Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders

Abstract

There remains much scientific, clinical, and ethical controversy concerning the use of electroconvulsive therapy (ECT) for psychiatric disorders stemming from a lack of information and knowledge about how such treatment might work, given its nonspecific and spatially unfocused nature. The mode of action of ECT has even been ascribed to a "barbaric" form of placebo effect. Here we show differential, highly specific, spatially distributed effects of ECT on regional brain structure in two populations: patients with unipolar or bipolar disorder. Unipolar and bipolar disorders respond differentially to ECT and the associated local brain-volume changes, which occur in areas previously associated with these diseases, correlate with symptom severity and the therapeutic effect. Our unique evidence shows that electrophysical therapeutic effects, although applied generally, take on regional significance through interactions with brain pathophysiology.magnetic resonance imaging | voxel-based morphometry | unipolar depression | hippocampus E lectroconvulsive therapy (ECT) is the oldest well-established procedure for somatic treatment of unipolar and bipolar disorders (1); however, its precise mechanism of action is still unclear (2). Our current understanding is that the antidepressant effect of ECT is partially mediated by seizure-induced neurotrophic effects, resulting in increased rates of neurogenesis, synaptogenesis, and glial proliferation, particularly in the hippocampus (3-5). Modern neuroimaging experiments have shown a critical role for the subgenual cortex (Brodmann area 25) (6) and deep brain stimulation of this area also results in alleviation of symptoms (7,8). Concerns regarding structural brain damage caused by ECT have been largely attenuated because of a lack of experimental evidence for ECT-induced neuronal damage (9). The scarce in vivo evidence for ECT-induced structural brain plasticity comes from region-of-interest (ROI) imaging studies reporting ECT-related hippocampal volume increases (10) that correlate with clinical outcome (11,12). Limited by an ROI approach and a lack of adequate control groups, these studies may have incompletely detected the effects of right unilateral ECT and failed to distinguish them from pharmacologically induced changes or indeed the effects of disease.We decided to resolve these ambiguities by carrying out a study with drug responsive (no-ECT) and drug-resistant (ECT) patients with either uni-or bipolar depression ( Fig. 1 and Table 1). The two psychiatric conditions are considered separate from pathophysiological and nosological viewpoints. A group of normal volunteers was included to control for non-ECT-associated confounds and to provide a way of assessing ECT-associated therapeutic effects. All subjects were recruited and imaged using structural magnetic resonance at entry (time point 1, TP1). If unresponsive to drugs, patients had ECT administered unilaterally to the right hemisphere. All study participants were imaged again at 3 mo (TP2) and 6 mo (TP3). ECT was giv...

Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression

“…This is in line with previous studies (Nordanskog et al, 2010;Tendolkar et al, 2013;Abbott et al, 2014;Dukart et al, 2014;Nordanskog et al, 2014;Bouckaert et al, 2015;Jorgensen et al, 2015;Ota et al, 2015;Sartorius et al, 2016). Only two studies found an association between hippocampal volume increase and therapeutic efficacy (Dukart et al, 2014;Joshi et al, 2015). Our data suggest that the hippocampal volume increase after ECT is transient and reverts to baseline within 6 months, even though the antidepressant effect is sustained.…”

“…Moreover, the hippocampus and brain regions that mediate emotional and cognitive regulation are anatomically connected, lending support to the role of the hippocampus in depressionrelated circuitry (Price and Drevets, 2010;Abbott et al, 2014). Several recent magnetic resonance imaging (MRI) studies have described hippocampal volume changes following ECT (Nordanskog et al, 2010;Tendolkar et al, 2013;Abbott et al, 2014;Dukart et al, 2014;Nordanskog et al, 2014;Joshi et al, 2015;Jorgensen et al, 2015;Ota et al, 2015;Bouckaert et al, 2015;Sartorius et al, 2016). Some of these studies have also addressed structural changes in other brain areas relevant to depressive disorders, such as dorsolateral prefrontal cortex, orbitofrontal cortex (Jorgensen et al, 2015), lateral temporal cortex (Bouckaert et al, 2015), caudate nucleus (Bouckaert et al, 2015), and amygdala (Tendolkar et al, 2013;Jorgensen et al, 2015;Joshi et al, 2015;Ota et al, 2015;Sartorius et al, 2016).…”

Can We Find Any Sustained Neurofunctional Alteration in Remitted Depressive Patients with a History of Modified Electroconvulsive Therapy?

“…Although several previous research studies have shown the increase in the GM volume of HPC after ECT (Dukart et al, 2014;Jorgensen et al, 2016;Ota et al, 2015), the morphometry carried out in this study showed no significant differences between the ECT and non-ECT groups in the GM volume of all ROIs, i.e., the left and right hemi-spheres of the cerebrum and HPC. The observational durations after ECT in those previous studies [within 3 months (Dukart et al, 2014), 1 -4 weeks (Jorgensen et al, 2016), and 9.0 ± 14.6 days (Ota et al, 2015)] were shorter than that in our study (0.86 ± 1.59 years). This might be a reason for the absence of a significant difference in GM volume between the ECT and non-ECT groups in our study.…”

“…Recent neuroimaging studies have revealed structural and functional differences in the human brain before and after an ECT series (Dukart et al, 2014;Jorgensen et al, 2016;Ota et al, 2015). Some studies have shown an increase in the GM volume of bilateral HPCs after ECT (Jorgensen et al, 2016;Ota et al, 2015); others have shown that an ECT series significantly contributes to the increase in the GM volume of the right HPC, but not to that of the left HPC (Dukart et al, 2014;Abbott et al, 2014). Moreover, recent functional magnetic resonance imaging (MRI) studies of ECT in depression have shown some laterality of neuronal connectivity of HPC.…”

On electroconvulsive therapy in depression : Clinical, cognitive and neurobiological aspects

“…In this population, they found only a right-sided increase, and suggested that predominant side of stimulation could be of importance. The laterality to a right sided hippocampus increase after ECT was also shown by Dukart et al (Dukart et al 2014), again suggesting a relation between side of stimulation and hippocampal volume increase. This hypothesis is not supported in our study, in which the increase in left hippocampus was more significant than in the right, despite a predominance of right unilateral treatments.…”