People with major mental disorders such as schizophrenia and bipolar disorder are at increased risk for medical symptoms including overweight, obesity, high cholesterol or triglycerides, diabetes, and the metabolic syndrome, all of which increase risk of cardiovascular disease (heart attack), cerebrovascular disease (or strokes), and other medical difficulties. In a 2013 review article in the journal Bipolar Disorders, researcher Chittaranjan Andrade discussed the use of statins to prevent cardiovascular events in people with major mental disorders.
Statins decrease lipids, and have significant benefits in decreasing cardiac events, but their use is low among psychiatric populations. Psychiatric patients often receive less cardiac care. It may be up to their psychiatrists to push for aggressive prevention of cardiac illnesses.
The most significant side effect of statins is the possibility that they can increase risk of diabetes. In a meta-analysis by Preiss et al., intensive dosing with statins increased the risk of diabetes but also lowered the risk of cardiovascular events. In a year, 1,000 patients would get two extra cases of diabetes but 6.5 fewer cases of cardiovascular events. For patients at high risk for heart attack or stroke, a cardiovascular event is more dangerous than diabetes, so it makes sense to treat these patients with statins. In patients at lower risk, there is some evidence that diabetes risk was a problem mostly in patients with other risk factors for diabetes, including metabolic syndrome, impaired fasting glucose levels, a body mass index of 30 kg/m2 or higher, or glycated haemoglobin A (1c) above 6%.
Most studies of statins are conducted on patients in middle age, but there is a rationale for treating even younger patients with statins. Patients with bipolar disorder develop cardiovascular disease more than a decade earlier than controls. There is some evidence that cholesterol deposits in arteries begin even before age 20, and are cumulative. The risk-benefit ratio for statin use improves with years of use, so starting it earlier may lead to better prevention. Long-term use may reduce the risk of Alzheimer’s disease and Parkinson’s disease and some cancers in addition to reducing heart attacks and strokes.
Despite the risk of diabetes, it is important to consider statin use in psychiatric patients, especially those who receive antipsychotic medications. Read more
A recent twin study suggests that the genes that confer risk for bipolar disorder may also be associated with verbal ability and sociability. Considerable evidence has suggested that people with bipolar disorder have greater intelligence and creativity than the normal population. Positive qualities like these may make people with bipolar disorder attractive mates, leading to the continued propagation of genes that promote bipolar disorder. (One might expect lower than normal rates of reproduction in people with bipolar disorder due to the difficulties the illness creates, as occurs with schizophrenia, but people with bipolar disorder have normal rates of reproduction, suggesting that any obstacles to mating are balanced by other particularly attractive qualities.)
Researchers led by Rachel G. Higier used a Swedish registry of twins to investigate whether people with bipolar disorder and their fraternal or identical twins without the illness have better verbal ability and sociability. Bipolar patients and their twins (who would be expected to have similar genetic and familial risks but without the negative impact of the illness and medications for it) were compared to patients with schizophrenia and their twins and normal controls. The well twins of bipolar patients scored higher on a scale of positive temperament than the bipolar patients, schizophrenia patients and their twins, and controls. The twins of bipolar patients also scored better than schizophrenia patients and their twins and controls on tests of verbal learning and fluency, while the bipolar patients showed lower levels of cognitive function (likely due to their illness).
The researchers conclude that the genes that put families at risk for bipolar disorder also confer positive traits like verbal ability and positive temperament that make people with bipolar disorder attractive mates. Even though bipolar disorder may reduce these traits somewhat, people with the illness still are more creative than the general population and often very successful.
In a poster at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Larissa Portnoff reported that NF-kB, a marker of inflammation that can be measured in two types of white blood cells (lymphocytes and monocytes), was significantly elevated in adolescents who had bipolar disorder compared to healthy control participants.
Several other inflammatory markers have been linked to bipolar disorder, including c-reactive protein (CRP) and TNF alpha. The new data about NF-kB suggests that another inflammatory pathway is overactive in the disorder. NF-kB levels did not correlate with the severity of manic or depressive symptoms, as do levels of some other inflammatory markers.
At the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Robert Findling reported on a double blind, placebo controlled 36-week study of lamotrigine for children and adolescents with bipolar I disorder. The doses designed for maintenance treatment averaged about 225 mg/day, achieved by very slow increases over time in order to reduce the risk of a serious rash.
Findling found that lamotrigine was more effective than placebo in extending the time until a patient required an intervention for a new mood episode among the older children in the study (aged 13 to 17). Among the younger children in the study (aged 10 to 12), lamotrigine’s effects were not statistically significant compared to placebo. Findling and colleagues concluded that lamotrigine appeared effective in delaying time to onset of a new episode in adolescents with bipolar I disorder.
Lamotrigine is approved by the Federal Drug Administration (FDA) for bipolar disorder in adults only.
At the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, Fung et al. presented a meta-analysis of treatments for autism that ranked them in terms of statistical effect size, ranging from 0.9 (large), to 0.5 to 0.8 (medium), to <0.4 (small). The only drug with a large effect size was risperidone, at 0.9. Most effect sizes were medium, including aripiprazole at 0.8 and N-acetylcysteine (NAC) at 0.7. Both clonidine and methylphenidate had effect sizes of 0.6, and tianeptine’s was 0.5.
Fung and colleagues noted that the first two on the list, the atypical antipsychotics risperidone and aripiprazole, often have problematic side effects (such as sedation, weight gain, and motor symptoms) that must be balanced against their effectiveness. In contrast, NAC is well tolerated with few side effects, and two placebo controlled studies showed that it was effective both alone and as an adjunctive treatment to the antipsychotic risperidone.
At the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Adelaine Robb reported that in 81 children with mania (aged 7-17), lithium was superior to placebo in reducing the severity of mania measured on the Young Mania Rating Scale. There had been some debate about the efficacy of lithium in young children with mania, but this study clearly indicates lithium’s effectiveness. The drug is approved by the Federal Drug Administration (FDA) for use in patients with bipolar disorder aged 12 and up.
Another researcher, Vivian Kafrantaris, found that in children who averaged 14.5 years of age, lithium increased the volume of the corpus callosum, a bundle of neural fibers that connects the brain’s right and left hemispheres. Lithium also normalized white matter integrity in other neural fiber tracts—the cingulum bundle and the superior longitudinal fasciculus. The authors concluded that lithium may “facilitate microstructural remodeling of white matter tracts involved in emotional regulation.”
Editor’s Note: There is much research showing that in adults, lithium has positive effects on the brain, including increases in hippocampal and cortical grey matter volume. Now it appears that lithium can improve white matter integrity in the developing brain as well.
Researcher Amanda Roten reported at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry that adolescents who stopped heavy marijuana use showed improvements in multiple areas of learning and memory. These data support previous findings that pot can cause impairments in cognitive functioning, but that abstaining from the drug can bring about improvement relative quickly.
These data contrast with some others. A 2009 study by J. Jacobus et al. in the journal Pharmacology Biochemistry and Behavior suggested that some changes in brain structure resulting from marijuana use, such as decreases in cortical volume, can persist for one to three months following abstinence.
Madeline Meier, another researcher at the meeting, reported that 1,037 participants who used marijuana persistently from about age 13 to age 38 lost an average of 8 IQ points. Controlling for years of education and other potential confounds such as alcohol and drug use did not affect these findings. Moreover, Meier found that “cessation of cannabis use did not fully restore IQ among adolescent-onset cannabis users.”
Editor’s Note: The popular view that marijuana is a benign substance overlooks some key facts. The main pharmacological effect of pot is amotivational syndrome, causing apathy and lack of drive to participate in work, study, and other activities. Heavy use of pot doubles the risk of psychosis, and this risk is further increased if a user has a common genetic variation in the enzyme catechol-o-methlyl transferase (COMT), which metabolizes dopamine. The more efficient allele of COMT (known as val-56-val, identifying two valine amino acids) lowers frontal cortex dopamine more, and increases the risk of delusions and hallucinations. Marijuana alters brain structure and impairs memory. It may now be legal in some states, and while reducing penalties for smoking marijuana may be a good idea, this does not mean the drug is a harmless substance.
The moral of the story is that avoiding marijuana use in the first place, especially for people with bipolar disorder, should make it easier to get well and stay well. For current marijuana users, N-acetylcysteine (NAC, a nutritional supplement available without a prescription from health food stores) has been shown to help adolescents decrease marijuana use more than placebo.
Researcher Charles Popper gave a talk at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry on the benefits of nutritional supplements designed to provide multiple vitamins and minerals to children with bipolar disorder and other dyscontrol syndromes, such as attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder. Popper reviewed the literature on the substantial incidence of vitamin and mineral deficiencies among these children.
A modicum of data support the effectiveness of supplements for children with these disorders. One of these supplements is called EMPowerPlus and is sold online. It is moderately expensive and must be given under the supervision of a knowledgeable treating physician. While it is relatively safe in medication-free children, Popper says it can exacerbate withdrawal reactions from some psychotropic medications.
In addition, EMPowerPlus greatly increases lithium-related side effects, in patients taking lithium, the dose must be reduced to about one-tenth of a normal dose for those who are adding EMPowerPlus.
Popper and another researcher, Mary Fristad, have both seen excellent responses to this type of supplementation in children with bipolar disorder who have been unresponsive to more traditional drugs.
In another study by Rita Aouad et al., 72.3% of 980 children with a variety of psychiatric diagnoses had insufficient vitamin D levels (values < 30 nanograms/ml) and 26.7% had vitamin D deficiency (values < 20 nanograms/ml). These data support the rationale for vitamin D supplementation, especially in those who have low levels to start with.
In a huge study of Swedes, compared to offspring of young fathers (aged 20–24), offspring of older fathers (over age 45) are 24.7 times more likely to develop bipolar disorder. Older paternal age was also associated with other risks of mental disorders, such as autism, attention deficit hyperactivity disorder (ADHD), suicide attempts, substance abuse and psychosis, but the strongest finding was of a relationship with bipolar disorder.
Mutations that occur during the production of sperm may be responsible for the increased risk of illness in the offspring of older fathers.
The population-based cohort study published by Brian M. D’Onofrio et al. in the journal JAMA Psychiatry included all individuals born in Sweden between 1973 and 2001.
New research suggests that the ratio of cortisol to C-reactive protein (CRP), a marker of inflammation, may be a biomarker of depression that affects men and women differently. In women, lower ratios of cortisol to CRP were associated with more severe depression symptoms, including poor quality sleep, sleep disturbances, and decreased extraversion. In men, higher ratios of cortisol to CRP were associated with more daytime disturbance and greater anxiety. The study by E.C. Suarez et al. was published in the journal Brain, Behavior, and Immunity.
Further work must be done to confirm whether low cortisol and high inflammation predicts depression in women, while the opposite (high cortisol and low inflammation) predicts depression in men.