Unlocking the mechanisms of electroconvulsive therapy

Many people's knowledge of electroconvulsive therapy (ECT) begins and ends with somewhat unflattering media portrayals of the treatment. However, many studies suggest that it is an effective tool for many of those whose severe major depressive disorder hasn't responded to medication and other standard treatments (though some scientists question these findings).

The technique, which involves applying electrodes to the head and delivering a series of brief electrical pulses, is also sometimes used to treat depression in people with bipolar disorder. For these groups, ECT often helps, with about three quarters of treated patients showing improvements.  

Even so, write Tommaso Toffanin at the University of Ferrara, Italy and colleagues in a new paper in Acta Neuropsychiatrica, surprisingly little is known about how exactly ECT works.

One suggestion is that it works by increasing 'cortical thickness' — the depth of the cortex, the outermost layer of the brain. To investigate whether this is the case, Toffanin and team scoured the literature for suitable studies, identifying 10. These studies involved a total of 253 patients who received ECT, the overwhelming majority of which had major depressive disorder or treatment-resistant depression, as well as 143 healthy controls, who did not have ECT.

By comparing an initial MRI brain scan, done in the week prior to the ECT session, and another done during the week after treatment, the researchers observed that in most studies, ECT boosted the thickness of temporal, insular and, to a lesser extent, frontal areas of the cortex. (These changes were mainly in the vicinity of the electrode, or electrodes.) Abnormalities in all of these regions have been linked to major depression.

Cortical thickening also occurred in some other regions, including the fusiform gyrus (which is involved in the recognition of objects, including faces), the entorhinal cortex (which is involved in memory and navigation, as well as time perception) and the anterior cingulate cortex (which is important for motivation, decision-making and learning, among other things.) Again, all of these regions have been implicated in major depressive disorder and depression in bipolar disorder.

One of the reasons for thinking that cortical thickening might improve depression comes from studies of people on anti-depressant drugs. Some of this work has linked cortical thickening to successful drug treatment.

However, in the new review, cortical thickening in just one region was linked to improvements in clinical symptoms of depression — the right lateral occipital gyrus, which is involved in the perception of faces and emotion. And, in the single study that conducted a further MRI six months after the ECT, cortical thicknesses had returned to pre-treatment levels, but patients continued to report improvements in their depression.

So, are changes to cortical thickness driving the beneficial effects of ECT for depression — or is something else going on?

Other research has found that ECT boosts the production of two key growth factors in the brain. The first is brain-derived neurotrophic factor. This protein supports the growth of new brain cells and promotes neuroplasticity — the ability of the brain to form and reorganise connections between neurons. ECT has also been shown to increase levels of vascular endothelial growth factor, which is critical for the growth of blood vessels and which also promotes the growth of new brain cells. (Physical exercise notably also boosts levels of both these growth factors — and can alleviate depression.)

One result of changes in levels of these growth factors, as a result of ECT, might be increased cortical thickness. But this may not be the key reason why ECT can alleviate depression. By boosting neuronal plasticity, ECT may also 're-wire' the brain — and this re-wiring might instead be responsible for the benefits for patients.

Toffanin and colleagues stress that the studies included in their review suffered from various limitations. For example, only six had a control group, and of those, not all found differences in cortical thicknesses between patients and healthy controls. Also, most of the studies did not have the gold-standard randomised controlled design. The sample sizes were also relatively small. All of these issues make it harder to draw firm conclusions about the impact of ECT on cortical thickness.

So while these studies certainly suggest that ECT triggers changes in the thickness of various regions of the cortex that are known to be implicated in depression, it's not clear whether that thickening in particular is the cause of improvements in symptoms. To understand exactly how ECT alleviates depression — and, hopefully, to develop even more effective treatments — we need more research into the precise brain changes that are triggered by this procedure, as well as those that accompany successful treatment with anti-depressant drugs.

Regardless of potential mechanisms, ECT is likely to remain a controversial treatment within the Psychology community, with some questioning not only the ethics of the procedure, but also its effectiveness. Concerns have also been raised over whether patient experience has been properly captured in research explorations, and psychologists, such as the University of East London's John Read, have undertaken global attempts to address this gap.

Read the paper in full.