Neurotrophic Effects of Electroconvulsive Therapy: A Proton Magnetic Resonance Study of the Left Amygdalar Region in Patients with Treatment-Resistant Depression

Abstract

Negatively balanced neurotrophic factors may be important in precipitating clinical depression. Recently, it has been reported that antidepressant therapy may exert positive neurotrophic effects. The aim of this study was to detect probable neurotrophic changes during electroconvulsive therapy (ECT). For this purpose, N-acetylaspartate (NAA), an amino acid exclusively located in neurons, and other brain metabolites such as glutamine/glutamate (Glx), choline (Cho), and creatine (Cr) were measured in patients by localized proton magnetic resonance spectroscopy. A total of 28 severely depressed patients (DSM-IV) were enrolled, and the left amygdalar region was investigated by proton STEAM spectroscopy before and after unilateral ECT. The results were compared with 28 age-and gender-matched controls using nonparametric paired and unpaired tests. A significant increase in NAA was observed only in ECT responders (n ¼ 14; p ¼ 0.019). Five out of 14 nonresponders to ECT monotherapy were remeasured following a clinical improvement after continued ECT combined with antidepressants and were then found also to present a significant increase in NAA. In all successfully treated patients, parallel observations, that is, increased levels, were made for Glx, whereas Cho and Cr were unchanged. In conclusion, our preliminary finding of increased NAA concentrations after successful ECT may indicate a probable neurotrophic effect of ECT. Neuropsychopharmacology (2003) 28, 720-725.

Effect of Manganese Chloride on the Neurochemical Profile of the Rat Hypothalamus

“…Studies of psychiatric disorders have also shown that NAA levels can increase, suggesting a restoration or repair of neuronal viability (Moore et al, 2000;Mickael et al, 2003). The administration of lithium chloride to humans increased whole brain NAA levels, suggesting an increase of neuronal viability.…”

Physiologic and Characteristic Distributions of Glutamate/Glutamine in Patients with Major Depressive Disorder

“…To investigate appropriate regions for measuring Glx in depression, we will need to examine a younger group. In addition, we could not clarify whether medications and treatments had affected the patient condition -because these were reported to increase or reverse Glx in previous studies 6) 7) . Patients in our study generally had severe depressive conditions and were receiving antidepressants before admission.…”

“…The sizes of each ROI voxel was 1.5×1.5×1.5 cm 3 for the amygdala and DLPFC and 1.5×1.5×2.0 cm 3 for the ACC (Figure 1). Voxel position for the left amygdala region comprised the maximum of amygdala gray matter and the anterior onethird of the hippocampus 7) . The ACC voxel abutted upon the anterior portion of the corpus callosum posteriorly.…”

“…In recent years, quantification studies of brain Glx in patients with MDD using 1 H-MRS have been carried out that showed significant reductions in Glx in several brain regions 3)4) . Such regions include the anterior cingulate cortex (ACC) 5) 6) , dorsolateral prefrontal cortex (DLPFC) 7) , dorsomedial prefrontal cortex 8) , amygdala 7) , and hippocampus 9) , areas also thought to be associated with mood regulation and the pathophysio- According to our review of prior studies, the region showing the greatest reduction in Glx has not been investigated in individual patients. We therefore aimed to investigate the physiologic and characteristic distribution of Glx in each region within individuals, and to compare differences between healthy controls and patients with MDD.…”

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

“…In mood disorders, there is a great deal of interest as to whether antidepressant and mood stabilizing treatments have a neurotrophic or neuroprotective effect in patients (34,35), with some (36, 37), but not all (38), literature reporting increases in hippocampal volume with antidepressant treatment. A similar positive effect is seen with antidepressants and mood stabilizers in the orbital frontal cortical volume of patients with bipolar disorder (Hilary Blumberg, personal communication).…”