A 2016 study in the journal Psychoneuroendocrinology confirms that high levels of inflammatory cytokines in the blood are linked to higher risk of depression following a stroke.
The study, by Hee-Ju Kang and colleagues, followed 222 stroke sufferers for one year. Two weeks following the stroke, their levels of inflammatory cytokines IL-6 and IL-18 were measured. They were also assessed for depression both at the two-week point and one year later. The researchers also observed whether or not the participants were treated with statins, which are often prescribed to lower stroke risk and also have anti-inflammatory effects.
Those participants who had depression following their strokes (either at two weeks or at one year) tended to be older, to have a history of depression or stroke, to have a more severe stroke, and to have a stroke location toward the front of the brain.
Having any depression following the stroke was associated with higher levels of IL-6 and IL-18. This was particularly true of those participants who were not taking a statin. Among those taking statins, the statins may have interfered with the link between inflammatory cytokines and post-stroke depression. In the statin group, the only significant finding was a link between levels of IL-6 and depression at the two-week mark.
Depression has been linked to increases in medical problems such as cardiovascular disease. A new study shows that depression is linked to increased risk of stroke, even when symptoms of depression are in remission.
The 2015 study, by Paola Gilsanz and colleagues in the Journal of the American Heart Association, focused on health and retirement. It included over 16,000 adults aged 50 and up who were interviewed every two years about their health history.
Previous studies have shown a link between depression and stroke risk. Like those studies, the study by Gilsanz and colleagues found that people who were depressed during two consecutive interviews were more than twice as likely to have a stroke in the subsequent two-year period than those who reported few depressive symptoms in the first two visits.
What is new is that in this study, people who were depressed in the first interview but not in the second interview were still at 66% greater risk for a stroke than those with no depression. Those who were depressed only during the second interview not at greater risk for a stroke, implying that depression takes more than two years to affect stroke risk.
Gilsanz and colleagues suggest that they don’t know how depression, remission, and stroke risk interact over the longer term. It is possible that stroke risk diminishes the longer a patient’s depression stays in remission.
It is not clear why depression increases strokes, though some have speculated that depression causes irregular heartbeats. There is not as yet any support for that theory, but high blood pressure, rigid veins, or sticky platelets may be other explanations.
Research continues on pioglitazone, a drug typically used to treat diabetes but with other positive effects on depression and stroke risk. Some researchers are working on determining whether the drug increases the risk of developing certain cancers, including bladder, prostate, and pancreatic cancers. A recent study by James D. Lewis and colleagues in the journal JAMA found no statistically significant increase in risk of bladder cancer among patients taking the drug, but the researchers said they also couldn’t rule out that the drug may increase this risk, as has been seen in previous studies. The study by Lewis did show an increase in pancreatic and prostate cancers in patients taking pioglitazone, but the researchers did not determine whether this was caused by the drug.
Another recent study by Walter N. Kernan and colleagues in the New England Journal of Medicine reported that pioglitazone reduced the incidence of stroke and heart attack in patients with a history of stroke or blocked blood vessels in the brain but without a diagnosis of diabetes. Patients who received pioglitazone also experienced side effects including weight gain, edema (an increase in fluids in the body’s tissues) and serious bone fractures.
Pioglitazone has had positive effects in bipolar depression and may one day be used as a treatment for bipolar disorder. For now, it may be worthy of consideration for the treatment of diabetes in patients who also have bipolar depression.
One-third of people who have strokes face depression afterward. New research is looking to expand the safe options for the treatment of depression following strokes. At the 2015 meeting of the Society of Biological Psychiatry, researchers led by Leandro Valiengo presented their successful randomized, sham-controlled double-blind study of transcranial direct current stimulation for post-stroke depression. Forty-eight people who had depression following a stroke were randomized to receive either a sham procedure or tDCS in twelve 30-minute sessions over a period of six weeks. After the six weeks, those who received tDCS had fewer symptoms of depression, more remission, and better response. There were no serious side effects.
TDCS is very low-level electrical current that has a positive (anode) or negative (cathode) electrode. Anodal stimulation of the cortex is usually associated with positive effects on mood and cognition. TDCS sessions in this study consisted of 2-mA anodal left/cathodal right dorsolateral prefrontal stimulation.
Editor’s Note: Placebo-controlled studies have repeatedly indicated that patients who have a stroke show better neurological and psychiatric response afterward when they are given an selective serotonin reuptake inhibitor (SSRI) antidepressant, whether or not they have depression or a prior history of depression. If a neurologist does not suggest treatment with an SSRI after a stroke, ask why not. Since antidepressants increase brain levels of brain-derived neurotrophic factor (BDNF) and increase neurogenesis, they could help with post-stroke recovery.
A balance test may indicate declining cognitive health and risk for stroke. Researchers led by Yasuharu Tabara had previously found that balancing on one leg became more difficult for people with age. Now the same team has found that this type of postural instability is associated with decreases in cognitive functioning and with risk of stroke. Fourteen hundred participants with an average age of 67 were challenged to balance on one leg for up to 60 seconds. They also completed computer surveys, magnetic resonance imaging (MRI) scans, and a procedure to measure the thickness of their carotid artery. Those who could not balance on one leg for 20 seconds or longer were more likely to have cerebral small vessel disease.
Editor’s Note: Whether exercise would reverse this vulnerability remains to be seen, but lots of other data suggest the benefit of regular (even light) exercise on general health.
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
Lifetime Heart Disease Risk Increases Dramatically When One or More Risk Factors Are Present in Middle Age
A meta-analysis of 18 studies that was published by Donald Lloyd-Jones in the New England Journal of Medicine in 2012 shows that increasing cardiovascular risk factors during middle age can dramatically increase a person’s risk of experiencing fatal cardiovascular disease, fatal coronary heart disease, nonfatal heart attack, or stroke later in life.
Data were analyzed from 257,384 patients, who included black and white men and women spanning a 50-year range of birth cohorts. The studies examined cardiovascular risk factors such as smoking, cholesterol levels, diabetes, and blood pressure at ages 45, 55, 65, and 75.
Having even one risk factor at age 55 dramatically increased the lifetime risk of cardiovascular disease compared to having no risk factors, and having more risk factors during middle age increased risk even further. Among people with no risk factors at age 55 (meaning cholesterol under 180mg/dL, blood pressure under 120 mm Hg systolic and 80 mm HG diastolic, nonsmoking and nondiabetic), men had 4.7% risk of death from cardiovascular disease by age 80 (compared to 29.6% for those with 2 or more risk factors). Women had a 6.4% risk of death from cardiovascular disease by age 80 (compared to 20.5% among those with 2 or more risk factors).
Lifetime risk of death from cardiovascular disease and coronary heart disease and risk of nonfatal heart attack were about twice as high in men, while risk of stroke was similar for men and women.
Across race, trends were similar, but this finding can be misleading. While African-Americans have more cardiovascular risk factors than whites, they are also more likely to die at younger ages from other causes before developing serious cardiovascular illnesses. Large studies with Latino and Asian American participants were begun too recently to provide robust data about long-term risk, but this research is expected to become available soon.
Editor’s Note: Watch your risk factors for heart disease, including high blood pressure, cholesterol, weight, and blood sugar. The more risk factors one has, the greater the increased risk of fatal cardiovascular illness.
Depression is also a risk factor for coronary artery disease, and should be treated just as aggressively and persistently as the other risk factors. Exercise is one element of a healthy lifestyle that can positively affect all of these risk factors. Implementing a healthy diet and exercise regimen by middle age will have long-term positive effects in reducing risks in older ages.