity, CNS development and cellular process. In total, these two genetic components contributed to 20-30% of the genetic load.Obviously, 20-30% is a significant shared genetic contribution but it leaves important genetic contributions specific to each of the six conditions. The authors conclude in their discussion:".. it could be hypothesized that a common (pathologic) molecular infrastructure located to neural projections, cytoplasm (or possibly both) may be necessary to induce a primary vulnerability to develop a neuropsychiatric disorder. Further distinct molecular processes which build-up on top of this common infrastructure ultimately lead, in certain patients, to the development of one or another specific neuropsychiatric disorder."This type of study provides significant insight into the complexity of genetic influences in neuropsychiatric disorders.Examining shared genetic influences in different conditions can aid in understanding common pathophysiology mechanisms for distinct neuropsychiatric disorders. Additionally, these types of studies show the limitations of current diagnostic classification systems and may aid in future refinement of diagnostic systems.Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below. Photo of flamingo is from the author's files.Follow the author on Twitter at WRY999.Lotan A, Fenckova M, Bralten J, Alttoa A, Dixson L, Williams RW, & van der Voet M (2014). Neuroinformatic analyses of common and distinct genetic components associated with major neuropsychiatric disorders. Frontiers in neuroscience, 8 PMID: 25414627... Read more »

Lotan A, Fenckova M, Bralten J, Alttoa A, Dixson L, Williams RW, & van der Voet M. (2014) Neuroinformatic analyses of common and distinct genetic components associated with major neuropsychiatric disorders. Frontiers in neuroscience, 331. PMID: 25414627

November 26, 2014
11:06 AM
411 views

Treatment Resistance in Eating Disorders

by William Yates, M.D. in Brain Posts

Clinicians treating patients with eating disorders find the challenge great with many treatment-resistant cases.To some extent, this is true of any clinical disorder. Outpatient treatment rolls and inpatient samples are over-represented by those failing to respond to initial interventions.A medical example is helpful here. Endocrinologists specializing in diabetes see more complicated cases where glucose control is difficult and diabetic complications are common.Diabetics with easy glucose control and no complications do not need to see an endocrinologists. To an endocrinologist, clinical practice seems to point to the disease as a treatment-resistant and clinically challenging disorder.Nevertheless, treatment resistance in eating disorders is a significant issue that has been recently summarized in a nice review by Dr. Katherine Halmi.Here are my notes from review of the Halmi manuscript using her key headings:Core eating disorder psychopathologyAdolescent eating disorder subjects lack insight into the seriousness of illnessMany do not acknowledge need for treatmentBody weight, exercise and dieting provide a distraction from other life problemsMalnutrition in eating disorders contributes to cognitive impairment, treatment engagement problemsBulimia treatment resistance has been linked to greater depression, lower BMI and social adjustment problems Psychiatric and psychological comorbidityU.S. National Survey found high rates of psychiatric comorbidity in eating disorders (56% in anorexia nervosa, 95% in bulimia nervosa and 79% in binge eating disorder)Anxiety disorders rates are elevated in eating disorders with obsessive compulsive disorder and social anxiety disorder two common conditionsAnxiety disorders can contribute to resistance of treatment of eating disorder symptomsCluster B personality disorders are elevated in bulimia nervosa and appear related to higher rates of substance dependence in this disorderPerfectionism is common in anorexia nervosa. Early onset and high perfectionism traits contribute to higher treatment resistance Biological featuresSerotonin receptor and transporter function appear to influence course of illness in eating disodersGABA receptor genotype appears to be related to level of trait anxiety in both bulimia nervosa and anorexia nervosaGABA receptor abnormalities are also possibly related to treatment resistance Treating refractory patientsQuetiapine, olanzapine, haloperidol and duloxetine are drugs with some promise in treatment resistant anorexia nervosaNovel psychotherapies including CBT and the Maudsley Model target key features of resistance in anorexia nervosaTreatment resistant bulimia nervosa may respond to sequential treatment strategies that include partial hospitalization, selective serotonin reuptake inhibitor (SSRI) drugs and cue exposureBinge eating disorder may respond to high dose SSRI therapy or topiramate in a graduated dosing scheduleThis review points to the key elements for treatment of the difficult eating disorder patient.This population needs access to specialized hospitalization units, psychopharmacology expertise and specialized psychotherapy services.Dr. Halmi notes advances in the treatment of this population may require advances in understanding the neurobiology and neurocircuitry for the disorder.Readers with more interest in this summary can find the free full-text manuscript by clicking on the DOI link in the citation below.Winter snow scene is from the author's files.Follow the author on Twitter @WRY999Halmi, K. (2013). Perplexities of treatment resistence in eating disorders BMC Psychiatry, 13 (1) DOI: 10.1186/1471-244X-13-292... Read more »

Halmi, K. (2013) Perplexities of treatment resistence in eating disorders. BMC Psychiatry, 13(1), 292. DOI: 10.1186/1471-244X-13-292

November 17, 2014
10:55 AM
316 views

Eating Disorders in Obesity: DSM-IV and DSM-5

by William Yates, M.D. in Brain Posts

The recent revision of the American Psychiatric Associations Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) altered several eating disorder diagnostic criteria.Some have expressed concern that these revisions are overly broad and may result in over diagnosis in some clinical populations. One clinical population where this is a concern is obesity.A research study has been recently published addressing this issue.Jennifer Thomas and colleagues at Harvard University and Massachusetts General Hospital recruited a series of subjects from an obesity program for eating disorder diagnostic assessment.All subjects completed an assessment for presence of an eating disorder diagnosis using both DSM-IV and DSM-5 criteria.For DSM-IV eating disorder diagnoses, the research team used a validated module from a validated measure known as SCID-IV. For DSM-5 eating disorder diagnosis an early structured interview developed by the DSM-5 Eating Disorders Task Group was used.The key findings from the study included:Prevalence rates for eating disorders using DSM-5 criteria did not increase compared to DSM-IV criteriaBulimia nervosa prevalence rates were 2% in both interviewsBinge eating disorder prevalence rates were 9% in both interviewsAn additional 20% of the obese sample met residual eating disorder criteria in both interviewsObese individuals with a formal eating disorder diagnosis endorsed higher rates of psychological impairment, depression and anxiety validating the impact of eating disorder comorbidity.Assessment for the presence of eating disorders is an important part of treatment planning. Eating disorders are more prevalent in obese populations are relatively easy to diagnose.Some studies have found poor outcomes in obese populations with severe binge eating behaviors.Treatment of a comorbid eating disorder in obese populations may improve weight and psychological outcomes.Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link below.Photo of a bottle-nosed dolphin is from the author's files.Follow the author on Twitter WRY999Thomas JJ, Koh KA, Eddy KT, Hartmann AS, Murray HB, Gorman MJ, Sogg S, & Becker AE (2014). Do DSM-5 eating disorder criteria overpathologize normative eating patterns among individuals with obesity? Journal of obesity, 2014 PMID: 25057413... Read more »

Thomas JJ, Koh KA, Eddy KT, Hartmann AS, Murray HB, Gorman MJ, Sogg S, & Becker AE. (2014) Do DSM-5 eating disorder criteria overpathologize normative eating patterns among individuals with obesity?. Journal of obesity, 320803. PMID: 25057413

November 12, 2014
11:14 AM
398 views

Binge Eating Linked to Risk for Irritable Bowel Syndrome

by William Yates, M.D. in Brain Posts

Binge eating is defined as the recurrent rapid consumption of high calorie meals accompanied by a feeling that eating is out of control.Bulimia nervosa is an eating disorder characterized by binge eating paired with a purging behavior such as self-induced vomiting.Binge eating without purging is receiving increased clinical and research attention.Binge eating is a relative common component in elevated body mass index and obesity. Successful behavior and drug treatment for obesity often includes a significant reduction in the frequency of binge eating.Binge eating is frequently accompanied by symptoms of gastrointestinal disorders such as gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). However, these GI symptoms and disorders are also increased in obesity. These relationships have made it difficult to determine the specific effects of binge eating on GI symptoms as it is possible these effects may occur through an obesity mechanism.Christine Peat along with colleagues from the University of North Carolina and Sweden recently published a study teasing out relationships between binge eating, BMI and GI symptoms.This study used data from the Swedish Twin Study of Adults: Genes and Environment (STAGE). For the current study, over 23,000 twin pairs were interviewed for presence of lifetime history of binge eating, weight history and presence of gastrointestinal symptoms.The key findings from this study included the following:Gastrointestinal reflux symptoms were present in 15.7% of men and 28.9% of womenIrritable bowel syndrome (broad definition) was present in 3.7% of men and 8.1% of womenBinge eating was linked to to higher rates of GERD and IBSHowever, when BMI was controlled binge eating was independently related to IBS but not related to GERD The authors propose three potential mechanisms for this link between binge eating and IBS.Stress may be a common factor as it is known that stress can precipitate bingeing episodes and increase IBS symptomsIBS may cause dietary restriction including periods of fasting. Fasting is known to increase later risk for binge eating as the body attempts to compensate via a strong hunger mechanismBinge eating of large quantities of high fat foods may directly produce IBS symptoms as the GI system responds to a feeding load The take home message for clinicians treating IBS is that it is important to assess for the presence of binge eating. Successful reduction in the frequency of binge eating may contribute to a successful reduction in IBS symptoms. Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of flowers from Dingle, Ireland is from the author's files.Follow the author on Twitter WRY999Peat CM, Huang L, Thornton LM, Von Holle AF, Trace SE, Lichtenstein P, Pedersen NL, Overby DW, & Bulik CM (2013). Binge eating, body mass index, and gastrointestinal symptoms. Journal of psychosomatic research, 75 (5), 456-61 PMID: 24182635... Read more »

Peat CM, Huang L, Thornton LM, Von Holle AF, Trace SE, Lichtenstein P, Pedersen NL, Overby DW, & Bulik CM. (2013) Binge eating, body mass index, and gastrointestinal symptoms. Journal of psychosomatic research, 75(5), 456-61. PMID: 24182635

November 11, 2014
11:13 AM
374 views

Anorexia Nervosa: Brain Connectivity Abnormalities

by William Yates, M.D. in Brain Posts

Functional magnetic resonance imaging is providing a new tool for understanding brain circuitry in normal brain development and in brain disorders. Anorexia nervosa is an restrictive calorie eating disorder often resistant to treatment.No effective drug treatment for anorexia nervosa currently exists and psychotherapy is often only partially effective. A better understanding of the brain pathophysiology in anorexia nervosa is needed to aid in treatment development.Stephanie Kullman along with colleagues at the University of Tubingen recently published a study of brain connectivity in twelve women with anorexia nervosa.This study used a resting state functional connectivity approach with magnetic resonance imaging. In functional connectivity studies, the brain is studied during rest and levels of coherent activity between brain regions measured. The authors of this study noted anorexia nervosa commonly includes motor hyperactivity and so they used both a non-athlete and athlete female control group for comparision.The primary findings from this study included the following:The brain inferior frontal gyrus (IFG) in both the left and right sides demonstrated reduced effective connectivity Decreased effective connectivity was noted between the right IFG and the cingulateIncreased effective connectivity was noted between the right IFG and the bilateral orbitofrontal gyrus regionIncreased effective connectivity was noted between the left IFG and the bilateral insular cortexThe authors note the inferior frontal cortex is a key region for executive functions, or control of complex cognitive functions. Disturbance of executive function in anorexia nervosa may contribute to food consumption and activity decision making.The authors note their study found a link between level of physical hyperactivity in individual patients with anorexia nervosa and reduced IFG connectivity. Women with the highest level of physical activity had the lowest levels of IFG connectivity.The areas of increased connectivity in this sample of patients with anorexia contribute to processing of the salience of stimuli. The authors note the insular cortex is a "multisensory neural node" involved in integration of "perception, emotion, interoceptive awareness, cognition and gustation". Disturbance of connectivity balance between the IFG and insular cortex may contribute to anxiety and fear related to somatic sensations.The findings in this imaging study occurred in the context of active illness in anorexia nervosa. It would be interesting to follow these findings with recovery and weight restoration.Additionally, modification of functional connectivity disturbances in anorexia may hold promise for new drug development and more effective psychological interventions.Readers with more interest in this study can access the free full-text manuscript by clicking on the citation link below.Image of brain with highlighted inferior frontal gyrus is from a screen shot from the Brain Tutor app for the iPad from the author's files.Follow the author on Twitter @WRY999Kullmann S, Giel KE, Teufel M, Thiel A, Zipfel S, & Preissl H (2014). Aberrant network integrity of the inferior frontal cortex in women with anorexia nervosa. NeuroImage. Clinical, 4, 615-22 PMID: 24936412... Read more »

Kullmann S, Giel KE, Teufel M, Thiel A, Zipfel S, & Preissl H. (2014) Aberrant network integrity of the inferior frontal cortex in women with anorexia nervosa. NeuroImage. Clinical, 615-22. PMID: 24936412

November 10, 2014
10:05 AM
338 views

Eating Disorders Linked to Higher Autoimmune Disease Rates

by William Yates, M.D. in Brain Posts

There is increasing evidence for inflammation contributing to risk for a variety of psychiatric disorders.I previously summarized research supporting use of anti-inflammatory drugs in the treatment of depression.A recent study from Finland supports an inflammation link to the eating disorder categories.The key elements of the design of this study included:Subjects: 2342 subjects admitted for treatment in the Eating Disorders Unit at the central hospital in Finland. Four controls were identified for each case matched by age, gender and place of residenceIdentification of presence for autoimmune diseases: Cases and controls were examined for the presence of one of 30 autoimmune diagnoses in their Hospital Discharge RegisterStatistical analysis: Period and lifetime rates for autoimmune disorders were compared between eating disorder cases and control using logistic regression modeling with calculation of odds ratios and 95% confidence intervals. Here are the important findings from the study:Eating disorders subjects had a 5.6% rate for presence of any autoimmune disease compared to only 2.8% of controls (Odds ratio 2.13, 95% confidence interval 1.71-2.65)Rates for autoimmune disorders were increased across all eating disorder diagnostic categories including anorexia nervosa, bulimia nervosa and binge eating disorderWithin autoimmune disease subtypes, endocrinological and gastroenterological diseases were statistically increased in eating disordersType I diabetes and Crohn's disease were individual autoimmune disorders found at higher rates in eating disorders The authors note there are several methods that could explain the association between autoimmunity and eating disorder risk. Higher rates of autoantibodies against peptides that control appetite and stress response could contribute to eating disorder risk.Additionally, the authors note disturbed eating may contribute to disturbance of the microbiome of the gut. Gut microbiome is a known regulator of autoimmunity and a contributor to allergies and type I diabetes risk.The authors noted additional specific autoimmune disorders may be increased in eating disorders but due to small sample size their study may have not found a statistical association.Systemic lupus erythematosis rates were increased in the eating disorder group but this was one of the individual disorders that failed to reach statistical significance.The take home message for clinicians treating eating disorder patients is to be vigilant for the presence of autoimmune medical disorders in this population. Accurate and early detection of autoimmune disorders in those with eating disorders may contribute to improved medical outcomes.Readers with more interest can access the free full text manuscript by clicking on the PMID link below.Photo of street scene in Dingle, Ireland is from the author's files.Follow the author on Twitter @WRY999Raevuori A, Haukka J, Vaarala O, Suvisaari JM, Gissler M, Grainger M, Linna MS, & Suokas JT (2014). The increased risk for autoimmune diseases in patients with eating disorders. PloS one, 9 (8) PMID: 25147950... Read more »

Raevuori A, Haukka J, Vaarala O, Suvisaari JM, Gissler M, Grainger M, Linna MS, & Suokas JT. (2014) The increased risk for autoimmune diseases in patients with eating disorders. PloS one, 9(8). PMID: 25147950

November 5, 2014
12:19 PM
314 views

Anorexia Nervosa as a Disorder of Perception

by William Yates, M.D. in Brain Posts

A key feature in anorexia nervosa is the disturbance in perception of the body.This perceptual disturbance is encapsulated in criteria 3 from DSM-5: "Disturbance in the way in which one's body weight or shape is experienced, undue influence of body weight or shape evaluation, or denial of the seriousness of the current low weight" Santino Guadio from Italy and colleagues recently published a nice summary of the support for body image disturbance in anorexia nervosa. This study focused on research in the neuropsychology of anorexia nervosa.This review is informative in outlining the components involved in sensory perception.Here are the key findings from their review following their perception components outline.Tactile perceptionWhat it is: identifying touch stimuli and discriminating differences in stimuliHow it is tested: finger identification test, tactile estimation task (estimating distance between two tactile stimuli in different body sitesFindings in anorexia nervosa: Patients with anorexia nervosa perform poorly on identifying finger perception when blindfolded and two fingers are stimulated. Anorexia nervosa is also associated with overestimation of distance between stimulation sites over multiple body partsHaptic perceptionWhat it is: ability to identify shapes by touch when no visual input is availableHow it is tested: Identifying figures and shapes with eyes closed using hands for sensory inputFindings in anorexia nervosa: Patients with anorexia nervosa perform more poorly than controls on correctly identify shape and form when unable to see an object. This deficit appears to be present during both active illness with weight loss and persists following weight restoration.PropioceptionWhat it is: identification of body and limb position in spaceHow it is tested: identification of right-left orientation, ability to place a rod in a vertical postion as body position is modified and no visual sensation is providedFindings in anorexia nervosa: Patients with anorexia nervosa show impaired spatial orientation perception as well as deficits in correctly identifying right-left orientation.Haptic-visual-proprioception integration:What it is: Ability to estimate correct physical properties using both haptic and visual stimuliHow it is tested: Two objects of identical weight but difference size are presented for touch and sight input. Subjects estimate weight of two objects relative to each otherFindings in anorexia nervosa: Subjects with anorexia nervosa show reduction in size-weight performance and reduction integration of visual and haptic information.Visual-tactile-proprioception integration:What it is: use and integration of three sensory modalities, sight, touch and body positionHow it is tested: rubber hand test where subjects estimate position of left index finger before and after visuotactile stimulations.Findings in anorexia nervosa: Patients with anorexia nervosa show impairment in two components of visuo-tactile-propioception integrationInteroceptive perception:What it is: ability to identify and process internal bodily sensations such as heartbeart, intestinal activity, hunger, painHow it is tested: participants are asked to count their own heartbeats and this count is compared to actual heart rate. Findings in anorexia nervosa: Patients with anorexia nervosa show impaired perception of heartbeat compared to controlsThe authors note they found a relatively few well-designed studies of perception in anorexia nervosa. Although the number of studies is small, this review supports a multi-modal impairment in perception in patients with anorexia nervosa compared to controls.The authors note perception is known to be processed through the brain parietal lobe. They propose that parietal lobe dysfunction may impair perception in anorexia nervosa. This perceptual impairment may contribute to the body image disturbance found in the illness.Look for an expansion of studies of perception in anorexia nervosa. Pairing neuropsychological perception studies with advanced brain imaging research techniques may be powerful strategy.Readers with more interest in this topic can access the free full-text manuscript by clicking on the citation link below.Figure of parietal lobe is from an iPad screenshot from the app Brain Tutor.Follow the author on Twitter WRY999.Gaudio S, Brooks SJ, & Riva G (2014). Nonvisual multisensory impairment of body perception in anorexia nervosa: a systematic review of neuropsychological studies. ... Read more »

Gaudio S, Brooks SJ, & Riva G. (2014) Nonvisual multisensory impairment of body perception in anorexia nervosa: a systematic review of neuropsychological studies. PloS one, 9(10). PMID: 25303480

November 4, 2014
10:52 AM
374 views

Anorexia Nervosa: Fasting and Starvation Brain Effects

by William Yates, M.D. in Brain Posts

Brain research in anorexia nervosa presents several challenges.Current knowledge of cognitive function in anorexia supports impairment in set shifting and global brain processing or central coherence.However, there are two issues that complicate understanding the underlying brain effects in anorexia nervosa.First, individuals with anorexia nervosa often have additional anxiety and mood disorders. It can be difficult to tease out the specific effects of anorexia nervosa from the effects of these comorbid conditions.Second, fasting and starvation are common metabolic issues in anorexia. These metabolic stresses can also influence brain function.Sarah Pender and colleagues from University College London and Spain recently published a research study on the neuropsychology of starvation.The key elements of their study included the following elements:Subjects: Healthy females recruited by poster in a university sample. Subjects were required to not have a lifetime history of any psychiatric disorder including anorexia nervosa.Measures: A test of set-shifting ability using a test called the rule-change task. A test of local versus global cognitive processing style. A second test of global processing known as the group embedded figures task.Metabolic status: Each subject was studied on the above measures after eating and following a period of 18 hours of fasting. The authors then compared performance on these neuropsychology tests in the fasting versus satiated state. The main findings from the study included findings in set-shifting and central coherence.Set-shifting: Performance on set-shifting was not slowed or impaired in the fasting state compared to the satiated state. However, fasting appeared to increase the difficulty (or effort) to set shift.Central coherence: During the fasting state, subjects shifted processing to a stronger local processing style and a weaker global processing style. This is consistent with reduced central coherence with fasting.A relevant potential confounding variable in this type of task is the contribution of anxiety and depression in neuropsychological task performance.I previously collaborated with Dr. Rebecca Marshall and other colleagues at the Laureate Institute of Brain Research in a study of neuropsychological function in a group of women with a variety of eating disorders. In this study, we found subjective anxiety ratings contributed to a significant about of variance in neuropsychological performance in eating disorders. Additionally, we found executive function impairment, a component of central coherence in 30 % of the clinical sample.Pender and colleagues looked for effects of anxiety and depression in their study and did not find any confounding effects. Obviously, their sample was likely to only have minimal sub-clinical levels of anxiety/depression given the requirement for no current or lifetime psychiatric problem for enrollment.The authors conclude even short-term fasting "might trigger weak central coherence, and thus play a role in maintaining behaviors characteristic of AN". The authors also note the brain effects of fasting, starvation and anorexia nervosa may have difficulty participating in psychotherapy. Psychotherapy requires a more global processing style to be effective.Readers with more interest in this research can access the free full-text manuscripts by clicking on the PMID link in the citations below.Photo of brain corpus callosum activated during right-left brain coherence is from an iPad screen shot from the 3D Brain app.Follow the author on Twitter WRY999Pender, S., Gilbert, S., & Serpell, L. (2014). The Neuropsychology of Starvation: Set-Shifting and Central Coherence in a Fasted Nonclinical Sample PLoS ONE, 9 (10) DOI: 10.1371/journal.pone.0110743Billingsley-Marshall RL, Basso MR, Lund BC, Hernandez ER, Johnson CL, Drevets WC, McKee PA, & Yates WR (2013). Executive function in eating disorders: the role of state anxiety. The International journal of eating disorders, 46 (4), 316-21 PMID: 23354876... Read more »

Pender, S., Gilbert, S., & Serpell, L. (2014) The Neuropsychology of Starvation: Set-Shifting and Central Coherence in a Fasted Nonclinical Sample. PLoS ONE, 9(10). DOI: 10.1371/journal.pone.0110743

Billingsley-Marshall RL, Basso MR, Lund BC, Hernandez ER, Johnson CL, Drevets WC, McKee PA, & Yates WR. (2013) Executive function in eating disorders: the role of state anxiety. The International journal of eating disorders, 46(4), 316-21. PMID: 23354876

October 30, 2014
11:20 AM
419 views

Alcoholism as a Reward System Dysfunction

by William Yates, M.D. in Brain Posts

Alcoholism and other addictive behaviors often occur together within individual patients.For example, individuals with alcoholism commonly also are smokers and meet criteria for a diagnosis of nicotine dependence.This co-occurrence suggests multiple types of addiction may share genetic and environmental risk factors. Additionally, there might be a common neurobiological mechanism in play for many addictions.Kenneth Blum and other leading alcoholism researchers recently published a review that proposed a theory of addiction they labelled the "Reward Deficiency Solution System".Here are some of my notes on the key points outlined in their literature review:IntroductionThe goal of the review was to find common mechanisms for addictions--both those related to a substance and those not substance related, i.e. obesity or pathological gamblingGenetic studies linking alcoholism to the dopamine 2 receptor (DRD2) date back to 1990Over 3000 studies have been published on the DRD2 receptor and addictions since 1990Studies have not universally supported a DRD2 link to addictions but many do support the linkIs Dopamine Deficit or Over Supply at Fault?Dopamine transporter gene one (DAT1) deficit status has been linked to obesity possibly through a dysregulation in food rewardPolymorphisms that involve D2 and D4 reduce reward response to food and lead to weight gainfMRI research in children and adolescents have shown that an increased dopamine-related neurotransmission in the striatum may be a risk factor for obesitySo, both deficit and oversupply of dopamine may influence addiction risk including risk for obesityIs There a Solution to Reward Deficiency Syndrome (RDS)?Dopamine antagonists such as naltrexone and acamprosate have had limited successStudies of a newly developed drug KB220Z, a dopamine agonist are promisingKB220Z studies in mice show increased brain enkephalin and reduced alcohol-seeking behavior KB220Z studies in humans has been linked to reduced alcohol withdrawal, lower addiction treatment drop out rates and reduced craving scores across multiple substance types including alcohol, cocaine, heroin and nicotineKB220Z activates the brain reward center known as the nucleus accumbens and increases activation of the prefrontal-cerebellar-occipital brain circuitGenetic and Functional Mechanisms in RDSWe lack understanding of how genes regulate functional networks related to addiction circuitryAddicts do show reduced fMRI resting state network connectivityKB220Z appears to reverse these resting state connectivity deficits in addictsStudying genomic contributions to brain connectivity patterns in reward may be a powerful strategy for addiction drug developmentMy Comments: This review highlights the weakness of our current state of knowledge for understanding how genetics, brain neurochemistry and brain circuitry influence addition. However, I do agree with the reviewers that progress is being made and that brain circuitry imaging may be a valuable tool in future progress.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.Molecular model of dopamine is from a Wikepedia Commons file authored by sbroolsFollow the author on Twitter @WRY999Blum K, Febo M, McLaughlin T, Cronjé FJ, Han D, & Gold SM (2014). Hatching the behavioral addiction egg: Reward Deficiency Solution System (RDSS)™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric. Journal of behavioral addictions, 3 (3), 149-56 PMID: 25317338... Read more »

Blum K, Febo M, McLaughlin T, Cronjé FJ, Han D, & Gold SM. (2014) Hatching the behavioral addiction egg: Reward Deficiency Solution System (RDSS)™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric. Journal of behavioral addictions, 3(3), 149-56. PMID: 25317338

October 28, 2014
11:59 AM
386 views

Night Owls Show Increased Alcohol Use Risk

by William Yates, M.D. in Brain Posts

Humans commonly display a circadian rhythm preference for getting up early in the morning or staying up late at night (night owls).This sleep timing, or diurnal preference appears to have genetic contributions.Additionally, diurnal preference may contribute to risk for alcohol consumption as more alcohol is consumed later in the day and during the night time.Nathaniel Watson and colleagues at the University of Washington and the University of Texas recently explored the relationship between diurnal preference and alcohol use using a twin study design.The key elements of their study design included the following elements:Study sample: 2,945 individuals from the University of Washington Twin RegistryMeasures: Diurnal preference was assessed using the reduced Morningness-Eveningness Questionnaire (rMEQ). Alcohol use phenotype was assessed by asking individuals about frequency and quantity of alcohol consumed including frequency of binge drinking (6 or more drinks on a single occasion).Statistical analysis: Quantitative genetic modeling was used to find genetic and environmental contributions to diurnal preference. Diurnal preference patterns were compared on drinking phenotypes.The important findings from their study were:Genetic factors accounted for 37% of variance in diurnal preference with the remaining variance accounted for by non-shared environmental factorsDiurnal preference types (morning versus evening) did not differ in frequency of alcohol consumptionEvening preference twins (night owls) reported statistically greater quantities of alcohol consumed and more frequent binge drinkingThe authors note the human circadian clock in controlled by a group of genes working through the brain region known as the suprachiasmic nucleus. Additionally, one of these clock genes NPAS2 has previously been shown to be related to average weekly alcohol consumption.A weakness in this twin study is the relatively small group of questions targeting alcohol use with formal assessment for meeting criteria for alcohol abuse or dependence.However, as the authors highlight, diurnal preference"may be an important pathway of risk for genetic factors that promote alcohol use"Future genetic and epidemiologic studies of alcoholism may benefit by including assessment of diurnal preferences.Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of a western scrub jay is from the author's files.Follow the author on Twitter @WRY999Watson NF, Buchwald D, & Harden KP (2013). A twin study of genetic influences on diurnal preference and risk for alcohol use outcomes. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 9 (12), 1333-9 PMID: 24340296... Read more »

Watson NF, Buchwald D, & Harden KP. (2013) A twin study of genetic influences on diurnal preference and risk for alcohol use outcomes. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 9(12), 1333-9. PMID: 24340296

October 27, 2014
11:10 AM
370 views

Brain Imaging In Alcoholic Brain Thiamine Deficiency

by William Yates, M.D. in Brain Posts

Chronic consumption of large quantities of alcohol can produce severe deficiency of thiamine (vitamin B1).This can precipitate an acute brain failure known as Wernicke's encephalopathy. Wernicke's encephalopathy is characterized by sudden onset of mental status changes, eye muscle impairment and disturbed gait or ataxia.Other illnesses can also produce this level of severe thiamine deficiency. A partial list of these non-alcoholism causes for thiamine deficiency with encephalopathy includes:Gastric bypass surgerySevere vomiting of pregnancyAnorexia nervosaDietary thiamine deficiency (beriberi)AIDSHemodialysis Gaetana Manzo and colleagues recently summarized what is known about the brain imaging findings in alcohol and non-alcohol-related Wernicke's encephalopathy.They note the typical brain imaging findings in Wernicke's encephalopathy identified with MRI using T2w and FLAIR scanning include:Hyperintensities in bilateral thalamusHyperintensities in bilateral mammillary bodiesHyperintensities in the periaqueductal areas Signal intensity alterations can also be seen in other atypical areas including the medula, pons, cerebellum, corpus callosum and the frontal-parietal cortex.The authors note in some cases of Wernicke's encephalopathy, MRI signal intensities may be absent. There are no current valid estimates of how often this occurs as Wernicke's encephalopathy is a relative rare condition.Brain imaging may be helpful in discriminating Wernicke's encephalopathy due to alcohol from other causes.The authors note that alcohol-related thiamine deficiency due to alcohol is supported with the following findings:Atrophy of the mamillary bodies and cerebellar vermis due to previous attacksAbsence of hyperintensities in atypical regions Emerging brain imaging technologies diffusion tensor imaging (DTI) and MR spectroscopy may hold additional promise for differential diagnosis.The authors note brain hyperintensities in thiamine deficiency tend to resolve over time with thiamine supplementation and clinical reversal of the neurological symptoms. This finding supports a causal link and a pathophysiological mechanism between the hyperintensities and the signs and symptoms of Wernicke's encephalopathy.Clinicians need to keep thiamine and other vitamin deficiencies in mind when carrying for heavy drinking populations.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of western scrub jay is from the author's files.Follow the author on Twitter @WRY999Manzo G, De Gennaro A, Cozzolino A, Serino A, Fenza G, & Manto A (2014). MR imaging findings in alcoholic and nonalcoholic acute Wernicke's encephalopathy: a review. BioMed research international, 2014 PMID: 25050351... Read more »

Manzo G, De Gennaro A, Cozzolino A, Serino A, Fenza G, & Manto A. (2014) MR imaging findings in alcoholic and nonalcoholic acute Wernicke's encephalopathy: a review. BioMed research international, 503596. PMID: 25050351

October 23, 2014
10:20 AM
362 views

Smartphone App Boosts Alcoholism Treatment Outcome

by William Yates, M.D. in Brain Posts

Smartphone apps and other mobile technology are emerging as promising tools in medical treatment.A recent randomized study published in JAMA Psychiatry found evidence that a smartphone app improves alcoholism treatment outcomes.David Gustafson and colleagues conducted a study funded by the National Institute of Alcohol Abuse and Alcoholism.A series of 349 adults with DSM-IV alcohol dependence were enrolled as they entered a alcoholism residential treatment program.Approximately half of the subjects were provided with a smartphone that had an app known as Addiction-Comprehensive Health Enhancement Support System (A-CHESS).The smartphone with A-CHESS app provided the following support:An audio-guided relaxation programA GPS alert system when users neared a high-risk drinking location (i.e. a bar previously used by the participant)A two-way message system between treatment team and participantA panic button that allowed users to notify two support contactsA log function that allowed the research team to monitor smartphone services usedThe key findings from the study included the following for the A-CHESS assigned group:Statistically significant reductions in number of risky drinking days compared to controls (1.39 days per month versus 2.75 days per month)Higher rates of abstinence at 4-, 8- and 12-month follow-up periodsReduction in number of risky drinking days was correlated with number of A-CHESS pages viewed and number of days the service was accessedThe authors noted that some outcome measures were not improved in the A-CHESS group compared to controls including frequency of negative consequences related to drinking.The cost of the smartphone and A-CHESS app was estimated at $597 per patient during the study.This study does demonstrated the feasibility and potential utility of using smartphones and treatment augmentation apps for those with alcohol dependence.The specific components promoting improved outcomes in this study are unable to be identified.However, the results are encouraging and support further research efforts and evolution of smartphone app design for enhancing the treatment of alcohol dependence and other addictions.Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of grosbeak is from the author's files.Follow the author on Twitter WRY999Gustafson DH, McTavish FM, Chih MY, Atwood AK, Johnson RA, Boyle MG, Levy MS, Driscoll H, Chisholm SM, Dillenburg L, Isham A, & Shah D (2014). A smartphone application to support recovery from alcoholism: a randomized clinical trial. JAMA psychiatry, 71 (5), 566-72 PMID: 24671165... Read more »

Gustafson DH, McTavish FM, Chih MY, Atwood AK, Johnson RA, Boyle MG, Levy MS, Driscoll H, Chisholm SM, Dillenburg L.... (2014) A smartphone application to support recovery from alcoholism: a randomized clinical trial. JAMA psychiatry, 71(5), 566-72. PMID: 24671165

October 21, 2014
11:25 AM
343 views

Sleep Problems in Alcoholism Treatment

by William Yates, M.D. in Brain Posts

In a previous post, I summarized a research study six month outcome of insomnia in a group of subjects treated for alcoholism.This study found a high persistence of insomnia despite reduction, and in many cases abstinence, from alcohol.A second study recently published by investigators at the National Institute of Health provides some additional insight into this topic.Gwenyth Wallen and colleagues studied a series of 164 participants admitted to a 4-6 week inpatient program for alcohol dependence.Subjects had an average inpatient length of stay of 32 days. Sleep problems were assessed using a combination of four measures:Pittsburgh Sleep Quality Index (PSQI): The PSQI was completed on the second and 28th day of treatment. A global score of 5 or more is highly reliable as a marker for sleep problems.Epworth Sleepiness Scale (ESS): The ESS is a measure of daytime sleepiness and was collected weekly during the study.Sleep Diaries: Sleep diaries were use to validate actigraphy data and provide an overall subjective rating of nightly sleep on a 0=very poorly to 10=excellent sleep.Actigraphy: Actigraphy data (measurement of activity throughout night) was collected using actigraphy wristbands and analyzed using computerized sleep scoring software.The key findings in the study included:90% of subjects at baseline and 51% at 4 weeks were classified with a sleep disorder by the PSQI25% of subjects reported excessive daytime sleepiness-this rate did not change during the course of treatmentActigraphy data showed improvement in sleep efficiency (sleep time divided by time in bed) and decreased time awake after sleep onsetHowever, total sleep time was low at both 2 and 28 days (about 5.4 hours per night) and subjects did not have a statistically significant mean increase in subjective sleep quality (6.33 at 2 days and 6.5 at 28 days)The authors note their study supports the potential value of actigraphy in identifying persistent sleep problems in alcoholics completing inpatient treatment programs. The actigraphy watches used in this study (Respironics-Actiwatch 2) retails for around $1000. The advent of smart watches and smartphone apps that measure activity during sleep provides an opportunity to extend measurement of sleep variables. I have previous reviewed the iPhone app Sleep Cycle here.The correlation of these consumer activity-based monitors with clinical monitors needs to be studied.Readers with more interest in this research study can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of grosbeak is from the author's files.Follow the author on Twitter WRY999Wallen GR, Brooks AT, Whiting B, Clark R, Krumlauf MC, Yang L, Schwandt ML, George DT, & Ramchandani VA (2014). The prevalence of sleep disturbance in alcoholics admitted for treatment: a target for chronic disease management. Family & community health, 37 (4), 288-97 PMID: 25167069... Read more »

Wallen GR, Brooks AT, Whiting B, Clark R, Krumlauf MC, Yang L, Schwandt ML, George DT, & Ramchandani VA. (2014) The prevalence of sleep disturbance in alcoholics admitted for treatment: a target for chronic disease management. Family , 37(4), 288-97. PMID: 25167069

October 20, 2014
10:56 AM
353 views

Persistent Insomnia and Alcoholism

by William Yates, M.D. in Brain Posts

Sleep problems complicate the treatment and recovery in alcoholism. Heavy alcohol consumption modifies the nature of sleep architecture.A high blood alcohol concentration at bedtime may promote sleep early in the sleep cycle.However, as alcohol levels decline, sleep is often interrupted with limiting rapid eye movement (REM) sleep duration.Shortened total sleep time with alcohol can produce a lack of feeling well rested on awakening.For those with alcoholism or alcohol dependence, successful treatment and alcohol abstinence can restore a normal sleep pattern. However, the clinical picture appears more complicated.Kirk Brower and colleagues at the University of Michigan published an important summary of the effects of alcoholism treatment on sleep.In their study, 267 subject with alcoholism in treatment were assessed for sleep problems at baseline and again six months later.The key findings from their study included:47% of subjects had insomnia at baseline60% of all subjects with insomnia at baseline had persistent insomnia six months laterWomen and those with greater psychiatric severity had higher rates of insomnia persistenceSubjects who reduced drinking quantities had improvement in sleepHowever, a quarter of subjects who maintained abstinence reported persistent insomniaThe authors noted their findings have significant implications for treatment and monitoring of alcohol dependence patient populations.A significant high level of insomnia persistence despite abstinence is important. This group of persistent insomniacs need formal sleep assessment and many might benefit from an overnight sleep lab study known as polysomnography.The current study did not assess specifically for sleep apnea but they note sleep apnea may contribute to sleep problems in many recovered alcoholics.Successful restoration of normal sleep in abstinence may promote higher rates of alcoholism recovery. Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of street scene from Galway, Ireland is from the author's files.Follow the author on Twitter WRY999Brower KJ, Krentzman A, & Robinson EA (2011). Persistent insomnia, abstinence, and moderate drinking in alcohol-dependent individuals. The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions, 20 (5), 435-40 PMID: 21838842... Read more »

Brower KJ, Krentzman A, & Robinson EA. (2011) Persistent insomnia, abstinence, and moderate drinking in alcohol-dependent individuals. The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions, 20(5), 435-40. PMID: 21838842

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