Lengthier descriptions and additional topics are available in
Updates by Chapter. Online access to full journal articles may
require subscription; if so, check access through your library.
Author of Vaccine-Autism Paper Sues for Libel
Andrew Wakefield, author of the paper that started the furor over a now discredited link between childhood vaccines and autism (see p 418), filed a defamation suit on January 3, 2012. Named in the suit are the British Medical Journal, the journal's editor, Fiona Godlee, and journalist Brian Deer, who exposed the fraud. Evidence that Wakefield used fraudulent data to make his point led to retraction of the journal article and the loss of his license to practice medicine. Wakefield also accused the journal of a conflict of interest because it receives money from vaccine makers GlaxoSmithKline and Merck. Wakefield sued Deer in 2005 over a documentary accusing him of fraud, but withdrew the suit when the judge demanded more evidence. ScienceInsider, January 5, 2012.
New Standards for Autism Diagnosis
The Diagnostic and Statistical Manual (DSM), the guide used for diagnosing psychiatric and psychological disorders, is undergoing revision. Among other changes, the new version, DSM-5, intends to correct what many regard as overdiagnosis of autism, by tightening the critera introduced in DSM-IV. A major proposed change—collapsing two of the three categories of symptoms into one group, because deficits in communication and deficits in social interaction almost always appear together—has statistical support from studies at the Cleveland Clinic and at University College London. Some advocate the stricter critera, including experts who believe the current standards identify non-autistic individuals, and some parents who want more state aid focused on children with severe autism. Scientific American News, January 30, 2012. Others believe the new standards set the bar too high and will deny needed benefits to those with less severe symptoms, including insurance coverage and special instruction. In a Finnish study of 26 8-year-olds diagnosed by DSM-IV standards, only 12 qualified under the stricter DSM-5 criteria. Journal of the American Academy of Child & Adolescent Psychiatry, Vol 50, 583-592.
New Help for Stroke Victims
Researchers have thought that GABA released by the brain following traumatic injury to calm runaway activity also interferes with recovery, but blocking this inhibition has yielded mixed results. A drug that blocks GABA receptors on the cell but does not affect those at snapses may offer a solution. Drug-treated mice with experimenter-induced strokes regained 50% more function in their limbs than mice receiving control therapy. Nature, Vol 468, 305-309.
The Promise of Two-Photon Microscopy
A new version of two-photon microscopy, which uses fluorescent dyes to image specific types of tissue and even track neural activity, can image individual pairs of pre- and post-synaptic neurons and their connections. The developer has been able to follow changing connectivity in the mouse retina during the second week of life, and he hopes to refine our understanding of how the developing brain reorganizes its connections. Science Daily, October 31, 2010. Another researcher is imaging activity in neural networks of 1,000 neurons; he hopes to learn more about the neural replay that goes on in circuits following a learning experience, which is believed to be how the brain turns the neural information into a permanent memory. The Dana Foundation: Grants.
Clinical Trials With Human Embryonic Stem Cells
The U.S. Food and Drug Administration has approved a clinical trial testing the safety of human embryonic stem cell injections in patients with spinal cord injury; of course, the researchers will also test to see if the patients benefit from the therapy. Science Insider, October 12, 2010. The FDA has also approved a second trial to test stem cells in treating progressive loss of vision in children with advanced macular dystrophy. In earlier testing, the procedure prevented mice with a version of the disease from going blind. Science Insider, November 22, 2010. In the meantime, a district court judge issued an injunction against President Obama's lifting of the ban on federal funding, on the basis that federal funding violates the Dickey-Wicker Amendment; however, a U.S. Court of Appeals lifted that injunction. CNN U.S., April 29, 2011. Outcome in the courts may be important; research has found that adult stem cells do not proliferate as well as embryonic stem cells and they have a shorter life span. Stem Cells, February, 2010.
Treating Binge Drinking With Gene Therapy
Because the GABAA receptor is involved in producing alcohol's effects, addiction therapists often prescribe GABA blockers in the treatment of alcoholism. Now researchers have shown that genetic manipulation of the receptor can dramatically reduce binge drinking in rats bred to prefer alcohol (they don't typically imbibe). After RNA injections into the amygdala, GABAA receptor density decreased by 65%; binge drinking dropped profoundly in the ensuing 6 days and returned to previous levels by day 14. Proceedings of the National Academy of Sciences, Vol 108, 4465-4470.
Dramatic Increase in Diabetes Projected
The Centers for Disease Control and Prevention estimates that the number of new cases of diabetes will increase in the U.S. from its 2010 level of 14% to 25%-28% of the population by 2050, even if preventive interventions are undertaken. The projection is based on the incidence of prediabetes and diabetes, current life expectancy, and population increases among high-risk subgroups. Population Health Metrics, 2010, 8:29.
Sensing Dietary Deficits
Detection of nutrients often involves learned taste preference, but in other cases there is a more direct biological mechanism. When a rat eats a food lacking one of the indispensable amino acids (IACs, nine amino acids the body requires for synthesizing proteins) that it needs, activity increases in the anterior piriform cortex (APC); the rat will turn away from the food within 20 minutes. Even a slice of APC tissue will show an increase in excitatory postsynaptic potentials when placed in a nutrient bath missing any one of the IACs. This suggests that the APC can detect IAC levels directly, thus monitoring conditions in its own environment. Journal of Neuroscience, Vol 31, 1583-1590.
Childhood Predictors of Adult Homosexuality
The conclusion that children who later become homosexual typically show more gender nonconformity—behavior more typical of the other sex, along with a preference for other-sex playmates and companions—has been based on memories provided by the individuals and/or their families. When researchers at Northwestern University rated childhood videos of homosexual and heterosexual men and women for gender nonconforming behavior, the results indicated that both boys and girls who were homosexual as adults were less conforming than the other subjects. Developmental Psychology, Vol 44, 46-58.
Love Modifies Olfactory Responses to Other-Sex Friends
The attention hypothesis claims that sexual and romantic bonding increases attraction between the partners; according to the deflection hypothesis, it reduces attention to other members of the other sex. Results of a new study supported the deflection hypothesis: The higher women rated their romantic love for their boyfriends, the less able they were to distinguish the body odors of male friends from those of strangers; there was no effect on their ability to recognize their boyfriends' odors. Hormones and Behavior, Vol 55, 280-284.
Roots of Criminal Behavior in Childhood
Adult psychopaths have, on average, an 18% reduction in amygdala volume, which is associated with reduced fear responding; in a remarkable study, Raine followed 1800 children who showed impaired fear conditioning at age 3 and found that 20 years later they were much more likely to become criminal offenders. American Journal of Psychiatry, Vol 167, 56-60.
Updates by Chapter. Online access to full journal articles may
require subscription; if so, check access through your library.
Author of Vaccine-Autism Paper Sues for Libel
Andrew Wakefield, author of the paper that started the furor over a now discredited link between childhood vaccines and autism (see p 418), filed a defamation suit on January 3, 2012. Named in the suit are the British Medical Journal, the journal's editor, Fiona Godlee, and journalist Brian Deer, who exposed the fraud. Evidence that Wakefield used fraudulent data to make his point led to retraction of the journal article and the loss of his license to practice medicine. Wakefield also accused the journal of a conflict of interest because it receives money from vaccine makers GlaxoSmithKline and Merck. Wakefield sued Deer in 2005 over a documentary accusing him of fraud, but withdrew the suit when the judge demanded more evidence. ScienceInsider, January 5, 2012.
New Standards for Autism Diagnosis
The Diagnostic and Statistical Manual (DSM), the guide used for diagnosing psychiatric and psychological disorders, is undergoing revision. Among other changes, the new version, DSM-5, intends to correct what many regard as overdiagnosis of autism, by tightening the critera introduced in DSM-IV. A major proposed change—collapsing two of the three categories of symptoms into one group, because deficits in communication and deficits in social interaction almost always appear together—has statistical support from studies at the Cleveland Clinic and at University College London. Some advocate the stricter critera, including experts who believe the current standards identify non-autistic individuals, and some parents who want more state aid focused on children with severe autism. Scientific American News, January 30, 2012. Others believe the new standards set the bar too high and will deny needed benefits to those with less severe symptoms, including insurance coverage and special instruction. In a Finnish study of 26 8-year-olds diagnosed by DSM-IV standards, only 12 qualified under the stricter DSM-5 criteria. Journal of the American Academy of Child & Adolescent Psychiatry, Vol 50, 583-592.
New Help for Stroke Victims
Researchers have thought that GABA released by the brain following traumatic injury to calm runaway activity also interferes with recovery, but blocking this inhibition has yielded mixed results. A drug that blocks GABA receptors on the cell but does not affect those at snapses may offer a solution. Drug-treated mice with experimenter-induced strokes regained 50% more function in their limbs than mice receiving control therapy. Nature, Vol 468, 305-309.
The Promise of Two-Photon Microscopy
A new version of two-photon microscopy, which uses fluorescent dyes to image specific types of tissue and even track neural activity, can image individual pairs of pre- and post-synaptic neurons and their connections. The developer has been able to follow changing connectivity in the mouse retina during the second week of life, and he hopes to refine our understanding of how the developing brain reorganizes its connections. Science Daily, October 31, 2010. Another researcher is imaging activity in neural networks of 1,000 neurons; he hopes to learn more about the neural replay that goes on in circuits following a learning experience, which is believed to be how the brain turns the neural information into a permanent memory. The Dana Foundation: Grants.
Clinical Trials With Human Embryonic Stem Cells
The U.S. Food and Drug Administration has approved a clinical trial testing the safety of human embryonic stem cell injections in patients with spinal cord injury; of course, the researchers will also test to see if the patients benefit from the therapy. Science Insider, October 12, 2010. The FDA has also approved a second trial to test stem cells in treating progressive loss of vision in children with advanced macular dystrophy. In earlier testing, the procedure prevented mice with a version of the disease from going blind. Science Insider, November 22, 2010. In the meantime, a district court judge issued an injunction against President Obama's lifting of the ban on federal funding, on the basis that federal funding violates the Dickey-Wicker Amendment; however, a U.S. Court of Appeals lifted that injunction. CNN U.S., April 29, 2011. Outcome in the courts may be important; research has found that adult stem cells do not proliferate as well as embryonic stem cells and they have a shorter life span. Stem Cells, February, 2010.
Treating Binge Drinking With Gene Therapy
Because the GABAA receptor is involved in producing alcohol's effects, addiction therapists often prescribe GABA blockers in the treatment of alcoholism. Now researchers have shown that genetic manipulation of the receptor can dramatically reduce binge drinking in rats bred to prefer alcohol (they don't typically imbibe). After RNA injections into the amygdala, GABAA receptor density decreased by 65%; binge drinking dropped profoundly in the ensuing 6 days and returned to previous levels by day 14. Proceedings of the National Academy of Sciences, Vol 108, 4465-4470.
Dramatic Increase in Diabetes Projected
The Centers for Disease Control and Prevention estimates that the number of new cases of diabetes will increase in the U.S. from its 2010 level of 14% to 25%-28% of the population by 2050, even if preventive interventions are undertaken. The projection is based on the incidence of prediabetes and diabetes, current life expectancy, and population increases among high-risk subgroups. Population Health Metrics, 2010, 8:29.
Sensing Dietary Deficits
Detection of nutrients often involves learned taste preference, but in other cases there is a more direct biological mechanism. When a rat eats a food lacking one of the indispensable amino acids (IACs, nine amino acids the body requires for synthesizing proteins) that it needs, activity increases in the anterior piriform cortex (APC); the rat will turn away from the food within 20 minutes. Even a slice of APC tissue will show an increase in excitatory postsynaptic potentials when placed in a nutrient bath missing any one of the IACs. This suggests that the APC can detect IAC levels directly, thus monitoring conditions in its own environment. Journal of Neuroscience, Vol 31, 1583-1590.
Childhood Predictors of Adult Homosexuality
The conclusion that children who later become homosexual typically show more gender nonconformity—behavior more typical of the other sex, along with a preference for other-sex playmates and companions—has been based on memories provided by the individuals and/or their families. When researchers at Northwestern University rated childhood videos of homosexual and heterosexual men and women for gender nonconforming behavior, the results indicated that both boys and girls who were homosexual as adults were less conforming than the other subjects. Developmental Psychology, Vol 44, 46-58.
Love Modifies Olfactory Responses to Other-Sex Friends
The attention hypothesis claims that sexual and romantic bonding increases attraction between the partners; according to the deflection hypothesis, it reduces attention to other members of the other sex. Results of a new study supported the deflection hypothesis: The higher women rated their romantic love for their boyfriends, the less able they were to distinguish the body odors of male friends from those of strangers; there was no effect on their ability to recognize their boyfriends' odors. Hormones and Behavior, Vol 55, 280-284.
Roots of Criminal Behavior in Childhood
Adult psychopaths have, on average, an 18% reduction in amygdala volume, which is associated with reduced fear responding; in a remarkable study, Raine followed 1800 children who showed impaired fear conditioning at age 3 and found that 20 years later they were much more likely to become criminal offenders. American Journal of Psychiatry, Vol 167, 56-60.
On the Trail of Stuttering Genes
In the movie "The King's Speech," King George's therapist concluded that his stuttering had environmental origins; at the same time, twin studies indicate that the malady is 50% to 70% heritable. Dennis Drayna, by studying intermarried families in Pakistan, has identified 10 mutations in three genes that account for 5%-10% of stuttering cases. New England Journal of Medicine, Vol 362, 677-685. The three genes are all involved in the function of lysosomes—cellular sacs where debris is recycled—and Drayna speculates that neurons involved in speech production are particularly vulnerable to the metabolic effects of lysosome disruption. Researcher Luc De Nil, in a presentation at the meeting of the 2011 American Association for the Advancement of Science, reported that the brains of stutterers have anomalies in both white and gray matter, along with overactivation of speech areas and underactivation of the auditory area. AAAS EurekaAlert, February 20, 2011.
Restoring Vision
We finally have a 1500-electrode retinal implant (see p 300)! With it, a patient can read large print and identify common objects, such as a knife and cup. Proceedings of the Royal Society B, Vol 278, 1489-1497 (click here for video). Optogenetic restoration of sight has been found safe in mice and may enter human trials within two years. Molecular Therapy, doi:10.1038/mt.2011.69. You can see one of the mice locating the exit in a water maze here. Also, the U.S. FDA has approved clinical trials to determine the safety and tolerability of human embryonic stem cells in the treatment of macular degeneration. Advanced Cell Technology Press Release, May 16, 2011.
Parkinson's Increases With Pesticide Exposure
Evidence continues to mount for pesticide exposure as a contributor to Parkinson's disease. Exposure to ziram and paraquat was associated with an 80% increase in risk, and the addition of maneb tripled the risk. Combinations of different pesticides apparently have a greater effect than a single pesticide because they affect different mechanisms leading to dopaminergic cell death. European Journal of Epidemiology, DOI 10.1007/s10654-011-9574-5.
Learning From Mistakes Begins Around Age 12
In a study of learning in three age groups, the dorsolateral prefrontal cortex and the superior parietal cortex responded more to positive feedback in 8-9 year olds and about equally in 11-13 year olds, but more strongly to negative feedback in 18-25 year olds. This suggests that children learn best from positive feedback until about the age of 12, then negative feedback becomes more important. The response shifted earlier in the anterior cingulate cortex, which is interesting because of that area's role in conflict monitoring and directing cognitive responses to conflict (Science, Vol 303, 1023-1026.).
Alzheimer's Brain Deficient in β-Amyloid Clearance
It has long been believed that the accumulation of β-Amyloid in the Alzheimer's brain was due to overproduction, but there has been no direct evidence for this process. Using metabolic labeling, researchers at Washington University in Saint Louis found no differences between patients and controls in β-Amyloid production, but clearance was impaired in the patients. This information should be useful in devising treatments for the disease and, possibly, for earlier detection. Science, Vol 330, 1774.
Autism is Marked by Gene Expression Anomalies
In the normal brain, more than 500 genes are activated to different degrees in the frontal lobes compared to the temporal lobes; however, in the autistic brain these differences in gene expression are almost nonexistent. In addition, the study of deceased brains found reduced expression in genes previously associated with autism which are responsible for neuron function and communication. Nature, Vol 474, 380-384.
Aging and the Brain
In a study of individuals over age 70 with mild cognitive impairment, treatment with folic acid and vitamins B6 and B12 slowed brain atrophy by 30%. PLoS ONE, Vol 5, e12244. In a second study, of individuals aged 72-92 years, connectivity throughout the whole brain network was associated with the maintenance of processing speed, visuospatial functions, and executive functioning (planning, behavioral monitoring and control). Journal of Neuroscience, Vol 31, 1204-1212.
Mice Explain Link Between Flu and Schizophrenia
We know that maternal influenza increases the risk for schizophrenia in offspring, but we haven't understood why. Researchers infected pregnant mice with a mouse-adapted influenza virus, then studied their adult offspring. The mice showed behavioral alterations, including reduced spontaneous locomotion, increased responsiveness to hallucinogens, and diminished antipsychotic-like effect of a glutamate agonist. Examination of their brains showed that the number and activity of 5-HT2A serotonin receptors was increased, while mGlu2 glutamate receptors were downregulated in frontal cortex. Journal of Neuroscience, Vol 31, 1863-1872.
Consciousness as an Interactive Network
Many theorists now believe that consciousness involves a widely-distributed neuronal network. Researchers first observed that auditory stimulation activated the temporal cortex in minimally conscious patients and patients in a vegetative state, as well as in non-patients. When the tone's frequency changed, the "surprise" effect resulted in the temporal cortex sending a message to the frontal cortex. In the non-patients and minimally conscious patients, the frontal cortex then communicated back to the temporal cortex. But in the vegetative patients, this feedback was absent, providing additional support for the network view of consciousness. Science, Vol 332, 858-862.
In the movie "The King's Speech," King George's therapist concluded that his stuttering had environmental origins; at the same time, twin studies indicate that the malady is 50% to 70% heritable. Dennis Drayna, by studying intermarried families in Pakistan, has identified 10 mutations in three genes that account for 5%-10% of stuttering cases. New England Journal of Medicine, Vol 362, 677-685. The three genes are all involved in the function of lysosomes—cellular sacs where debris is recycled—and Drayna speculates that neurons involved in speech production are particularly vulnerable to the metabolic effects of lysosome disruption. Researcher Luc De Nil, in a presentation at the meeting of the 2011 American Association for the Advancement of Science, reported that the brains of stutterers have anomalies in both white and gray matter, along with overactivation of speech areas and underactivation of the auditory area. AAAS EurekaAlert, February 20, 2011.
Restoring Vision
We finally have a 1500-electrode retinal implant (see p 300)! With it, a patient can read large print and identify common objects, such as a knife and cup. Proceedings of the Royal Society B, Vol 278, 1489-1497 (click here for video). Optogenetic restoration of sight has been found safe in mice and may enter human trials within two years. Molecular Therapy, doi:10.1038/mt.2011.69. You can see one of the mice locating the exit in a water maze here. Also, the U.S. FDA has approved clinical trials to determine the safety and tolerability of human embryonic stem cells in the treatment of macular degeneration. Advanced Cell Technology Press Release, May 16, 2011.
Parkinson's Increases With Pesticide Exposure
Evidence continues to mount for pesticide exposure as a contributor to Parkinson's disease. Exposure to ziram and paraquat was associated with an 80% increase in risk, and the addition of maneb tripled the risk. Combinations of different pesticides apparently have a greater effect than a single pesticide because they affect different mechanisms leading to dopaminergic cell death. European Journal of Epidemiology, DOI 10.1007/s10654-011-9574-5.
Learning From Mistakes Begins Around Age 12
In a study of learning in three age groups, the dorsolateral prefrontal cortex and the superior parietal cortex responded more to positive feedback in 8-9 year olds and about equally in 11-13 year olds, but more strongly to negative feedback in 18-25 year olds. This suggests that children learn best from positive feedback until about the age of 12, then negative feedback becomes more important. The response shifted earlier in the anterior cingulate cortex, which is interesting because of that area's role in conflict monitoring and directing cognitive responses to conflict (Science, Vol 303, 1023-1026.).
Alzheimer's Brain Deficient in β-Amyloid Clearance
It has long been believed that the accumulation of β-Amyloid in the Alzheimer's brain was due to overproduction, but there has been no direct evidence for this process. Using metabolic labeling, researchers at Washington University in Saint Louis found no differences between patients and controls in β-Amyloid production, but clearance was impaired in the patients. This information should be useful in devising treatments for the disease and, possibly, for earlier detection. Science, Vol 330, 1774.
Autism is Marked by Gene Expression Anomalies
In the normal brain, more than 500 genes are activated to different degrees in the frontal lobes compared to the temporal lobes; however, in the autistic brain these differences in gene expression are almost nonexistent. In addition, the study of deceased brains found reduced expression in genes previously associated with autism which are responsible for neuron function and communication. Nature, Vol 474, 380-384.
Aging and the Brain
In a study of individuals over age 70 with mild cognitive impairment, treatment with folic acid and vitamins B6 and B12 slowed brain atrophy by 30%. PLoS ONE, Vol 5, e12244. In a second study, of individuals aged 72-92 years, connectivity throughout the whole brain network was associated with the maintenance of processing speed, visuospatial functions, and executive functioning (planning, behavioral monitoring and control). Journal of Neuroscience, Vol 31, 1204-1212.
Mice Explain Link Between Flu and Schizophrenia
We know that maternal influenza increases the risk for schizophrenia in offspring, but we haven't understood why. Researchers infected pregnant mice with a mouse-adapted influenza virus, then studied their adult offspring. The mice showed behavioral alterations, including reduced spontaneous locomotion, increased responsiveness to hallucinogens, and diminished antipsychotic-like effect of a glutamate agonist. Examination of their brains showed that the number and activity of 5-HT2A serotonin receptors was increased, while mGlu2 glutamate receptors were downregulated in frontal cortex. Journal of Neuroscience, Vol 31, 1863-1872.
Consciousness as an Interactive Network
Many theorists now believe that consciousness involves a widely-distributed neuronal network. Researchers first observed that auditory stimulation activated the temporal cortex in minimally conscious patients and patients in a vegetative state, as well as in non-patients. When the tone's frequency changed, the "surprise" effect resulted in the temporal cortex sending a message to the frontal cortex. In the non-patients and minimally conscious patients, the frontal cortex then communicated back to the temporal cortex. But in the vegetative patients, this feedback was absent, providing additional support for the network view of consciousness. Science, Vol 332, 858-862.