Revisiting Hemispheric Asymmetry in Mood Regulation: Implications for rTMS for Major Depressive Disorder

Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD.

Gender differences in positive screen for depression and diagnosis among older adults in Chile

Background Different factors are associated with late life depression and diagnosis, including gender. It has also been reported that depression among older people is underdiagnosed. As a result, the mental health needs of this group are insufficiently met. The aim of this study was to explore gender differences in the factors associated with positive screens for depression and self-reported diagnosis among older adults in Chile. Methods Data from 3786 older adults who participated in the Social Protection Survey in 2016 were analysed. PHQ-9 was used to identify screen-positive cases. Self-reported diagnosis of depression was used to determine the proportion of people with a screen-positive result who had received a diagnosis of depression. Logistic regression models were used to determine sociodemographic and health factors associated with depression and underdiagnosis in older men and women. Results The prevalence of a screen-positive result was 20.91% (5.83% major depressive disorder) among men, and 36.38% (12.43% major depressive disorder) among women. 18.77% of men and 34.11% of women with a positive depression screening had received a diagnosis. More educated men were more likely to receive a diagnosis. Older age was associated with a lower probability of diagnosis among older women. Conclusions Our results suggest that depressive disorders are undiagnosed in a high proportion of older adults in Chile. Gender is a relevant factor in the underdiagnosis of depression in this group. Further research is needed to understand the factors involved in these gaps, to improve detection and provide timely support and treatment.

Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice

Major depressive disorder is caused by gene–environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the underlying mechanisms remain elusive. Herein, the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) between mice inoculated with gut microbiota from major depressive disorder patients or healthy controls were detected, to identify the effects of gut microbiota-dysbiosis on gene regulation patterns at the transcriptome level, and in further to explore the microbial-regulated pathological mechanisms of depression. As a result, 200 mRNAs, 358 lncRNAs, and 4 miRNAs were differentially expressed between the two groups. Functional analysis of these differential mRNAs indicated dysregulated inflammatory response to be the primary pathological change. Intersecting these differential mRNAs with targets of differentially expressed miRNAs identified 47 intersected mRNAs, which were mainly related to neurodevelopment. Additionally, a microbial-regulated lncRNA–miRNA–mRNA network based on RNA–RNA interactions was constructed. Subsequently, according to the competitive endogenous RNAs (ceRNA) hypothesis and the biological functions of these intersected genes, two neurodevelopmental ceRNA sub-networks implicating in depression were identified, one including two lncRNAs (4930417H01Rik and AI480526), one miRNA (mmu-miR-883b-3p) and two mRNAs (Adcy1 and Nr4a2), and the other including six lncRNAs (5930412G12Rik, 6430628N08Rik, A530013C23Rik, A930007I19Rik, Gm15489, and Gm16251), one miRNA (mmu-miR-377-3p) and three mRNAs (Six4, Stx16, and Ube3a), and these molecules could be recognized as potential genetic and epigenetic biomarkers in microbial-associated depression. This study provides new understanding of the pathogenesis of depression induced by gut microbiota-dysbiosis and may act as a theoretical basis for the development of gut microbiota-based antidepressants.