Physical activity and light to moderate drinking (as is often associated with the Mediterranean diet) are recommended as ways to reduce risk for heart disease and type 2 diabetes. New research shows that among healthy people, symptoms of depression can counteract the anti-inflammatory benefits of both exercise and light to moderate alcohol consumption.
C-reactive protein (CRP) is a cardiometabolic risk marker. High measures of CRP are a sign of inflammation. Leisure-time physical activity and light to moderate alcohol intake (defined as about half a drink per day for women and one drink per day for men) are associated with lower levels of CRP. Depression is associated with higher levels.
A study by Edward C. Suarez et al. published recently in the journal Brain, Behavior, and Immunity examined 222 nonsmoking men and women aged 18-65 years. These participants were physically healthy and had no history or diagnosis of psychiatric conditions. Participants recorded the amount of alcohol they consumed and the amount of physical activity in which they participated. CRP levels in their fasting blood samples were measured, and they also completed an inventory of depressive symptoms.
Those people who were physically active had lower levels of CRP, but the 4.5% of participants with depressive symptoms did not see any anti-inflammatory benefits from physical activity. Similarly, light to moderate drinking was associated with lower levels of CRP only in men who were not depressed.
Depression did not seem to affect other markers of physical health in this study, such as levels of triglycerides or cholesterol.
Editor’s Note: This study suggests that treating depressive symptoms should be a part of any plan to reduce cardiovascular risk. It seems that depression has effects that go beyond psychological distress and may prevent patients from reaping the benefits of their healthy behaviors. The effect of depression in preventing heart healthy changes in CRP could be one of many factors mediating the high levels of cardiovascular risk in depression. People with depression are twice as likely to have a heart attack than those without depression.
Research has connected cardiovascular fitness with depression risk and treatment. A Swedish study published last year in the British Journal of Psychiatry examined records of men conscripted into the military at age 18 and compared their cardiovascular fitness at the time with hospital records from later decades. Low cardiovascular fitness at the time of conscription was associated with increased risk for serious depression.
Editor’s Note: This study provides more evidence that exercise, which increases cardiovascular fitness and decreases many of the elements of the metabolic syndrome, is good for cardiovascular and neuropsychological health, including mood stability. It is noteworthy that exercise also increases both brain-derived neurotrophic factor or BDNF (important for neural development and long-term memory) and neurogenesis (in animals), effects shared by almost all treatments with antidepressant properties. Making exercise a routine part of a regimen aimed at medical and psychiatric health is a great idea.
As childhood obesity has increased over the past several decades, the metabolic syndrome has also become more prevalent among children and adolescents. The metabolic syndrome consists of five measures related to obesity: elevations in fasting glucose levels or insulin resistance, a high proportion of LDL (“bad” cholesterol) to HDL (“good” cholesterol), elevated triglycerides, hypertension, and abdominal obesity or high waist circumference. A patient with three of these abnormalities would be diagnosed with the metabolic syndrome.
In adults, the metabolic syndrome has been associated with neurocognitive impairments. Researchers decided to look at adolescents with the metabolic syndrome to determine whether these brain effects are a result of long-term metabolic impairment or whether they can take place after short-term periods of poor metabolism as well. In a study published by Yau et al. in the journal Pediatrics last year, 49 adolescents with the metabolic syndrome were compared to 62 adolescents without the syndrome who had been matched for similar age, socioeconomic status, school grade, gender, and ethnicity.
The adolescents with the metabolic syndrome had lower scores on tests of math, spelling, attention, and mental flexibility, as well as a trend for lower overall intelligence. In brain measures such as hippocampal volume, amount of brain cerebrospinal fluid, and microstructural integrity in white matter tracts, the seriousness of the metabolic syndrome correlated with the level of abnormality on these measures.
Editor’s Note: It seems as though even short-term problems with metabolism can lead to brain impairments like lower cognitive performance and decreased integrity of brain structures. These effects are even seen before vascular disease and type 2 diabetes are manifest.
It is doubly important, in terms of both cardiovascular and neurobiological risks, to look out for one’s medical and psychiatric health. Reducing the abnormal components of the metabolic syndrome should produce benefits for both the cardiovascular system and the central nervous system.
Almost 40% of patients with bipolar illness in the US have the metabolic syndrome, so considerable effort will be required to improve this public health crisis.
Many patients with depression require two or more treatments in order to achieve remission. In a 2011 study by Trivedi et al. published in the Journal of Clinical Psychiatry, patients with major depressive disorder who had not responded adequately to selective serotonin reuptake inhibitor (SSRI) antidepressants improved when an exercise regimen was added to their regular treatment.
The patients, aged 18-70 years old, were all sedentary at the start of the trial. They were randomized to one of two exercise regimens: a high dose regimen (16 kcal/kg per week, equivalent to walking at about 4 mph for 210 minutes per week) or the low dose (4 kcal/kg per week, equivalent to walking at 3 mph for about 75 minutes per week). Both groups improved significantly by the end of the study. Remission rates (adjusted for differences between groups) were 28.3% for the high dose group and 15.5% for the low dose group.
The rates of improvement with exercise were similar or better to those commonly seen with other augmenting agents such as lithium, T3, buspirone, and atypical antipsychotics, but without side effects and other inconveniences such as blood monitoring.
Other studies have indicated that exercise by itself and in combination with other treatments has efficacy in depression. Exercise can change serotonin and norepinephrine function and can increase brain-derived neurotrophic factor (BDNF), a, and neurogenesis in the hippocampus.
The researchers looked for moderating variables that may have affected the outcomes of various participants. Men, regardless of family history of mental illness, had better remission rates in the high dose group. Women without a family history of mental illness also improved more in the high dose group, while women with a family history of mental illness improved more in the low dose group, though this finding was statistically nonsignificant.
While the researchers observed that those in the high-dose group did exercise more than those in the low-dose group, participants in the high-dose group had more difficulty sticking to their exercise regimen. It may be that even though high doses of exercise offer slightly higher rates of remission, lower doses may be more effective clinically if patients can stick to the low-dose regimen better.
A 2013 article by Smith et al. in the journal Diabetes, Obesity, and Metabolism reports that obese patients treated with the combination of bupropion (Wellbutrin) and naltrexone (Revia) had excellent weight loss and reduction in body fat compared to those treated with either drug alone or with placebo. The combination resulted in about a 14% reduction in body fat, while placebo, bupropion alone, and naltrexone alone each brought about only a 3-4% reduction.
Editor’s Note: Researcher Roger McIntyre is an expert on the metabolic syndrome in patients with bipolar illness and has been using this combination with success in patients with mood disorders. He finds the combination of bupropion and naltrexone more helpful than the anticonvulsants topiramate (Topomax) or zonisamide (Zonegran) or the anti-diabetes drug metformin.
Since obesity and the metabolic syndrome occur in approximately 40 to 50% of bipolar patients and significantly increases cardiovascular risks such as heart attack and stroke, and since bupropion is widely used in the treatment of bipolar depression, this combination appears worthy of consideration for those with obesity. Its use should be accompanied by a good diet and an exercise regimen. Decreasing cardiovascular risk is a very important component of the treatment of bipolar disorder, and the combination of bupropion and naltrexone could have substantial benefits.
A decades-long study in New Zealand suggests that people who use marijuana persistently during adolescence lose 8 IQ points by adulthood compared to their peers who never use marijuana. Quitting or reducing cannabis use after adolescence did not restore the intellectual abilities in those who used it persistently in their youth. This is the first study of its kind that controlled for differences in functioning that existed before adolescence.
Participants took part in neuropsychological testing at the age of 13, prior to any cannabis use, and then were periodically interviewed about their use of the drug (at the ages of 18, 21, 26, 32, and 38). At age 38 they underwent IQ testing again.
Although persistent cannabis users tended to have fewer years of education, the lack of education was not responsible for the difference in adult IQ.
Those participants who only began using cannabis persistently in adulthood did not see a decline in IQ, suggesting that the adolescent brain is particularly susceptible to damage from cannabis use.
Synthetic marijuana, otherwise known as spice, skank, or K2, is not only vastly more potent than the tetrahydrocannabinol (THC) in marijuana plants, but it also lacks cannabidiol (CBD), the calming, antipsychotic substance also present in the plants. This makes spice much more likely to induce major psychiatric effects.
New evidence links use of spice during pregnancy to a tragic birth defect, anencephaly, or absence of the cerebral cortex. It can also lead to the later development of attention-deficit hyperactivity disorder, learning disabilities, memory impairment, depression, and aggression.
Effects of THC on gestation may occur as early as two weeks after conception, meaning by the time a woman realizes she is pregnant, the fetus may have been harmed by exposure to the drug.
Other new finding associate use of spice with acute coronary syndrome and the kind of acute kidney injury that can lead to the organ shutting down.
Editor’s Note: It has now been found that synthetic marijuana, or spice, can lead to psychosis, delirium, acute coronary syndrome (heart attack) in young people, and now kidney dysfunction, in addition to causing birth defects if used by pregnant women. Not only is spice made up of more potent THC without the calming effects of CBD, but it is often laced with unknown contaminants, which are likely the cause of the heart and kidney damage.
Smoking regular marijuana is bad enough—it doubles the risk of psychosis and may precipitate the onset of schizophrenia. It may also cause long-lasting effects on cognitive function. Since many states are legalizing marijuana, it is important to know the risks. In any case the risks are much more serious with the synthetic product, and synthetic marijuana should be avoided at all costs.
Bumetanide has been used for decades to treat fluid retention in those with heart failure or liver or kidney disease. In the brain, it allows chloride ions to leave cells more easily. Scientists researching pediatric seizures think that reducing the chloride inside brain cells helps GABA neurons’ inhibitory functions work better. This led to speculation that bumetanide could be useful in neonatal epilepsy and autism.
In a 2012 study by French researchers including Eric Lemonnier that was published in the journal Translational Psychiatry, 60 patients aged 3 to 11 who had been diagnosed with autism or Asperger’s syndrome were given either placebo or 1mg of bumetanide daily for 3 months. By the end of the study, the children who received bumetanide showed an average reduction of 5.6 points on the Childhood Autism Rating Scale (CARS), which is assessed from observing behavior during videotaped sessions of children playing with their caregiver and questioning the child’s parents. Children taking placebo showed a reduction of 1.8 points (a statistically significant difference). Clinicians in the study rated almost twice as many children who took bumetanide as having made a significant or a small improvement. Stereotyped behavior and restricted interest were the areas of behavior that seemed to improve most after treatment with bumetanide. Patients with milder autism when the study began tended to improve more than those who started out with more severe symptoms. Symptoms returned to previous levels within a month the study’s end.
Bumetanide’s side effects are well known. It can sometimes cause decreases in potassium in the blood (hypokalemia), so the children’s potassium levels were monitored closely. One child was withdrawn from the study for hypokalemia, which can predispose one to cardiac arrhythmias.
Physical punishment of children has long been a controversial subject. A 2012 article by Afifi et al. in the journal Pediatrics suggests that having experienced harsh physical punishment during childhood is associated with mood disorders, anxiety disorders, substance abuse and dependence, and personality disorders in adulthood.
In this study harsh physical punishment included pushing, grabbing, shoving, slapping, or hitting. Participants who had experienced more severe maltreatment in childhood (including physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect, and exposure to violence between intimate partners) were excluded from the study, and the results were adjusted for sociodemographic variables and family history of dysfunction, suggesting that physical punishment was the mediator of these effects.
Research has shown that serotonin-selective reuptake inhibitor (SSRI) antidepressants can be useful for severe premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). According to a 2006 article by Steiner et al. in the Journal of Women’s Health, there are various ways that SSRIs can be used to treat PMS symptoms such as irritability, depressed mood, dysphoria, bloating, breast tenderness, appetite changes, and psychosocial function, including intermittent dosing just in the two weeks prior to PMS. Usually doses for PMS are lower than those used to treat depression.
For those with mood symptoms that continue throughout the month, continuous (daily) dosing may improve PMS symptoms. For those whose mood symptoms worsen during PMS, continuous dosing can be intermittently increased from around the time of ovulation to a few days after the period begins. For those women with mood symptoms only during PMS, intermittent dosing only during those weeks between ovulation and the period seems to be helpful and minimizes side effects of the SSRIs.
Editor’s Note: While SSRIs sometimes take weeks to reach maximum benefit for those with depression, intermittent dosing for women with severe PMS seems to be helpful. This may be because SSRIs acutely increase the neurosteroid allopregnanolone, which enhances GABA-A receptor activity, associated with improvement in mood and anxiety.