While past research on mood disorders has targeted structural and functional abnormalities in the brain, newer research has considered targets such as inflammation, metabolism, and cell resilience. Exercise can have positive effects on systems that regulate metabolism, immune function, and cellular respiration, and therefore improve affective and cognitive difficulties.
At the 2014 meeting of the International Society for Bipolar Disorders, Mohammad Alsuwaidan presented a meta-analysis of the effects of exercise in mood disorders gleaned from English-language studies between 1966 and July 2008. Exercise increased brain norepinephrine, serotonin, and phenylethanolamine (PEA).
Alsuwaidan believes runner’s high, the feelings of euphoria people often experience after strenuous exercise, may not be linked to opiate (or endorphin) release, as most people believe, but instead to release of PEA or the cannabinoid anandamide, which activates CB 1 cannabinoid receptors, decreases GABA, and increases dopamine in the nucleus accumbens, the reward center of the brain.
Exercise also increases neurogenesis and the production of brain-derived neurotrophic factor (BDNF), which supports the growth of neurons and synapses. Marathon runners also have a post-race elevation in the anti-inflammatory cytokines IL-10 and IL-1Ra.
In people who are out of shape, exercise increases oxidative stress and other toxicities that do not occur with in those who exercise more regularly. Alsuwaidan extolls the benefits of high impact exercise five to seven times per week, and engaging a trainer to encourage exercise. Four minutes of intense exercise (such that you sweat and are not able to talk) is about equal to 45 minutes of mild exercise.
About a year ago we reported that exercise was recommended for patients with fibromyalgia and chronic fatigue syndrome. The case for exercise has been bolstered by a 2013 analysis published by the Cochrane Collaboration, a nonprofit research network. The authors reviewed five randomized clinical trials that compared resistance training with a control or another type of physical activity in a total of 219 women. Resistance training is exercise that is performed against resistance with the intention of improving muscle strength, and can include weights, resistance machines, or elastic resistance bands. The authors found that in the studies they analyzed, resistance training was both beneficial and safe for women with fibromyalgia, and that aerobic exercise helped reduce pain.
As reported in Medscape Medical News, lead author Angela Busch said, “It appears that people with fibromyalgia can benefit from this form of exercise, but we noted that the programs we examined involved supervised exercise and started low and gradually increased the resistance. There are particular health benefits associated with resistance exercise (e.g. increasing bone strength, which is important for preventing osteoporosis), so it is good to know that clinicians can safely [recommend] this form of exercise.”
Whether patients will widely accept this recommendation remains to be seen since some doctors have advised only rest. The key to avoiding pain exacerbation while adding an exercise regimen may be, like in much of medicine, to start slow.
Editor’s Note: The antidepressant milnacipran (Savella) is the most recent drug to receive Federal Drug Administration approval for the treatment of fibromyalgia. Pregabalin (Lyrica) and duloxetine (Cymbalta) were approved for fibromyalgia in 2007 and 2008, respectively.
Exercise increases brain-derived neurotrophic factor (BDNF), a protein that protects neurons and is important for learning and memory. In a study of mice who were trained to find objects, sedentary mice could not discriminate between familiar object locations and novel ones 24 hours after receiving weak training, while mice who had voluntarily taken part in exercise over a 3-week period could easily distinguish between these locations after the weak training.
Mice who received sodium butyrate (NaB) after training behaved similarly well to those who had exercised. Sodium butyrate is a histone deacetylase (HDAC) inhibitor, meaning it helps keep acetyl groups on histones, around which DNA is wrapped, making the DNA easier to transcribe. In this case the easy transcription of DNA enables learning under conditions in which it might not usually take place.
Both sodium butyrate and exercise promote learning through their effects on BDNF in the hippocampus. They make the DNA for BDNF easier to transcribe, suggesting that exercise can put the brain in a state of readiness to create new or more lasting memories.
New research shows that psychotherapy lowers the risk of relapse in unipolar major depression more than “treatment as usual” does, and also heads off depression in children at high risk.
At the 2013 meeting of the American Psychiatric Association, researcher Pim Cuijpers reviewed 32 trials of cognitive behavior therapy, intensive behavioral therapy, and problem solving therapy used for the prevention of depression and found that these therapies were associated with a 21% lower risk of relapse compared to treatment as usual.
There were five critical elements that made these therapies useful: they supported coping with depression, and they included exercise, mindfulness, internet-based cognitive behavior therapy, and problem solving.
Among those who presented at the meeting, Greg Clarke of Kaiser Permanente, Oregon discussed an 8-week course on coping with stress given to a group of adolescents (aged 14 to 16) who had four times the normal risk of developing depression because each had a parent with depression. Clarke found a significant reduction in depression among the adolescents who received therapy compared to controls.
Insomnia can be a precursor to a first depression or to recurrent depression. Cognitive behavior therapy was more effective in improving sleep than a comparative sleep hygiene course.
Researcher Judy Garber presented data showing that cognitive behavior therapy was effective in 13- to 17-year-olds who had a parent with depression and had themselves had a prior depression or were currently sub-syndromal. The effect of the therapy was only significant if the parent was not depressed at intake.
Bicycling at speeds of 77–80 rpm seems to benefit patients with Parkinson’s disease. After neuroscientist Jay Alberts and one of his patients rode a tandem bicycle across Iowa to raise awareness of the illness, he noticed that her symptoms had improved. He had ridden in front, setting a pace that forced her to pedal faster. Their experience inspired the study, in which 26 patients with Parkinson’s were assigned to either ride a stationary bike at their own pace, or ride at a forced rate, where a trainer in the front seat of a tandem bicycle controlled the pedaling rate, which was at least 30% faster than the voluntary rates. After 8 weeks of thrice-weekly pedaling, the forced-rate group saw a 35% improvement in symptoms, compared to no improvement in the voluntary-rate group.
Study authors used functional connectivity magnetic resonance imaging (fcMRI) to measure levels of blood oxygen in the brain before, immediately after, and 4 weeks after the 8 weeks of exercise therapy. In the fast pedaling group, task-related connectivity between the primary motor cortex and the posterior part of the thalamus improved. Some cortical regions in the brain showed less activity, suggesting that Parkinsons’ patients who usually must use these areas to compensate for their motor deficits required less of this alternative brain activity after the exercise therapy. The research was presented at the Radiological Society of America’s annual meeting in 2012.
At the 2012 meeting of the Collegium Internationale Neuro-Psychopharmacologicum (CINP), a symposium was held to discuss fibromyalgia and chronic fatigue syndrome, two illnesses that remain mysterious.
Fibromyalgia is more common in women than in men and is characterized by aching all over, decreased sleep, stiffness upon waking, and most prominently, being tired all day, as well as a host of other symptoms including headache, dizziness, and gastrointestinal upset. Researcher Siegried Kasper suggested that treating fibromyalgia requires more than just medication. His approach is known as MESS, which stands for medication, exercise, sleep management, and stress management.
Medications to treat the illness include milnacipran (not available in the US), duloxetine (Cymbalta, a serotonin-norepinephrine reuptake inhibitor or SNRI), or pregabalin (Lyrica), and if tolerated, low doses of the tricyclic amitriptyline (Elavil).
According to Kasper, SSRIs and anti-inflammatory drugs don’t work, and benzodiazepines decrease the deepest phase of sleep (stage 4) and can exacerbate the syndrome.
Recommended exercise is moderate, graded (to a pulse of about 120, or at a level where the patient can still talk, but can’t sing), and should be done in the early morning rather than the late afternoon where it might interfere with sleep.
Good sleep hygiene is recommended, such as keeping the same sleep schedule every day and abstaining from caffeine (even in the morning).
Working on developing active coping strategies for stressors that are likely to occur is a good idea. Mindfulness and other meditative techniques may also be helpful. Joining a support group (that encourages exercise rather than discouraging it) was also recommended.
Chronic Fatigue Syndrome
At the CINP meeting researcher Simon Wessely discussed chronic fatigue syndrome (CFS), which has many overlaps with fibromyalgia. He reported that careful controlled study of more than 15,000 individuals has not indicated that the illness is associated with a viral infection. Just as many people with and without chronic fatigue syndrome were found to be infected with a virus.
However, like the myth that vaccines cause autism, the myth that chronic fatigue is associated with a virus remains popular despite the lack of evidence. A large randomized study validated Wessely’s treatment techniques, but he has continued to be vilified for the position that the illness is not virally based. The study showed that patients who participated in cognitive behavior therapy and graded exercise improved more than those who received conventional medical management.
Wessely thought the most important cognitive change to make was accepting that exercise is not harmful for patients with chronic fatigue syndrome, and is in fact helpful and therapeutic. Many older treatment approaches had advocated rest, rest, and more rest, or even “intensive rest.” However, Wessely indicated that this would be counter-productive, as the patient would lose muscle mass and cardiovascular conditioning, and would become even more tired and chronically fatigued.
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.
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.
Patients with Bipolar Depression Have a Higher Mortality Rate, Especially if They Also Have Cardiovascular Disease
In a large longitudinal study of depressed patients in Taiwan that was published in the Journal of Psychiatric Research this year, Chang et al. found that after 10 years, patients with bipolar depression (N=1,542) had significantly higher mortality rate than those with other types of depression (N=17,480). Patients with bipolar depression were twice as likely to have died from suicide or accidental death than were patients who had other types of depression. When cardiovascular disease was also present in both groups, patients with bipolar disorder were also four times more likely to have died from suicide or accidental death than those with other types of depression.
Editor’s Note: These data again emphasize the critical importance of patients with bipolar disorder carefully looking after their medical and cardiovascular health both early on and throughout the entire course of their illness.
Much of the excess medical mortality in bipolar disorder is attributed to cardiovascular disease, and now those with cardiovascular disease also appear more prone to suicide. This should be a call to action to improve the long-term treatment of both bipolar disorder and its common comorbidity, cardiovascular disease.
Get your medical illness treated!
It will improve your health and longevity. Especially treat these signs of the metabolic syndrome, a major risk factor for cardiovascular disease:
- Cholesterol–Increase “good” cholesterol (high-density lipoproteins or HDLs) and lower “bad” cholesterol (low-density lipoproteins or LDLs)
- High Triglycerides–Triglycerides should be below 150 mg/dL
- Blood Pressure–Aim for 130/85 mmHg or lower
- Blood Sugar–Fasting blood sugar (glucose) should stay below 100 mg/dL
- Overweight & Obesity–Keep waist circumference under 40” for men or 35” for women
Exercise is good for all of these!