422 posts · 323,161 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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- November 16, 2011
- 02:59 PM
- 693 views
CBT and Exercise Reduce Pain in Fibromyalgia
by William Yates, M.D. in Brain Posts
Cognitive Behavior Therapy or (CBT) is a form of psychotherapy originally developed for the treatment of major depression. Modifications of CBT for a variety of other neuropsychiatric disorders quickly emerged and now the demand for CBT exceeds the supply of trained therapists. Efforts to extend the benefits seen with CBT now includes telephone and internet-based methods. CBT hold promise in management of pain from a variety of medical conditions. This promise requires the development of novel strategies to move CBT into primary care settings. John McBeth and colleagues in Scotland and England, recently published a large study of telephone-delivered CBT in primary care patients identified with chronic widespread pain found in fibromyalgia.This study randomized patients with widespread chronic pain to one of four treatment options:Treatment as usual--a control interventionTelephone-based CBT for six monthsGraded exercise training for 6 monthsBoth telephone-based CBT and graded exercise training for 6 monthsThe telephone-based CBT included an initial assessment of one hour followed by seven weekly sessions lasting 30 to 45 minutes. A booster session was held at 3 months and at 6 months. Elements of the CBT therapy included:Assessment included selection of two to three patient-defined goalsA CBT manual developed for the study was providedBehavioral activation--changing level of activity and the pace it is completedCognitive restructuring--identifying thinking styles that might contribute to pain or reaction to painLifestyle changes--modifying lifestyle to improve sleep, reduce fatigue and reduce irritabilityThe exercise group received an exercise assessment from a fitness training followed by monthly appointments with their trainer. They were encouraged to get to the gym on their own at least twice per week and on other days participate in brisk walking or other activities that might improve cardiorespiratory fitness.The primary outcome for this study was a patient global assessment at six months where individual subjects were asked to rate change in health since beginning the trial. Those who rated their health as "much better" or "very much better" were considered responders to the intervention. The response rates at six months for each of the interventions were:Treatment as usual--8%Telephone-based CBT for six months--30%Graded exercise training for 6 months--35%Both telephone-based CBT and graded exercise training for 6 months--37%All intervention groups were superior to treatment as usual. A second global health rating at 9 months found a small increase in response rate in the CBT group.This study suggests that telephone-based CBT is worthy of consideration as a mainstream intervention for the chronic pain associated with fibromyalgia. It would have been nice to see a little higher response rates in the active interventions. However, chronic pain is a treatment-resistant condition where any new pathways to improvement are welcomed.Photos of butterflies from author's private collection.McBeth, J., Prescott, G., Scotland, G., Lovell, K., Keeley, P., Hannaford, P., McNamee, P., Symmons, D., Woby, S., Gkazinou, C., Beasley, M., & Macfarlane, G. (2011). Cognitive Behavior Therapy, Exercise, or Both for Treating Chronic Widespread Pain Archives of Internal Medicine DOI: 10.1001/archinternmed.2011.555... Read more »
McBeth, J., Prescott, G., Scotland, G., Lovell, K., Keeley, P., Hannaford, P., McNamee, P., Symmons, D., Woby, S., Gkazinou, C.... (2011) Cognitive Behavior Therapy, Exercise, or Both for Treating Chronic Widespread Pain. Archives of Internal Medicine. DOI: 10.1001/archinternmed.2011.555
- November 14, 2011
- 12:51 PM
- 771 views
Mirtazapine Linked to Reduced Methamphetamine Use
by William Yates, M.D. in Brain Posts
Molecular Model of MirtazapineMethamphetamine abuse and dependence are often resistant to treatment intervention with high relapse rates. Pharmacological augmentation of behavioral treatments may provide one strategy to improve the outcome of methamphetamine addiction.Potential mechanisms for pharmacological augmentation in methamphetamine abuse include reduction id drug craving, blocking the hedonic effect of drug use, reducing dysphoria during methamphetamine withdrawal or treatment of underlying psychiatric disorders such as anxiety and mood disorders.No drug is currently approved for methamphetamine abuse--this is unfortunate given that pharmacological options exist for alcohol, nicotine and opioid abuse.Mirtazapine, a generically available antidepressant drug (Trade name Remeron) facilitates the release of several CNS monoamines including norepinephrine, serotonin and dopamine. It has relatively low impact on sexual function. It's primary drawback has been a tendency to increase appetite and increase weight. Since many methamphetamine abusers are underweight, this adverse effect may be less problematic.Colfax and colleagues recently published a small randomized placebo-controlled clinical trial of mirtazapione in methamphetamine abuse. The key elements of the clinical trial include:Diagnosis: methamphetamine dependence by DSM-IV-TR criteriaUrine drug testing positive for methamphetamine metabolitesNo acute medical or psychiatric illnessNo current major depressionNo recent use of antidepressant drugsClinical trial drug: mirtazapine 30 mg or placebo for 12 weeksOutcome measure: methamphetamine urine drug testsThis clinical trial focused on a group of male methamphetamine abusers who have sex with men. This demographic group is known to have increased risk for sexually transmitted disease including HIV making treatment advances important.Methamphetamine-positive drug urine sample rates in the active mirtazapine drug assigned group dropped from 73% at baseline to 44% at study end. The placebo group had no significant change with 67% positivity at baseline and 63% positivity at study end.The research team noted that the efficacy of mirtazapine for methamphetamine use seemed to be independent of any antidepressant effect. The study participants reported only fair adherence to the study drug during the trial. The authors note this might indicate the effect of mirtazapine might be greater in groups with higher adherence. The mediocre adherence does underscore a hurdle for any pharmacologic intervention in those with methamphetamine abuse.This clinical trial was relatively small with thirty subjects in the mirtazapine group and thirty subjects in the placebo group. Additionally, generalizability is limited due to the restricted demographic profile of the study group. However the magnitude of reduction in methamphetamine-positive drug rates in the mirtazapine is impressive. Mirtazapine holds promise as a potential new strategy for methamphetamine abuse, but the results of this study will need confirmation before wide adoption in clinical practice.Molecular model of mirtazapine from the Creative Commons file at Wikipedia authored by Ben Mills.Colfax GN, Santos GM, Das M, Santos DM, Matheson T, Gasper J, Shoptaw S, & Vittinghoff E (2011). Mirtazapine to reduce methamphetamine use: a randomized controlled trial. Archives of general psychiatry, 68 (11), 1168-75 PMID: 22065532... Read more »
Colfax GN, Santos GM, Das M, Santos DM, Matheson T, Gasper J, Shoptaw S, & Vittinghoff E. (2011) Mirtazapine to reduce methamphetamine use: a randomized controlled trial. Archives of general psychiatry, 68(11), 1168-75. PMID: 22065532
- November 11, 2011
- 12:36 PM
- 815 views
Testosterone Boosts Sexual Function in Men on SSRIs
by William Yates, M.D. in Brain Posts
Selective serotonin reuptake inhibitor antidepressants (SSRIs) such as fluoxetine (Prozac) continue to be a common first-line treatment for major depression and a variety of anxiety disorders. Although generally well tolerated, sexual side effects are common in both men and women taking SSRIs.There are a variety of options for managing sexual side effects. These can include reducing the dose of the SSRI, switching (or augmenting) with antidepressants without sexual side effects or in men considering a trial of an erectile dysfunction drug such as sildenafil (Viagra).Now a small clinical trial suggests that testosterone gel may be another option for men with SSRI-related sexual dysfunction.A team of researchers from Israel and the United States combined to perform a randomized placebo-controlled trial of testosterone gel in men with low or low-normal serum testosterone levels. The key elements of this randomized trial published in The Journal of Sex and Marital Therapy include:Male subjects with DSM-IV major depression currently or within last yearTaking one of eight SSRI drugsCurrent HAM-D depression severity rating scale of twelve or greaterMorning total testosterone levels less than or equal to 350 ng/dlRandomized to receive testosterone gel (5 gram/day) versus placebo gelPrimary sexual function outcome measured by the International Index of Erectile Function (IIEF)It should be noted this present study was a secondary analysis from data collected to determine if testosterone augmentation would improve depression in men partially responsive to SSRI treatment. This explains the requirement that at least moderate depressive symptoms were required for participation in the study. The second reference below is the results manuscript for the testosterone augmentation in depression study. This study found limited support for testosterone augmentation in depression.The testosterone augmentation group showed an improvement in IIEF scores in a variety of domains compared to the placebo group. This included improvement in subscales in the domains of sexual desire, erectile function and orgasmic function.The authors were unable to demonstrate a correlation between testosterone levels and improved sexual functioning ratings. Of note, some of the participants with low screening testosterone on more accurate testing later on admission samples showed normal testosterone levels. These individuals appeared to have as much improvement in sexual function measures as men with low serum testosterone levels.The authors note they were unable to distinguish whether impaired sexual function in this sample of subjects was due to SSRI treatment, major depression or a pre-existing hypothalamic-pituitary-gonadal functioning. Nevertheless, they note their study supports "the need for systematic clinical research to determine the therapeutic utility--including the effect on sexual function--of androgen replacement in depressed men, and the proper sequence of treatment".It should be noted that although testosterone gel is approved for use in hypogonadism in men, it is not approved for sexual dysfunction in men with normal serum testosterone levels. Testosterone therapy poses significant risk and should only be considered in the context of a medical evaluation by a physician. Testosterone supplementation may increase risk for prostate cancer. Subjects in the study described here were required to have normal prostate specific antigen levels (PSA less than 4.0 ng/ml) to participate in the study.Photo of green sea turtle from Loggerhead Marinelife Center of Juno Beach, Florida from author's personal file.Amiaz R, Pope HG Jr, Mahne T, Kelly JF, Brennan BP, Kanayama G, Weiser M, Hudson JI, & Seidman SN (2011). Testosterone gel replacement improves sexual function in depressed men taking serotonergic antidepressants: a randomized, placebo-controlled clinical trial. Journal of sex & marital therapy, 37 (4), 243-54 PMID: 21707327Pope HG Jr, Amiaz R, Brennan BP, Orr G, Weiser M, Kelly JF, Kanayama G, Siegel A, Hudson JI, & Seidman SN (2010). Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment. Journal of clinical psychopharmacology, 30 (2), 126-34 PMID: 20520285... Read more »
Amiaz R, Pope HG Jr, Mahne T, Kelly JF, Brennan BP, Kanayama G, Weiser M, Hudson JI, & Seidman SN. (2011) Testosterone gel replacement improves sexual function in depressed men taking serotonergic antidepressants: a randomized, placebo-controlled clinical trial. Journal of sex , 37(4), 243-54. PMID: 21707327
Pope HG Jr, Amiaz R, Brennan BP, Orr G, Weiser M, Kelly JF, Kanayama G, Siegel A, Hudson JI, & Seidman SN. (2010) Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment. Journal of clinical psychopharmacology, 30(2), 126-34. PMID: 20520285
- November 8, 2011
- 03:08 PM
- 928 views
Neuropsychology and the Cerebellum: Part II
by William Yates, M.D. in Brain Posts
Cerebellum in Purple from Inferior View of BrainIn a previous post I summarized some of the recent understanding of the role of the cerebellum in a variety of neuropsychological domains.The recent review by O'Halloran and colleagues also included a discussion of the cerebellum in several neuropsychiatric disorders. I will highlight the key components from the review in autism spectrum disorder, ADHD and schizophrenia/mood disorders.Autism Spectrum and the CerebellumIndividuals with Asperger's disorder demonstrated soft cerebellar dysfunction signs including posteral instability, pointing accuracy deficits and timing deficitsAutism in children is associated with smaller cerbellar vermis lobesDiffusion tensor imaging (DTI) brain white matter imaging studies show decreased axonal density emanating from the right cerebellumThese findings suggest that in autism "the reduction in cerebellar feedback to supratentorial regions may play a key role in these individuals' difficulty in appreciating social cues"ADHD and the CerebellumIndividuals with ADHD also show some soft neurological signs of cerebellar dysfunction including gait and postural deficitsBoys and girls with ADHD show reduced cerebellar volumes in vermis lobes (different from the lobes decreased in autism spectrum disorder)Greater decrease in cerebellar volumes are seen in children with ADHD not treated with stimulants suggesting stimulant medication may reduce cerebellar abnormalities in ADHDThe medial cerebellum appears to contribute to the regulation of attention and this area of the cerebellum may contribute to attentional deficits in ADHDSchizophrenia, Mood Disorders and the CerebellumReduced cerebellar white and gray matter volumes have been found in multiple studies of schizophreniaReduced cerebellar vermis volumes have been found in both unipolar and bipolar affective disorderBipolar disorder has been linked to reduced white matter volume in the left cerebellar hemisphereThe potential for treatment interventions involving the cerebellum is intriguing and worthy of further exploration. The authors note one study of implantation of a device to stimulate the cerebellar vermis reduced psychotic symptoms in a small sample of eleven subjects. Transcranial magnetic stimulation over the lateral cerebellum stimulates the prefrontal cortex on the opposite side.I hope that better understanding of the role of the cerebellum in a variety of neuropsychiatric disorders provides opportunities for novel treatment development.O'Halloran CJ, Kinsella GJ, & Storey E (2011). The cerebellum and neuropsychological functioning: A critical review. Journal of clinical and experimental neuropsychology PMID: 22047489... Read more »
O'Halloran CJ, Kinsella GJ, & Storey E. (2011) The cerebellum and neuropsychological functioning: A critical review. Journal of clinical and experimental neuropsychology. PMID: 22047489
- November 7, 2011
- 03:59 PM
- 896 views
Neuropsychology and the Cerebellum: Part I
by William Yates, M.D. in Brain Posts
Cerebellum Highlighted in PurpleWhen in medical school I remember memorizing the functions of the cerebellum with the acronym ETC standing for equilibrium, tone (motor) and coordination.I won't mention how long ago that was but I will note that until about the last 20 years or so, this was the common view of the limits of the cerebellum.Within the last twenty years, the function of the cerebellum is being understood to expand to a much more complex list of domains.This increased understanding of the role of the cerebellum stems from study of patients with hereditary cerebellar disorders, i.e. spinocerebellar ataxia, localized strokes involving the cerebellum, advances in neuroanatomy and brain imaging studies related to brain function such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Christopher O'Halleran and colleagues from Australia have recently reviewed the neuropsychological functions linked to the cerebellum in an article published in the Journal of Clinical and Experimental Neuropsychology. Additionally, they have pointed out this brain region appears linked to several clinical neuropsychiatric conditions including: autism, ADHD and schizophrenia.The cerebellum appears to have "localization of discrete cognitive processes". The anterior cerebellum contributes to sensory and motor function while the posterior cerebellum is involved in cognitive processes. Medial portions of the cerebellum participate in emotional regulation.Here are some of the neuropsychological domains of emerging knowledge associated with the cerebellum:... Read more »
O'Halloran CJ, Kinsella GJ, & Storey E. (2011) The cerebellum and neuropsychological functioning: A critical review. Journal of clinical and experimental neuropsychology. PMID: 22047489
- October 27, 2011
- 11:30 AM
- 982 views
Brain White Matter Changes Increase Dementia Risk
by William Yates, M.D. in Brain Posts
Diffuse White Matter Hyperintentsity in CADASILApproximately a year ago, I reviewed some of the growing evidence of the clinical significance of brain white matter intensities or lesions. Magnetic resonance imaging identifies these types of lesions but their significance had been unknown.The review noted that white matter hyperintensities appear to increase future risk for several disorders including stroke and dementia. Additionally, these lesions have increase mortality rates in some follow up studies.Now an additional study has examined the effect of these lesions on dementia. Inaba and colleagues examined the progress of cognitive decline in a group of elderly individuals participating in the Honolulu-Asia aging study.The study followed 267 men between the ages of 74 and 95. At baseline, brain MRI scans were rated for the presence and grade level of white matter lesions. A cognitive function test (Cognitive Abilities Screening Instrument) was obtained at baseline and five years later repeated. Significant cognitive decline was defined as a drop of 12 points or more over the five year period.Subjectives with significant white matter lesions had higher rates of cognitive decline (34.4%) compared to the control group without these lesions (22.4%).Men with the lesions were more likely at baseline to have a diagnosis of hypertension and show evidence of a small infarct (stroke) on MRI. They did not differ on rates of depression or smoking history. Baseline differences on potential confounding variables were controlled in this study using multivarThe effect of white matter lesions on cognitive decline appeared to be stronger in those without the gene known to be associated with Alzheimer's disease risk (ApoE).The authors propose that white matter lesions may reflect damage to brain connectivity tracts. This could result in slowing speed of neural transmission. This may be the mechanism for neuropsychological studies linking white matter lesions to reduced cognitive processing speed, attention and executive function.Further research is needed to identify potential preventive interventions to reduce the risk of these lesions. MRI brain image showing white matter hyperintensities in a frontal to occipital distribution from a patient with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). From the Wikipedia Commons file authored by Bohlega S, Al Shubili A, Edris A, Alreshaid A, Alkhairallah T, AlSous MW, Farah S, Abu-Amero KK.Inaba M, White L, Bell C, Chen R, Petrovitch H, Launer L, Abbott RD, Ross GW, & Masaki K (2011). White matter lesions on brain magnetic resonance imaging scan and 5-year cognitive decline: the Honolulu-Asia aging study. Journal of the American Geriatrics Society, 59 (8), 1484-9 PMID: 21718274... Read more »
Inaba M, White L, Bell C, Chen R, Petrovitch H, Launer L, Abbott RD, Ross GW, & Masaki K. (2011) White matter lesions on brain magnetic resonance imaging scan and 5-year cognitive decline: the Honolulu-Asia aging study. Journal of the American Geriatrics Society, 59(8), 1484-9. PMID: 21718274
- October 24, 2011
- 01:22 PM
- 677 views
Preterm Birth and Epilepsy Risk
by William Yates, M.D. in Brain Posts
Albert Pujols Spring Training 2011Infants born preterm and with low-birth weight have increased risk of a variety of neuropsychiatric problems including autism, ADHD and epilepsy.The link between preterm birth and adolescent and early adulthood epilepsy has been demonstrated. But few studies have examined the link between preterm birth and epilepsy later in life.Crump and colleagues recently published results of their research on this topic in the journal Neurology.This study used the Swedish Birth registry for individuals born between 1973 and 1979 (age at study 27 to 42 years of age). Subjects were group into those born between 23-31 weeks, 32-34 weeks, 35-36 weeks, 37-42 weeks (normal pregnancy duration) and 43 weeks or more (post-term).Epilepsy cases were identified by those with a hospitalization for epilepsy or the prescription of one of three anti-epileptic drugs: phenytoin, phenobarbital or levetiracetam. Other drugs used for epilepsy were excluded as many have indications for non-epileptic disorders.Using a multivariate model, the research team corrected for potential confounding variables including fetal growth (deviation from expected weight at gestational age), gender, single versus twin pregnancy, birth order, maternal age, maternal marital status, maternal education, family income and family history of epilepsy.Using the epilepsy hospitalization case identification resulted in the following odds ratio after adjustment for confounding variables:23-31 weeks Odds ratio 4.9832-34 weeks Odds ratio 1.9835-36 weeks Odds ratio 1.7637-42 weeks Odds ratio 1.00>=43 weeks Odds ratio 0.89Estimates for those identified by antiepileptic risk were similar although this group showed a statistically increased odds ratio for those born post-term (43 weeks or more).So this study estimates that adults born most preterm have approximately a five fold increase in epilepsy as an adult. This risk appears to diminish with increasing maturation.The authors note their study highlights the need for continued efforts to reduce the risk of preterm birth. Preterm birth is linked to a variety of potential modifiable factors: smoking, alcohol or illicit drug use, poor nutrition, low or high pre-pregnancy BMI and infections during pregnancy.Additionally, efforts to improve neonatal care in those born preterm may also contribute to lowering of adulthood epilepsy and other neuropsychiatric disorders.Photo of Albert Pujols from the author's private collection. Pujols recently joined Babe Ruth and Reggie Jackson as hitters with three home runs in a single World Series game. Crump C, Sundquist K, Winkleby MA, & Sundquist J (2011). Preterm birth and risk of epilepsy in Swedish adults. Neurology, 77 (14), 1376-82 PMID: 21968843... Read more »
Crump C, Sundquist K, Winkleby MA, & Sundquist J. (2011) Preterm birth and risk of epilepsy in Swedish adults. Neurology, 77(14), 1376-82. PMID: 21968843
- October 19, 2011
- 04:35 PM
- 645 views
Shift Work Linked to Multiple Sclerosis Risk
by William Yates, M.D. in Brain Posts
Fiery Skipper ButterflyMultiple sclerosis (MS) is a neurological disorder characterized by t cell-mediated inflammation involving the myelin sheath that covers neurons. The inflammation can occur in the brain or peripheral nervous system.When inflammation damages the myelin sheath, the axons become less efficient in function. Since the inflammation associated with MS can occur nearly anywhere axons are found, the variety of types of neurological symptoms is diverse.The rates of MS vary across geographical locations and across racial and cultural groups. A common estimate of the prevalence of MS is one per thousand individuals . But a variety of risk factors appear to increase risk.Some of the important risk factors associated with MS include:Age between 20 and 40Female genderFirst degree relative with MS (increases risk 10 to 30 fold)Other autoimmune disorder, i.e. thyroiditis, type 1 diabetes mellitus, inflammatory bowel disease (Crohns disease, ulcerative colitis)Caucasian raceObesityLiving in a temperate climateNorthern European family of origin, i.e. ScandanavianHistory of viral infections, i.e. Ebstein-Barr (mononucleosis) virusCigarette smokingVitamin D deficiencyNow a epidemiological study from Sweden has reported that doing shift work early in life may also increase risk for later development of MS. The authors of this study report that shift work has been implicated in several other conditions including immune thyroid problems, heart disease and cancer.Shift work was defined this research as "permanent or alternating working hours other than ordinary day work". This would include evening and night shift workers and workers beginning work before 7 am. The researchers looked at two independent Swedish study samples and examine age of performing shift work and as well as duration/intensity of shift work.Potential confounding variables controlled in the analysis included: gender, ancestry, smoking status, sun exposure habits and serum vitamin D levels.Using a case-control design, the research team found both samples demonstrated a link between early age shift work and risk of later development of MS. There did appear to also be a duration effect---those beginning shift work as a teenager and working three or more years in shift work by age 20 showed the largest effect with a two-fold increase in rates of MSThe authors propose this shift work association may be due to interaction between circadian rhythms and immunological system function. Proinflammatory cytokines peak during the night when cortisol is typically low and melatonin levels high. Additionally, shift workers may have impairment in sleep. Sleep deprivation appears to have significant negative effects on immune function via changes in "number of circulating lymphocytes, natural killer cells and antibody titers".This is an important study that needs replication. It does support further study of the potential role of shift work on sleep and immune function and a variety of clinical neuroscience disorders. The study suggests if shift work is necessary, it may be best to delay it until individuals pass through the adolescent developmental period.Photo of Fiery Skipper butterfly from the author's collection.Risk factor list from factors listed in manuscript as well as from the Mayo Clinic website on MS.Hedström, A., Åkerstedt, T., Hillert, J., Olsson, T., & Alfredsson, L. (2011). Shift work at young age is associated with increased risk for multiple sclerosis Annals of Neurology DOI: 10.1002/ana.22597... Read more »
Hedström, A., Åkerstedt, T., Hillert, J., Olsson, T., & Alfredsson, L. (2011) Shift work at young age is associated with increased risk for multiple sclerosis. Annals of Neurology. DOI: 10.1002/ana.22597
- October 18, 2011
- 03:05 PM
- 749 views
Elite Tennis Performance: Gender and Age Effects
by William Yates, M.D. in Brain Posts
Elite tennis performance is attained by development of a complex set of cognitive and musculoskeletal skills. Understanding some of the patterns for development of elite tennis performance may provide insight into some of the effects of gender and age on adolescent and early adult development.A research team from France recently published a study of elite tennis performance by studying top 10 ranked world tennis players beginning in 1968. They examined each elite tennis players performance over the lifespan of their career. The goals of the research was to examine the timing of reaching peak performance, the length of peak performance, the differences between male and female tennis players and any changes that might have occurred over the last 40 years.A key variable in this study was the match winning percentage during each year of the elite tennis players career. Here is a summary of some of the key findings from the study:Female elite number one ranked tennis players reach peak performance earlier then men (21.5 years versus 23.7 years of age)Female elite players reaching the highest world rank of 2 to 10 reach peak performance earlier than similarly ranked male players (22.7 years versus 24.2 years)Female and male elite tennis players have similar career lengths (15.5 years versus 14.7 years)More recent elite female and male tennis players (first professional played after 1985) are younger at their first match as well as their last matchTennis players appear to have an earlier peak performance than other athletes--25 years of age seems to be the year of peak performance for several other sports compared to an average of about 22 to 23 for elite tennis players.The manuscript has an interesting figure comparing the percentage victory rates by age for Stefanie Graf and Pete Sampras. The figure demonstrates an effect found for the entire sample: number one women have a higher winning percentage at peak than their male counterparts and their peak is reached at an earlier age.The authors noted that although elite tennis players are getting younger, their total career tennis performance (tennis capital) does not seem to be declining. Starting younger is leading to earlier retirement but not any decline in career generation. Earlier adolescent growth spurts in girls compared to boys appears to translate into an earlier peak performance within the gender group for tennis and a variety of other sports. The authors note that the majority of tennis players have a career that resembles a parabola with an ascent phase, a plateau phase and a decline phase. Some individuals deviate this pattern based on career-ending injuries, pregnancy or other factors.This is an interesting study. It poses a question to be answered in a few more decades. Is the trend for earlier elite performance continuing and how long can this trend last?Photo of monarch butterfly from the author's collection.GUILLAUME, M., LEN, S., TAFFLET, M., QUINQUIS, L., MONTALVAN, B., SCHAAL, K., NASSIF, H., DESGORCES, F., & TOUSSAINT, J. (2011). Success and Decline Medicine & Science in Sports & Exercise, 43 (11), 2148-2154 DOI: 10.1249/MSS.0b013e31821eb533... Read more »
GUILLAUME, M., LEN, S., TAFFLET, M., QUINQUIS, L., MONTALVAN, B., SCHAAL, K., NASSIF, H., DESGORCES, F., & TOUSSAINT, J. (2011) Success and Decline. Medicine , 43(11), 2148-2154. DOI: 10.1249/MSS.0b013e31821eb533
- October 17, 2011
- 02:53 PM
- 744 views
Family History of Alzheimer's: Biomarker Findings
by William Yates, M.D. in Brain Posts
West Coast Lady ButterflyFamily history provides patients and clinicians valuable information about risk for a variety of clinical neuroscience diseases. Alzheimer's disease is one of the dementing disorders that appears to run in families and has had a gene (APOE4) identified with increased risk.Whether family history of Alzheimer's disease is simply a reflection of increased risk for the APOE4 risk gene is unclear. Chengjie Xiong and colleagues at Washington University in St. Louis recently published an informative study of the effect of a family history of Alzheimer's disease on several biomarkers of the disorder.They studied 269 cognitively normal adults between the ages of 43 and 76 years of age. All subjects were classified as Alzheimer's disease family history positive or negative based on the following criteria:Positive family history-at least one biological parent diagnosed with Alzheimer's disease by the age of 80Negative family history-both biological parents living to 70 without Alzheimer's diseaseUsing this classification, 160 subjects were classified as having a positive family history of Alzheimer's with 109 classified as having a negative family history.Subjects in the study underwent a series of studies looking for biomarkers of Alzheimer's disease risk:Cerebrospinal fluid tau protein levelsPittsburgh Compound B levels in the brain assessed by positron emission tomographyBrain volume assessment using MRI imagingWhite matter connectivity estimates using diffusion tensor imagingSubjects were genotyped to assess APOE4 risk status. This allowed the research team to tease out the role of family history independent of APOE4 status.In this cognitively normal cohort, positive family history of Alzheimer's independent of APOE4 status was linked to several biomarkers of Alzheimer's: cerebrospinal fluid proteins tau and alpha beta 42, brain Pittsburgh compound B binding levels and diffusion tensor white matter defects in the brain corpus callosum.The authors conclude that their findings "point to the likelihood of non-APOE susceptibility genes for Alzheimer's disease, consistent with recent reports of multiple risk genes (PICALM, CR1 and CLU).."So knowing your family history for Alzheimer's disease is important. It will become more important when future research provides evidence for effective prevention and early intervention strategies. Xiong, C., Roe, C., Buckles, V., Fagan, A., Holtzman, D., Balota, D., Duchek, J., Storandt, M., Mintun, M., Grant, E., Snyder, A., Head, D., Benzinger, T., Mettenburg, J., Csernansky, J., & Morris, J. (2011). Role of Family History for Alzheimer Biomarker Abnormalities in the Adult Children Study Archives of Neurology, 68 (10), 1313-1319 DOI: 10.1001/archneurol.2011.208... Read more »
Xiong, C., Roe, C., Buckles, V., Fagan, A., Holtzman, D., Balota, D., Duchek, J., Storandt, M., Mintun, M., Grant, E.... (2011) Role of Family History for Alzheimer Biomarker Abnormalities in the Adult Children Study. Archives of Neurology, 68(10), 1313-1319. DOI: 10.1001/archneurol.2011.208
- October 12, 2011
- 04:03 PM
- 857 views
Pedophilia and the Progranulin Gene
by William Yates, M.D. in Brain Posts
Solution Structure Model of Peptide Subdomain of GranulinThe development of pedophilic urges among pedophiles typically occurs during sexual maturation in adolescence. However, in a minority of cases, pedophilic urges may emerge later in life. An interesting case report has been published in the journal Biological Psychiatry describing a case of late-onset pedophilia.In the case description a 49 year old married man presented to a neurology clinic in with recent onset of pedophilic urges toward girls. His wife confirmed that these types of urges had not been present until approximately the last 12 months. At the time of initial presentation, neurological and neuropsychological testing was normal. A brain CT scan showed "mild assymetric frontal atrophy". The patient was placed on olanzapine (an atypical antipsychotic) and fluoxetine (a selective serotonin reuptake inhibitor). This treatment appeared to reduce the pedophilic urges.Over a period of follow up, the patient demonstrated increased increase in aggressive personality and personality changes. He had mild memory impairment but was able to continue working, Six years later he was admitted to the hospital due to increased behavioral and clinical deterioration.At this assessment, brain MRI showed increased bilateral frontal atrophy with decreased blood flow to the frontal lobe on SPECT imaging. Neuropsychological testing showed selective impairment in frontal lobe function with a normal score on the Minimental Status Exam, a screening test for Alzheimers dementia.The patient at this time met criteria for the diagnosis of frontotemporal dementia (FTD). This type of dementia has recently been linked to the progranulin gende (PGN). The patient in the case report had genetic analysis completed with evidence of a point mutation in the progranulin gene. The authors reviewed a growing literature suggesting progranulin is a key neurotrophic protein that appears important in sexual behavior development. With frontotemporal dementia, the loss of frontal lobe function in the disease contributes to behavioral disinhibition and social inappropriateness.Although case reports have limited generalizability, this report suggests that late-onset pedophilic urges and behaviors should prompt suspicion of frontotemporal dementia.Model of Granulin from the Wikipedia Creative Commons file authored by Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute.Rainero, I., Rubino, E., Negro, E., Gallone, S., Galimberti, D., Gentile, S., Scarpini, E., & Pinessi, L. (2011). Heterosexual Pedophilia in a Frontotemporal Dementia Patient with a Mutation in the Progranulin Gene Biological Psychiatry DOI: 10.1016/j.biopsych.2011.06.015... Read more »
Rainero, I., Rubino, E., Negro, E., Gallone, S., Galimberti, D., Gentile, S., Scarpini, E., & Pinessi, L. (2011) Heterosexual Pedophilia in a Frontotemporal Dementia Patient with a Mutation in the Progranulin Gene. Biological Psychiatry. DOI: 10.1016/j.biopsych.2011.06.015
- October 11, 2011
- 01:55 PM
- 798 views
B12, Cognition and Brain Aging
by William Yates, M.D. in Brain Posts
Molecular Model of B12-cyanocobalaminVitamin B12 is known to be important in the preservation of cognitive function in elderly populations. I have previously reported on a study suggesting B vitamin supplementation may be related to reduction in the rate of brain atrophy associated with aging.A study of vitamin B12-related markers, cognition and brain MRI measures was recently published in the journal Neurology. This study lends support to the importance of B12 and brain aging. Additionally, the study suggests testing simply for blood vitamin B12 blood levels may not be the most sensitive method of assessing B12 status.Tangney and colleagues from Rush University Medical Center collected serum B12-related markers in a series of 112 elderly individuals. An average of 4.5 years later, this cohort had standardized cognitive testing and brain MRI structural assessments.B12-related serum markers assessed at baseline in this study included:vitamin B12 levelshomocysteine levelsmethylmalonic acid (MMA) levelscystathionine levels2-methylcitric acidCognitive function tests obtained at follow up included:perceptual speedvisual working memorysemantic memoryepisodic memoryperceptual organization/visuospatialglobal cognitionMRI measurements included total brain volume, presence of cerebral infarcts and volume of brain abnormalities known as white matter hyperintensities. The clinical significance of brain white matter hyperintensities is unclear. However, in a previous post I reviewed a study suggesting these lesions are linked to higher rates of stroke, dementia and mortality.The authors found global cognitive function was linked to all B12-related serum markers except for serum B12 levels itself. Performance on several specific cognitive tests was impaired with specific B12-related markers (MMA levels with perceptual speed and episodic memory impairment, cystathionine and 2-methyl citric acid with impaired episodic and semantic memory). As for the brain MRI measurements, elevated homocysteine levels were linked to decreased brain volume and increased volume of white matter hyperintensities.Homocysteine levels increase with vitamin B12 deficiency. However, there are other pathways to elevated homocysteine. In contrast, elevated MMA levels are specific to vitamin B12 deficiency. The authors of this study suggest vitamin B12 deficiency may have adverse brain effects in more than one pathway--through increased MMA levels and cognitive impairment and through increased homocysteine levels and increased white matter hyperintensities and reduced brain volume. They note "Marginal vitamin B12 status in older age is frequently missed by measurement of serum vitamin B12 levels alone".Molecular model of vitamin B12 cyanocobalamin from Wikipedia Commons file authored by Ben Mills.Tangney, C., Aggarwal, N., Li, H., Wilson, R., DeCarli, C., Evans, D., & Morris, M. (2011). Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination Neurology, 77 (13), 1276-1282 DOI: 10.1212/WNL.0b013e3182315a33... Read more »
Tangney, C., Aggarwal, N., Li, H., Wilson, R., DeCarli, C., Evans, D., & Morris, M. (2011) Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination. Neurology, 77(13), 1276-1282. DOI: 10.1212/WNL.0b013e3182315a33
- October 10, 2011
- 12:28 PM
- 839 views
Cannabis Use Linked to Lower Obesity Rates
by William Yates, M.D. in Brain Posts
Anecdotal evidence supports a temporary increase in appetite following the use of cannabis. However, there is very limited clinical research directed at the association of chronic cannabis use and body weight.Endogenous endocannabinoid compounds are popular targets of research to improve understanding the pharmacology of appetite and weight regulation. Rimonabant, a selective antagonist/inverse agonist for the CB1 receptor was briefly approved for weight reduction before being removed because of safety concern. Research on cannabanoid drugs and receptors continues in a hope to develop an effective and safe drug for the treatment of obesity.However, a new study published in The American Journal of Epidemiology suggests the association of cannabis and body weight may be more complex than thought. Le Strat and Le Foll examined two United States general population surveys (NESARC and NCS-R) for reported prevalence of obesity and frequency of cannabis use. Subjects in each of these surveys were split into four groups with prevalence in (men and women):No cannabis use in last 12 months (94.3%, 97.3%)Cannabis use more than once a year to less than once a month (2.0%, 1.2%)Cannabis use once a month to two days per week (1.9%, 0.8%)Cannabis use three days per week to daily (1.8%, 0.7%)When obesity rates (BMI level of >30) were compared between the four groups, the rates were surprising to me. The odds ratios found in the study are plotted below. The rates of obesity are set a one for non-users and odds ratios for obesity for both surveys by frequency of cannabis use. The results show approximately 33% reduction in rates in obesity in the cannabis user groups.The odds estimates in the figures in this blog are an average of adjusted odds ratios controlling for potential confounding variables such age, gender, cigarette smoking status, education, income and other non-cannabis drug use.The authors note their study is limited by reliance on self-report for height, weight and frequency of cannabis use. They also note their study was unable to control for potential diet and physical activity confounding issues.I would wonder if there may be additional confounders that explain this association at the general population. This association study does not show that obesity in cannabis abstainers will be reduced by initiating cannabis use.Nevertheless, I think this finding is counterintuitive to what most have assumed to be the effect of cannabis on appetite and weight. We will likely see more pre-clinical and clinical research on this topic.Photo of flowers, moth and lady bug from the authors collection. Figure is produced by the blog author from data provided in the following manuscript:Le Strat, Y., & Le Foll, B. (2011). Obesity and Cannabis Use: Results From 2 Representative National Surveys American Journal of Epidemiology, 174 (8), 929-933 DOI: 10.1093/aje/kwr200... Read more »
Le Strat, Y., & Le Foll, B. (2011) Obesity and Cannabis Use: Results From 2 Representative National Surveys. American Journal of Epidemiology, 174(8), 929-933. DOI: 10.1093/aje/kwr200
- October 6, 2011
- 11:47 AM
- 643 views
Genetic Link Between Sleep and Depression
by William Yates, M.D. in Brain Posts
Sleep problems present frequently in major depression and other mood disorders. A logical strategy in exploring genetic contributions to depression examines genetic contributions to sleep variability. Utge and colleagues from Finland have taken this approach in two recently published studies.In their first study, 14 candidate genes were explored in a sample of 1654 Finnish adults. Subjects were assessed for presence of depression alone, depression with early morning awakening and depression with clinically significant fatigue.The candidate genes in this study included genes related to serotonergic function, glutamatergic function, neural plasticity and the hypothalamic-pituitary axis (HPA). The study identifed four suggestive associations:The serotonin gene TPH2 was associated with depression with fatigue in womenThe glutamatergic gene CREB1 was associated with isolated depression (no fatigue/sleep disturbance) in menTwo glutamatergic genes (GAD1, GRIA3) and one neural plasticity gene (BDNF) were associated with depression accompanied by fatigue and sleep disturbance in womenOne HPA axis gene CRHR1 was associated with depression and early morning awakening in womenThe authors noted the GRIA3 association in women is an X-chromosome gene that also appeared in depression associated with early morning awakening reports in the female population alone. They noted a key weakness in this association study was the limited number of individuals with a diagnosis of depression. ... Read more »
Utge, S., Kronholm, E., Partonen, T., Soronen, P., Ollila, H., Loukola, A., Perola, M., Salomaa, V., Porkka-Heiskanen, T., & Paunio, T. (2011) Shared Genetic Background for Regulation of Mood and Sleep: Association of GRIA3 with Sleep Duration in Healthy Finnish Women. SLEEP. DOI: 10.5665/sleep.1268
Utge S, Soronen P, Partonen T, Loukola A, Kronholm E, Pirkola S, Nyman E, Porkka-Heiskanen T, & Paunio T. (2010) A population-based association study of candidate genes for depression and sleep disturbance. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 153B(2), 468-76. PMID: 19548263
- October 4, 2011
- 03:25 PM
- 800 views
The Course of Mood Disorders
by William Yates, M.D. in Brain Posts
Dr. William Coryell presented the October, 2011 Warren Frontiers in Neuroscience lecture at Laureate Psychiatric Clinic and Hospital in Tulsa, Oklahoma. Dr. Coryell has been key investigator in the NIMH Collaborative Depression Study or CDS. The CDS is one of the largest prospective studies of mood disorder, documenting the outcome of 950 subjects enrolled following an episode of depression or mania.Dr. Coryell's lecture covered a summary of results for the CDS from a number of manuscripts. Below are my notes and links to three manuscripts related to topics in the presentation.One key outcome variable in the CDS was percent of time in an episode. Each subject was interviewed every six to twelve months and the percent of time with clinically significant mood disorder symptoms present. Overall, in the entire sample, the percent of time ill during follow up of approximately 30 years was 32%. The presentation focused on what factors relate to poorer prognosis--spending a greater percentage of time ill during follow up.Anxiety Symptoms: Subjects completed an index of anxiety symptoms at baseline. For subjects with bipolar disorder and unipolar disorder, presence of obsessions/compulsion signs/symptoms at baseline was linked to poor prognosis.... Read more »
Solomon DA, Leon AC, Coryell WH, Endicott J, Li C, Fiedorowicz JG, Boyken L, & Keller MB. (2010) Longitudinal course of bipolar I disorder: duration of mood episodes. Archives of general psychiatry, 67(4), 339-47. PMID: 20368510
Fiedorowicz JG, Endicott J, Leon AC, Solomon DA, Keller MB, & Coryell WH. (2011) Subthreshold hypomanic symptoms in progression from unipolar major depression to bipolar disorder. The American journal of psychiatry, 168(1), 40-8. PMID: 21078709
Fiedorowicz JG, Leon AC, Keller MB, Solomon DA, Rice JP, & Coryell WH. (2009) Do risk factors for suicidal behavior differ by affective disorder polarity?. Psychological medicine, 39(5), 763-71. PMID: 18667100
- October 3, 2011
- 12:33 PM
- 697 views
Low-dose Doxepin for Insomnia in the Elderly
by William Yates, M.D. in Brain Posts
July Sunset Santa Fe, New MexicoI had previously reported on the use of low-dose doxepin for the treatment of insomnia. A new study on this topic has been published in the journal Sleep. Dr. Andrew Krystal from Duke University and colleagues presented results of an efficacy and safety trial of doxepin at 1 mg and 3 mg in a series of elderly subjects with chronic primary insomnia studied over a 12-week period.Long-term efficacy studies for insomnia are important because the condition is commonly chronic and long-term hypnotic treatment may be necessary.The key elements in the design of this study included:Subjects: Men and women 65 years of age and older with a DSM-IV-TR diagnosis of primary insomniaSleep study assessment: All subjects received a one-week placebo trial during which they underwent two night in a sleep laboratory. Subjects were required to greater than 10 minutes of sleep latency as well as be awake at least 60 minutes during the sleep period. In addition they were required to have a total sleep time of more than 240 minutes but less than 390 minutes during the placebo sleep study session. Subjects with evidence of sleep apnea during the sleep study were excluded.Drug randomization: 12-weeks of nightly treatment with placebo, one mg of doxepin or three mg of doxepinPrimary outcome measure: wake time after sleep onset on day one of randomization and also on day 29 and day 85 of studyDoxepin (one and three mg) reduced the time awake after sleep onset on the first night of drug treatment (night one 28 minutes and 43 minutes respectively for the one and three mg dose). This was statistically significant compared to placebo where time awake after sleep onset was reduced 11 minutes on night one. The therapeutic effect of doxepin on this key outcome measure was maintained throughout the 12-week study.Looking at components in the architecture of sleep, the three mg doxepin dose was associated with an increase in deep sleep (stage 3/4) on night one (33 minutes placebo and 42 minutes three mg doxepin). This increase was not noted by the end of the two week study. However, the time in REM sleep was increased at twelve weeks for three mg doxepin compared to placebo (67 minutes compared to 57 minutes for placebo). Subjects in the doxepin randomized group were no more likely to report problems with residual daytime sedation or alertness.The authors noted the study found no evidence of adverse events linked to doxepin at either the one or three mg dose. Cardiovascular effects are potentially important, because doxepin is a tricyclic antidepressant that can influence cardiac conduction and orthostatic blood pressure. However, no drug-related EKG or blood pressure problems were noted in this elderly cohort. Additionally, there was no evidence low dose doxepin was linked to weight gain, a problem seen at higher doses.This study confirms the efficacy and safety of low-dose doxepin in elderly individuals. Previous research showed this effect in individuals younger than 65 years. Since insomnia is common in the elderly, this study should provide clinicians and elderly insomniacs another potential treatment option.Photo of Santa Fe, New Mexico sunset from the author's collection.Krystal, A., Lankford, A., Durrence, H., Ludington, E., Jochelson, P., Rogowski, R., & Roth, T. (2011). Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia SLEEP DOI: 10.5665/sleep.1294... Read more »
Krystal, A., Lankford, A., Durrence, H., Ludington, E., Jochelson, P., Rogowski, R., & Roth, T. (2011) Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia. SLEEP. DOI: 10.5665/sleep.1294
- September 29, 2011
- 11:20 AM
- 746 views
Improving Dementia Diagnosis With a Sleep Marker
by William Yates, M.D. in Brain Posts
Dementia presents a growing challenge for clinicians both in the assessment as well as treatment domains. Autopsy remains the only definitive diagnostic intervention that can confirm Alzheimer's disease and the other forms of senile dementia including vascular dementia, dementia with Lewy bodies, frontotemporal dementia and other dementia variants.Since autopsy studies do not provide clinicians or their patients any direct benefits during the patient's lifetime, better diagnostic tests and clinical predictors are needed.A recent study from a team of neurologists, psychiatrists, sleep medicine specialists and pathologists from the Mayo Clinic supports the potential of a sleep disorder to aid in the diagnosis of dementia with Lewy bodies. Lewy bodies are distinct accumulations of proteins found in the brains of individuals with parkinsonism and Lewy body dementia. They are identified at autopsy by special stains viewed under a microscope.Dementia with Lewy bodies is often considered the second most common type of dementia. The clinical diagnostic criteria were revised in 2005 and include core and suggestive features. The core features include: fluctuations in cognitive abilities, parkinsonism and visual hallucinations. The suggestive features include: sensitivity to antipsychotic drugs, reduced brain dopamine uptake on functional brain imaging and presence of the sleep disorder known as REM sleep behavior disorder (RBD).The 2005 diagnostic guidelines for dementia with Lewy bodies can be made when patients have two of the core criteria or one of the core criteria and at least one suggestive criteria.REM sleep behavior disorder (RBD) is a sleep disorder characterized by violent (or other dangerous) behavior during the REM or dream or nightmare phase of sleep. This behavior can include punching, kicking, yelling, jumping out of bed often in response to specific content of the dream that is being experienced. Individuals with RBD can physically injure themselves or their bed partners with their violent behaviors.In normal individuals, REM sleep includes temporary muscle paralysis preventing individuals from physically responding to dreams or nightmares. Loss of this REM sleep paralysis can lead to development of RBD. RBD is felt to indicate disregulation of several brain neurotransmitter systems including dopamine, serotonin and acetylcholine. This dysregulation may explain extreme sensitivity of patients with RBD to adverse effects of a variety of psychotropic drugs including antidepressants and antipsychotics.The Mayo Clinic study included a prospective longitudinal study of a group of patients with dementia who were seen four times per year until their deaths. Postmortem autopsies were conducted on 234 patients. Seventy seven (33%) of the sample met pathological criteria for diffuse Lewy body disease.The authors looked specifically at RBD as a predictor of true diagnosis of dementia with Lewy body disease. They found that RBD was three times more powerful as a predictor of Lewy body dementia than any of the the core criteria of Lewy body dementia.This study confirms the value of RBD in diagnosing Lewy body dementia--in fact it supports moving RBD up to a core feature rather than a suggestive feature. A second multicenter study by Bliwise and colleagues has confirmed the high rates of RBD in Lewy body dementia compared to those with Alzheimer's disease.These findings should encourage clinicians to aggressively look for RBD in patients with dementia to aid differential diagnosis and the treatment planning in this challenging population.Photo of typical Santa Fe home architecture taken during sunset in Santa Fe, New Mexico from the author's collection. Ferman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O, Wszolek Z, Graff-Radford NR, Uitti R, Van Gerpen J, Pao W, Knopman D, Pankratz VS, Kantarci K, Boot B, Parisi JE, Dugger BN, Fujishiro H, Petersen RC, & Dickson DW (2011). Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology, 77 (9), 875-82 PMID: 21849645Bliwise, D., Mercaldo, N., Avidan, A., Boeve, B., Greer, S., & Kukull, W. (2011). Sleep Disturbance in Dementia with Lewy Bodies and Alzheimer’s Disease: A Multicenter Analysis Dementia and Geriatric Cognitive Disorders, 31 (3), 239-246 DOI: 10.1159/000326238... Read more »
Bliwise, D., Mercaldo, N., Avidan, A., Boeve, B., Greer, S., & Kukull, W. (2011) Sleep Disturbance in Dementia with Lewy Bodies and Alzheimer’s Disease: A Multicenter Analysis. Dementia and Geriatric Cognitive Disorders, 31(3), 239-246. DOI: 10.1159/000326238
- September 27, 2011
- 02:22 PM
- 859 views
Topiramate Augmentation in Major Depression
by William Yates, M.D. in Brain Posts
Molecular Model of the Drug TopiramateCurrently available antidepressants provide significant relief from major depression in many patients. However, a significant number of patients receive little or limited relief following an initial trial of a standard first-line drug from the selective serotonin re-uptake inhibitor class of agents.A common clinical strategy after initial drug non-response and non-remission is to consider pharmacological augmentation. Augmentation options for clinicians include lithium carbonate, triiodthyronine (thyroid hormone), a second antidepressant, an atypical antipsychotic or adding psychotherapy if it is not already being provided.Despite the number and range of augmentation options, additional options need to be explored given the persistence of depressive symptoms in many individuals. A small study from Iran suggests one alternative to consider may be the drug topiramate.Topiramate is a drug approved by the FDA for the treatment of epilepsy and migraine headaches in the United States. It is not approved for the treatment of any primary psychiatric disorder. The exact mechanism of action for topiramate is unknown although it is known to have effects on the sodium channel, gamma-amino butyric acid (GABA) receptors, glutamate receptors and act as a carbonic anhydrase inhibitor.Mowla and Kardeh have published a small study of 42 subjects randomized to topiramate or placebo. The key elements of the study include:Subjects: Adults with DSM-IV major depressive disorder who had failed to respond to eight weeks of treatment with an SSRI drug (fluoxetine, citalopram or sertraline)Drug: Topiramate 25 mg per day increased by 25 mg per week throughout the trial (mean dosage 175 mg/day) or placeboClinical trial design: Double-blind, randomized controlled trial with primary outcome measure the Hamilton Depression Rating scale (HAM-D) administered by a psychologist not involved in treatmentFifty three subjects started the study with 11 dropouts (six in the topiramate group and five in the placebo group). HAM-D scores statistically decreased more in the topiramate group (21.6 at baseline to 14.7 at 8 weeks) than in the placebo group (21.9 at baseline to 20.8 at 8 weeks). ... Read more »
Mowla A, & Kardeh E. (2011) Topiramate augmentation in patients with resistant major depressive disorder: a double-blind placebo-controlled clinical trial. Progress in neuro-psychopharmacology , 35(4), 970-3. PMID: 21291943
- September 26, 2011
- 12:29 PM
- 908 views
Fitness, Hippocampus and Forgetting
by William Yates, M.D. in Brain Posts
Hippocampus in Green from 3D Brain iPad AppCardiorespiratory fitness appears to be associated with a variety of benefits in cognitive functioning. The mechanisms for this benefit are unclear. Association studies do not provide evidence for the pathways between related variables. For understanding pathways, clinical trials, longitudinal studies and multivariate approaches are more powerful approaches.Amanda Szabo and colleagues at the University of Illinois at Urbana-Champaign recently published a multivariate study looking at fitness, hippocampus and forgetting in a group of elderly adults in the journal Neuropsychology. The hippocampus is a brain region known to crucial to working memory. Changes in hippocampal volume have been linked to age-related cognitive decline and the development of Alzheimer's disease.The key elements of design in this study included:Subjects: 158 older adults with a mean age of 66.5 yearsVariables: Fitness level as measured by VO2 estimate from a graded exercise test, brain hippocampal volume from a brain 3T MRI scan, spatial working memory task, subjective rating of forgetfulness (Frequency of Forgetting Questionnaire)Statistics: Path analysis examining direct and indirect effects of fitness on hippocampal volume, working memory test performance and subject rating of forgetfulness using the comparative fit index (CFI)The authors started with a presumed pathway model for the mechanism of the relationship between fitness and forgetfulness in the following pathway:fitness levels predict hippocampal volumehippocampal volumes predicts working memory function performanceworking memory performance predicts subjective forgetfulnessFitness levels were associated with a variety of sociodemographic and medical variables at baseline including: self-reported physical activity, presence of hypertension, cardiovascular disease, body mass index, education level, gender and age. These baseline variables were evaluated and controlled in the final pathway analysis.The authors found their predicted model held up in the analysis: "cardiorespiratory fitness is associated with the frequency of forgetting indirectly through its influence on hippocampal volume and, in turn, spatial working memory".The study noted fitness level is not the sole determinant of hippocampal atrophy. Age alone is an independent contributor of hippocampal atrophy. Fitness may reduce the effects of age-related hippocampal atrophy and forgetfulness but it is unable to reverse the effect. So fitness is not a panacea but it appears to be an important factor in maintaining cognitive function in later life. Now, I just wonder if my wife can help me find my running shoes?3D Brain image of the hippocampus in green screen shot from the author's collection.Szabo, A., McAuley, E., Erickson, K., Voss, M., Prakash, R., Mailey, E., Wójcicki, T., White, S., Gothe, N., Olson, E., & Kramer, A. (2011). Cardiorespiratory fitness, hippocampal volume, and frequency of forgetting in older adults. Neuropsychology, 25 (5), 545-553 DOI: 10.1037/a0022733... Read more »
Szabo, A., McAuley, E., Erickson, K., Voss, M., Prakash, R., Mailey, E., Wójcicki, T., White, S., Gothe, N., Olson, E.... (2011) Cardiorespiratory fitness, hippocampal volume, and frequency of forgetting in older adults. Neuropsychology, 25(5), 545-553. DOI: 10.1037/a0022733
- September 22, 2011
- 12:42 PM
- 912 views
Is Lithium a Potential Aid in Traumatic Brain Injury?
by William Yates, M.D. in Brain Posts
Lithium carbonate serves as a primary treatment option in the treatment of mania and bipolar affective disorder. An elemental metal, lithium has atomic number 3 in the periodic table of elements.The mechanism of action for lithium carbonate in bipolar disorder is unclear. Some of the proposed mechanisms for lithium in the central nervous system include:alteration of the neurotransmitter glutamate (affected by other drugs linked to therapeutic effect in bipolar disorder, i.e. sodium valproate and lamotrigine)alteration in gene expressioninactivation of the GSK-3B (glycogen synthase kinase) enzyme known to be involved in circadian clock regulationinteraction with the NO (nitrous oxide) signalling pathwayInhibition of the GSK-3B enzyme has been shown to have potential beneficial effects in stimulating neuroplasticity as it is associated with enhanced expression of brain-derived neurotrophic factor (BDNF). Fengshan Yu and colleagues at NIH and the University of Health Sciences have recently explored the effect of lithium on traumatic brain injury using a mouse model.In their experiment, mice received doses of lithium chloride ranging form 1.0 to 5.0 mEq/kg dose of lithium or placebo following a controlled episode of brain trauma under anesthesia. Doses were repeated daily for three days.Brain injury response to lithium treatment was monitoring using neuropathological techniques as well as behavior and motor coordination tests. The key results of the study include:Lithium chloride at 1.5 to 3.0 mEq/kg reduced brain lesion volume compared to controlLithium chloride reduced post-trauma related anxiety behavior during the outcome monitoringLithium chloride reduced breakdown of the blood-brain barriorShort-term and long-term motor coordination was better in the lithium groupThe authors note that their study suggests the neuroprotective effect of lithium administration following traumatic brain injury in the mouse model appears related to a GSK-3B mechanism. The study timed lithium administration to 3 hours after the trauma providing a realistic model for a trial in human clinical scenarios. They conclude "Our results that demonstrate its (lithium chloride) benefits in the mouse model pave the way for early clinical trials as potential treatment for TBI (traumatic brain injury) patients.CT of traumatic brain injury showing cerebral contusion, cerebral hemmorhage, subdural hematoma and skull fracture from Wikipedia Creative Commons. Source: Rehman T, Ali R, Tawil I, Yonas H (2008). "Rapid progression of traumatic bifrontal contusions to transtentorial herniation: A case report". Cases journal 1 (1): 203. doi:10.1186/1757-1626-1-203. PMID 18831756. http://www.casesjournal.com/content/1/1/203Yu F, Wang Z, Tchantchou F, Chiu CT, Zhang Y, & Chuang DM (2011). Lithium ameliorates neurodegeneration, suppresses neuroinflammation, and improves behavioral performance in a mouse model of traumatic brain injury. Journal of neurotrauma PMID: 21895523... Read more »
Yu F, Wang Z, Tchantchou F, Chiu CT, Zhang Y, & Chuang DM. (2011) Lithium ameliorates neurodegeneration, suppresses neuroinflammation, and improves behavioral performance in a mouse model of traumatic brain injury. Journal of neurotrauma. PMID: 21895523
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