Challenges in comparing the acute cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) vs. electroconvulsive therapy (ECT) in major depression: A systematic review

The present study aimed to systematically compare the cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) in head-to-head studies with major depression (MDD) patients. A systematic literature search identified six studies with 219 MDD patients that were too heterogeneous to reliably detect meaningful differences in acute cognitive outcomes after ECT vs. HF-rTMS. Cognitive effects of brain stimulation vary depending on the timeframe and methods of assessment, stimulation parameters, and maintenance treatment. Thus, acute and longer-term differences in cognitive outcomes both need to be investigated at precisely defined timeframes and with similar instruments assessing comparable functions.     

Dysbindin gene (DTNBP1) in major depressive disorder (MDD) patients: Lack of association with clinical phenotypes

Abstract

Objectives. Dystrobrevin binding protein 1 (Dysbindin) is a plausible candidate gene for major depressive disorders (MDD) due to its involvement in synaptic signaling, plasticity and localization in the brain. Methods. Two intronic SNPs of DTNBP1; rs760761 (P1320) and rs2619522 (P1763) were analyzed in 206 patients with DSM-IV MDD to investigate the functional impact of genotypes on susceptibility for depression and some clinical phenotypes. The Sequenom iPLEX assay (Sequenom, Cambridge, MA) was used for genotyping. Results and Conclusions. Despite the limited power of analysis, our results showed that these two SNPs in DTNPB1 gene were not related to clinical phenotypes such as melancholia, age at onset, suicidality and co-morbid anxiety disorders, as well as to treatment response phenotypes.     

Monozygotic twins affected with major depressive disorder have greater variance in methylation than their unaffected co-twin

Our understanding of major depressive disorder (MDD) has focused on the influence of genetic variation and environmental risk factors. Growing evidence suggests the additional role of epigenetic mechanisms influencing susceptibility for complex traits. DNA sequence within discordant monozygotic twin (MZT) pairs is virtually identical; thus, they represent a powerful design for studying the contribution of epigenetic factors to disease liability. The aim of this study was to investigate whether specific methylation profiles in white blood cells could contribute to the aetiology of MDD. Participants were drawn from the Queensland Twin Registry and comprised 12 MZT pairs discordant for MDD and 12 MZT pairs concordant for no MDD and low neuroticism. Bisulphite treatment and genome-wide interrogation of differentially methylated CpG sites using the Illumina Human Methylation 450 BeadChip were performed in WBC-derived DNA. No overall difference in mean global methylation between cases and their unaffected co-twins was found; however, the differences in females was significant (P=0.005). The difference in variance across all probes between affected and unaffected twins was highly significant (P<2.2 × 10⁻¹⁶), with 52.4% of probes having higher variance in cases (binomial P-value<2.2 × 10⁻¹⁶). No significant differences in methylation were observed between discordant MZT pairs and their matched concordant MZT (permutation minimum P=0.11) at any individual probe. Larger samples are likely to be needed to identify true associations between methylation differences at specific CpG sites.     

Histone deacetylases (HDACs) as therapeutic target for depressive disorders

Major depressive disorder (MDD) represents approximately 40% of the disability caused by mental illnesses globally. The poorly understood pathophysiology and limited efficiency of pharmacological treatment (based primarily on the principles of the monoaminergic hypothesis) make depression a serious medical, public and socio-economical problem. An increasing number of studies suggest that epigenetic modifications (alterations in gene expression that are not due to changes in DNA sequence) in certain brain regions and neural circuits represent a key mechanism through which environmental factors interact with individual's genetic constitution to affect risk of mental disorders. Accordingly, chromatin-based epigenetic regulation seems to be a promising direction for the development of new, more effective antidepressant drugs. Recently, several inhibitors of histone deacetylases (HDAC) have been extensively studied in the context of antidepressant action. So far, none of them has been used to treat depression in humans due to the low selectivity for specific HDAC isoforms, and consequently, a risk of serious adverse events. In this review, we focus on the HDAC inhibitors (HDACi) with the greatest antidepressant efficacy and their activity in the preclinical studies. Moreover, we discuss their potential therapeutic usefulness in depression and the main limitations.