The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.

BACKGROUND: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. METHODS: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. RESULTS: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean 6 SD of 1.04 6 1.03% (Cohen's d = 1.01, p , .001) and the subcortical gray matter volume increased by 1.47 6 1.05% (d = 1.40, p , .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation r = 2.44, p , .001), while total white matter volume remained unchanged (d = 20.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. CONCLUSIONS: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.

Electroconvulsive therapy (ECT) is an established treatment choice for severe, treatment-resistant depression, yet its mechanisms of action remain elusive. Magnetic resonance imaging (MRI) of the human brain before and after treatment has been crucial to aid our comprehension of the ECT neurobiological effects. However, to date, a majority of MRI studies have been underpowered and have used heterogeneous patient samples as well as different methodological approaches, altogether causing mixed results and poor clinical translation. Hence, an association between MRI markers and therapeutic response remains to be established. Recently, the availability of large datasets through a global collaboration has provided the statistical power needed to characterize whole-brain structural and functional brain changes after ECT. In addition, MRI technological developments allow new aspects of brain function and structure to be investigated. Finally, more recent studies have also investigated immediate and long-term effects of ECT, which may aid in the separation of the therapeutically relevant effects from epiphenomena. The goal of this review is to outline MRI studies (T1, diffusion-weighted imaging, proton magnetic resonance spectroscopy) of ECT in depression to advance our understanding of the ECT neurobiological effects. Based on the reviewed literature, we suggest a model whereby the neurobiological effects can be understood within a framework of disruption, neuroplasticity, and rewiring of neural circuits. An improved characterization of the neurobiological effects of ECT may increase our understanding of ECT's therapeutic effects, ultimately leading to improved patient care.

Electroconvulsive therapy (ECT) is considered to be the most effective acute treatment for otherwise treatment resistant major depressive episodes, and has been used for over 80 years. Still, the underlying mechanism of action is largely unknow. Several studies suggest that ECT affects the cerebral neurotransmitters, such as gamma-aminobutyric acid (GABA) and glutamate. Magnetic resonance spectroscopy (MRS) allows investigators to study neurotransmitters in vivo, and has been used to study neurochemical changes in the brain of patients treated with ECT. Several investigations have been performed on ECT-patients; however, no systematic review has yet summarized these findings. A systematic literature search based on the Prisma guidelines was performed. PubMed (Medline) was used in order to find investigations studying patients that had been treated with ECT and had undergone an MRS examination. A search in the databases Embase, PsycInfo, and Web of Science was also performed, leading to no additional records. A total of 30 records were identified and screened which resulted in 16 original investigations for review. The total number of patients that was included in these studies, ignoring potential overlap of samples in some investigations, was 325. The metabolites reported were N-acetyl aspartate, Choline, Myoinositol, Glutamate and Glutamine, GABA and Creatine. The strongest evidence for neurochemical change related to ECT, was found for N-acetyl aspartate (reduction), which is a marker of neuronal integrity. Increased choline and glutamate following treatment was also commonly reported.

Background: Prior studies suggest that activation of the tryptophan catabolism via the kynurenine pathway by proinflammatory cytokines may be involved in the pathophysiology of depression. Electroconvulsive therapy (ECT) is an effective treatment for major depression (MD) with immunomodulation as one of the proposed modes of action. Objective: The aim of this study was to investigate serum concentrations of tryptophan and kynurenine pathway metabolites in MD patients and healthy controls, and to explore the effect of ECT on components of the kynurenine pathway. Methods: The study included 27 moderately to severely depressed patients referred to ECT. Blood samples were collected prior to treatment and after the completed ECT-series. Baseline samples were also collected from 14 healthy, age-and sex-matched controls. Serum concentrations of tryptophan, kynurenine, 3-hydroxykynurenine (HK), kynurenic acid (KA), xanthurenic acid (XA), anthranilic acid (AA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA), picolinic acid (Pic), pyridoxal 5 0 -phosphat (PLP), riboflavin, neopterin and cotinine were measured. Results: Patients with MD had lower levels of neuroprotective kynurenine-pathway metabolites (KA, XA and Pic) and lower metabolite ratios (KA/Kyn and KA/QA) reflecting reduced neuroprotection compared to controls. The concentration of the inflammatory marker neopterin was increased after ECT, along with Pic and the redox active and immunosuppressive metabolite HAA. Conclusion:In this pilot study, we found increased concentrations of inflammatory marker neopterin and putative neuroprotective kynurenine metabolites HAA and Pic in MD patients after ECT. Further research in larger cohorts is required to conclude whether ECT exerts its therapeutic effects via changes in the kynurenine pathway.

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