Exercise and Depression by J.E

Antidepressant drugs effectively treat depression in the majority of patients, however up to 50% do not achieve full recovery and there is a risk of some symptoms persisting, and relapse and recurrence of depression occurring (Blake 2012). There is also a time lag for the onset of therapeutic drug effects and adverse side effects are often reported. Adherence to taking tablets can often be poor and patients prematurely discontinue antidepressant treatment. Alternative treatment options are therefore important.

Exercise can be used to treat depression. The effect of exercise is rapid and it can help to improve residual depression symptoms and prevent relapse. Antidepressants plus exercise also appears to be more effective than antidepressants alone for some people.

The current National Guidelines for exercise for all adults aged 18-64 are:

1. Adults should aim to be active daily. Over a week, activity should add up to at least 150 minutes (2½ hours) of moderate intensity activity in bouts of 10 minutes or more – one way to approach this is to do 30 minutes on at least 5 days a week.

2. Alternatively, comparable benefits can be achieved through 75 minutes of vigorous intensity activity spread across the week or combinations of moderate and vigorous intensity activity.

3. Adults should also undertake physical activity to improve muscle strength on at least two days a week.

4. All adults should minimise the amount of time spent being sedentary (sitting) for extended periods.

Individual physical and mental capabilities should be considered when interpreting the guidelines.

For individuals with mild or moderate depression, structured supervised exercise 3 times a week for 45-60 minutes for a period of 10-14 weeks is recommended. This is similar to the general national recommendations.

However, it has been suggested that this frequency and intensity of exercise may be too ambitious for depressed individuals – who often lack motivation and incentive to exercise. It has been argued that gradually increasing the intensity of exercise based on how the person perceives the effort involved (referred to as “preferred intensity”), rather than a prescribed intensity of effort, may lead to better psychological outcome in depressed patients (Callaghan et al. 2011). “Preferred intensity” introduces the exercise gently and in stages. The person has control over the level of exercise they can handle and hence this appears to increase enjoyment of the exercise.

The benefits of exercise are likely to be due to several factors – enjoyment and a sense of achievement from having done it; but also biological effects in the brain (see below). Preferred intensity exercise may help achieve some of these effects; but may be less likely to lead to the brain effects than more intense exercise. It is important that this is not taken as an argument just to exercise as hard as possible. Undertaking exercise must be sustainable. Doing it at too high an intensity, risks causing physical injury, with resultant negative impacts on a person’s psychological well- being and an inability to continue with exercise at least for a period of time. As a result, it is always critical that the amount and intensity of exercise is appropriate for the individual person and only increased gradually. As a rule of thumb: never increase the amount or intensity by more than 10% per week, and don’t increase at all one week in four.

Benefits of exercise on depression

Patients with depression who receive exercise treatment have higher rates of becoming free of symptoms than those who don’t exercise (Blumenthal et al. 1999). Those who’s depression is proving difficult to treat (for example not responding to a number of different medications and/or talking therapies) who are prescribed exercise alongside antidepressants showed a 21% response rate (that is at least a 50% improvement in depressive symptoms) and a 26% remission rate (that is becoming essentially free of symptoms) (Mura et al. 2014). This result was better than been treated by antidepressants alone. Exercise has also shown to be as effective as cognitive behavioural therapy (Greist et al. 1979, Lawlor et al. 2001).

The benefits of exercise are long lasting. Positive effects on depression have been shown to last for up to 12 months (DiLorenzo et al. 1999).

The relationship between exercise and depression is “dose dependent” – that is the more exercise you do, the bigger the effect on depression. The frequency of the exercise is important. More frequent exercise has a bigger effect on depression than lower frequency. This is also the case with regards to exercise intensity. However, note the important point made above about undertaking exercise too frequently or with too high an intensity, which potentially can ultimately lead to the complete opposite effect – making depression worse. So, it is important to tailor the amount of exercise to the individual; and increase slowly and carefully.

The psychological effects of exercise

Exercise can distract from depressing thoughts, can increase self- esteem, can provide a sense of achievement and improve social interaction. Listening to music or the words of music can reduce depressive thoughts. Setting yourself an achievable goal and succeeding in reaching that goal is not only good for your self-esteem; but will provide satisfaction through achieving the set goal. Joining an exercise group can help improve social interaction eg a running club, a yoga group, a gym.

Effect of exercise on mood regulating neurotransmitters

What is a neurotransmitter?

It is possible that the beneficial effects of exercise in depression are due to a direct effect on the neurotransmitters that we know control mood and anxiety (Cotman et al. 2002). Over the years there have been many studies of the effects of exercise on these neurotransmitters. This has been done using laboratory animals because it is not possible to measure these neurotransmitters in living people. The results of these studies have been varied and it seems that the species, strain and age of the animal can impact on what the effects of exercise are, and therefore have to be taken into account.

The results of these studies can be summarised in relation to the various hypotheses about individual neurotransmitters.

The ENDORPHIN hypothesis- A group of neurotransmitters in the brain are similar to opiates (drugs related to opium). These include beta endorphins. These are released following exercise and it has been suggested that a euphoric effect of these (sometimes described as a “runners high” for example) might result in an improvement of mood (Steinberg et al. 1985) (Persson et al. 2003, Persson et al. 2003).

The MONOAMINE hypothesis- “Monoamines” are a group of three neurotransmitters thought to be particularly important for mood regulation: serotonin (also known as 5-HT), noradrenaline and dopamine. It has previously been suggested that these neurotransmitters are low in depression. This does not seem to be the case, though there is evidence that they are maybe not functioning as well as normal. Almost all current antidepressants are thought to act by increasing levels of one or more of these neurotransmitters, or improving the way they work. This includes antidepressants like fluoxetine (Prozac) which are referred to as “SSRIs” or “selective serotonin reuptake inhibitors”. Their name reflects that they work on the neurotransmitter serotonin (5-HT). The way they work is by making more serotonin available in the synapse to carry the message from one brain cell to the next. Serotonin is made in the body from an amino acid called tryptophan. How much serotonin we have depends entirely on the supply of tryptophan. Tryptophan is known as an "essential" amino acid because the body does not produce it - we have to get it from our food. For reasons that are not entirely clear, exercise increases tryptophan, and hence serotonin.

Effect of exercise on hormones

What is a hormone? What is cortisol? What is the HPA Axis?

One hormone that is of particular interest in depression is the stress hormone cortisol (rodents eg rats- use the hormone corticosterone rather than cortisol, so human studies measure cortisol while many animals ones measure corticosterone). Cortisol is released at the end of a cascade of hormones.

Another hormone in the body which may be important in depression and how exercise (and other treatments) might work, is “Brain Derived Neurotrophic Factor” (BDNF). This is a hormone that is released within the brain and travels to other brain areas in blood and in the fluid that bathes the brain. It can also be measured (in small quantities) in the blood stream around the body. BDNF promotes and regulates the birth of new nerve cells (this is called neurogenesis)(Olson et al. 2006) (Lee et al. 2002), the growth and development of nerve cells, and the development of connections between them (including more synapses being created).

There is some evidence that in people with depression there are slightly lower levels of BDNF than in people who are well. There are also findings that many treatments know to work for depression, including antidepressants, can lead to slight increases in BDNF.

The HPA axis has been studied extensively in depression. On average people with depression have larger hypothalamuses, pituitaries and adrenal glands, and they have higher levels of cortisol in their blood. High levels of cortisol may impair the way that serotonin (5-HT) works).

Exercise reduces the HPA axis response has to stress and this relates to a reduction in depression (Brosse et al. 2002). This might be for many reasons including a reduction of cortisol impairing the action of serotonin (see above) or a reduction in cortisol inhibiting the birth of new neurones and their growth and development.

In humans, exercise, like antidepressants, is associated with increased levels of BDNF in people with depression.

Combining antidepressants with exercise appears to be more effective than either intervention alone in some people (Russo-Neustadt et al. 2001)

Other effects of exercise on the brain.

In addition to looking at effects of exercise on neurotransmitters and hormones, researchers have also examined the effects of exercise on the birth of new nerve cells (neurogenesis). There is some debate as to the significance of the relatively small number of new cells that are “born” compared with the total number in the brain. However, there are suggestions that these new nerve cells may play an important role in regulating the HPA axis, and if neurogenesis is decreased, the axis may tend to be too active leading to higher levels of cortisol.

This is not the only reason why neurogenesis has been of interest to researchers investigating depression and its treatment. Animal studies have demonstrated that stress leads to a reduction in the number of new cells being born. Conversely antidepressants and electroconvulsive shock treatment (ECT) lead to an increase. In addition, most types of exercise enhance neurogenesis, consistent with it having an antidepressant effect.

Of possible even more importance than the birth of a relatively small number of new nerve cells throughout life, it is known that the number and strength of connections between nerve cells can change quite substantially. Just as with neurogenesis, stress and administering corticosterone to animals can lead to a reduction in the number and quantity of connections, while antidepressants increase them. So too with exercise. This may be related to the effect of all of these treatments in increasing BDNF (see above).

Voluntary versus forced exercise

Exercise can be voluntary or forced. In a laboratory, a running wheel can be used to study voluntary exercise in rodents. A running wheel is a rewarding piece of running apparatus. As the rodent is free to exercise as and when it likes- there is no increase in the stress hormone corticosterone. This voluntary exercise can result in up to a 3 fold increase in neurogenesis (Olson et al. 2006). Forced exercise is studied using a treadmill. Researchers can control the speed, frequency, intensity, duration and timing of the exercise. The animal is forced to run even when not motivated to do so. The animal is gently prodded or experiences a small electric foot shock to induce it to exercise. This in itself may produce mental and physical stress. There may be an increase in corticosterone levels and a reduction in neurogenesis.

Not all treadmill running results in a stress response. Palmer et al. (1999) showed that rats trained on a treadmill for 20 weeks, gradually increasing speed and duration, minimised the stress evoking effects of running on a treadmill. Regular treadmill running results in the body adapting to the forced exercise and it provides a balance between the positive and negative effects of treadmill running. After several weeks, exercise no longer elevates the stress hormone corticosterone (Leasure et al. 2008), so that the positive effects on neurogenesis can be seen. Regular runners show a biological adaptation. Irregular runners experienced more stress and do not adapt as readily. Regular moderate physical exercise improves coping with stress (Byrne et al. 1993) which in itself may help reduce problems with depression.

Forced exercise can be seen in some military personnel, professional athletes and patients who have been prescribed an exercise program to follow which they are not motivated to do.


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