Cannabis May Produce More Brain Changes in Teens with Bipolar Disorder than in Healthy Teens

October 31, 2019 · Posted in Risk Factors · Comment 

smoking

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Benjamin Goldstein of Sunnybrook Research Institute in Toronto reported that adolescents with bipolar disorder who smoked marijuana had greater deficits in certain brain areas than did adolescents who did not have bipolar disorder. The areas affected included the dorsal lateral and rostral middle frontal cortex, and middle cortex. Goldstein concluded, “Adolescents with [bipolar disorder] may be particularly sensitive to the neurostructural effects of cannabis.”

Marijuana in general causes adverse changes in brain structure and cognition and vulnerability to paranoia and psychosis. Heavy use in adolescence is associated with an increased incidence of the onset of bipolar disorder and schizophrenia. The Goldstein data suggest several possible causal mechanisms. Those with bipolar disorder may already have brain abnormalities that are exacerbated by marijuana use. Alternatively, marijuana and bipolar disorder together may impact brain structure more than either factor alone would.

Alcohol Use Disorders That Begin Before Age 21 May Cause Lasting Changes to Amygdala

October 29, 2019 · Posted in Risk Factors · Comment 

prefrontal cortex and amygdalaIn a 2019 article in the journal Translational Psychiatry, researcher John Peyton Bohnsack and colleagues report that people with alcohol use disorders that began before they were 21 years of age show amygdala changes that people with alcohol use disorders that began after the age of 21 do not appear to have.

The amygdalas of those who began abusing alcohol in adolescence showed greater expression of the long non-coding RNA known as BDNF-AS. The increased BDNF-AS was associated with decreased levels of brain-derived neurotrophic factor (BDNF) in the amygdala. BDNF protects neurons and is important for learning and memory.

According to Bohnsack and colleagues, “Adolescence is a critical period in brain development and adolescent drinking decreases orbitofrontal cortex activity and increases amygdala activity leading to less executive control, more emotional impulsivity, alterations in decision-making, and [a higher risk of engaging] in risky behaviors and develop[ing] mental health problems later in life.”

Psychiatric Risks in Offspring of Parents with Bipolar/Unipolar Disorders

October 25, 2019 · Posted in Risk Factors · Comment 

familyAt the 2019 meeting of the International Society for Bipolar Disorders, researcher Martin Preisig and colleagues from Lausanne, Switzerland reported on a longitudinal study of mood disorders in offspring of parents with bipolar disorder, unipolar depression, or no history of psychiatric illness. The study included 446 children (with an average age of 10.1 years at the beginning of the study), who participated for an average of 11.9 years.

Preisig and colleagues determined symptoms and other factors that preceded psychiatric illness. They found that bipolar disorder in the offspring was preceded by sub-threshold hypomania, major depression, and conduct disorder. Bipolar disorder in the offspring was also predicted by parental early-onset bipolar disorder.

Major depression was preceded by separation anxiety disorder, and witnessing violence or being a victim of sexual abuse.

Preisig and colleagues concluded that not only did bipolar disorder and major depressive disorder have different familial origins, they also had different antecedents and risk factors.

Inflammation Associated with Cognitive Deficits

October 15, 2019 · Posted in Risk Factors · Comment 

woman thinking

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Katherine E. Burdick and colleagues at Brigham and Women’s Hospital and Harvard Medical School reported that in 240 patients with bipolar disorder who were not currently having a manic or depressive episode, markers of inflammation were associated with cognitive deficits.

Inflammation was associated with cognitive deficits in general, and there were also some relationships between specific inflammatory markers and types of cognitive processing. They found that the inflammatory markers TNF-alpha, TNFR1, and TNFR2 influenced cognitive flexibility. The inflammatory marker VEGF influenced reward processing, while IL-6/IL-6r influenced spatial processing. IL-1beta and IL-1RA influenced social cognition.

Burdick and colleagues found it was important to include both primary and secondary mediators of inflammation in their research “as the effects of the primary pro-inflammatory cytokines can be blocked by a number of decoy receptors and soluble antagonists.” Elevations in these can provide additional information about the function of the immune system.

Editor’s Note: Targeting inflammation with the anti-inflammatory treatments minocycline and celecoxib has been shown to improve depression. Now the role of anti-inflammatory drugs in improving cognition deserves further attention.

Mounting Evidence of Mitochondrial Dysfunction in Bipolar Disorder

July 16, 2019 · Posted in Risk Factors · Comment 
mitochondrion

mitochondrion

At the 2019 meeting of the International Society for Bipolar Disorders, researchers Ana Andreazza, Olivia Dean and colleagues reviewed substantial data that implicate mitochondrial dysfunction in the mood and energy fluctuations that make up bipolar disorder. Most of the neurobiological alterations known to occur in bipolar disorder have a relationship to mitochondria, which produce energy within cells. These alterations include abnormalities in glutamate, gene expression, apoptosis (cell death), oxidative stress, low ATP (a molecule that stores energy), altered ion pumps, increased intracellular calcium, and insufficient glutathionine (an antioxidant made up of three amino acids).

Coenzyme Q10 is a mitochrondrial enhancer of Complex I, an enzyme that is key to the first step in mitochondrial energy production. A 2018 controlled study by Maryam Mehrpooya and colleagues published in the Journal of Clinical Psychopharmacology found that 200mg/day of CoQ10 was more effective than placebo at reducing symptoms of bipolar depression when added to patients’ stable treatment regimens that included mood stabilizers and antidepressants. The effect size was large (0.87), and it took eight weeks for the benefit over placebo to appear. Response rate to CoQ10 was 72% compared to 12% to placebo.

Editor’s Note: Some formulations of CoQ10 do not cross the blood-brain barrier easily, so only a very small percentage of the CoQ10 gets into the brain. Thus, consumers should be careful about the type of product they purchase. The one made by Takeda Pharmaceutical Company is likely to be effective.

Early Predictors of Suicide and Lithium as an Anti-Suicide Drug

July 11, 2019 · Posted in Current Treatments, Risk Factors · Comment 

vitamin B6At the 2019 meeting of the International Society for Bipolar Disorders, researcher Gin S. Malhi discussed early predictors of suicide in people with bipolar disorder, such as younger age of illness onset, early life stressors, and family history of suicide. Impulsivity, hopelessness, cognitive deficits and substance use are risk factors, both for suicide in general and for an imminent suicide attempt. Proximal risk factors that indicate someone may make a suicide attempt soon include: mood swings, rapid cycling, increased depression, hospitalization, and severe anxiety.

Editor’s Note: Among all psychotropic drugs, lithium has the best data supporting its anti-suicide effects, both at therapeutic doses in patients with bipolar disorder and at trace levels in the water supply in the general population. People who live in locations where more lithium is naturally present in the water supply have lower rates of suicide than those who live in places with less lithium in the water. Malhi also noted that the antioxidant N-acetylcysteine (NAC), which has positive effects on mood and habitual behaviors, can reduce the incidence of lithium-induced dysfunction of the kidneys.

Obesity Associated with Inflammation and Brain Abnormalities

July 1, 2019 · Posted in Risk Factors · Comment 

obese family

At the 2019 meeting of the International Society for Bipolar Disorders, researcher David J. Bond reviewed the data on the multiple adverse effects of obesity in patients with bipolar disorder. These include increased cardiovascular risk, poorer response to treatment, brain abnormalities, and decreased cognitive function, which is correlated with the degree of overweight.

Editor’s Note: These data emphasize the importance of starting a nutritious diet early in life and sustaining it through adulthood, avoiding the drugs most associated with weight gain such as clozapine and olanzapine, and facilitating weight loss with drugs. There are several treatments that can aid in weight loss. One is the diabetes treatment metformin, starting at a high dose of 500mg twice daily, and increasing to 1000mg twice daily if tolerated. The anticonvulsants topiramate or zonisamide also promote weight loss. The most effective option is a combination of the antidepressant bupropion sustained release (at a dose of 150–300mg) plus the anti–substance abuse drug naltrexone (50mg). This combination was associated with a loss of 10% of body weight over 12 weeks in women with diabetes.

Red Meat Interacts with Bacteria in the Gut to Raise Heart Disease Risk

June 10, 2019 · Posted in Risk Factors · Comment 

steakA 2018 study by a group of researchers at the Cleveland Clinic have clarified the way that a diet heavy in red meat may lead to heart disease. The research centers on trimethylamine N-oxide (TMAO), a gut bacteria byproduct that is formed during digestion. When gut bacteria digest choline, lecithin, and carnitine, nutrients that are common in certain animal products and red meat, TMAO is produced.

In an article by Robert A. Koeth and colleagues in the European Heart Journal, the researchers show that diets that rely on red meat as the main protein source lead to more circulating TMAO than diets in which white meat or something other than meat is the primary source of protein. They found that in people who eat a lot of red meat, the kidneys are less efficient at expelling TMAO, and levels creep even higher. High levels of TMAO have been linked to hardening and narrowing of the arteries (atherosclerosis) and heart disease complications. High levels of TMAO in the blood can be a predictor of heart attack, stroke, and death.

The study of 113 participants consisted of three different diets that each participant followed in random order (with a washout period in between each diet). A month of eating a diet in which red meat was responsible for at least 25% of participants’ daily calories led to higher levels of TMAO in the blood and urine. TMAO increased threefold during the red meat diet periods compared to periods in which white meat or non-meat protein were the source of those calories, and in certain participants, TMAO increased as much as tenfold. When participants stopped eating the red meat diet, their TMAO levels fell over the following month.

Rich Western Diet Reprograms Immune Cells in Mice

June 4, 2019 · Posted in Risk Factors · Comment 

fat mouse

A 2018 article by Anette Christ and colleagues in the journal Cell describes the process by which a Western diet can trigger changes to the immune system in mice. The mice fed a calorically rich Western diet started to show systemic inflammation. Blood measures of inflammation returned to normal after the mice resumed their regular diet, but their immune responses remained heightened, as if the immune system had been trained to overreact.

The vast majority of deaths in Western cultures are caused by noncommunicable diseases such as type 2 diabetes and cardiovascular disease, which have been linked to lifestyle factors such as diet and exercise. The immune system has two wings: one that responds to specific pathogens, and one that mounts general protection against infection and is triggered by immune signaling receptors. However, according to Christ and colleagues, in addition to reacting when microbes are present, this second wing may also respond to “sterile” danger signs, such as consumption of a Western diet. The immune system may become trained to react this way chronically, something that the researchers believe may trigger inflammation in noncommunicable diseases.

The Western diet triggered epigenetic changes to the mice’s immune system. Epigenetic changes are ones that affect the structure of DNA, for example how tightly it is packaged. In the case of the Western diet, these changes resulted in a heightened immune system that launched strong inflammatory responses in reaction to even small stimuli. Myeloid cells from bone marrow were reprogrammed to proliferate and provide a stronger immune response.

The researchers also took human monocyte cells trained with LDL (“bad”) cholesterol and stimulated them with lipopolysaccharide (an inflammatory compound made of fat and sugar). The cells showed a heightened immune reaction similar to that seen in the mice.

Mice genetically engineered to lack the inflammasome NLRP3, which activates inflammatory responses, did not show the systemic inflammation or the enhanced myeloid activity when fed the Western diet, so Christ and colleagues believe NLRP3 may play an important role in mediating the immune response to the Western diet.

Eating Walnuts and Other Tree Nuts May Lower Cholesterol

May 29, 2019 · Posted in Risk Factors · Comment 

assorted tree nuts

In a 2018 meta-analysis and systematic review published in the American Journal of Clinical Nutrition, researcher Marta Guasch-Ferré and colleagues shared their analysis of 26 studies of the effects of diets rich in walnuts on blood lipids and cardiovascular health. The studies included a total of 1059 participants. The walnut-heavy diets were associated with lower total cholesterol, lower LDL (“bad”) cholesterol, and lower triglyceride concentrations. They were also associated with lower apolipoprotein B, a component of LDL.

When walnut-enriched diets were compared to American diets and Western diets, the benefits of the added walnuts on total cholesterol and LDL cholesterol were even more dramatic. The researchers described a Western diet as high in red and processed meats, high-fat dairy products, processed and artificially sweetened foods, and with little intake of fruits, vegetables, fish, legumes, or whole grains.

Compared to control diets, the diets rich in walnuts did not cause weight gain or an increase in body mass index (BMI), and they also did not affect blood pressure.

The studies included in the meta-analysis lasted from four weeks to one year, with a mean length of 8 weeks. The amount of walnuts ranged from 15 to 108 grams per day. In most cases, participants were given whole walnuts to incorporate into whatever daily meal plan they were following, which in some cases was their usual diet and in others was an intervention diet such as a Mediterranean diet or a low-fat diet.

Another meta-analysis published in the American Journal of Clinical Nutrition in 2015 by Liana C. Del Gobbo and colleagues analyzed 61 studies about the effects of tree nuts on cholesterol and related measures, and similarly found that eating tree nuts lowers total cholesterol, LDL cholesterol, ApoB, and triglycerides. Del Gobbo and colleagues wrote, “The major determinant of cholesterol lowering appears to be nut dose rather than nut type.” Tree nuts include walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts.

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