Adversity May Increase Risk of Mood Disorders
In adults with bipolar disorder, adversity in childhood has been associated with an earlier onset of bipolar disorder compared to those who did not experience some form of adversity such as verbal abuse, physical abuse, sexual abuse, loss of a parent, abandonment, or neglect. At the 2013 meeting of the Society of Biological Psychiatry, Nancy Low et al. reported that the number of these stressful life events a child experienced was associated with the number of their anxiety symptoms, psychiatric disorders, and lifetime substance abuse. Having experienced 3 or more adversities was associated with a 3.5-fold increased risk for developing a mood disorder and a 3-fold increase in anxiety disorders and alcohol or drug abuse.
While the study has not yet been published in a peer-reviewed journal, the abstract (#194) may be found in the meeting supplement, Volume 73, Number 9S of the journal Biological Psychiatry.
Editor’s Note: Low’s study is the first to report that childhood adversity is a risk factor for the onset of bipolar disorder in the general population.
Given the increasing evidence for the persistence of epigenetic marks on DNA and histones (which can’t change the sequence of genes but can change their structure) in those who have experienced such stressors in childhood, this could provide a mechanism for the long-term vulnerability of these children to the development of mood disorders and a variety of physical illnesses.
Loss of Appetite or Weight in Depressed Parents Predicts Depression in Children
Depression in a parent is one of the factors that best predicts whether a young person will develop depression. Since depression symptoms can vary greatly from person to person and some symptoms are known to be more heritable than others, new research is investigating whether a parent’s profile of symptoms affects their child’s likelihood of developing the illness. A 2013 study by Mars et al. in the Journal of Clinical Psychiatry suggests that loss of appetite or weight in a parent with depression is the symptom that most strongly predicts new onset of depression and depressive symptoms in their offspring.
The study observed 337 parent-child pairs. The parents (mostly mothers), who had a history of recurrent unipolar depression, ranged in age from 25–55 years, and their children ranged from 9–17 years. The study lasted four years, during which the families participated in three assessments. Parents’ symptoms were recorded and children were also assessed for symptoms or new development of depression. Thirty percent of the offspring whose parents reported weight loss or low appetite were found to have new onset of depression at followup, compared to nine percent of the offspring whose parents did not have these symptoms.
There are nine symptoms used to diagnose depression in the Diagnostic and Statistical Manual for Mental Disorders: low mood, loss of interest (anhedonia), loss of energy, change in appetite or weight, change in sleep, low self-esteem or guilt, suicidality, psychomotor slowing (retardation), and loss of concentration or indecisiveness. Of these, parental loss of appetite or weight was the only symptom that predicted depression in a child. Interestingly, the severity of parental depression or the presence of other health problems in the parent did not account for the emergence of illness in the children.
U.S. Patients with Bipolar Disorder Have More Stressors in Childhood and Prior to Illness Onset
In research published since 2008, our Editor-in-Chief Robert M. Post and colleagues in the Bipolar Collaborative Network have compared patients with bipolar disorder in the United States to those in Germany and the Netherlands. Compared to the European sample, patients in the US have more genetic vulnerability to bipolar disorder (by having a parent with bipolar disorder), earlier onsets of their illness, more complicated courses of illness, greater treatment resistance, and more medical comorbidities. Patients in the US also have more psychosocial stress.
The researchers are now turning their attention to these psychosocial vulnerabilities, and in a new paper that will be published in Psychiatry Research (late in 2013 or early in 2014), the authors show that patients in the US had more stressors both in childhood and just prior to the onset of their illness. Childhood stressors analyzed in the study were verbal abuse, physical abuse, and sexual abuse. Stressors in adulthood included indicators of a lack of social support, troubles with finances or employment, lack of access to health care, and medical comorbidities.
The stressors patients experienced just prior to their most recent episode of bipolar illness were related to: stressors in childhood, an earlier age of illness onset, anxiety and substance abuse comorbidity, lower income, both parents having an affective illness such as depression, and feeling more stigma.
The new research suggests that for patients with bipolar disorder in the US, adverse life events in childhood and later in life are more prevalent than they are for patients in the Netherlands or Germany. Earlier and more effective approaches to these stressors, such as the Family-Focused Therapy developed by David Miklowitz and Kiki Chang, could potentially slow the onset or progression of bipolar illness in this country.
Ambien Linked to Emergency Room Visits, Among Other Risks
Zolpidem, better known by one of its trade names, Ambien, is widely prescribed for the short-term treatment of insomnia. It can sometimes cause adverse reactions, particularly among women and the elderly. The Substance Abuse and Mental Health Services Administration (SAMHSA) has reported that over a recent 5-year period, emergency department visits for adverse reactions to zolpidem increased by almost 220%.
Peter Delaney, Director of SAMSHA’s Center for Behavioral Health Statistics and Quality, suggested that doctors should consider alternative strategies for treating insomnia, including improving sleep hygiene by avoiding caffeine, exercising regularly, and sleeping in a quiet, dark room. He also suggested that doctors should be aware of what other medications a patient is taking, and ideally all of a patient’s prescriptions should be collected from the same pharmacy, so the pharmacist can act as a second pair of eyes identifying possible drug interactions.
Women and men metabolize zolpidem differently, and according to Sam Fleishman of the American Academy of Sleep Medicine, many women can still be impaired by the drug 8 hours after taking it. In 2013, after reports of adverse reactions to zolpidem increased, the Federal Drug Administration (FDA) required manufacturers of drugs containing zolpidem to reduce the recommended dose for women by half, from 10 mg to 5 mg, or 12.5 mg to 6.25 mg for the extended-release version. The FDA also suggested halving the dosage prescribed to the elderly, and reducing the recommended dose for men.
Some of the adverse reactions to drugs containing zolpidem include daytime drowsiness, dizziness, hallucinations, sleepwalking, and even “sleep driving.” When combined with antianxiety medications, narcotic pain relievers, or alcohol, zolpidem’s sedative effects can be enhanced to dangerous levels.
Safe Upper Limit of Vitamin D Identified
A recent study confirmed that low levels of vitamin D can increase risk of death and determined a safe upper limit for vitamin D levels. The research, published by Yosef Dror et al. in the Journal of Clinical Endocrinology & Metabolism, showed that safe blood levels of vitamin D are between 20 and 36ng/mL. People with levels above or below this range were at greater risk of mortality or acute coronary syndrome.
Dror suggests that calcium supplement dosages should be specifically tailored to individuals based on levels in their blood.
The research comes from 54 months of data collection during which 422, 822 members of Clalit Health Services, an Israeli health maintenance organization, were tested for vitamin D levels. Only 3% percent of this population were at risk because of high levels of the vitamin, while 62% were at risk due to low levels of vitamin D.
Editor’s Note: Watch out for low vitamin D3. Even if a patient’s levels of D3 are in the normal range, supplementation can help antidepressants work better. According to a study published in the Australian and New Zealand Journal of Psychiatry, adding 1500 IU of vitamin D3 to the treatment regimen of depressed patients taking fluoxetine (Prozac) improved their response significantly.
High Level of Calcium Intake and Supplements May Be Harmful
In a study of over 60,000 women, Swedish researcher Karl Michaëlsson et al. found that those women with the highest intakes of calcium (>1400mg/day) were at higher risk of mortality, particularly from cardiovascular causes such as cardiovascular disease and heart disease (but not stroke), than women with calcium intakes of between 600 and 1000mg/day. The research was published in the journal BMJ in 2013.
While calcium dietary supplements were not associated with elevated risk per se, those women with the highest calcium intake levels who also took supplements had a risk of mortality from all causes that was more than 2.5 times that of women with similar total calcium intake who did not take supplements.
Calcium levels in blood are tightly controlled by the body, but very low or very high calcium intake levels can override this control, causing imbalances.
The efficacy of calcium supplements for conditions such as osteoporosis or chronic kidney disease has not been established, and a healthy balanced diet and avoidance of water filters that remove calcium from drinking water may be best.
Salt Implicated in Autoimmune Diseases
Autoimmune diseases, in which the body’s immune system begins to attack healthy tissue, have become much more common in recent decades. Some autoimmune problems are related to overproduction of TH17 cells, immune cells that produce a particular inflammatory protein (interleukin-17), but it is not clear why some people’s bodies start producing too many TH17 cells. Three studies published in the journal Nature in 2013 suggest that salt may play a role. They were recently summarized in Scientific American.
In the first study, researchers developed a model of how TH17 cells are controlled. In the second, they observed how immune cells are produced over a period of several days. The researchers noticed that a protein called serum glucocorticoid kinase 1 (SGK1), which is known to regulate salt in cells, seemed to act as a signal for TH17 production. Mouse cells in high-salt environments had more SGK1 and produced more TH17. The third study confirmed the connection with salt using both mouse cells and human cells.
While mice with multiple sclerosis (an autoimmune disease) worsen on a high-salt diet, it is not clear that salt in the diet is related to TH17 production. It is also not clear that slowing TH17 production is the answer to autoimmune diseases since autoimmunity differs across patients and disorders. However, in any event, low-salt diets are recommended for general health concerns, such as blood pressure.
Childhood Adversity and Epigenetic Pockmarks
Maltreatment in childhood may have a lasting impact on health through epigenetics. Epigenetics refers to the idea that events and substances in the environment can affect the structure of DNA by adding chemicals (often methyl or acetyl groups) onto DNA and histones (structures around which DNA is wound) in such a way that the DNA is more or less likely to be transcribed and activated to produce new proteins. Thus our DNA is shaped not only by the genetic inheritance we receive from our parents, but also by events in the environment (which do not alter the sequence of DNA but can influence how easily the DNA gets turned on to produce proteins in our bodies.)
A 2013 study by Divya Mehta et al. published in the Proceedings of the National Academy of Sciences analyzed the childhood backgrounds of adult patients with PTSD and found that patients’ profiles of disease-related gene expression and DNA methylation in blood differed greatly depending on whether or not they had experienced abuse in childhood. Adults who had been abused as children were about twice as likely to show patterns of DNA methylation accompanying their PTSD-related changes in gene expression.
The implication of this research is that childhood trauma can leave a kind of epigenetic pockmark on a person’s DNA, affecting the way the DNA produces proteins, potentially for the rest of that person’s life.
Obesity and Bipolar Disorder
David Bond presented research at the 2013 meeting of the International Society of Bipolar Disorder about the connections between obesity and the course of bipolar disorder. Bipolar disorder has some of the highest rates of obesity among all psychiatric illnesses. Obese patients with bipolar disorder have more episodes of depression, more suicide attempts, worse response to psychiatric medications, and more cognitive impairment between episodes of illness.
Bond also found that higher body mass index (BMI) was associated with reduced white and gray matter volume in the brain, greater cognitive impairment, increased risk of Alzheimer’s disease, and increased glutamate concentration in the hippocampus (which is potentially neurotoxic) and decreased NAA (a marker of neuronal integrity). Those with 7% weight gain or higher in the first year of treatment show a greater loss of volume in the frontal and temporal lobes.
Editor’s Note: These data again speak to the importance of maintaining good lifestyle habits such as proper diet and exercise to attempt to slow or prevent the development of obesity. Also avoiding medications for bipolar disorder with the greatest liability for weight gain and using some that can help with weight loss would be good topics for discussion with a treating physician.
Iodine Deficiency in Pregnancy Bad for Fetus
A study published in the Lancet reports that even mild iodine deficiency during pregnancy can have adverse effects on IQ and cognitive development in the fetus. This occurs because of the deficiency’s effects on thyroid function.
Editor’s Note: Eat fish, drink milk and take a vitamin supplement with 140 to 150mcg of iodine.
