Summary: Neuroinflammatory signaling molecules are elevated in bipolar disorder patients compared to controls. Marked increases in proinflammatory cytokines are also observed in the brains of teen suicide victims. Brain inflammation, immune system dysregulation and the loss of self-tolerance are key factors in the management of BP and major depression.

A paper just published in the Journal of Psychiatric Research offers further evidence for the role of neuroinflammation resulting from immune system dysregulation in bipolar disorder. The authors state:

“Bipolar disorder (BD) is associated with considerable higher chronic medical comorbidities, overweight and obesity. Adipokines are adipocyte-derived secretory factors which have functions in immune response and seem to be associated with both BD and overweight. The aim of this study was to evaluate the plasma levels of adipokines (adiponectin, resistin and leptin) and TNF-α and its receptors (sTNFR1 and sTNFR2) in BD overweight patients in comparison with overweight controls.”

The authors measured plasma levels of adiponectin, resistin, leptin, TNF-α and TNF-α soluble receptors in thirty bipolar patients along with thirty controls matched by age, gender and body-mass index (BMI). The subjects were also assessed by Mini-International Neuropsychiatric Interview, Young Mania and Hamilton Depression rating scales. What did the data show?

“BD patients presented increased plasma levels of adiponectin, leptin and sTNFR1.”

This is but one drop in a sea of emerging evidence for the role of brain inflammation and immune dysregulation in neuropsychiatric disorders that clinicians should consider in comprehensive case management. The authors conclude:

“This study provides further support to the hypothesis of the immune/inflammatory imbalance in BD.”

Another study in the same journal documents a marked increase in proinflammatory cytokines in the frontal lobes of teenagers attempting suicide. The authors observe:

“”Proinflammatory cytokines play an important role in stress and in the pathophysiology of depression—two major risk factors for suicide. Cytokines are increased in the serum of patients with depression and suicidal behavior; however, it is not clear if similar abnormality in cytokines occurs in brains of suicide victims.”

So they evaluated 24 teenage suicide victims and 24 matched normal control subjects for gene and protein expression levels of the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tissue necrosis factor (TNF)-α in the prefrontal cortex (PFC). Again we see the markers for brain inflammation:

“Our results show that the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α were significantly increased in Brodmann area 10 (BA-10) of suicide victims compared with normal control subjects.”

This is the deepest biological expression of the loss of self-tolerance in these disorders. Autoimmune inflammatory conditions require evaluation of all the known underlying causal factors that may contribute to the loss of self and chemical tolerance in order to design the most helpful treatment plan. The authors conclude:

“These results suggest an important role for IL-1β, IL-6, and TNF-α in the pathophysiology of suicidal behavior and that proinflammatory cytokines may be an appropriate target for developing therapeutic agents.”

-

Summary: The use of selective serotonin reuptake inhibitors (SSRIs, such as Prozac®, Celexa®, Lexapro®, Luvox® and Paxil®) taken during pregnancy—especially the first trimester—appears to increase the risk of autism spectrum disorders. There are evidence-based alternatives to SSRIs that support brain health without putting the fetus at risk.

A study recently published in the journal Archives of General Psychiatry draws attention to a risk of autism spectrum disorders (ASDs) born to mothers who took SSRI antidepressants during their pregnancy. The authors observe:

“The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.”

Therefore they set out to…

“…systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.”

In order to do so they compared the data for 298 children with ASD to 1507 randomly selected control children, along with the data for both their mothers. Their findings support a cautionary approach to the prenatal use of SSRIs:

“Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8).”

In other words, the increase in risk for the whole year before delivery was 220%, but limiting the investigation to the first trimester it was 380%. Interestingly…

“No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors.”

Meaning that it wasn’t a history of mental health treatment the year before delivery but specifically the use of SSRIs that accounted for the increased risk of ASDs. The authors conclude:

“Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders.”

This would be a troubling dilemma were it not for the fact that therapies supporting brain health are available to treat depression. Serotonin production and signaling, when indicated, can be supported in a physiological and sustainable manner that promotes the brain health of mother and fetus. A categorization and description of key resources that applies to adults as well as children is available in the Parents’ Guide To Brain Health.

-

Summary: Broad-spectrum antibiotics are very commonly prescribed for kids, especially with respiratory conditions, when they are not indicated.

A study just published in the journal Pediatrics disappointingly documents that antibiotics are still grossly overused in pediatric practice. The authors state:

“Antibiotics are commonly prescribed for children with conditions for which they provide no benefit, including viral respiratory infections. Broad-spectrum antibiotic use is increasing, which adds unnecessary cost and promotes the development of antibiotic resistance.”

This is more than a matter of promoting antibiotic-resistant pathogens. As more insight emerges into the profound importance of the human microbiome (indigenous microbial flora), the serious immune and metabolic consequences  implications of damaging the microbial flora are becoming more apparent. The authors set out to…

“…provide a nationally representative analysis of antibiotic prescribing in ambulatory pediatrics according to antibiotic classes and diagnostic categories and identify factors associated with broad-spectrum antibiotic prescribing.”

They examined data from the National Ambulatory and National Hospital Ambulatory Medical Care surveys from 2006 to 2008 for the percentage of visits for patients younger than 18 years for whom antibiotics were prescribed, their category, and the associated diagnoses. The guidelines for judicious use of broad-spectrum antibiotics have obviously not hit home:

“Antibiotics were prescribed during 21% of pediatric ambulatory visits; 50% were broad-spectrum, most commonly macrolides. Respiratory conditions accounted for >70% of visits in which both antibiotics and broad-spectrum antibiotics were prescribed. Twenty-three percent of the visits in which antibiotics were prescribed were for respiratory conditions for which antibiotics are not clearly indicated, which accounts for >10 million visits annually.”

Research is needed to investigate to what degree this may contribute to the rising tide of autoimmune disease and allergy. The authors conclude:

“Broad-spectrum antibiotic prescribing in ambulatory pediatrics is extremely common and frequently inappropriate.”

-

Summary: Brazil nuts protect against vascular disease in overweight female adolescents.

Recent research published in the journal Nutrition & Metabolism offers evidence that Brazil nuts, besides being more effective at raising serum selenium levels than selenium taken as a supplement, improve the lipid profile and protect against blood vessel damage. The authors state:

“Obesity is a chronic disease associated to an inflammatory process resulting in oxidative stress that leads to morpho-functional microvascular damage that could be improved by some dietary interventions. In this study, the intake of Brazil nuts (Bertholletia excelsa), composed of bioactive substances like selenium, α- e γ- tocopherol, folate and polyunsaturated fatty acids, have been investigated on antioxidant capacity, lipid and metabolic profiles and nutritive skin microcirculation in obese adolescents.”

Their study subjects comprising obese female adolescents were randomized to a group that consumed 15-25 g/day of Brazil nuts in capsules for 16 weeks and a placebo group. Anthropometry, metabolic-lipid profiles, oxidative stress, capillary diameters, functional capillary density, red blood cell velocity (RBCV) were measured at baseline (T0) and after the Brazil nut intervention (T1). What did the data show?

“At T1, BNG [the Brazil nut group] had increased selenium levels, RBCV and RBCVmax and reduced total (TC) and LDL-cholesterol. Compared to PG [placebo group], Brazil nuts intake reduced TC, triglycerides and LDL-ox and increased RBCV.”

In other words, compared to the placebo group, the Brazil nut cohort had better blood vessel function, lower total and LDL cholesterol and, importantly, reduced oxidized cholesterol (LDL-ox, the truly ‘bad’ cholesterol). Naturally, they also had higher selenium levels. The authors conclude:

“Brazil nuts intake improved the lipid profile and microvascular function in obese adolescents, possibly due to its high level of unsaturated fatty acids and bioactive substances.

-

A study just published in the journal Pediatrics brings to light how quickly foods in sack lunches can reach temperatures that risk food-borne illness even when presumably safe measures are taken. The authors obtained data that would apply to sack lunches under other conditions, such as personal food carried for air travel, when they set out to…

“…measure the temperatures of foods in sack lunches of preschool-aged children before consumption at child care centers.”

They examined foods packed by parents for 235 children with noncontact temperature guns 1.5 hours before the foods were served to the children. The temperature measurements were made immediately after removing them individually from the sacks (91% of which were insulated). The type of food and number of ice packs in the lunch sack were recorded. What did they find?

“Approximately 39% of the 705 lunches analyzed had no ice packs, 45.1% had 1 ice pack, and 88.2% of lunches were at ambient temperatures. Only 1.6% of perishable items were in the safe temperature zone. Even with multiple ice packs, the majority of lunch items (>90%) were at unsafe temperatures.“

Yikes! Even refrigeration wasn’t so helpful—only 0.9% of the items stored there (4 out of 458) were an acceptable temperature, although this is probably due to how long the lunches stayed at room temperature before refrigeration and/or the insulated bags kept out the cold. The authors conclude:

“Results of this study provide evidence that how parents pack their preschool-aged child’s lunch has potential effects on the temperature of the food packed and may result in foodborne illness when left uncorrected. Education of parents and the public must focus on proper methods of packing lunches that allow the food to remain in the food safety zone. “

This can account for a lot of unexplained gastrointestinal illness. Moreover, foodborne gastroenteritis can be a trigger for long-lasting autoimmune and allergic disorders. Although this study focused on a pediatric population, the same concerns apply to adult sack lunches and portable meals.

-

Imbalances or deficiencies in essential fatty acids which are critical brain components can contribute to depression and neurological disorders. A study just published online in the journal Acta Pædiatrica delineates the decisive difference they make in adolescents. The authors set out to…

“…study the relationship between polyunsaturated fatty acids (PUFA) status and depression in adolescents with eating disorders (ED) and weight loss.”

They measured essential fatty acids (FA) in the red blood cell membranes of 217 adolescents with eating disorders. As the clinicians reading this know, erythrocyte fatty acids also reflect the fatty acid status of the brain. The study subjects were also examined for depression by clinical interviews and psychological self-report instruments. A clear-cut picture emerged from the data:

“Adolescents with ED and depression did not differ from those with ED only in terms of age, BMI, weight loss and duration of disease. In their FA profile depressed adolescents had lower proportions of eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), the end products of the ω3 PUFA series. The ratio of long chain (>18 carbons) ω6/ω3 PUFA was therefore higher in depressed adolescents. Indices of desaturase activites did not differ between depressed and not depressed adolescents.”

In other words, the only difference among the factors examined in this study between the adolescents with and without depression  was their essential fatty acid status. Thus the authors conclude:

“Low ω3 status is related to depression in adolescents with ED. This cannot be explained by differences in weight (loss) and duration of disease, nor by differences in PUFA processing by desaturases. Data suggest a lower dietary intake of ω3 PUFA in those with depression. Further investigations should determine whether ω3 PUFA status improves by refeeding only or whether supplementation with PUFA is warranted.”

See also the Parents’ Guide To Brain Health for additional evidence of the role of fatty acids, along with information on the other important aspects.

-

With the unprecedented expansion of overweight, obesity and pre-diabetes in the pediatric population it is becoming increasing important to evaluate metabolic status with appropriate blood tests at a younger age. Anything that makes this task less onerous is desirable. A welcome study just published in the journal Pediatrics offers evidence that fasting may not be necessary to reliably evaluate lipid status in children. The authors state:

“Fasting lipid panels are recommended to screen for lipid abnormalities; however, fasting can be difficult for children and make screening difficult. Results of studies in adult patients are raising questions of whether fasting is needed before lipid screening.”

They examined total cholesterol (TC), HDL (high-density lipoprotein), LDL (low-density lipoprotein), and triglyceride cholesterol components in relation to fasting in 12,744 children aged 3 to 17 (varying times for young children and the usual fasting for those older than 12 years). The data appear to give kids a break:

“TC, HDL, LDL, or triglyceride values were available for 12 744 children. Forty-eight percent of the TC and HDL samples and 80% of the LDL and triglyceride samples were collected from children who had fasted ≥8 hours. Fasting had a small positive effect for TC, HDL, and LDL, resulting in a mean value for the sample that was 2 to 5 mg/dL higher with a 12-hour fast compared with a no-fast sample. Fasting time had a negative effect on triglycerides, which resulted in values in the fasting group that were 7 mg/dL lower.”

Furthermore…

“For TC, nonfasting screening inappropriately classifies ≈1% of children as normal, who would have had borderline values with fasting. In addition, ≈1% of children with borderline nonfasting values would actually have elevated results if fasting. For LDL, 1.2% of children with borderline fasting levels would have normal results postprandially, and 1.6% of children with increased calculated LDL while fasting, would now be considered to have borderline results. For triglycerides,≈4% of the children classified with normal triglycerides when fasting would have elevated values postprandially.”

In other words, most of the time the difference between fasting and non-fasting in children is not clinically significant.

The authors conclude:

“Comparing a nationally representative cross-section of children who had fasted for various lengths of time, we demonstrated that nonfasting measurements of TC, calculated LDL, and HDL cholesterol values had only small differences from fasting values. Although statistically significant, these differences are unlikely to result in important clinical changes in the results of screening for cholesterol abnormalities. …Across a large, nationally representative sample of children, the levels of TC, HDL, non-HDL cholesterol, and LDL cholesterol vary minimally on the basis of fasting time. It is not known if these small differences in lipoprotein components consistently weaken or strengthen the usefulness of lipid values for the assessment of current health risks or prediction of future cardiovascular risks, but it is clear that testing regardless of fasting status would reduce barriers to screening. Therefore, future research with people in longitudinal samples is warranted. If those results confirm our findings, professional societies might wish to reconsider their recommendations and encourage providers follow lipid screening guidelines at the point of care, regardless of fasting status.”

It will be helpful if future studies can offer data specifically quantifying the impact of fasting versus non-fasting on subsequent cardiovascular and metabolic risks. However, on the basis of the evidence we have now, my personal preference is to make it as easy on the kids as possible. Fasting a galloping pediatric metabolism risks a low blood sugar state that is not only globally miserable but elicits a vasoconstrictive autonomic response that makes phlebotomy much more difficult and traumatic.

-

A study just published in the journal Pediatrics documents the association of interpersonal violence in young adulthood with earlier head injury. The authors state:

“The purpose of this study was to examine differences in interpersonal violence among individuals who reported a head injury compared with those who did not report a head injury.”

They examined 8 years of data for 850 kids in 4 public high schools in a Midwestern city, looking specifically at the years from mid-adolescence to the transition into young adulthood, correlating levels of interpersonal violence with reports of head injury. Multivariate regression analyses, controlling for variables such as race, gender, and previous violence, as well as risk behaviors such as alcohol and marijuana use, were used to determine whether head injury was associated with subsequent violent behavior. What did the data show?

“Participants who had ever experienced a head injury before young adulthood reported more interpersonal violence in young adulthood than participants who had never had a head injury. In multivariate analyses, respondents who had a head injury in the past year reported more subsequent interpersonal violence than respondents who had not had a head injury.”

As noted in our Parents’ Guide To Brain Health even a mild traumatic brain injury can set in motion a cascade of effects that compromise brain function for cognition, impulse control and regulation of emotions. There are remedial measures that can help if the problem is recognized and properly assessed when we keep in mind the authors’ conclusion:

“Our findings support other studies that link history of head injury to later interpersonal violence.“

-

A clinical report just published in the journal Pediatrics by the American Academy of Pediatrics makes it clear why children and adolescents should not consume sports and energy drinks. The authors state:

“Sports and energy drinks are being marketed to children and adolescents for a wide variety of inappropriate uses.”

The authors define the categories of sports versus energy drinks, discuss their misuse, and exhort doctors to screen for their consumption while understanding why it has become so widespread. Their hope is to eliminate the use of these beverages by children and adolescents in most cases. They state:

“Rigorous review and analysis of the literature reveal that caffeine and other stimulant substances contained in energy drinks have no place in the diet of children and adolescents. Furthermore, frequent or excessive intake of caloric sports drinks can substantially increase the risk for overweight or obesity in children and adolescents.”

While this is a common sense assertion, some readers may feel more satisfied by the extensive evidence documented at length in the report itself.

-

The use of antibiotics demands great care and discrimination. A paper just published in Gut, An International Journal of Gastroenterology & Hepatology offers further evidence that disruption of the microbial ecology can promote autoimmune disorders. The authors state:

“The composition of the intestinal microflora has been proposed as an important factor in the development of inflammatory bowel diseases (IBD). Antibiotics have the potential to alter the composition of the intestinal microflora. A study was undertaken to evaluate the potential association between use of antibiotics and IBD in childhood.”

They examined all Danish singleton children born from 1995 to 2003 (577,627 children) for correlations between antibiotic prescriptions and IBD while taking into consideration potential confounding variables. They then calculated rate ratios (RRs) of IBD according to antibiotic use. Their data painted a compelling picture:

“IBD was diagnosed in 117 children during 3,173,117 person-years of follow-up. The RR of IBD was 1.84 for antibiotic users compared with non-users. This association appeared to be an effect on Crohn’s disease (CD) alone (RR 3.41) and was strongest in the first 3 months following use (RR 4.43) and among children with ≥7 courses of antibiotics (RR 7.32).”

In other words, there was an 84% increase in IBD for antibiotic users versus non-users. The increase in Crohn’s disease was particularly dramatic—341% in general, 443% in the first 3 months after antibiotic use, and a whopping 732% for children who had seven or more courses of antibiotics. The authors conclude:

“Antibiotic use is common in childhood and its potential as an environmental risk factor for IBD warrants scrutiny. This is the first prospective study to show a strong association between antibiotic use and CD in childhood.”

While, as the authors concede, an observational study does not establish causality, prudence dictates that care be taken in evaluating each patient for propensities to autoimmune disorders, and to apply appropriate pro- and prebiotic support during and after antimicrobial therapy.

-