This is an ambitious issue. Still, it can only scratch the surface of our brains. I chose to focus on brain/mental problems watching seniors finding relief, and improvement, just by singing on the CBS evening news August 31st. I hope you find the articles below helpful. At least read the titles. If you are going to skip them, read this before you go: as noted ad nauseum, Alzheimer’s and practically all other brain problems are due to poor diets, toxic environments, and unmitigated stress.
Hugo Rodier, MD
AD/HD in teens linked to higher digital media use
The Wall Street Journal (7/17, Hernandez, Morris, Subscription Publication) reports that frequent use of digital media by adolescents may be associated with an increased risk for attention-deficit/hyperactivity disorder (AD/HD), researchers concluded after following some 2,500 teenagers over two years. The findings were published in the Journal of the American Medical Association.
CNN (7/17, Howard) reports that the study’s “results ‘affirm the 2016 American Academy of Pediatrics guidelines to prioritize activities that promote adolescent executive functioning and well-being, including sleep, physical activity, distraction-free homework, and positive interactions with family and friends,’ wrote” Jenny Radesky, M.D., “who was a lead author of the academy’s guidelines for young children.”
PTSD, stress-related psychiatric disorders linked to higher risk of several autoimmune diseases in study. Reuters (6/19, Rapaport) reports, “People who suffer from posttraumatic stress disorder (PTSD) and other stress-related psychiatric issues may be more likely to develop autoimmune diseases than individuals who” do not, researchers found. The ABC News (6/19, Tawagi) website reports that for the study, investigators examined “the medical records of 100,000 people with stress-related psychiatric disorders between 1981 and 2013 in Sweden and” then compared “them to 120,000 of their siblings and nearly 1.1 million unrelated people who had no stress-related disorders.” The study revealed that “compared to those without stress-related disorders,” people with stress-related disorders “were at an increased risk of 41 different autoimmune diseases – and patients with PTSD were at an increased risk of having multiple autoimmune diseases, including rheumatoid arthritis, psoriasis, Crohn’s disease and celiac disease.” The findings were published in the June 19 issue of the Journal of the American Medical Association.
Youngsters face increased risk of mental health, behavioral problems if their parents experienced traumatic events in childhood.
The ABC News (7/9, Powell) website reports research published online July 9 in Pediatrics “finds that traumatic events in childhood increase the risk of mental health and behavioral problems not just for that person but also for their children.” For the study, researchers “used a national sample of families from previous research – parents who had participated in a 2014 Child Development Supplement and 2,529 of their children who had complete data in the 2014 Childhood Retrospective Circumstances Study.” The study revealed an association “between children with a high rate of behavioral problems and parents who had experienced a greater number of adverse childhood events.”
HealthDay (7/9, Norton) reports children of parents who had experienced “abuse or other adversities” as children were themselves “twice as likely to have been diagnosed with attention-deficit/hyperactivity disorder” and “four times as likely to have been diagnosed with any mental health disorder.”
Diabetes in pregnant women may be linked to higher risk of autism in offspring.
The New York Post (6/25, Laneri) reports that research suggests “a mom’s diabetes can raise her child’s risk for autism.”
HealthDay (6/25, Reinberg) reports, “Whether it’s type 1, type 2 or gestational diabetes, which specifically affects pregnant women, having the blood sugar disease might be linked to an increased autism risk, the researchers said” after having collected “data on more than 419,000 children born from 1995 through 2012 in Kaiser Permanente Southern California hospitals.” The findings were published online in the Journal of the American Medical Association and presented at the American Diabetes Association annual meeting.
Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity,
The Journal of Clinical Endocrinology & Metabolism, Volume 103, Issue 7, 1 July 2018, Pages 2552–2562
Comment: If you are thinking PCOS has nothing to do with the brain, ask a woman you know well if it impacts her thinking and emotions.
Sarcopenic obesity tied to Alzheimer’s disease.
The Washington Times (7/5, Kelly) reports researchers found that sarcopenic obesity, a condition in which the patient is “of a normal weight but with more fat than muscle,” is linked to Alzheimer’s disease. The researchers found that people with sarcopenic obesity “performed poorly on cognitive function tests compared to” people with just sarcopenia or just obesity. The findings were published in the J. Clinical Interventions in Aging.
Fitness in middle age may lower risk of future depression, cardiovascular disease.
The New York Times (6/27, Bakalar) reports, “Physical fitness in middle age is tied to a lower risk of later-life depression and death from cardiovascular disease,” researchers concluded after studying “17,989 men and women, average age 50, from 1971 to 2009,” following “them from the time they initiated Medicare coverage through 2013.” The study revealed that “people in the highest” fitness category “were 16 percent less likely to have depression, 61 percent less likely to have cardiovascular illness without depression, and 56 percent less likely to die from cardiovascular disease after becoming depressed,” when compared to people “in the lowest fitness category.” The findings were published online June 27 in JAMA Psychiatry.
Workplace noise in daytime affects sleep quality.
Reuters (6/14, Crist) reports that research suggests “being exposed to a noisy workplace all day may cause stress that carries over into the evening and reduces sleep quality.” Investigators “found that when workers had higher occupational noise exposure, they had higher blood pressure and higher levels of the stress-hormone cortisol after work, and got less restful sleep that night, compared to days with lower daytime noise exposure.” The findings were published online in Sleep Medicine.
J. Neurology May 29, 2018; 90 (22) Sauna bathing reduces the risk of stroke in Finnish men and women
How Does the Gut Microbiome Differ in Patients With Relapsing MS Versus Controls?
NASHVILLE—The microbiome composition of patients with multiple sclerosis (MS) may differ significantly from that of healthy controls, according to data presented at the 2018 CMSC Annual Meeting in Nashville. Ruminococcus torques, Ruminococcus obeum, and Lactospiraces bacterium showed a significantly higher abundance in the relapsing-remitting MS population, compared with healthy controls, and these associations were confirmed at the genus level. Associations with Escherichia coli and Oscillibacter also were significant and confirmed at the genus and family levels. Bacteroides fragilis and Roseburia were more abundant in healthy donors than in patients with relapsing-remitting MS, and Haemophilus parainfluenzae and Sutterella wadsworthensis were more abundant in healthy donors at the species, genus, and family levels.
Aggressive BP lowering may reduce risk of MCI.
USA Today (7/25, Weintraub) reports researchers have found that “aggressively lowering blood pressure in people at high risk for heart attacks and stroke also reduced their likelihood of developing mild cognitive impairment (MCI), a condition that often leads to dementia.” The researchers found that patients who were “treated to reduce their systolic blood pressure…to 120 mm Hg were 19 percent less likely to develop mild cognitive impairment than those whose blood pressure was targeted to 140 mm Hg.”
The Wall Street Journal (7/25, Loftus, Subscription Publication) reports the findings were presented at the Alzheimer’s Association International Conference.
Bloomberg News (7/25, Cortez) reports that based on the study’s results, drugs that lower blood pressure could “reduce the risk of memory loss and dementia.”
Women’s reproductive history affects risk of Alzheimer’s
The Washington Post (7/22, Bahrampour) reports researchers at Kaiser Permanente found that “women who had had three or more children had a 12 percent lower risk of dementia in later life than those with fewer children,” while “women who didn’t get their first period until age 16 or 17 had a 31 percent higher risk of dementia than those who began menstruating at 13, and that women who stopped menstruating at age 45 or earlier had a 28 percent higher risk of dementia than women who stopped menstruating after age 45.” The article also mentions another study found “women who spend more cumulative months pregnant – especially in the first trimester – have a lower risk of developing dementia,” which suggests that changes in the immune system that occur during pregnancy, rather than estrogen, which peaks in the third trimester, may decrease the risk of dementia. Researchers presented their findings at the Alzheimer’s Association International Conference.
Late-life hypertension may contribute to Alzheimer’s
The AP (7/11, Marchione) reports researchers found that “high blood pressure late in life might harm the brain,” and may be linked to Alzheimer’s disease. The researchers “found more signs of damage and one of the hallmarks of Alzheimer’s disease in the brains of those with higher blood pressure than among those with pressure closer to normal.” The findings were published online in Neurology.
TIME (7/11, Park) reports the researchers “measured the blood pressure of nearly 1,300 elderly people, aged 59 to 102 years, and followed them until they died, on average eight years after enrolling in the study,” and then “performed autopsies on the brains to document the presence of brain lesions, including signs of Alzheimer’s disease.” The researchers found “evidence that blood pressure may be one of the many factors that can contribute to aging brain processes, including the formation of lesions and hallmark features of diseases like Alzheimer’s.”
MedPage Today (7/11, George) reports the researchers also found that “late-life systolic and diastolic blood pressure were separately associated with the number of brain infarcts at autopsy, as was faster decline in systolic blood pressure over time.”
High blood pressure over 50 increases risk of dementia.
The New York Times (6/12, Bakalar, Subscription Publication) reports that a new study has found that elevated blood pressure at 50 is linked to an increased risk for dementia. The Times explains that the researchers controlled for “many risk factors, including stroke, heart failure and other cardiovascular diseases,” and “they found that a systolic blood pressure at age 50 of 130 or greater was independently associated with a 38 percent increased risk of dementia.” The study was published in the European Heart Journal.
Differences in Brain Volume by Residential Exposure to Greenness.
J. Environ Health Perspect;2018 DOI:10.1289/EHP3465
Comment: the greener your pastures, the bigger the brain.
Iron Deficiency, Anemia, and Low Vitamin B-12 Serostatus in Middle Childhood Are Associated with Behavior Problems in Adolescent Boys.
The Journal of Nutrition, Volume 148, Issue 5, 1 May 2018, Pages 760–770
Comment: Anemia and B vitamin deficiencies are mostly due to poor diets.
A good night’s sleep is critical for teens’ metabolism.
The New York Times (7/17, Bakalar) reports that researchers conducted a study involving “829 boys and girls, average age 13.” The study revealed that “shorter sleep duration and poorer sleep efficiency were associated with higher systolic blood pressure, lower HDL cholesterol, higher triglycerides and higher glucose levels, all indicators of poorer metabolic health.” The findings were published online in Pediatrics.
Babies introduced to solid foods at three months may sleep longer through the night.
CNN (7/9, Scutti) reports, “Both the UK National Health Service and the American Academy of Pediatrics recommend that mothers exclusively breastfeed until about six months of age and then begin to introduce solid foods.” Now, a new study suggests that “an alternative feeding plan is also safe for babies.” Researchers found that “introducing a child to solid baby foods after just three months was associated with a small but significant improvement in nighttime sleep and slightly fewer wakings throughout the week compared with babies who began eating solids later, according to a study published” online in JAMA Pediatrics. Newsweek (7/9, Gander) points out, “The findings” also “contradict current recommendations by the Center for Disease Control and Prevention, which advises parents to move babies on to solid food at six months old.”
Learning to play piano may help children build up language skills.
TIME (7/1, Ducharme) reported research indicates learning to play the piano may help children “build up their language skills.” As youngsters’ “ears become trained to distinguish between different pitches and tones at the piano…they also seem to get better at parsing subtle differences between spoken words, a key element of language acquisition,” the study revealed. The findings were published online in the Proceedings of the National Academy of Sciences.
Depression: low levels of acetyl-l-carnitine.
USA Today (7/31, Molina) reports that “people with depression” appear to have “low levels of acetyl-L-carnitine [LAC], which helps the body produce energy,” researchers say. The findings were published online in the journal Proceedings of the National Academy of Sciences.
Newsweek (7/31, Gander) reports that investigators arrived at the study’s findings after testing “blood samples from 116 participants, 71 with depression and 45 without.” The study also found that “patients with very low LAC levels were more likely to have more serious depressive symptoms and to have developed depression earlier in life.” Additionally, there was “a higher chance they had experienced childhood trauma and were resistant to treatments for depression.” The Philadelphia (PA) Inquirer (7/31, Haydon) also covers the story.
Cured Meats Strongly Tied to Increased Mania Risk. Medscape – Jul 19, 2018.
Eating nitrate-cured meats such as beef jerky and other processed meat snacks has been strongly linked to an increased risk for mania, new research shows. A study of roughly 1100 adults showed that those who were hospitalized for a manic episode were more than three times more likely to have ever eaten nitrate-cured meats than those who did not have a history of a serious psychiatric disorder.
“We looked at a number of different dietary exposures, and cured meat really stood out. It wasn’t just that people with mania have an abnormal diet,” lead investigator Robert Yolken, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, said in a statement. The study was published online July 18 in Molecular Psychiatry.
New fathers also suffer from postpartum depression.
Reuters (7/23, Rapaport) reports that research suggests “fathers of young children may be almost as likely as new mothers to experience symptoms of depression.”
Medscape (7/23, MacReady, Subscription Publication) reports that investigators found that “of the fathers screened in a large, population-based cohort, 4.4% had a positive result for depression, which is similar to the percentage of mothers who screened positive, at 5.0%.” The findings were published online in JAMA Pediatrics.
Antidepressants Work for Major Depression! Not so Fast. Behind the Elation, the Same Old Story.
Medscape – Jun 13, 2018.
A highly touted recent meta-analysis[1] has been greeted with screams of elation: “Antidepressants work!” Even Medscape has shared in these shouts of joy. Why is the medical community and psychiatric profession so primed to convince itself, once and for all, that its favorite drugs work? Maybe because, deep down, we know they don’t.
The latest attempt to trick ourselves into believing that the past few decades of prescribing antidepressants has been an effective strategy comes from one of the most prestigious medical journals, The Lancet. The published meta-analysis’ basic finding—since repeated all over the press—is that antidepressants work because they are all better than placebo. What they don’t tell you is that they are hardly any better than placebo, and that the only drugs with clinically meaningful benefits are the ones that are used rarely today, the older tricyclic agents.
In the past decade, several other meta-analyses have looked at randomized clinical trials of antidepressants for major depressive disorder (MDD), usually conducted by pharmaceutical companies for government registration.[2] They have found, repeatedly, that antidepressants either are not more effective than placebo, or they are slightly more effective, with an effect size that does not translate into clinically meaningful benefit. The effect sizes seen are about a 2-point improvement versus placebo on the Hamilton Depression Rating Scale, which is lower than the minimum threshold of a 3-point improvement for clinically meaningful benefit set by an earlier 2004 guidance by the UK’s then-named National Institute for Health and Clinical Excellence.[3]
They have found, repeatedly, that antidepressants either are not more effective than placebo, or they are slightly more effective. Another way of looking at it is via “Cohen’s d,” which describes the differences between mean scores divided by standard deviation. This allows us to directly, simply compare studies with different scales and the absolute benefit they show. A general rule of thumb with Cohen’s d is that a score of 0 to 0.25 indicates small to no effect, 0.25-0.50 a mild benefit, 0.5-1 a moderate to large benefit, and above 1.0 a huge benefit. It is a convention that a Cohen’s d of 0.5 or larger is a standard threshold for clinically meaningful benefit. The meta-analyses conducted over the past decade find an overall effect size of about 0.31 to 0.32 for modern antidepressants,[2,4] which is small and below clinically meaningful benefit.
What the Meta-analysis Actually Showed: This latest meta-analysis[1] claims to have found something different—that antidepressants are effective. In fact, its results are basically the same as in prior analyses, confirming that almost all antidepressants are ineffective or at least not in a clinically meaningfully way, when examined as a whole compared with placebo. In other words, the only thing this study confirms is that prior studies were right when they reported that antidepressants “don’t work.” he authors looked at 522 randomized clinical trials of 21 antidepressants versus placebo in MDD in over 100,000 patients. Overall, all antidepressants were more effective than placebo. In the “network” analysis, which allows for the direct and indirect comparison of multiple treatments, the authors report the lowest direct efficacy for reboxetine (odds ratio [OR], 1.36) and the highest efficacy (OR, 2.13) for the tricyclic antidepressant amitriptyline.
If these results were accepted at face value, we would conclude that clinicians should feel confident that all antidepressants are effective in MDD in general, and they would lean towards the agents listed above that were “more” effective, and against those that were “less” effective. Unfortunately, that isn’t the case.
On the positive side, the authors included much unpublished data (52% of all of the studies). Because of this, their results are not limited to or mostly influenced by the published literature, which is known to be markedly biased in favor of antidepressant drug efficacy. (This is because pharmaceutical companies usually have not published negative studies of antidepressants.)
On the negative side, nowhere in this dense and detailed paper did the authors report the absolute effect size of benefit with antidepressants on the depression rating scales used. Instead, they provide odds ratios, which are relative effect sizes over placebo. A drug might be 50% better (an OR of 1.50), but this could be a difference between 2 points with drug and 3 points with placebo on a depression rating scale (a tiny and clinically meaningless effect). Or it could be a difference between 20 points with drug and 30 points with placebo on the scale (a huge and clinically meaningful effect). In other words, how much better did patients get?
Additional Data Reveal Study’s Actual Findings: The real truth isn’t found within the published paper but rather within a busy table on page 142 of the online appendix. It is here where the authors report what we want: the actual difference between drugs and placebo, before and after treatment, on the depression rating scales. Here we see that the Cohen’s d standardized mean difference effect sizes range from a low of 0.19 to a high of 0.62 with amitriptyline. Thus, amitriptyline exceeds the clinically meaningful threshold of 0.50, with a traditional meta-analytic method. No other drug does so, with the closest second place being fluvoxamine, with a P value of 0.44.
Looking at all of the agents, 10 drugs have P values less than 0.30, which is very small and clinically meaningless, whereas four have effect sizes from 0.30 to 0.34. Thus, 74% (14/19) of antidepressants clearly have little or no clinically important benefit in this analysis (for some reason, no data are provided in this table with two of the drugs). Four drugs have effect sizes of 0.37-0.44, and as noted, one agent exceeds the 0.50 threshold (amitriptyline).
Perhaps a clearer conclusion than anything else is the well-proven fact that the tricyclic antidepressants are more effective than newer agents (there were no monoamine oxidase inhibitors in this meta-analysis). The main point to conclude from the above description is that almost all antidepressants had small, clinically meaningless benefits. And only one agent exceeds the threshold of a Cohen’s d effect size of 0.50 or greater, which can be considered clinically meaningful benefit.
The Honest Conclusion: In short, one has to go to page 142 of the appendix to find the real result of all this effort: This meta-analysis confirms the results of prior meta-analyses which found that antidepressants have small overall effects in “MDD” and do not provide major clinical benefit in general. One has to go to page 142 of the appendix to find the real result of all this effort. This conclusion puts aside the more important issue of the scientific validity of the MDD concept itself, which the authors ignore completely. Our profession seems devoted to believing that antidepressants “work.” They don’t, at least not for “MDD.” Maybe the problem is with “MDD”—which is a heterogeneous clinical syndrome that is not valid scientifically as a single diagnosis[5]—rather than with antidepressants. In other words, these drugs do something biologically, but maybe we aren’t giving them to the right clinical group of patients to see benefits.
The only clear take-away from this analysis, besides confirming the prior analyses that antidepressants are not very effective, is that amitriptyline is the most effective antidepressant tested, and apparently, it’s the only one with clinically meaningful benefit. That’s it. On the larger question of antidepressants as a class, you have two options: Either antidepressants don’t work or MDD doesn’t work. Take your pick.
- Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391:1357-1366.
- Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008;5:e45.
- Clinical Practice Guideline (no 23). Depression: management of depression in primary and secondary care. 2004. National Institute for Clinical Excellence.
- Turner EH, Rosenthal R. Efficacy of antidepressants. BMJ. 2008;336:516-517.
- Ghaemi SN, Vöhringer PA, Vergne DE. The varieties of depressive experience: diagnosing mood disorders. Psychiatr Clin North Am. 2012;35:73-86.
Over a third of adults on meds that increase risk of depression.
The Washington Post (6/12, Johnson) “Wonkblog” reports, “More than a third of American adults are taking prescription” medicines, “including hormones for contraception, blood pressure medications and medicines for heartburn, that carry a potential risk of depression,” researchers concluded after analyzing data from “a detailed survey of thousands of American adults taken every two years between 2005 and 2014, in which people opened their medicine cabinets and showed researchers all the prescription” medications “they had taken in the last month.” Those people were also evaluated for depression.
U.S. News & World Report (6/12, Lardieri) reports the study revealed that “approximately 15 percent of adults who used three or more of these medications simultaneously experienced depression, compared to five percent not taking the” medications, seven “percent taking only one” medicine, and nine “percent taking two” medications simultaneously. The study authors also “observed the symptoms in” medicines “that listed suicide as a side effect but also saw similar results when they excluded participants taking psychotropic medications, which is considered an indicator of underlying depression unrelated to medication use.” The findings were published online June 12 in the Journal of the American Medical Association.
