Juggling to make connections

Several studies have investigated whether exercise can prevent loss of white matter. The study by Scholz et al. is of particular interest. In it, healthy students were given juggling kits and told to learn to juggle by practising 30 minutes every day for 6 weeks. Before and after this 6 week period, the jugglers and a control set of non-jugglers had their brains scanned by diffusion tensor imaging (fDTI). At the end of the study, the brains of the jugglers showed increased fractional anisotropy indicative of an increase in white matter compared to the controls. Importantly, after 4 weeks of non-juggling, the jugglers’ new white matter remained in place. Juggling appears to boost the connectivity of the brain.

Practice makes perfect

Dr Hilleke Hulshoff Pol, Utrecht, Netherlands, wanted to find out whether it was practice or new skill acquisition that had caused this effect and whether brain connectivity could be changed in schizophrenia. She was well placed to do so. As all Dutch people learn to cycle from a young age, using this fact allowed an experiment to be devised that would untangle the effects of learning and practice.

Exercise is our base-state. It’s non-exercise that may be the culprit in many deleterious conditions, including psychiatric illness

A total of 33 patients with schizophrenia and 48 healthy controls were assigned to exercise (cycling) or life as usual (LAU) for 6 months. DTI scans taken before and after this period showed that, regardless of disease state, regular physical exercise significantly increased the integrity of white matter fibre tracts. LAU promoted decreased fibre integrity. Importantly, it’s the practice not the acquisition of a skill that drives these changes. In the process, both groups improved their cardiovascular fitness.

Aerobic exercise enhances CACR

Aerobic exercise improves symptoms in schizophrenia, including cognitive impairments. Berend Malchow, Munich, Germany, explained his study in which the effects of ergometer training on a stationary-bike and add-on computer-assisted cognitive remediation (CACR) training were assessed. Schizophrenia patients and healthy controls underwent 3 months of endurance training (30min, 3 times/wk). At 6 weeks into training, CACR (30min, 2 times/wk) was added. A second group of schizophrenia patients played table football and had CACR training for the same period.

After 3 months, a significant improvement in Global Assessment of Functioning (GAF), Social Adjustment Scale-II (SAS-II), social/leisure activities and household functioning adaptation was seen in patients receiving endurance training plus CACR but not in the group playing table football plus CACR. Negative symptoms, improved significantly in the schizophrenia endurance training plus CACR group from week 6 to the end of the 3-month training period. Thus, the addition of CACR to the exercise intervention appears highly beneficial.

Once they start, they will finish

Regular physical exercise significantly increases the integrity of white matter fibre tracts

Some other important findings were disclosed. Firstly, patients did not like table football! It may sound trivial but for a programme to work, an exercise that patients enjoy would be more likely to succeed. Secondly, if patients began the endurance training and attended the first 2-3 sessions, they stuck with the programme. Thirdly, patients were chased if they missed a session – and because they liked the person chasing them, attendance was 92%. Fourthly, patients doing the endurance training became physically fitter – which can only be a good thing. Interestingly, their lactate responses to exercise were poor compared to healthy controls.

Morphologically, scanning data showed little or no impact on grey matter, especially the hippocampus. Unlike in Dr Pol’s study, however, no impact on white matter was seen, no improvement in FA was noted and there was no carry over effect.

Exercise – love it or loathe it?

Andreas Meyer-Lindenberg, Mannheim, Germany, had a conflicted take on exercise. While a firm advocate of the value of exercise, he himself hates it! But the evidence he presented made it clear that exercise is essential for our mental wellbeing.

It is known that in mice and men, compared to sedentary controls, exercise increases grey matter hippocampal volume and a sedentary life style has the opposite effect – it brings about a decrease in grey matter volume. Thus, it appears you have to keep on exercising to maintain hippocampal brain volume. As Dr Meyer-Lindenberg pointed out, this is fine for mice who have been shown to like running but not so good for human couch potatoes.

Hippocampal neurogenesis is exercise-induced

The hippocampus is an area of the brain with the capacity for renewal. Could changes in hippocampal volume associated with exercise be due to enhanced neurogenesis? The effects of hippocampal irradiation on grey matter volume in exercising mice suggest this to be the case. Only in mice with an intact hippocampus did exercise promote expansion of grey matter volume. By comparing exercising and non-exercising mice brains with DCX-staining, a marker of neurogenesis, neurogenesis was shown to occur only in the exercising mice.

You have to keep on exercising to maintain hippocampal brain volume, which is fine for mice, but not so good for human couch potatoes

Thus, in mice, the pernicious decrease in grey matter can be prevented through exercise. And it has been show that mice, like men, get a runner’s high. Wheel running increases endocannabinoids and reduces both anxiety and sensation of pain in mice. Maybe this is why mice are hooked on running.

Exercise is our base-state

If this is an evolutionary mechanism for grey matter maintenance, it would appear that exercise is our base-state and it’s non-exercise that may be the culprit in many deleterious conditions, including psychiatric illness.

ESPRIT is a German study of patients with post-acute schizophrenia. It is known that patients with schizophrenia spend much of their time sedentary. One ESPRIT study arm will examine the effects of adding an atypical antipsychotic in combination with either exercise, cannabidiol or Integrated Social Cognitive and Behavioural Skills to their usual care. Recruitment is ongoing for this 36 month study.

If grey matter volume reduction in the human brain has to be maintained through exercise, how can we induce couch potatoes - with and without schizophrenia-  to rise from their sofas? That’s the 64 million dollar question. Table football is not the key, however.