Longer Periods of Untreated Depression Linked to More Brain Inflammation

June 27, 2018 · Posted in Course of Illness, Risk Factors · Comment 

depressed womanA 2018 study by researchers Elaine Setiawan, Sophia Attwells and colleagues reports that inflammation seems to increase with duration of untreated unipolar depression. This implies that depression may be a progressive illness, and later stage depression may require different treatments than early stage depression, such as those that directly target inflammation.

The study published in the journal The Lancet Psychiatry used positron emission tomography (PET scan) to examines levels of translocator protein in the brain. Higher levels of translocator protein indicate activation of microglia, the brain’s immune cells, which can respond to trauma or injury.

The study included 80 participants between the ages of 18 and 75. Ten had a history of more than 10 years of depression, ten had experienced fewer than 10 years of depression, and 30 comprised a healthy comparison group.

The best predictors of high levels of translocator protein were duration of untreated major depressive disorder, total illness duration, and duration of antidepressant exposure. These three factors explained about half of the variation in translocator protein levels. Those participants whose depression went untreated for 10 years or longer had inflammation levels 29–33% higher than those whose depression was untreated for 9 years or less.

Participants who had received antidepressant treatment appeared to avoid an average yearly increase in the extent of their microglial activation.

The study took place at Canada’s Centre for Addiction and Mental Health.

Editor’s Note: Since inflammation is a predictor of poorer response to antidepressants, these data add a further neurochemical rationale to the already strong clinical rationale for earlier and more sustained antidepressant treatment and prevention. Virtually all treatment guidelines suggest that after two or three prior unipolar depressions, patients should receive long-term (lifelong) antidepressant treatment.

There is now a large body of data, including a 2012 article by this editor Robert M. Post and colleagues in the Journal of Psychiatric Research that too many episodes can hurt the brain, and the current study adds to this perspective. Avoiding preventive treatment for too long may actually foster the development of more episodes and more treatment resistance. A good mantra is “prevent episodes, protect the brain.”

Consensus is now also building that comprehensive long-term treatment is indicated after a first manic episode. A 2013 article by Lars Kessing and colleagues in the British Journal of Psychiatry suggested that high quality initial treatment can improve the long-term course of illness. Moreover, a 2016 article by Jan-Marie Kozicky and colleagues and a 2017 article by Christine Demmo and colleagues, both in the journal Bipolar Disorders, suggest that after a first mania, cognition recovers over the next year only if no further episodes occur in that time.

Playing Tackle Football Before Age 12 May Be Bad for the Brain

May 3, 2018 · Posted in Risk Factors · Comment 

a football on grass

A 2017 study found that men who began playing American tackle football before age 12 were more likely to have depression, apathy, problems with executive functioning, and behavioral issues in adulthood than their peers who began playing football after age 12. Duration of football play did not seem to matter—those men who stopped playing football after high school were just as likely to be affected in adulthood as those who went on to play football in college or professionally.

The study by Michael L. Alosco and colleagues was published in the journal Translational Psychiatry. It included 214 men (average age 51) who had played football in their youth, but not other contact sports. The men reported their own experiences with depression, apathy, cognitive function, and behavioral regulation. Those who began football before age 12 were twice as likely to report impairment in behavioral regulation, apathy, and executive function than those who began playing later. Those who started younger were also three times more likely to have clinical depression in adulthood than those who started older.

According to Alosco and colleagues, between ages 9 and 12, the brain reaches peak maturation of gray and white matter volume, and synapse and neurotransmitter density also increases. The repeated head injuries that can occur during youth football play during this time may disrupt neurodevelopment, with lasting negative effects.

One drawback to the study was that recruitment was not random—men who volunteered for the study might have done so due to a recognition of their own cognitive problems. However, the results suggest more study is needed, and caution is encouraged when making decisions about youth football participation. Some youth football leagues have begun placing greater limits on the type of contact allowed during play.

Children Who Are Bullied Have Poorer Mental Health

April 30, 2018 · Posted in Risk Factors · Comment 

girl being bullied

A 2017 study of twins between the ages of 11 and 16 found that being bullied around age 11 caused anxiety, depression, hyperactivity and impulsivity, inattention, and conduct problems, some of which lasted for years. Participants recorded their experiences with physical or verbal bullying, social manipulation, and property attacks (trying to break one’s belongings, for example).

The effects of bullying decreased over time. The bullied children were still significantly more anxious than their non-bullied twins two years later, but this difference faded by the five-year mark. However, paranoid thoughts and cognitive disorganization did persist for 5 years.
The twin study design helped researchers zone in on the causal effect bullying might have on the children’s mental health, rather than other factors the twins shared, such as genetics or family environment. The study included 11,108 twins born in England and Wales.

The research by Timothy Singham and colleagues was published in the journal JAMA Psychiatry. Interestingly, the researchers found that prior mental health difficulties increased children’s likelihood of being bullied, such that being bullied could be considered a symptom of preexisting vulnerabilities. Singham and colleagues suggest that in addition to interventions to reduce bullying and address familial factors that might make children susceptible to bullying, children should also be taught resilience skills.

In Animals, Exposure to High Fat Diet During Pregnancy Can Affect Offspring’s Neurological Development

March 19, 2018 · Posted in Risk Factors · Comment 

baby macaque feeding

New research in non-human primates suggests that exposure to a high fat diet during pregnancy and in early development prior to weaning can increase the offspring’s propensity for anxiety later in life.

The new research echoes 2010 findings about rats. Researcher Staci D. Bilbo and colleagues reported in the journal of the Federation of American Societies for Experimental Biology that in rats, a high fat diet during pregnancy and lactation led to offspring with greater body weight, increased inflammation, and problems with anxiety and spatial learning. Switching to a standard diet after weaning did not eliminate these outcomes.

The recent research by Jacqueline R. Thompson and colleagues, published in the journal Frontiers in Endocrinology in July 2017, suggests that maternal nutrition in the primate during pregnancy and lactation can have long-lasting effects on offspring’s neurological development, altering the brain and endocrine system. These changes occurred even if the offspring began a normal diet after weaning.

65 female Japanese macaques were divided into two groups, one that received a high-fat diet and one that received a normal diet. In the offspring of mothers who ate a high-fat diet, the researchers found impaired development of neurons containing serotonin. The offspring of the high-fat diet group also showed behavioral alterations such as increased anxiety.

The high rates of obesity in the US and other developed nations make these findings particularly important. The researchers suggest that 64% of women in the US who are of reproductive age are overweight, and 35% are obese. Co-author Elinor Sullivan suggested that the findings from the study could motivate mothers to make healthy nutritional decisions, not only for themselves but for their children as well.

Phthalates in Plastics and Creams Cause Epigenetic Changes to Sperm

March 16, 2018 · Posted in Genetics, Risk Factors · Comment 

sperm

A recent study suggests that chemicals called phthalates that are used to make plastic flexible and to improve the texture of lotions, creams, and powders have effects on human sperm. Phthalates have become common in our environment since the invention of plastics, and most people have detectable levels of phthalate metabolites in their bodies.

The study, published by Haotian Wu and colleagues in the journal Human Reproduction in 2017, measured DNA methylation in a group of men’s sperm and compared this to levels of phthalate metabolites in the men’s urine.

DNA methylation changes the structure of a DNA strand. Extra methyl groups are attached to the strand, affecting the way it is transcribed, even though the inherited genetic sequence on the DNA strand remains the same. Changes like these to the structure of DNA and histones, which give DNA its helix shape, are known as epigenetic changes.

Wu and colleagues found 131 regions of DNA methylation in the men’s sperm that they could link to at least one of the phthalate metabolites found in the men’s urine.

Sperm takes 72 days to mature. Wu and colleagues suggest that exposure to phthalates in plastics or personal care products during this period may cause alterations to sperm, which could potentially affect the ease of conception or the development of potential offspring. The changes the researchers observed affected genes related to growth, development, and cellular function and maintenance.

In addition to chemical exposure, stressors and drug use can also bring about epigenetic changes to sperm. A father’s offspring may then have altered risk of drug use or other behaviors as a result of these epigenetic changes.

Phthalates, which can disrupt the endocrine system, have previously been found to alter men’s hormone levels and to hurt sperm quality. This is the first study to find that in people, phthalate concentrations measured before conception are associated with DNA methylation in sperm. This was a fairly small study in 48 men, and it remains to be studied whether the changes to sperm affect the offspring’s prenatal and early childhood development.
In addition to their presence in flexible plastics, phthalates may also be found in products such as shaving cream, shampoo, soaps, and detergents.

Gabapentin May Increase Opioid-Related Deaths

February 2, 2018 · Posted in Current Treatments, Risk Factors · Comment 

topiramateThe anticonvulsant gabapentin is sometimes prescribed for chronic pain conditions along with opioids. A 2017 article by researcher Tara Gomes in the journal PLOS Medicine reports that compared to opioid prescriptions alone, co-prescription of gabapentin increases the risk of an opioid-related death by 49%. The risk was increased by 60% for those receiving moderate or high doses of gabapentin (those above 900 mg/day).

The increased risk when the drugs are taken together may be because both gabapentin and opioids depress the respiratory system. Opioids also slow the gastrointestinal system, meaning that more gabapentin is absorbed by the intestines than occurs when gabapentin is prescribed alone.

Gomes and colleagues looked at cases of patients who were prescribed opioids and had opioid-related deaths, and matched these with similar patients who had not died while taking prescription opioids during the same time period. The researchers found that having taken gabapentin in the previous 120 days dramatically increased the risk of death from opioid-related causes.

Gomes and colleagues suggest that caution should be used when prescribing gabapentin and opioid drugs at the same time.

PTSD Increases Risk of Lupus

January 24, 2018 · Posted in Risk Factors · Comment 

woman paintingA new large 2017 study in the journal Arthritis and Rheumatology reports that post-traumatic stress disorder (PTSD) in women triples their risk of developing the autoimmune disease lupus. The study included 54,763 civilian women whose health data was tracked over a period of 24 years.

Not only did PTSD increase lupus risk, but any traumatic event doubled lupus risk compared to women who were not exposed to trauma.

The researchers, led by Andrea L. Roberts, were taken by surprise at the strong links between trauma and lupus. Trauma was more of a risk factor for lupus than smoking.

Diet Drinks May Worsen Glucose Control, Making Type 2 Diabetes More Likely

January 12, 2018 · Posted in Risk Factors · Comment 

Many people substitute diet drinks containing artificial sweeteners for sugary drinks in the hopes of reducing their diabetes risk. However, new research suggests that artificial sweeteners alter the gut’s response to glucose in a way that could actually worsen diabetes risk.

At the 2017 meeting of the European Association for the Study of Diabetes, researcher Richard Young described a small study in which he and his colleagues compared the effects of artificial sweeteners to those of placebo in healthy adults. Seventeen participants consumed an amount of artificial sweetener equivalent to what would be found in 1.2 to 1.5 liters of diet beverage per day for two weeks, while 16 participants received placebo.

Young and colleagues determined that glucose absorption and glycemic response increased in the participants who consumed the artificial sweetener. Those who consumed the sweetener absorbed 20% more glucose than those in the placebo group. While before the study the two groups had similar blood glucose levels, these rose by 24% in those who consumed the artificial sweetener.

Consuming artificial sweetener also seemed to affect the gut peptide GLP-1, which limits the rise in blood glucose after meals. The two groups had similar GLP-1 responses before the study, but after consuming artificial sweetener, participants showed a 34% reduction in GLP-1 response to glucose absorbed in the intestines.

Changes like these could increase the risk of type 2 diabetes. Young explained that artificial sweeteners may reduce the body’s ability to control blood sugar levels, leading to high glucose, and possibly predisposing those who consume artificial sweeteners to type 2 diabetes. Young and colleagues have previously found that switching from sugar to artificial sweeteners does not predict a lower risk of type 2 diabetes.

This study was the first of its kind in humans. Larger studies will help to clarify the effects of artificial sweeteners on glucose control.

Exercise in Childhood Decreases Depression Symptoms Two Years Later

January 8, 2018 · Posted in Risk Factors · Comment 

A 2017 study in the journal Pediatrics found that higher rates of moderate to vigorous physical activity at ages six and eight was linked to fewer symptoms of depression at age 10.

The study included 795 six-year-olds who were tracked for four years. Their physical activity was measured by accelerometry, the same type of technology found in smartphones and other consumer products that can track a person’s daily steps. Depression symptoms were assessed via interviews with the children and their parents.

While exercise seemed to reduce depression symptoms, sedentary behavior did not predict later depression.

Minimizing Cardiovascular Risk in Bipolar Disorder

January 5, 2018 · Posted in Comorbidities, Risk Factors · Comment 

heartAt the 2017 meeting of the American Association of Child and Adolescent Psychopharmacology, researcher Ben Goldstein gave an overview on cardiovascular risk and bipolar disorder. He noted a study by Nicole Kozloff and colleagues in the Journal of Affective Disorders in 2010 that indicated that onset of cardiovascular disorder occurred an average of 17 years earlier in those with BP I (at age 40-45 years) compared to controls (at age 55-60 years). Several risk factors made onset of cardiovascular disorder more likely, including diabetes, obesity, and the metabolic syndrome (which consists of any three of the five following symptoms: high cholesterol, triglycerides, blood sugar, blood pressure, and waist circumference).

Risk factors include pathophysiological and behavioral mechanisms and certain medications. Pathophysiological mechanisms include inflammation, oxidative stress, and autonomic and endothelial dysfunction.

Behavioral mechanisms include poor diet, exercise, sleep, and increases in tobacco and alcohol use.

Medications could also contribute, with the most to least problematic for weight gain including, among atypical antipsychotics: clozapine, olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, and lurasidone. Among mood stabilizers, worst to best for avoiding weight gain are: valproate, lithium, carbamazepine, oxcarbazepine, and lamotrigine.

Goldstein has data from retinal vascular photography (RVP), whereby blood vessels can be observed directly. As opposed to in adults, in youth large vessels are more problematic and arteriolar to venous ratio is abnormally higher in bipolar children compared to normal controls. This ratio is lower in bipolar adults, also reflecting increased cardiovascular risk.
Given the huge loss of life expectancy in bipolar disorder, primarily from cardiovascular disorders, Goldstein urges greater and earlier attention to reducing the pathophysiological, behavioral, and pharmacological mechanisms for poor health. These should be pursued in parallel with attempts at mood stabilization. Read more

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