Longitudinal alterations in mRNA expression of the BDNF neurotrophin signaling cascade in blood correlate with changes in depression scores in patients undergoing electroconvulsive therapy.

Electroconvulsive therapy (ECT) appears to be the most effective treatment for severe depression. However, its mechanisms of action are incompletely understood. Evidence suggests ECT enhances neuroplasticity and neurogenesis. While studies on ECT-induced neuroplasticity focused on brain-derived neurotrophic factor (BDNF), other factors of the BDNF/TrkB signaling cascade remain underinvestigated. We assessed longitudinal changes in depression scores, serum BDNF protein levels, and mRNA expression of BDNF/TrkB related genes (BDNF, AKT1, ERK1, CREB), NR3C1 and IGF1 in peripheral blood in 19 treatment-resistant depressed patients undergoing ECT. We also analysed DNA methylation patterns at various timepoints to explore possible epigenetic regulation of mRNA expression. Using multilevel regression, we found a negative association between depression scores and blood-based mRNA expression of BDNF/TrkB related genes and NR3C1. Expression of BDNF, ERK1 and NR3C1 increased significantly over time (BDNF: ß = 0.0295, p = 0.003; ERK1: ß = 0.0170, p = 0.034; NR3C1: ß = 0.0035, p = 0.050). For these three genes changes in mRNA expression were highly correlated (R = 0.59 - 0.88) with changes in DNA methylation for multiple CpG sites in the respective genes. Also, serum BDNF protein levels increased across the study period (ß = 0.11, p = 0.001). Our findings show that the antidepressant effects of ECT are associated with changes in expression of BDNF and its signaling molecules and that these molecular markers can be detected in peripheral blood. Alterations in DNA methylation could be a key mechanism whereby ECT influences gene expression.

Successful electroconvulsive therapy for depression in a man with cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a condition characterised by accumulation of amyloid beta protein (Aß) in the wall of cerebral blood vessels which increases the risk of intracranial haemorrhage and contributes to cognitive impairment. We describe the case of a man around the age of 70 with 'probable' CAA according to the modified Boston criteria and severe depression whose depression was treated successfully with electroconvulsive therapy (ECT). To the best of our knowledge, there are no earlier published reports of ECT in a patient with CAA. We briefly discuss possible safety measures for these patients, the impact of ECT on cognition in CAA and a possible influence of ECT on Aß clearance.

Attentional bias and general orienting processes in bipolar disorder.

Attentional biases for emotional stimuli and general orienting processes were examined in bipolar disorder, using a modified dot-probe task with a spatial cueing paradigm incorporated in it. Bipolar patients in a euthymic state (i.e., remission), bipolar patients in a mildly depressed state, and non-psychiatric controls participated. General orienting results showed that within the patient group as a whole, measures of depressed mood were positively associated with a relative inability to disengage attention. Attentional bias results showed that bipolar patients in a mildly depressed state, in comparison with controls, directed their attention away from depression-related words and positive words. The bias away from positive words was equally present in both patient groups and part of a trait effect, demonstrated by the comparison of patients in a euthymic state and controls. The bias away from depression-related words was mood state-dependent and within the patient group as a whole correlated negatively with measures of depressed mood. It is proposed that biases for emotional stimuli are related to the transition of mood states, characteristic for bipolar disorder.