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Physician, Writer and Bird Photographer. Translating Neuroscience Research Into Better Care for Brain Disorders.
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- September 2, 2015
- 12:48 PM
- 83 views
Managing Fatigue in Match-Play Tennis
by William Yates, M.D. in Brain Posts
The 2015 U.S. Tennis Open is in full swing and I ran into an interesting recent manuscript summarizing fatigue in tennis.Fatigue has multiple elements including changes in muscle performance, blood markers of lactic acid and other compounds as well as brain central perception factors.Long multi-set matches can last four or five hours. Obviously, at the end of this type of exertion, players have had to adjust to effects of significant fatigue.Reid and Duffield review the key elements of fatigue in match-play tennis. Their review highlights the significant lack of data to understand fatigue in tennis. I will break my notes and comments into the components of their scholarly review.Physiological ProfileMaximum heart rates during tennis typically range between 60-80% of max with oxygen consumption around 70% of maximumLactic acid levels fluctuate but do not typically reach levels seen with anaerobic exerciseBlood markers of muscle damage after matches show significant increases in muscle related CPK enzymesDehydration can contribute to impaired muscle performance as can deprivation of glycogen stores. These effects are largely prevented by professional tennis players use of fluids and oral carbohydrates in the course of playPhysiological effects are significant with long matches but unlikely to be a key element of fatigueMovement CharacteristicsGPS and movement tracking devices are allowing more precise analysis of movement characteristics over the course of 3 or 4 hour matchesMovement analysis suggests a 5% reduction in amount of movement during the course of a 3 to 4 hours match. Additionally, when long matches occur over consecutive days, movement can be reduced by up to 15% on day 4 compared to day 1The effect of these movement reductions with play is unclear and it has not been demonstrated that this factors is lessened in those who win long matches Changes in Mechanical, Contractile and CognitiveThe reduction in tennis stroke accuracy (i.e. % of first serves in play) with long duration of play is unclearSome studies suggest velocity reductions with fatigue are not automatically linked to reduction of stroke accuracyOne element of the development of expertise in tennis is to show smaller levels of velocity reduction and inaccuracy with long duration of playMatch play over 2 hours reduces contractile muscle strength by 10-25%Being interested in the brain, I noted the review found that mental fatigue and physical fatigue are correlatedElite players use their perception of their level of physical fatigue during the course of a matchMotivation and cognitive factors may be able to delay or ignore physical fatigue perception later in match in elite playersThe review notes that what is known about fatigue in tennis is often limited to players of average skill. Information about elite players is very limited.However, with the evolution of sophisticated movement and physiological analysis, tennis is ready for a data and science upgrade to understand and enhance elite tennis player performance.Readers with more interest on this topic can access the free full-text manuscript by clicking on the PMID link below.Kaleidoscopic photo of monarch butterfly on milkweed flower is from the author's files.Follow the author on Twitter @WRY999Reid M, & Duffield R (2014). The development of fatigue during match-play tennis. British journal of sports medicine, 48 Suppl 1 PMID: 24668384... Read more »
Reid M, & Duffield R. (2014) The development of fatigue during match-play tennis. British journal of sports medicine. PMID: 24668384
- July 21, 2015
- 12:29 PM
- 174 views
Mediterranean Diet and Alzheimer's Disease Prevention
by William Yates, M.D. in Brain Posts
There is an urgent need to identify strategies to prevent or delay the onset of Alzheimer's disease and other forms of dementia.The role of diet as a prevention strategy is controversial. Some research evidence supports a role for a Mediterranean diet in cognitive health and dementia prevention.A recent brain imaging study adds to this evidence. Dr. Lisa Mosconi and colleagues at New York University School of Medicine completed a cross-sectional study of brain magnetic resonance imaging and diet was completed in 52 older cognitively normal individuals.The key elements of the design of this study were:Subjects: Community subjects participating in a longitudinal brain imaging study with a mean age of 54 years (standard deviation 12 years). Approximately 2/3 of the subjects were women.Study measures: Dietary information was collected using the Harvard/Willet food frequency questionnaire and subjects were rated on adherence to a Mediterranean diet using the MeDi. This scale rates intake of fruit, vegetables, legumes, cereal and fish as beneficial with dairy and meat intake rated detrimental. Information on dietary fat and alcohol were also used rated for a nine-item Mediterranean diet score. Subjects scoring greater than 5 were rated as Mediterranean diet adherent. Brain imaging: All subjects completed a cross-sectional brain MRI using a 1.5 Tesla scanner. Volumetric brain measures were calculated using FreeSurfer software.Statistical analysis: Multivariate general linear modeling was used to assess the correlation of diet (high vs low Mediterranean diet adherence) with correction for a variety of potential confounding variables including age, gender, family history of Alzheimer's disease, APOE gene status and BMI. The brain analysis focused on regions of the brain known to show atrophy with Alzheimer's dementia. This analysis showed Mediterranean diet adherent subjects with statistically significant greater brain thickness measures in the left brain hemisphere for:entorhinal cortexorbitofrontal cortexposterior cingulate cortexThis effect was found in the uncorrected volumetric data and the relationship remained with correction for age and total intracranial volume measures.The authors note previous brain imaging studies have linked cognitive decline and dementia with atrophy of the left hemisphere regions of the brain found significantly linked to Mediterranean diet adherence in this study.An additional brain area of atrophy in Alzheimer's is the hippocampus a region not addressed in the current research study.The take home message here is that this study:"provides support for further exploration of dietary behavior as a possible AD (Alzheimer's disease) prevention strategy".The sample size is this study is relatively small and will need replication in other larger sample sizes. There was no correlation with neuropsychological scores and Mediterranean diet in this study. This is not surprising as the subjects were recruited as being cognitively normal.It will be interesting to see in the longitudinal follow up if Mediterranean Diet adherence relates to neuropsychological performance and brain atrophy over time.Readers with more interest in this research can find the free full-text manuscript by clicking on the PMID link in the citation below.Photo of macaw is from the author's files.Follow the author on Twitter @WRY999.Mosconi L, Murray J, Tsui WH, Li Y, Davies M, Williams S, Pirraglia E, Spector N, Osorio RS, Glodzik L, McHugh P, & de Leon MJ (2014). Mediterranean Diet and Magnetic Resonance Imaging-Assessed Brain Atrophy in Cognitively Normal Individuals at Risk for Alzheimer's Disease. The journal of prevention of Alzheimer's disease, 1 (1), 23-32 PMID: 25237654... Read more »
Mosconi L, Murray J, Tsui WH, Li Y, Davies M, Williams S, Pirraglia E, Spector N, Osorio RS, Glodzik L.... (2014) Mediterranean Diet and Magnetic Resonance Imaging-Assessed Brain Atrophy in Cognitively Normal Individuals at Risk for Alzheimer's Disease. The journal of prevention of Alzheimer's disease, 1(1), 23-32. PMID: 25237654
- July 15, 2015
- 12:32 PM
- 175 views
Fitness Boosts White Matter Integrity in Aging
by William Yates, M.D. in Brain Posts
Cardiovascular fitness has been correlated with a variety of beneficial effects on brain structure and cognition.These correlations have not proven causality but they do support continued imaging and brain function studies.Scott Hayes from the VA Boston Healthcare System and Boston School of Medicine recently published an information study on this topic.Brain white matter integrity is now open for study using diffusion tensor imaging, available from high-resolution magnetic resonance imaging (MRI).In the current study, the research team used the following key elements in their study design:Subjects: 34 younger adults between 18-31 years of age and 33 older adults between 55-82 years of age free of significant medical, neurological illness without a history of traumatic brain injury.Fitness Testing Protocol: All subjects completed cardiopulmonary exercise testing via treadmill testing to determine fitness levels via an estimation of peak oxygen consumption.Imaging Protocol: Brain MRI using 3 Tesla Siemens scannerStatistical Analysis: Measures of white matter integrity were compared between younger and older age groups. Additionally, peak VO2 was used as a covariate interaction term. The research team found some interesting results including the following: 1. Older age contributed significantly to measures of impairment in white matter microstructure across a wide anatomical distribution of the white matter tracts2. Older adults with higher level fitness estimates had higher measures of white matter integrity approaching that seen in younger adults in the following brain regions:spleniumsagittal stratumposterior corona radiatasuperior parietal lobe3. Fitness levels in young adults were not correlated to measures of white matterThe positive association of better white matter integrity with higher levels of cardiovasular fitness seemed to occur at about the 75th percentile performance for VO2 by age. The older age high fitness group in this study had a mean estimated peak VO2 of 37.0 ml/kg per min compared to 23.7 in the low fitness older group.The authors note that fitness in older men has significant brain benefits but cannot completely eliminate the effects of brain aging on white matter integrity. Some regions appear more benefited by higher fitness levels than others.A key limitation of the current study is the cross-sectional design. The cross-sectional design limits causality interpretation between fitness and brain aging. It is possible a genetic or other factor contributes to both fitness and brain aging.This study does not inform on the potential benefits of an exercise intervention to increase VO2 on white matter integrity.Additionally, it does not inform on the potential of using fitness exercise to prevent or reduce the cognitive impairment linked to degenerative diseases such as Alzheimer's disease. Nevertheless, this study does add to the growing evidence of a link between exercise and brain health. A positive effect on the brain white matter integrity may be a key component of this association.Readers with more interest in this study can access the free full-text manuscript by clicking on the citation link below.Image of corona radiata (posterior region area linked to improved integrity with higher fitness levels in current study) is a screen shot from the iPad app Brain Tutor.Follow the author on Twitter at WRY999Hayes SM, Salat DH, Forman DE, Sperling RA, & Verfaellie M (2015). Cardiorespiratory fitness is associated with white matter integrity in aging. Annals of clinical and translational neurology, 2 (6), 688-98 PMID: 26125043... Read more »
Hayes SM, Salat DH, Forman DE, Sperling RA, & Verfaellie M. (2015) Cardiorespiratory fitness is associated with white matter integrity in aging. Annals of clinical and translational neurology, 2(6), 688-98. PMID: 26125043
- July 13, 2015
- 12:31 PM
- 177 views
Alzheimer's Disease: The Promise of Diabetes Drugs
by William Yates, M.D. in Brain Posts
Current pharmacologic interventions in Alzheimer's disease (AD) have limited effectiveness.Most of the current AD drugs available promise to slow the rate of progression but fail to reverse or prevent the disease.Novel strategies for AD drug treatment are desperately needed and one promising class of agents are the newer drugs for treatment of diabetes. How might a diabetes treatment drug potentially treat a brain disease like AD?A recent review article in World Journal of Diabetes summarizes what is known about the neuroprotective effect of the anti-diabetic drug liraglutide (trade name Saxenda in the U.S.). This review article is extensive but I will try to summarize the key points.1. Long-acting glucagon-like peptide-1 (GLP-1) is a naturally occuring peptide known to promote insulinotropic activity and glucose homeostasis2. GLP-1 is primarily excreted in the gut but receptors for the compound are found throughout the body including the brain.3. GLP-1 is a key component of the gut-brain axis and along with the vagal nerve helps regulate energy metabolism, insulin secretion, appetite and weight control.4. Liraglutide is a recently approved GLP-1 receptor agonist with an effect similar to naturally occuring GLP-1.5. Liraglutide along with regulating glucose in type 2 diabetes has brain anti-inflammatory, anti-oxidant, microglia inhibition and neuroprotective actions.6. Higher doses of liraglutide promote weight loss and the drug has recently been approved for weight loss in the U.S.7. Preclinical trials suggest liraglutide may improve cognitive function in AD and may have beneficial effects on AD biomarkers such as beta amyloid brain levels.8. Future research combining liraglutide with dipeptidyl peptidase-4 (DPP-4) inhibitors may lead to a "therapeutic dream team" combination for both diabetes and neurodegenerative diseases including AD9. Basic research suggests brain insulin resistance is a key mechanism in AD and other central neurodegenerative disorders. Brain insulin resistance may be reduced or eliminated by the use of centrally acting anti-diabetic drugs like liraglutide.10. Preclinical studies also find evidence that liraglutide "modulates synaptic plasticity by enhancing long-term potentiation" and improves learning an memory in rat models of AD.This review makes some quite remarkable predictions about the potential for GLP-1 drugs in brain disorders including AD. Whether these predictions will be true is yet to be seen.Certainly we can expect to see more research using anti-diabetic drugs in AD and other brain diseases.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.Photo of great egret is from the author's files.Follow the author on Twitter @WRY999Candeias EM, Sebastião IC, Cardoso SM, Correia SC, Carvalho CI, Plácido AI, Santos MS, Oliveira CR, Moreira PI, & Duarte AI (2015). Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide. World journal of diabetes, 6 (6), 807-27 PMID: 26131323... Read more »
Candeias EM, Sebastião IC, Cardoso SM, Correia SC, Carvalho CI, Plácido AI, Santos MS, Oliveira CR, Moreira PI, & Duarte AI. (2015) Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide. World journal of diabetes, 6(6), 807-27. PMID: 26131323
- July 8, 2015
- 12:54 PM
- 224 views
Brain Imaging and Alzheimer's Disease Prediction
by William Yates, M.D. in Brain Posts
Enhanced early detection of risk for Alzheimer's dementia and other forms of dementia is key to prevention and early intervention.Brain imaging holds promise as a pre-clinical disease risk assessment tool in Alzeimer's dementia.Dementia risk has been linked to several brain imaging abnormalities found with magnetic resonance imaging. These abnormalities have included atrophy of the brain hippocampus, medial temporal lobe as well as white matter hyperintensities.A recent study from France examined whether brain MRI findings can improve Alzheimer's and other dementia prediction over conventional known risk factors.Here are the key elements of the design of this study:Subjects: French citizens 65 years and old living at home participating in a longitudinal study of dementia with interviews two, four, six and ten years after baseline interviewBrain imaging: 1.5 Tesla MRI with estimation of white matter lesion volume, hippocampal volume (right and left summed) and total brain volumeDementia diagnosis: all subjects screened at each interview, with targeted neuropsychological testing and neurologist consensus assessmentStandard dementia risk model variables: age, gender, education, smoking status, alcohol use, functional daily living skills, cognition screening tests, cardiovascular disease, diabetes status, systolic blood pressure and apolipoprotein epsilon 4 status.The research team found a statistically significant smaller hippocampal and total brain volume at baseline in those later developing dementia. White matter lesion scores showed a trend (p.076) with later dementia.However, adding the imaging data to the standard dementia risk model did not add statistically to the predictive power for all-cause dementia to the model.The baseline imaging in this study took place around the year 1999 to 2000. Since then, more specific brain imaging tools targeted towards Alzheimer's have emerged including amyloid plaque markers. These enhanced imaging tools may have better power at adding power to our prediction models.Readers with more interest in this research study can access the free full-text manuscript by clicking on the link in the citation below.Photo of meerkats from the Cincinnati Zoo are from the author's files.Follow the author on Twitter @WRY999Stephan BC, Tzourio C, Auriacombe S, Amieva H, Dufouil C, Alpérovitch A, & Kurth T (2015). Usefulness of data from magnetic resonance imaging to improve prediction of dementia: population based cohort study. BMJ (Clinical research ed.), 350 PMID: 26099688... Read more »
Stephan BC, Tzourio C, Auriacombe S, Amieva H, Dufouil C, Alpérovitch A, & Kurth T. (2015) Usefulness of data from magnetic resonance imaging to improve prediction of dementia: population based cohort study. BMJ (Clinical research ed.). PMID: 26099688
- July 7, 2015
- 11:16 AM
- 223 views
Brain Deficits in Visual Hallucinations
by William Yates, M.D. in Brain Posts
One the early things I was taught in my neuroscience training was that new-onset visual hallucinations need to be assessed for medical or "organic causes".Auditory hallucinations were felt to be more characteristic of schizophrenia.One medical disorder linked to visual hallucinations is dementia with Lewy bodies (DLB). DLB is second to Alzheimer's disease in producing neurodegenerative dementia. Visual hallucinations is a hallmark of DLB and is found in up to 70% of clinical samples with the disorder.A recent study from France provides insight into the neuroanatomical correlates of visual hallucinations in DLB.Researchers in this study used single-photon emission computed tomography (SPECT) in a group of 36 subjects with DLB who reported visual hallucinations.This group of cases was compared to 30 subjects with DLD who did not report visual hallucinations.Specific differences in blood flow were noted with visual hallucinations. Visual hallucinations subjects had diminished cerebral perfusion in the following regions.Left anterior cingulate cortexLeft orbitofrontal cortexLeft cuneusDeficits in regional cerebral perfusion in several areas correlated with the severity of visual hallucinations:Bilateral anterior cingulate cortexLeft orbitofrontal cortexRight parahippocampal gyrusRight inferior temporal cortexLeft cuneusThe authors note the cuneus (also known as Brodmann's area 18). This region is known as a secondary visual integration area. Reduced blood flow to this region may contribute to visual processing errors and the subjective sensation of visual hallucinations. Perfusion deficits in more anterior regions may contribute to inability to recognize the visual hallucinations as abnormal.This study is one of many emerging showing specific clinical features of neuropsychiatric disorders may relate to specific neuroanatomical deficits and impairment.Readers with more interest in this topic can access the free full-text manuscript by clicking on the citation below.Image of left cingulate cortex is an iPad screen shot from the app 3D Brain from the author's files.Follow the author on Twitter @WRY999Heitz C, Noblet V, Cretin B, Philippi N, Kremer L, Stackfleth M, Hubele F, Armspach JP, Namer I, & Blanc F (2015). Neural correlates of visual hallucinations in dementia with Lewy bodies. Alzheimer's research & therapy, 7 (1) PMID: 25717349... Read more »
Heitz C, Noblet V, Cretin B, Philippi N, Kremer L, Stackfleth M, Hubele F, Armspach JP, Namer I, & Blanc F. (2015) Neural correlates of visual hallucinations in dementia with Lewy bodies. Alzheimer's research , 7(1), 6. PMID: 25717349
- June 30, 2015
- 12:55 PM
- 161 views
Bipolar Disorder: Novel Clinical Trials II
by William Yates, M.D. in Brain Posts
This is the second post reviewing recent novel trials for the treatment of bipolar disorder.Again, for my sources I am using are clinicaltrials.gov and PubMed.Clicking on the study title will take you to the clinicaltrials.gov site for more detailed protocol information.Allopurinol Maintenance Study for Bipolar DisorderThis completed study examined the effect of 300 to 600 mg per day of allopurinol on mania prevention. Allopurinol is a drug used primarily for the treatment of gout or kidney stones. The drug lowers serum levels of uric acid. Uric acid in elevated in mania and potentially has a contribution role in mania. A small international randomized placebo-controlled study of allopurinol found significant improvements in acute mania. Quetiapine Alone Versus Quetiapine Plus Lithium for ManiaPhysicians have a variety of drug choices in the treatment of the manic phase of bipolar disorder. In this study, manic subjects were randomized to 600 to 800 mg of quetiapine with or without lithium dosed from 500 mg to 2000 mg per day. The study was conducted in China and the results showed that quetiapine alone was as effective as quetiapine plus lithium in reducing symptoms of mania.Internet-Based Interventions for Bipolar DisorderThis study is currently recruiting subjects between the ages of 21 to 65 years of age with a diagnosis of bipolar I, II or NOS. Subjects are randomized to one of three arms including: 1.) moderated discussion board, 2.) moderated discussion board plus psychoeducation or 3.) moderated discussion board, psychoeducation and interactive psychosocial tools. The study is sponsored by the VA Palo Alto System and primary outcome measures include assessment of depression and mania symptoms.Bipolar Depression Treatment with Deep Brain Repetitive Transcranial Magnetic StimulationThis study is currently recruiting subjects in Brazil and is sponsored by the University of Sao Paulo. The study uses a type of coil that is felt to be able to reach deeper areas of the brain felt to be important in mood regulation. Subjects must meet depression criteria at entry and the primary outcome measure is the Hamilton Rating Scale for Depression.Citations below are provided for more information on the treatments in the above studies. Readers can access abstracts by clicking on the link in the citation.Photo of giraffe from the Cincinnati Zoo is from the author's files.Follow the author on Twitter: @WRY999Jahangard, L., Soroush, S., Haghighi, M., Ghaleiha, A., Bajoghli, H., Holsboer-Trachsler, E., & Brand, S. (2013). In a double-blind, randomized and placebo-controlled trial, adjuvant allopurinol improved symptoms of mania in in-patients suffering from bipolar disorder Pharmacopsychiatry, 46 (06) DOI: 10.1055/s-0033-1353345Lauder S, Chester A, Castle D, Dodd S, Gliddon E, Berk L, Chamberlain J, Klein B, Gilbert M, Austin DW, & Berk M (2015). A randomized head to head trial of MoodSwings.net.au: an Internet based self-help program for bipolar disorder. Journal of affective disorders, 171, 13-21 PMID: 25282145Rapinesi C, Bersani FS, Kotzalidis GD, Imperatori C, Del Casale A, Di Pietro S, Ferri VR, Serata D, Raccah RN, Zangen A, Angeletti G, & Girardi P (2015). Maintenance Deep Transcranial Magnetic Stimulation Sessions are Associated with Reduced Depressive Relapses in Patients with Unipolar or Bipolar Depression. Frontiers in neurology, 6 PMID: 25709596... Read more »
Jahangard, L., Soroush, S., Haghighi, M., Ghaleiha, A., Bajoghli, H., Holsboer-Trachsler, E., & Brand, S. (2013) In a double-blind, randomized and placebo-controlled trial, adjuvant allopurinol improved symptoms of mania in in-patients suffering from bipolar disorder. Pharmacopsychiatry, 46(06). DOI: 10.1055/s-0033-1353345
Lauder S, Chester A, Castle D, Dodd S, Gliddon E, Berk L, Chamberlain J, Klein B, Gilbert M, Austin DW.... (2015) A randomized head to head trial of MoodSwings.net.au: an Internet based self-help program for bipolar disorder. Journal of affective disorders, 13-21. PMID: 25282145
Rapinesi C, Bersani FS, Kotzalidis GD, Imperatori C, Del Casale A, Di Pietro S, Ferri VR, Serata D, Raccah RN, Zangen A.... (2015) Maintenance Deep Transcranial Magnetic Stimulation Sessions are Associated with Reduced Depressive Relapses in Patients with Unipolar or Bipolar Depression. Frontiers in neurology, 16. PMID: 25709596
- June 25, 2015
- 11:42 AM
- 180 views
Bipolar Disorder: Novel Clinical Trials I
by William Yates, M.D. in Brain Posts
To finish out the bipolar disorder topic month I will review some of the novel clinical trials in this condition.Clinicaltrials.gov is a valuable resource in searching for active and recently completed clinical trials.Here are some of the rostered trials from this site related to bipolar disorder that caught my attention.Sensoril for Bipolar DisorderSensoril is the trade name for the natural product ashwagandha an herbal extract from the herb Withania somnifera. This trial was sponsored through the University of Pittsburgh. It has been completed and the results were published in 2013. The study targeted some of the cognitive impairment associated with bipolar disorder. The results pointed to some evidence for improvement in working memory, reaction time and social cognition with the drug.Mindfulness Therapy on Disrupted Sleep in Bipolar DisorderThis trial sponsored by Massachusetts General Hospital is listed as currently recruiting subjects. The study compares a form of mindfulness therapy compared to brief supportive therapy on total sleep time in a group of subjects with bipolar disorder and sleep complaints. Sleep problems including both insomnia and hypersomnia are common in bipolar and new innovative interventions are needed.N-Acetyl Cysteine and Aspirin as Adjunctive Treatment for Bipolar DisorderThis trial is sponsored by the University of Texas Health Science Center, Houston and is also listed as currently recruiting subjects. Subjects receive aspirin, n-acetyl-cysteine or both in addition to their usual bipolar disorder drug treatment regimen. The study seeks to see if an anti-inflammatory drug or an antioxidant drug can reduce depression symptoms. Minocycline and Aspirin in the Treatment of Bipolar DepressionThis study is sponsored by the Laureate Institute of Brain Research in Tulsa in collaboration with the Stanley Medical Research Institue and the University of Oklahoma. Subjects are eligible for enrollment if they have bipolar disorder and are currently depressed. Subjects receive aspirin, minocycline or a combination compared to placebo and are monitored for change in depression scores as measured by the Montgomery-Asberg Depression Rating. Disclosure: I am a participating research psychiatrist in this protocol. Readers with more interest in these trials can find more information by going to clinicaltrials.gov and typing in bipolar disorder in the search box. Additionally, specific trial information can be access by clicking on the link in the headings for this post.I have listed some of the relevant citations related to these trials below.In the next post I will look at four more novel trials in bipolar disorder.Photo of boat on beach in Mexico is from the author's files.Follow the author on Twitter: @wry999Chengappa KN, Bowie CR, Schlicht PJ, Fleet D, Brar JS, & Jindal R (2013). Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder. The Journal of clinical psychiatry, 74 (11), 1076-83 PMID: 24330893Deckersbach T, Hölzel BK, Eisner LR, Stange JP, Peckham AD, Dougherty DD, Rauch SL, Lazar S, & Nierenberg AA (2012). Mindfulness-based cognitive therapy for nonremitted patients with bipolar disorder. CNS neuroscience & therapeutics, 18 (2), 133-41 PMID: 22070469Savitz J, Preskorn S, Teague TK, Drevets D, Yates W, & Drevets W (2012). Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2x2 clinical trial. BMJ open, 2 (1) PMID: 22357572... Read more »
Chengappa KN, Bowie CR, Schlicht PJ, Fleet D, Brar JS, & Jindal R. (2013) Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder. The Journal of clinical psychiatry, 74(11), 1076-83. PMID: 24330893
Deckersbach T, Hölzel BK, Eisner LR, Stange JP, Peckham AD, Dougherty DD, Rauch SL, Lazar S, & Nierenberg AA. (2012) Mindfulness-based cognitive therapy for nonremitted patients with bipolar disorder. CNS neuroscience , 18(2), 133-41. PMID: 22070469
Savitz J, Preskorn S, Teague TK, Drevets D, Yates W, & Drevets W. (2012) Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2x2 clinical trial. BMJ open, 2(1). PMID: 22357572
- June 24, 2015
- 11:02 AM
- 172 views
Bipolar Disorder Link to Rheumatoid Arthritis
by William Yates, M.D. in Brain Posts
Finding links between disorders felt to be distinct is a helpful tool in understanding genetics and pathophysiology. An example would be the discovery that individuals with genetically determined elevated cholesterol levels had higher rates of cardiovascular disease. This led to drug development of cholesterol lowering agents leading to reduced rates of cardiovascular disease and mortality.A recent population-based study from a research team in Taiwan identified an increased risk of bipolar disorder in patients with rheumatoid arthritis.In their study, 2,570 patients with a diagnosis of rheumatoid arthritis were identified from a national insurance database.A comparison group of 2,570 patients without rheumatoid arthritis were identified as a control group.The key finding from the study was an approximate doubling of the risk for a diagnosis of bipolar disorder in those with rheumatoid arthritis (odds ratio 2.13, 95% confidence interval 1.12-4.24). Rheumatoid arthritis patients had additional elevated bipolar riks if they also had asthma, cirrhosis of the liver or an alcohol use disorder. The research team noted a possible explanation for increased risk of bipolar disorder following rheumatoid arthritis is inflammatory immune dysfunction.Peripheral markers of inflammation in rheumatoid arthritis have been linked to upregulation of central nervous system inflammation. The authors note peripheral markers of inflammation known as cytokines may reach the brain through blood brain barrier leaks, active transport, activation of endothelial cells or cytokine receptor binding.The clinical implications of this finding are important. Early active treatment of rheumatoid arthritis may reduce risk for central nervous system complications including bipolar disorder. Clinicians treating patients with rheumatoid arthritis should actively monitor for emergence of mood disorders including bipolar disorder. One potential confounding issue in this study is the potential for rheumatoid arthritis medications to induce mood symptoms. Corticosteroid drugs such as prednisone are commonly used in rheumatoid arthritis. This class of drug is known to induce insomnia and hypomanic or manic states in some individuals.Reader with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.Photo of water lilies is from the author's files. Follow the author on Twitter @WRY999Hsu CC, Chen SC, Liu CJ, Lu T, Shen CC, Hu YW, Yeh CM, Chen PM, Chen TJ, & Hu LY (2014). Rheumatoid arthritis and the risk of bipolar disorder: a nationwide population-based study. PloS one, 9 (9) PMID: 25229610... Read more »
Hsu CC, Chen SC, Liu CJ, Lu T, Shen CC, Hu YW, Yeh CM, Chen PM, Chen TJ, & Hu LY. (2014) Rheumatoid arthritis and the risk of bipolar disorder: a nationwide population-based study. PloS one, 9(9). PMID: 25229610
- June 23, 2015
- 12:11 PM
- 239 views
Bipolar Disorder Linked to Increased Dementia Risk
by William Yates, M.D. in Brain Posts
A variety of risk factors have been identified in Alzheimer's disease and other types of dementia.The risk for dementia following major psychiatric syndromes in mid-life is an important research area.Renate Zilkens and colleagues in Australia recently published an informative study of psychiatric disorders and later dementia risk. This study used a population-based case control methodology.The key elements in the design of this study included the following:Subjects: General population in Western AustraliaData sources: inpatient, outpatient and emergency medical records along with death recordsCases: Incident cases of dementia between ages of 65 and 84 years of ageControls: Age and sex-matched individuals without incident dementia diagnosisPsychiatric diagnoses: medical record diagnoses that were required to be present at least ten years prior to dementia onsetStatistical analysis: odds ratio using conditional logistic regressionThe research group in this study used a variety of models to assess risk based on specific medical and psychiatric disorders.For simplicity, I have used data from the study to put together the summary graph in this post.This graph estimates later dementia odds ratios for specific disorders when that disorder is present during the 65-69 year age period.There is evidence of a strong increase in risk for dementia following bipolar disorder diagnosis (odds ratio 4.71, 95% confidence interval 2.29 to 9.65). Bipolar disorder is the psychiatric disorder with the second highest odds ratio being topped only by schizophrenia with an estimated odds ratio of 12.1. The odds ratio with depression was only slight lower than that associated with a diabetes diagnosis (odds ratio 2.77 vs 3.47). Anxiety disorder had a small but statistically significant increased odds ration for later dementia (odds ratio 1.37, 95% confidence interval 1.14-1.65)Alcoholism diagnosis by age 65 years of age is also associated with a marked increase in dementia risk (odds ratio 4.14, 95% confidence interval 2.25 to 7.61).The authors note their findings support the role of psychiatric disorders in contributing to brain vascular abnormalities that can contribute to later cognitive decline. Additionally, they note there is increasing evidence that psychiatric disorders are associated with brain inflammation and immune system dysfunction, areas know to contribute to cognitive decline.This study is important is suggests at lease five psychiatric disorders need to be considered as potential risk factors for dementia (bipolar disorder plus schizophrenia, depression, anxiety and alcoholism). Adding these risk factors may allow for improvement in detection and prevention efforts.Additionally, the finding suggest dementia populations may have higher rates of psychiatric disorders. These psychiatric disorders can complicate dementia management and increase the need for psychiatric assessment and consultation in geriatric care settings.Readers with more interest in this topic can access the free full-text manuscript by clicking on DOI link below.Follow the author on Twitter @WRY999Zilkens, R., Bruce, D., Duke, J., Spilsbury, K., & Semmens, J. (2014). Severe Psychiatric Disorders in Mid-Life and Risk of Dementia in Late- Life (Age 65-84 Years): A Population Based Case-Control Study Current Alzheimer Research, 11 (7), 681-693 DOI: 10.2174/1567205011666140812115004... Read more »
Zilkens, R., Bruce, D., Duke, J., Spilsbury, K., & Semmens, J. (2014) Severe Psychiatric Disorders in Mid-Life and Risk of Dementia in Late- Life (Age 65-84 Years): A Population Based Case-Control Study. Current Alzheimer Research, 11(7), 681-693. DOI: 10.2174/1567205011666140812115004
- June 10, 2015
- 12:58 PM
- 242 views
Brain Default Network in Psychotic Bipolar Disorder
by William Yates, M.D. in Brain Posts
In a previous post I reviewed a summary of research related to genetics and improved diagnosis in bipolar disorder.One key point in this review was a highlight of the promise for integrating genetic with imaging research in bipolar disorder and other neuropsychiatric disorders.An example of this type of integrated research has been recently published in PNAS by a group of Yale University, the University of New Mexico and the University of Texas Southwestern Medical Center.This study used functional magnetic resonance imaging (fMRI) default mode network (DMN) across a group of subjects with psychotic bipolar disorder, schizophrenia and healthy controls. Additionally, study included imaging a group of unaffected relatives of the psychotic bipolar subjects and schizophrenia.Subjects also had genetic analyses available for comparison with any imaging results that would emerge in the study.The research team identified three circuit components in the DMN. The included the networks below (also identified by color as highlighted in group name):Anterior DMN--Medial prefrontal cortex-anterior cingulate caudate DMNInferior posterior DMN--posterior cingulate caudate, inferior parietal lobule, middle temporal gyrus, cuneus/pre-cuneusSuperior posterior DMN--cuneus/pre-cuneus, inferior parietal lobule, cingulateThe key findings from the study include the following:Measures of hypoconnectivity in all three networks were identified in the psychotic bipolar and schizophrenia groups compared to controls.Unaffected psychotic bipolar disorder relatives had normal DMN measures in the three networks while the unaffected schizophrenic relatives showed hypoconnectivity in on one of the three networks.Genetic analysis revealed five genetic links to a brain connectivity sub-DMNs.Genes identified in this brain mapping linkage had previously been linked to psychosis and mood disordersThe five genetic clusters identified in this study were related to specific brain developmental and neuronal processes:NMDA long-term potentiationProtein kinase A regulationImmune response signalingGuidance of axonal developmentSynaptogenesisThe authors note an important advance in their study is the ability to"dissect the underlying biological/molecular pathways and processes that might mediate genetic risk of psychosis via a valuable, noninvasive imaging marker."Default mode network imaging and analysis is advancing as a promising research and clinical tool. It holds the promise of improving diagnostic accuracy and potentially improvement in targeting best treatment interventions for many brain disorders.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.Image of the cingulate fiber connectivity anatomy is an iPad screen shot from the app Brain Tutor.Follow the author on Twitter WRY999Meda SA, Ruaño G, Windemuth A, O'Neil K, Berwise C, Dunn SM, Boccaccio LE, Narayanan B, Kocherla M, Sprooten E, Keshavan MS, Tamminga CA, Sweeney JA, Clementz BA, Calhoun VD, & Pearlson GD (2014). Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 111 (19) PMID: 24778245... Read more »
Meda SA, Ruaño G, Windemuth A, O'Neil K, Berwise C, Dunn SM, Boccaccio LE, Narayanan B, Kocherla M, Sprooten E.... (2014) Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 111(19). PMID: 24778245
- June 8, 2015
- 01:10 PM
- 249 views
Genetics Leading to Better Bipolar Disorder Diagnosis
by William Yates, M.D. in Brain Posts
I wanted to alert Brain Posts readers to an important new review of genetics and diagnosis in brain disorders including bipolar disorder.One hope for the emerging genetics research in mental disorders is a better diagnostic classification system.The current psychiatric diagnostic system is hampered by use of a primary symptoms and signs approach leading to messy heterogeneous groups of clinical conditions.Elliot Gerson has been a giant in neuroscience genetics for quite some time and recently published an important manuscript titled: "Genetic and genomic analyses as a basis for new diagnostic nosologies" in the journal Dialogues in Clinical Neuroscience.Gershon notes current clinical diagnostic categories in psychiatry fail three of five tests for diagnostic validity described by Feigher in 1972:family study clusteringcourse of illness laboratory testsThere is promise for using genetic and genomic findings to improve diagnostic validity in psychiatric disorders. Gershon goes on to outline what is currently known in psychiatric genetics and how future genetic research can lead to "biologically coherent diagnostic entities".Here is my summary on what I see as the key points in the review:The number of common gene single-neucleotide polymorphisms (SNPs) linked to brain disorders is growing (from 10 to over 100 for schizophrenia an example)Summing risk across known schizophrenia SNPs using risk profile scores accounts for 7% of genetic variance in schizophrenia (this increases to up to 23% of variance when broader phenotypic systems are used)A similar SNP risk profile approach separates bipolar disorder groups from controlsLarger sample sizes may increase this SNP genetic variance understanding in schizophrenia and bipolar disorderSome SNPs contribute to risk for more than one disorder i.e. schizophrenia, bipolar disorder and major depression showing weakness of current classification systemCommon genome-wide SNP data may be a promising path to defining better diagnostic categoriesRare variants such as copy number variations (CNVs) may also be promising for improved psychiatric diagnosisChromosome 22q11 deletion (DiGeorge syndrome or velocardiofacial syndrome) occurs in 1/4000 births and has high penetrance for psychiatric diagnosis although nonspecific (23% autism sprectrum, 68% schizophrenia, 26% bipolar disorder)Brain molecular network modeling also holds promise as a basis for diagnosisMany known risk genes for psychiatric illness have been linked to key brain network nodesGenetic variants could be mapped to human molecular networks and this map may lead to predictable "therapeutic targets"Brain connectivity networks (fMRI) may be a promising alternate approach to psychiatric diagnosisThe validity criteria for psychiatric diagnosis described by Feighner in 1972 continue to be a gold standard. Emerging genetic, genomic and brain connectivity research may be part of the tool set that has been missing. Applying these tools to better diagnosis holds promise for new and better treatment and the reduction in pain and suffering for many brain disorders.Interested readers can access the free full-text manuscript of the Gerson and Grennan review by clicking on the PMID link in the citation below.Photo of brown pelican and ruddy turnstone is from the author's files.Follow the author on Twitter WRY999Gershon ES, & Grennan KS (2015). Genetic and genomic analyses as a basis for new diagnostic nosologies. Dialogues in clinical neuroscience, 17 (1), 69-78 PMID: 25987865... Read more »
Gershon ES, & Grennan KS. (2015) Genetic and genomic analyses as a basis for new diagnostic nosologies. Dialogues in clinical neuroscience, 17(1), 69-78. PMID: 25987865
- June 5, 2015
- 11:04 AM
- 261 views
Bipolar Disorder Guidelines: NICE Update
by William Yates, M.D. in Brain Posts
Clinicians treating bipolar disorder and patients with a bipolar disorder diagnosis are aided by the availability of expert opinion guidelines.In the last post, I reviewed a study that found decreased rates of suicidal behavior in bipolar patients treated with antidepressant drugs.This review prompted me to look for a recent consensus update on assessment and treatment of bipolar. One recent update came from the UK National Institute for Health and Care Excellence or NICE. This guideline is freely available and I will post a link at the end of this blog post.I will focus on psychopharmacology in my review but the reader is encouraged to take a look at these excellent guidelines for other details.The recommendations from the guideline for general maintenance treatment of bipolar disorder in adults in specialty care:Do not use gabapentin or topiramateAntipsychotic drugsLithium therapyValproate therapyLamotrigine therapyRecommendations for treatment of mania in specialty care:If manic bipolar patient is taking antidepressant consider stopping itElectroconvulsive therapy is an intervention that should be considered in those with severe and prolonged maniaThe further treatment of mania follows the maintenance list as above: antipsychotics (haldol, olanzapine, quetiapine or risperidon), lithium, valproate and lamotrigine Recommendations for treatment of bipolar depression in specialty care:Make sure full psychological services are used as a base in treatmentAdd fluoxetine plus olanzapine or quetiapine on it's ownIf no response to initial antidepressant treatment consider a trial with lamotrigineAs you can see from these depression guidelines, the use of standard antidepressants in bipolar depression is not recommended. The exception to this is the use of fluoxetine (covered with olanzapine).The full pdf guideline from NICE is 59 pages and I would encourage interested reader to go to the website and download the full guide. You can do that by clicking HERE .Photo of baseball player Albert Pujols in spring training is from the author's files.Follow the author on Twitter @WRY999Kendall T, Morriss R, Mayo-Wilson E, Marcus E, & Guideline Development Group of the National Institute for Health and Care Excellence (2014). Assessment and management of bipolar disorder: summary of updated NICE guidance. BMJ (Clinical research ed.), 349 PMID: 25258392... Read more »
Kendall T, Morriss R, Mayo-Wilson E, Marcus E, & Guideline Development Group of the National Institute for Health and Care Excellence. (2014) Assessment and management of bipolar disorder: summary of updated NICE guidance. BMJ (Clinical research ed.). PMID: 25258392
- June 4, 2015
- 10:58 AM
- 293 views
Antidepressants Linked to Lower Suicide in Bipolar Disorder
by William Yates, M.D. in Brain Posts
Bipolar disorder is known to have a marked increased lifetime risk for suicide.There has been limited study of the effect of specific interventions in the risk of suicidal behavior and completed suicide.A recent study has added to our understanding of this topic using data from the Collaborative Depression Study or CDS.The CDS is a large longitudinal stud funded by the NIMH that enrolled a large sample of subjects with bipolar I disorder, bipolar II disorder and unipolar depression.Subject were followed intensely after a research diagnostic assessment every six months. Follow up interviews including information about antidepressant treatment, mood state, suicidal ideation and suicidal behaviors. This was a significantly ill cohort. Twenty-four subjects committed suicide during the five year period of follow up.Subjects receiving drug treatment with bipolar disorder had statistically lower suicidal behavior (but not in the unipolar group). The estimated level of reduction of suicidal behavior by diagnosis group was:Bipolar I disorder: 54% reduction (95% confidence interval 31% to 69%)Bipolar II disorder: 35% reduction (95% confidence interval 1% to 57%)Unipolar disorder: 12% reduction (95% confidence interval 36% reduction to 22% increase) The authors note some clinicians are less likely to use antidepressants in bipolar depression due to concern about inducing mania or more rapid cycling. They note their study supports a link between antidepressant use and reduced suicidality in bipolar disorder.Many clinicians recommend chronic use of mood stabilizers with intermittent antidepressant use in bipolar disorder during depressive episode only. This may reduce potential risk for the use of antidepressants in bipolar disorder. The authors note some previous studies support a specific role for the mood stabilizing drug lithium to reduce suicide risk in bipolar disorder.The psychopharmacologic treatment of bipolar disorder is a complicated process that needs to be customized to individual patient comorbidity, tolerance, medical comorbidity and past treatment response. Patients with bipolar disorder are best managed in a setting of expert medical care, family support and longitudinal monitoring. Patients are best served when they make decisions about drug treatment options in this type of setting.The CDS cohort study was done prior to the evolution of the use of the novel antidepressant drug treatment lamotrigine in bipolar disorder. Lamotrigine is an antiepileptic drug that is increasing used in bipolar disorder and is an FDA approved drug for maintenance therapy. The FDA also has approved aripiprazole and the combination of olanzapine plus fluoxetine for the treatment of depression in bipolar disorder.Readers with more interest in the above study can access the free full-text manuscript by clicking on the PMID link in the citation below.Slide showing symptoms in the manic phase of bipolar disorder is an original slide from the author's files. Follow the author on Twitter: @WRY999Leon AC, Fiedorowicz JG, Solomon DA, Li C, Coryell WH, Endicott J, Fawcett J, & Keller MB (2014). Risk of suicidal behavior with antidepressants in bipolar and unipolar disorders. The Journal of clinical psychiatry, 75 (7), 720-7 PMID: 25093469... Read more »
Leon AC, Fiedorowicz JG, Solomon DA, Li C, Coryell WH, Endicott J, Fawcett J, & Keller MB. (2014) Risk of suicidal behavior with antidepressants in bipolar and unipolar disorders. The Journal of clinical psychiatry, 75(7), 720-7. PMID: 25093469
- June 2, 2015
- 03:41 PM
- 271 views
Neurobiology of Child Neglect/Abuse: Nemeroff Lecture Notes
by William Yates, M.D. in Brain Posts
I had the opportunity to attend the Warren Neuroscience Lecture presented by Dr. Charles Nemeroff in Tulsa, OK on June 2, 2015.Dr. Nemeroff has been an international leader in research in mood and anxiety disorders. His recent focus has been on the effects of adverse childhood environments on risk for adult mood and anxiety disorders. Here are my notes that summarize some of the key points from his lecture.Introduction:Stress is an important factor in understanding depressionEarly life stress is a risk factor for later adult depressionGenes account for a significant portion of the variation in risk following stress exposureBrain systems that regulate emotions are disrupted during episodes of major depressionPsychiatry research slowed by complexity of brain, multiple cell types, complex heterogeneous disorders. But we are beginning to understand the key role genes play in a variety of key disorders. Genetic factors account for 65% of bipolar disorder variance, 50% of schizophrenia variance and around 35% of variance in major depression.Early childhood abuse and neglect is common. Recent surveys estimate prevalence rates for each of the following:Physical abuse 15-28% of general population in U.S.Sexual abuse in 11-21% Emotional abuse in 11-36%Parental divorce or separation in 25%Early childhood abuse and neglect has multiple effects in neurobiology and later adult mood and anxiety disorder risk:Increased adult cerebral spinal marker of stress known as corticotrophin releasing factor (CRF)Increase serum ACTH and cortisolIncrease inflammatory markers such as interleukin-6Decreased cerebral spinal fluid oxytocin that may impair social function and bonding with childrenReduced brain cortex thickness and hyperactivy amygdala responseIncreased adult PTSD and depressionIncreased adult rates of substance abuseIncreased risk of suicidal behavior and completed suicideThere is a growing body of evidence that ten or more genes influence vulnerability to childhood abuse and neglect including genes regulating the HPA axis, serotonin function and a gene known as FKBP5. These genetic effects may interact with environmental stresses to reduce or amplify stress vulnerability. Stress may be viewed as a teratogen that influences genetic features through epigenetic and gene regulation effects.For clinicians there are important treatment implications:Major depression in the context of moderate to severe childhood abuse is less responsive to medication or to psychotherapy interventionChildhood abuse and neglect in bipolar disorder is linked to early onset, greater severity and poor treatment response.During the discussion following the lecture Dr. Nemeroff noted the importance of population-based efforts to reduce societal levels of exposure to child abuse and neglect including:Early education with teacher training to look for evidence of abuse/neglectIncreased training for primary care physicians treating infants/childrenIncreased training and funding for social services that evaluate and treat children referred for child abuse/neglectIncreased detection and surveillance for sexual predatorsMore research in the treatment of sexual disorders including pedophilia. There is almost no NIH funding in this area and little research interest and activity.Below I have added citations featured in the presentation to allow readers with more interest to delve into some of the primary research studies.Image is this post is "PBB Protein CRH image" from Wikipedia chapter on CRH. Image by ProteinBoxBot. Licensed under Public Domain via Wikimedia Commons Follow the author on Twitter @WRY999Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH, & Nemeroff CB (2000). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA, 284 (5), 592-7 PMID: 10918705... Read more »
Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH, & Nemeroff CB. (2000) Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA, 284(5), 592-7. PMID: 10918705
Heim C, Mletzko T, Purselle D, Musselman DL, & Nemeroff CB. (2008) The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biological psychiatry, 63(4), 398-405. PMID: 17825799
Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB.... (2008) Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299(11), 1291-305. PMID: 18349090
Saveanu, R., & Nemeroff, C. (2012) Etiology of Depression: Genetic and Environmental Factors. Psychiatric Clinics of North America, 35(1), 51-71. DOI: 10.1016/j.psc.2011.12.001
- May 26, 2015
- 10:18 AM
- 245 views
Conduct Disorder as a Substance Abuse Risk Factor
by William Yates, M.D. in Brain Posts
In this series of research reviews on conduct disorder several important findings are evident.Conduct disorder (CD) commonly evolves into adult antisocial personality disorderConduct disorder in children often presents along with attention deficit hyperactivity disorder and learning problemsCD in childhood and adolescence raises risk for alcohol, drug and nicotine dependence.Margaret Sibley and colleagues recently published a study of CD and ADHD and later initiation and escalation of the use of alcohol, cigarettes and cannabis.In her study, 113 children with ADHD were assessed between the ages of 5 and 18 years of age. A control group of 65 children without ADHD were similarly assessed during this developmental period.Twelve percent of the childhood ADHD later met criteria for a diagnosis of CD. This contrasts with only 1.5% of the control group. Also noteworthy was the high rate of oppositional defiant disorder in the ADHD group (59%) compared to only 5% of the control group.Significant differences emerged in substance use. These key findings included the following:ADHD adolescents were more likely to have ever smoked a cigarette (47% v 28%) and were much more likely to be daily smokers (27% v 6%).ADHD adolescents were not more likely not more likely to have ever tried marijuana (53% v 51%) but were more likely to use on at least a weekly frequency (23% v 8%).There were no differences in the ADHD group compared to controls in ever use of alcohol or frequent drinkingMaternal drinking in early childhood was the strongest predictor of adolescent alcohol useThe authors also found another important finding:"escalating CD symptoms in childhood were viewed as a mediator of the relationship between ADHD and cigarette and marijuana use."The authors noted in the longitudinal data analysis that increasing ADHD symptom endorsement predicted more CD symptoms. More CD symptoms was the strongest predictor of later substance use.The take home message for clinicians is early identification and treatment of ADHD in children is important. Early identification and treatment of ADHD holds the promise for modifying later CD and substance use morbidity.This is an important study teasing out some of the issues in ADHD/CD overlap and later substance use risk. Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.Graphic figure is an original created by the author using Canva.Follow the author on Twitter @WRY999Sibley MH, Pelham WE, Molina BS, Coxe S, Kipp H, Gnagy EM, Meinzer M, Ross JM, & Lahey BB (2014). The role of early childhood ADHD and subsequent CD in the initiation and escalation of adolescent cigarette, alcohol, and marijuana use. Journal of abnormal psychology, 123 (2), 362-74 PMID: 24886010... Read more »
Sibley MH, Pelham WE, Molina BS, Coxe S, Kipp H, Gnagy EM, Meinzer M, Ross JM, & Lahey BB. (2014) The role of early childhood ADHD and subsequent CD in the initiation and escalation of adolescent cigarette, alcohol, and marijuana use. Journal of abnormal psychology, 123(2), 362-74. PMID: 24886010
- May 18, 2015
- 10:45 AM
- 222 views
Brain Imaging and Conduct Disorder: Temporal Lobe Abnormalities
by William Yates, M.D. in Brain Posts
Conduct disorder is a complex behavioral disorder with significant risk for later adult psychopathology.There is increasing evidence for a biological basis for conduct disorder.Twin studies show a significant genetic contribution to the disorder.Brain imaging studies also point to biological factors in conduct disorder.Gregory Wallace and colleagues recently published a structural MRI study of conduct disorder in 22 adolescents between the ages of 10 and 18. Conduct disorder subjects were compared to a group of 27 age-matched controls on imaging measures.This study focused on measures of brain cortex thickness, brain surface area and degree of brain folding or gyrus formation.Conduct disorder was linked to the following brain structural abnormalities:Reduced cortical thickness in the superior temporal lobesReduced gyrus formation in the ventromedial frontal cortexReduced volume of the the amygdala and striatum (putamen and pallidum) The research group also found a negative correlation between superior temporal lobe thickness and psychometric measures of callousness/unemotional styles.The mechanism for the temporal lobe to be involved in the symptoms of conduct disorder is unclear. Cortical thinning in this region has been found in adults with psychopathy. The authors note that amygdala/temporal lobe integration is necessary for stimulus-reinforcement learning. This integration may explain some of the deficits found in the current study.This study will be important for continuing research in the genetics and pathophysiology involved in conduct disorder. Intervention strategies will need to address potential biological deficits contributing to the behavioral and learning problems in conduct disorder.Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below.Image of brain with superior temporal lobe highlighted in green is an iPad screen shot from the Brain Tutor app.Follow the author on Twitter @WRY999Wallace GL, White SF, Robustelli B, Sinclair S, Hwang S, Martin A, & Blair RJ (2014). Cortical and subcortical abnormalities in youths with conduct disorder and elevated callous-unemotional traits. Journal of the American Academy of Child and Adolescent Psychiatry, 53 (4), 456-650 PMID: 24655655... Read more »
Wallace GL, White SF, Robustelli B, Sinclair S, Hwang S, Martin A, & Blair RJ. (2014) Cortical and subcortical abnormalities in youths with conduct disorder and elevated callous-unemotional traits. Journal of the American Academy of Child and Adolescent Psychiatry, 53(4), 456-650. PMID: 24655655
- May 14, 2015
- 10:31 AM
- 259 views
Male Depression Risk Via Childhood Conduct Disorder
by William Yates, M.D. in Brain Posts
Conduct disorder represents an important childhood-onset condition that commonly persists into adulthood.Adult antisocial personality disorder and substance abuse are known risks associated with conduct disorder.A recent study by Kenneth Kendler and Charles Gardner identified male conduct disorder as a risk factor for adult major depression.Their study using the Virginia Twin Registry examined 20 developmental risk factors in male and female twins for presence of recent adult major depression.A key finding in their study was gender specificity for several of the developmental risk factors. Many of the developmental risk factors increased risk for later depression in both males and females.However, several developmental risk factors showed a predominant effect in males. These male predominant risk factors included the following variables:Conduct disorderHistory of childhood sexual abuseDrug abusePast major depressionStressful life eventsConduct disorder and presence of drug abuse were classified as having moderate effect size in male gender predominance.Specific types of stressful life events were noted to have a strong male predominance. Stressful life events that included financial loss, occupational difficulty and legal problems were more commonly found in the male twins with depression.The authors note:"Our results with externalizing psychopathology are consistent with a wide range of studies finding that men have higher rates of conduct disorder and drug abuse and that both of these disorders are associated with a higher risk for major depression."The take home message for clinicians is that assessment of childhood conduct disorder is important in children, adolescents and adults. In adult males, childhood conduct disorder represents an important risk factor for adult major depression.Readers with more interest in this research can access the free full-text abstract and manuscript by clicking on the DOI link in the citation below.Photo of electus parrot pair is from the author's files.Follow the author on Twitter @WRY999Kendler, K., & Gardner, C. (2014). Sex Differences in the Pathways to Major Depression: A Study of Opposite-Sex Twin Pairs American Journal of Psychiatry, 171 (4), 426-435 DOI: 10.1176/appi.ajp.2013.13101375... Read more »
Kendler, K., & Gardner, C. (2014) Sex Differences in the Pathways to Major Depression: A Study of Opposite-Sex Twin Pairs. American Journal of Psychiatry, 171(4), 426-435. DOI: 10.1176/appi.ajp.2013.13101375
- May 7, 2015
- 10:30 AM
- 302 views
Conduct Disorder: Predictors, Gender and Genetics
by William Yates, M.D. in Brain Posts
Genetic factors contribute to risk for many childhood mental disorders.Gender issues in childhood psychopathology are also important factors.Boys show higher rates for conduct disorder (CD), oppositional defiant disorder (ODD) and attention deficit hyperactivity disorder (ADHD).Nora Kerekes and colleagues in Sweden and Australia examined a large twin study of childhood behavioral and neurobehavioral disorders. The aims of this study were to better understand the developmental and genetic features with attention to gender issues.Key features of design of this study included:Twin status identical (monozygotic-MZ) vs fraternal (dizygotic-DZ) was assigned via algorithm and saliva samplesClinical features were assessed using the Autism-Tics, AD/HD and other Comorbidities inventoryData analysis included descriptive statistics and twin gene-environment modelling As expected, ODD and CD rates were higher in boy twins than in girl twins. For ODD the boy:girl prevalence rates were 3.5%:2.1%. For conduct disorder the boy:girl prevalence rates were 1.3%:0.6%.The research team found two distinct neurodevelopmental predictors. Early concentration/attention problems led to an increase in later ODD in both boys and girls. Additionally, early social interaction problems was linked to increased CD rates in both genders.Higher monozygotic versus dizygotic twin concordance rates indicate a significant genetic contribution. The original figure above shows the MZ v DZ rates for the boy twins abstracted from the manuscript. All three behavioral disorders as well as autism spectrum disorder (ASD) showed significant genetic contributions in the boy twins.For girl twins a genetic contribution was identified for ODD, ADHD and ASD. Of note, CD rates were not increased in MZ girl twins compared to DZ girl twins.The authors note their findings have clinical implications including:Clinicians need to be aware of the differences between boys and girls with ODD and CDInattention problems are important but less evident that behavioral problems. Clinicians should be diligent in looking for attentional problems in girls as a risk for later CDSocial interaction problems are common predictors and common comorbid features in ODD and CDTreatment of ODD and CD in both boys and girls should include family interventions with multimodal interventions targeting improvement in "social interaction and communication abilities".This is an important study that emphasizes a comprehensive surveillance and assessment program for behavioral problems in both boys and girls.Readers with more interest in this study can access the free full-text manuscript by clicking on the DOI link in the citation below.Follow the author on Twitter @WRY999Kerekes, N., Lundström, S., Chang, Z., Tajnia, A., Jern, P., Lichtenstein, P., Nilsson, T., & Anckarsäter, H. (2014). Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study PeerJ, 2 DOI: 10.7717/peerj.359... Read more »
Kerekes, N., Lundström, S., Chang, Z., Tajnia, A., Jern, P., Lichtenstein, P., Nilsson, T., & Anckarsäter, H. (2014) Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study. PeerJ. DOI: 10.7717/peerj.359
- May 5, 2015
- 11:12 AM
- 273 views
Bad Boy. Bad Boy. Is It Conduct Disorder?
by William Yates, M.D. in Brain Posts
Defining the line between normal childhood behavior and more serious problems like conduct disorder (CD) is important.Conduct disorder is linked to a significant risk for a lifelong problem with aggression. Identifying CD early in life provides the hope that early intervention might reduce the later consequences of the disorder.The American Academy of Child and Adolescent Psychiatry has an excellent online resource center to understand conduct disorder. They note the condition is characterized by four key diagnostic features with onset in childhood:Aggression toward people and animalsDestruction of propertyFrequent lying/theftChronic violation of rulesA recent research study by Benjamin Lahey and Irwin Waldman analyzed the validity of conduct disorder in relationship to the other common childhood forms of psychopathology.They note a key diagnostic challenge is to differentiate conduct disorder from a similar disorder known as oppositional defiant disorder or ODD. The main conclusions from their literature review included the following:CD appears distinct from ODD in many waysCD more strongly predicts adult antisocial behavior compared to ODDIt may be of value to identify the type of aggressive behavior in cases of CD: proactive vs reactive, physical vs non-physical aggression towards otherAge of onset of CD may be an important signal. Early age of onset appears to have a worse prognosisCD in the context of a callous, unemotional, without regret may also be an important marker for severityCD is a male predominant disorder and there may be important differences in the manifestation of the disorder between boys and girlsFactor analysis finds CD to cluster in a broad group of externalizing disorders that includes ODD, ADHD hyperactivity and impulsivity and inattentionThis externalizing group of disorders appears distinct from a group of childhood internalizing disorders that includes social anxiety, obsessive compulsive disorder, separation anxiety and phobias including agoraphobiaExternalizing disorders appear to share some distinct genetic riskAlthough genetic factors appear key in CD and other externalizing disorders, environmental factors may interact with genetic risk to effect outcomeFuture research implications from this review include the methods needed for refining the CD phenotype, molecular genetic studies, nonshared environmental studies and studies of the neurobiology of CD and studies of gender differenceIt is likely that CD will share "neurobiological mechanisms with other prevalent forms of psychopathology" although is is likely there are mechanisms that will be specific or unique to CDThis review is a good place to start in understanding the phenotype of CD and how it is understood from a current research prospective.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.Image of toy dog is an original photo from the author's files.Follow the author on Twitter @WRY999Lahey BB, & Waldman ID (2012). Annual research review: phenotypic and causal structure of conduct disorder in the broader context of prevalent forms of psychopathology. Journal of child psychology and psychiatry, and allied disciplines, 53 (5), 536-57 PMID: 22211395... Read more »
Lahey BB, & Waldman ID. (2012) Annual research review: phenotypic and causal structure of conduct disorder in the broader context of prevalent forms of psychopathology. Journal of child psychology and psychiatry, and allied disciplines, 53(5), 536-57. PMID: 22211395
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