Archive for the ‘Children’s Health’ Category

Disorders of learning and behavior are linked to brain abnormalities

Saturday, August 28th, 2010

Rapidly developing science in this field is bringing to light more understanding of the biological basis of learning and behavioral disorders. A paper published not long ago in the journal Pediatrics introduces a classification of attention-deficit/hyperactivity disorder according to underlying organic causes. The authors first observe:

Attention-deficit/hyperactivity disorder is a neurobiological syndrome with an estimated prevalence among children and adolescents of 5%. It is a highly heritable disorder, but acquired factors in etiology are sometimes uncovered that may be amenable to preventive measures or specific therapy.

The others go on to suggest an organic theory and genetic and biochemical basis for attention-deficit/hyperactivity disorder along with an etiologic (causal) classification, taking into consideration environmental, prenatal, perinatal and postnatal factors including illnesses, injuries and deficiencies.

A series of studies published in Biological Psychiatry offer insight into how attentional and behavioral disorders are linked to variations in the very structure of the brain and its component anatomy. The authors of Structural Brain Imaging of Attention-Deficit/Hyperactivity Disorder observe:

“Many investigators have hypothesized that attention-deficit/hyperactivity disorder (ADHD) involves structural and functional brain abnormalities in frontal-striatal circuitry. Although our review suggests that there is substantial support for this hypothesis, a growing literature demonstrates widespread abnormalities affecting other cortical regions and the cerebellum…The most replicated alterations in ADHD in childhood include significantly smaller volumes in the dorsolateral prefrontal cortex, caudate, pallidum, corpus callosum, and cerebellum. These results suggest that the brain is altered in a more widespread manner than has been previously hypothesized.”

These authors refer to, among others, an earlier study published under the title Smaller prefrontal and premotor volumes in boys with attention-deficit/hyperactivity disorder.

Boys with ADHD had (on average) 8.3% smaller total cerebral volumes…Findings suggest that ADHD is associated with decreased frontal lobe gray and white matter volumes. More than one subdivision of the frontal lobes appears to be reduced in volume, suggesting that the clinical picture of ADHD encompasses dysfunctions attributable to anomalous development of both premotor and prefrontal cortices.

Later in the same journal Temporal Lobe Dysfunction in Medication-Naïve Boys With Attention-Deficit/Hyperactivity Disorder During Attention Allocation and Its Relation to Response Variability established that abnormalities could be documented in the temporal lobes as well:

“Patients showed significantly reduced brain activation in left and right superior temporal lobes, basal ganglia, and posterior cingulate…Brain abnormalities in patients with ADHD are not confined to fronto-striatal networks mediating executive functions but are also observed in temporo-striatal and cingulate regions…”

Biological Psychiatry was also the venue for documenting abnormalities in the corpus callosum (the structure connecting the right and left brain hemispheres) in Decreased Callosal Thickness in Attention-Deficit/Hyperactivity Disorder. The authors observe:

Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed structural abnormalities in the brains of affected individuals. One of the most replicated alterations is a significantly smaller corpus callosum (CC)…”

They used advanced imaging techniques to refine and further validate these observations:

“In close agreement with many prior observations, the CC was shown to be significantly thinner in ADHD subjects…Decreased callosal thickness may be associated with fewer fibers or a decrease in the myelination of fibers connecting the parietal and prefrontal cortices. This might affect interhemispheric communication channels that are necessary to sustain attention or motor control, thus contributing to symptoms of hyperactivity and impulsivity, or inattention, observed in ADHD.

Recently the same journal presented evidence of abnormalities in another brain region in the paper Ventro-Striatal Reductions Underpin Symptoms of Hyperactivity and Impulsivity in Attention-Deficit/Hyperactivity Disorder. This research is significant for its investigation of the reward centers in the brain. The authors observe:

“The neural bases of reward processes have barely been explored in relation to this disorder, in contrast to extensive neuroimaging studies that examine executive functions in patients with ADHD.”

The authors examined volumetric differences in the ventral striatum of ADHD children and found substantial correlations:

“The ADHD children presented significant reductions in both right and left ventro-striatal volumes. In addition, we found that the volume of the right ventral striatum negatively correlated with maternal ratings of hyperactivity/impulsivity…Our study provides neuroanatomical evidence of alterations in the ventral striatum of ADHD children…the negative correlations we observed strongly uphold the relation between the ventral striatum and symptoms of hyperactivity/impulsivity.

A paper published in the French medical journal L’Encéphale, sums up the ever-growing scientific literature in this field. Under the title Structural and functional neuroanatomy of attention-deficit hyperactivity disorder (ADHD), the authors observe:

“Three subtypes of the disorder have been proposed in the current clinical view of ADHD: inattentive, hyperactive-impulsive and combined type. Numerous problems are associated with ADHD: poor academic performance, learning disorders, subtle cognitive deficits, conduct disorders, antisocial personality disorder, poor social relationships, and a higher incidence of anxiety and depression symptoms into adulthood. ..From the neuropsychological viewpoint, impairment of the “hot” affective aspects of executive functions, like behavioural inhibition and attention and the more cognitive, “cool” aspects of executive functions like self-regulation, working memory, planning, and cognitive flexibility, are often reported by studies on ADHD. The hot executive functions are associated with ventral and medial regions of the prefrontal cortex (including the anterior cingulated cortex) and named “hotbrain” and the cool executive functions are associated with the dorsolateral prefrontal cortex and are called “coolbrain”.

The potential anatomical areas of interest are extensive:

“Convergent data from neuroimaging, neuropsychology, genetics and neurochemical studies consistently point to the involvement of the frontostriatal network as a likely contributor to the pathophysiology of ADHD…Moreover, a growing literature demonstrates abnormalities affecting other cortical regions and the cerebellum…Anatomical studies suggest widespread reductions in volume throughout the cerebrum and cerebellum, while functional imaging studies suggest that affected individuals activate more diffuse areas than controls during the performance of cognitive tasks…Furthermore, hypoactivation of the dorsal anterior cingulate cortex, the frontal cortex and the basal ganglia (striatum) have also been reported.”

As always, biological individuality rules—every child is different. Subsequent posts offer insights into the various underlying causes of these abnormalities in brain anatomy, how to test for them, and what to do about them.

Children with constipation: cow’s milk intolerance in more than one third

Wednesday, August 4th, 2010

A study recently published in the Journal of Pediatric Gastroenterology and Nutrition reminds us that bovine (cow’s) milk allergy or intolerance can cause childhood constipation even though the laboratory tests are negative. The authors first note:

“It has been reported that a number of children with constipation respond to a diet free of cow’s-milk (CM) proteins, although evidence is lacking to support an immunoglobulin E-mediated mechanism.”

They found that thirty-five of 69 children (51%) improved during an initial CM-free diet phase with a significant increase in bowel movements per week; 39% developed constipation during the CM challenge and improved during the second CM-free phase. Interestingly…

“Seventy-eight percent of the children with developmental delay responded to the CM-free diet.”

The authors conclude:

A clear association between CM consumption and constipation has been found in more than one third of children. However, analytical parameters do not demonstrate an immunoglobulin E-mediated immunologic mechanism.”

I want to draw your attention to the final comment about the absence of IgE antibodies. I have found any kind of antibody test (IgE, IgG, IgA) to be unreliable for the diagnosis of food allergy or intolerance due to numerous factors that can prevent their expression, resulting in false negatives (the allergy is present but undetected by the test). The immunological ‘gold standard’ is the elimination-provocation protocol (as conducted in this study).

There is a broad range of neurologic disorders in children with gluten sensitivity

Monday, July 26th, 2010

This paper recently published in the journal Pediatrics draws attention to our concern for the non-celiac manifestations of gluten sensitivity, especially the neurological dimension. The authors note importantly that:

“During the past 2 decades, celiac disease (CD) has been recognized as a multisystem autoimmune disorder. A growing body of distinct neurologic conditions such as cerebellar ataxia, epilepsy, myoclonic ataxia, chronic neuropathies, and dementia have been reported, mainly in middle-aged adults…The aim of the present study is to look for a broader spectrum of neurologic disorders in CD patients, most of them children or young adults.”

They found a much greater prevalence of neurological disorders in children with CD compared to normal controls: 51.4% to 19.9%, including hypotonia, developmental delay, learning disorders and ADHD, headache, and cerebellar ataxia.

The authors conclude:

“This study suggests that the variability of neurologic disorders that occur in CD is broader than previously reported and includes “softer” and more common neurologic disorders, such as chronic headache, developmental delay, hypotonia, and learning disorders or ADHD.”

Bear in mind that we are equally concerned with the neurologic manifestations of gluten sensitivity in the absence of celiac disease.

Adolescence, a dangerous time for alcohol excess—but so is anytime

Saturday, July 17th, 2010

Proceedings of the National AcademyAdding more concern to the reported increase in heavy alcohol consumption among adolescents is the emerging science regarding alcohol’s effect on the brain. This research just published in the Proceedings of the National Academy of Sciences elucidates the mechanism by which binge drinking damages the developing brain.

“Binge alcohol consumption in adolescents is increasing, and studies in animal models show that adolescence is a period of high vulnerability to brain insults. The purpose of the present study was to determine the deleterious effects of binge alcohol on hippocampal neurogenesis…”

The authors made a number of startling observations regarding the effect of alcohol on the brain’s center for short-term memory and adrenal regulation, the hippocampus:

“Heavy binge alcohol consumption over 11 mo dramatically and persistently decreased hippocampal proliferation and neurogenesis…Alcohol significantly decreased the number of actively dividing type 1, 2a, and 2b cell types…suggesting that alcohol interferes with the division and migration of hippocampal preneuronal progenitors. Furthermore, the lasting alcohol-induced reduction in hippocampal neurogenesis paralleled an increase in neural degeneration mediated by nonapoptotic pathways.”

Yikes. The authors sum up their findings with these memorable comments:

“Altogether, these results demonstrate that the hippocampal neurogenic niche during adolescence is highly vulnerable to alcoholThis lasting effect, observed 2 mo after alcohol discontinuation, may underlie the deficits in hippocampus-associated cognitive tasks that are observed in alcoholics.”

Journal of NeuroscienceA fascinating paper published last month in the Journal of Neuroscience now reveals how alcohol feeds an immune inflammatory attack on the brain:

Toll-like receptors play an important role in the innate immune response, although emerging evidence indicates their role in brain injury and neurodegeneration. Alcohol abuse induces brain damage and can sometimes lead to neurodegeneration. We recently found that ethanol can promote TLR4 signaling in glial cells by triggering the induction of inflammatory mediators and causing cell death, suggesting that the TLR4 response could be an important mechanism of ethanol-induced neuroinflammation.”

This is an extremely persuasive argument for moderation for anyone interesting in preserving brain health.

The authors go on to report that TLR4 is critical for ethanol-induced inflammatory signaling in glial cells by demonstrating that ‘turning off’ TLR4 prevents the neuroinflammatory brain damage:

“Our results demonstrate, for the first time, that whereas chronic ethanol intake upregulates…cytokine levels [interleukin (IL)-1β, tumor necrosis factor-{alpha}, IL-6] in the cerebral cortex,…TLR4 deficiency protects against ethanol-induced glial activation, induction of inflammatory mediators, and apoptosis. Our findings support the critical role of the TLR4 response in the neuroinflammation, brain injury, and possibly in the neurodegeneration induced by chronic ethanol intake.”

Science Translational Medicine 0710For us the main message is that excessive alcohol consumption fires up the brain’s glial cells (immune cells) and the resultant neuroinflammation does serious damage to the brain. This important research was highlighted in an editorial published last week in Science Translational Medicine which contains some notable comments:

“Ethanol is the most widely used psychotropic substance in the world, and chronic ethanol abuse leads to harmful changes in virtually every organ system in the body. Notably, this includes the brain, where consumption of alcohol can lead to irreversible changes in cognition, mood, and behavior. Although it has been known that this often involves degenerative, inflammatory-mediated processes, their precise nature has not been characterized. In a recent article, Alfonso-Loeches and colleagues report that much of the ethanol-induced inflammation in the brain depends on signaling through Toll-like receptors (TLRs). These receptors participate in innate immunity responses to infection but are also implicated in reactions to injury and degeneration in the brain.”

The editorial concludes with the compelling comparison of the brain damage done by activation by alcohol of neuroinflammation through Toll-like receptors with other common neurodegenerative conditions:

“These results suggest that TLRs play a critical role in alcohol-related brain changes, just as they have been previously implicated in Alzheimer’s disease, ischemic brain injury, and HIV infection.”

Inflammation ResearchBesides curtailing excess and enjoying alcohol only in moderation we may be able to use coffee as protective therapy. There is abundant evidence of the benefit of coffee for the liver, including this recent study published in the journal Inflammation Research. The authors present data that:

“Treatment with caffeine significantly attenuated the elevated serum aminotransferase enzymes and reduced the severe extent of hepatic cell damage, steatosis and the immigration of inflammatory cells… Furthermore, caffeine decreased serum and tissue inflammatory cytokines levels, tissue lipid peroxidation and inhibited the necrosis of hepatocytes. Kupffer cells isolated from ethanol-fed mice produced high amounts of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α), whereas Kupffer cells from caffeine treatment mice produced less ROS and TNF-α.”

The authors conclude:

“These findings suggest that caffeine may represent a novel, protective strategy against alcoholic liver injury by attenuating oxidative stress and inflammatory response.”

Experimental NeurologyCould this protective effect extend to the brain? There’s a lot of emerging evidence that suggests the answer is ‘yes’. Fascinating research published last month in the journal Experimental Neurology demonstrates that caffeine protects the brain from the kind of damage involved in Parkinson’s disease caused by pesticides:

“Environmental exposures suspected of contributing to the pathophysiology of Parkinson’s disease (PD) include potentially neurotoxic pesticides, which have been linked to an increased risk of PD. Conversely, possible protective factors such as…caffeine have been linked to a reduced risk of the disease. Here we assessed whether caffeine alters dopaminergic neuron loss induced by exposure to environmentally relevant pesticides (paraquat and maneb) over 8 weeks.”

The data led to a conclusion that increases my enthusiasm for exercising the French press:

Caffeine at 20 mg/kg significantly reduced TH+ neuron loss (to 85% of the respective control). The results demonstrate the neuroprotective potential of caffeine in a chronic pesticide exposure model of model of PD.”

Journal of Alzheimer's DiseaseAs for Alzheimer’s disease, a supplemental issue of the Journal of Alzheimer’s Disease has no less than 22 papers on the benefits of caffeine for AD and other neurodegenerative disorders. I suggest you have a look, drink alcohol in moderation (or not at all if you prefer), and enjoy your coffee and tea if there are no contraindications.

With alcohol, as with so many other substances and stimuli, we can appreciate the principle of hormesis: a small amount may have benefit while a larger amount is harmful.

Nuts for young girls

Saturday, July 10th, 2010

Cancer Causes & ControlA useful study was just published in the journal Cancer Causes & Control that examines the effect of nut consumption by young girls on breast disease and breast cancer.

“We examined the association between adolescent fiber intake and proliferative BBD [benign breast disease], a marker of increased breast cancer risk, in the Nurses’ Health Study II.”

They gathered data on diet and the emergence of breast disease confirmed by pathology for 29,480 females. A definite pattern emerged:

“Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD… High school intake of nuts was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk…than women consuming <1 serving/month.”

Taking into consideration other research I think we have to accept the likelihood that the beneficial fat in nuts confers some of the benefit. This adds to the weight of evidence in favor of nuts in a wholesome and preventative diet:

“These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influences subsequent risk of breast disease and may suggest a viable means for breast cancer prevention.”

High glycemic diets exacerbate acne

Thursday, July 8th, 2010

Journal of the American Academy of DermatologyThe authors of a paper recently published in the Journal of the American Academy of Dermatology observe that dermatologists have often dismissed the relationship between diet and acne:

“Historically, the relationship between diet and acne has been highly controversial. Before the 1960s, certain foods were thought to exacerbate acne. However, subsequent studies dispelled these alleged associations as myth for almost half a century. Several studies during the last decade have prompted dermatologists to revisit the potential link between diet and acne.”

Thankfully the perspective is becoming more realistic:

Dermatologists can no longer dismiss the association between diet and acne.”

Although much work remains to be done in order to make evidence based recommendations pertaining to various dietary factors and acne, on thing is clear:

Compelling evidence exists that high glycemic load diets may exacerbate acne.”

This is not surprising considering the inflammatory and hormonal consequences of overstimulating insulin production.

One way to prevent having a schizophrenic child

Saturday, July 3rd, 2010

PLoS OneAn important research article was just published in PLoS One (Public Library of Medicine) that shows a connection between the disruption of dopamine neurons when a maternal infection causes the iron supply of the fetus to drop and schizophrenia. The authors give some background:

Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring’s dopamine function.”

The authors measured the adverse behavioral and neurochemical changes from challenging the dopamine circuits with turpentine to trigger an inflammatory immune response, both with and without maternal iron supplementation. They demonstrated that…

Both the behavioral and neurochemical changes were prevented by maternal iron supplementation.

We already know that iron is a critical nutrient for dopamine production in the adult. Their conclusion sums up why prenatal iron status is important in preventing neurodevelopmental disorders including schizophrenia in the offspring.

DHA supplementation improves frontal brain activation and attention

Friday, June 4th, 2010

Am Journal Clin NutritionThis study recently published in the American Journal of Clinical Nutrition provides more evidence for the importance of essential fatty acids for brain function. In this case the authors are interested in the effect of docosahexaenoic acid (DHA) supplementation on prefrontal cortex regulation of attention.

“Emerging evidence suggests that docosahexaenoic acid (DHA, 22:6n–3)…positively regulates cortical metabolic function and cognitive development…The objective was to determine the effects of DHA supplementation on functional cortical activity during sustained attention in human subjects.”

After giving the randomly assigned test cohort DHA supplements they compared cortical activation patterns during sustained attention with those given placebo by functional magnetic resonance imaging (fMRI).

What did their data show?

“At 8 wk, erythrocyte [red blood cell] membrane DHA composition increased significantly from baseline in subjects who received low-dose (by 47%) or high-dose (by 70%) DHA but not in those who received placebo (–11%). During sustained attention, both DHA dose groups had significantly greater changes from baseline in activation of the dorsolateral prefrontal cortex than did the placebo group…The erythrocyte DHA composition was positively correlated with dorsolateral prefrontal cortex activation…”

That last phrase is especially important: DHA is not the only fatty acid that is important for neuronal (brain cell) function. EPA, arachadonic acid and others also play important roles. How do we know with certainty whether someone needs supplementation, which fatty acid should it be, and how much? The Essential Fatty Acid Profile measures the red blood cell membrane content of fatty acids (and is equivalent to the neuronal membrane composition) that we use is the lab technology used by these investigators.

The authors’ conclusion:

“Dietary DHA intake and associated elevations in erythrocyte DHA composition are associated with alterations in functional activity in cortical attention networks during sustained attention in healthy boys.”

For any brain-related disorder we need to objectively answer the questions “What is the brain fatty acid composition? Are there any deficiencies or imbalances? Is supplementation indicated?” When needed, the correct fatty acid supplementation can result in dramatic improvements.

Gluten-free diet can improve depression and behavioral problems in adolescents

Friday, May 28th, 2010

BMC PsychiatryAs the authors of this study published in the journal BMC Psychiatry observe:

“Coeliac disease in adolescents has been associated with an increased prevalence of depressive and disruptive behavioural disorders, particularly in the phase before diet treatment.”

We are equally concerned with the ‘non-celiac’ aspects of gluten sensitivity. Gluten related inflammation in the brain can manifest as a host of cognitive, emotional and neurodegenerative disorders in the absence of intestinal manifestations. This is often referred to as “silent celiac disease”:

“Coeliac disease is an under-diagnosed autoimmune type of gastrointestinal disorder resulting from gluten ingestion in genetically susceptible individuals. Non-specific symptoms such as fatigue and dyspepsia are common, but the disease may also be clinically silent.”

They further note that:

“”Depressive symptoms and disorders are common among adult patients with coeliac disease, and depressive and disruptive behavioural disorders are highly common also among adolescents, particularly in the phase before diet treatment. Recently 73% of patients with untreated coeliac disease – but only 7% of patients adhering to a gluten-free diet – were reported to have cerebral blood flow abnormalities similar to those among patients with depressive disorders.”

Their data revealed abnormalities in tryptophan assimilation (tryptophan is the amino acid precursor to serotonin) and prolactin levels in adolescents with celiac disease and depression prior to treatment. Consequently…

A significant decrease in psychiatric symptoms was found at 3 months on a gluten-free diet compared to patients’ baseline condition, coinciding with significantly decreased coeliac disease activity…”

They also make a fascinating observation that links gluten sensitivity, inflammation, and the serotonergic aspect of depression unrelated to malabsorption:

“…increased production of interferon-γ (IFN-γ), known to be the predominant cytokine produced by gluten-specific T-cells in active coeliac disease, can suppress serotonin function both directly and indirectly by enhancing tryptophan and serotonin turnover…even without malabsorption.”

To diagnose gluten sensitivity in the absence of celiac disease the gluten gene sensitivity test is the most reliable method for a number of reasons.

Early pregnancy folate associated with child hyperactivity

Monday, May 17th, 2010

Journal of Child Psychology and PsychiatryThe authors of this paper recently published in the Journal of Child Psychology and Psychiatry being by noting:

Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring.”

They correlated maternal red blood cell folate (RCF) at 14 weeks of pregnancy and total folate intake (TFI) from food and supplements with their childrens’ behavioral difficulties. What did the data show?

Lower maternal RCF and TFI in early pregnancy were associated with higher childhood hyperactivity and peer problems scores in the offspring….analyses showed significant inverse indirect associations of RCF with hyperactivity/inattention and peer problems via fetal brain growth.”

Their conclusion:

“…our data provide preliminary support for the hypothesis that lower folate status in early pregnancy might impair fetal brain development and affect hyperactivity/inattention and peer problems in childhood.”

Here we have another compelling reason to ascertain good folate status in early pregnancy, or (even better) before becoming pregnant. Although conventional blood tests for serum folate are not dependable, a convenient and reliable way to do determine folate adequacy is by measuring the organic acid formiminoglutamate in the urine.