1.Brain mechanisms underlying the emotion processing bias in treatment-resistant depression

DOI: 10.1101/2023.08.26.554837

https://www.biorxiv.org/content/10.1101/2023.08.26.554837v1

This study explores the neural mechanisms underlying emotion processing in treatment-resistant depression (TRD). Using stereotactic electroencephalography (sEEG), amygdala and prefrontal cortex (PFC) activity was recorded while participants rated happy and sad faces. TRD patients exhibited heightened amygdala responses to sad faces early on, and decreased responses to happy faces later, compared to controls. Additionally, TRD patients showed increased alpha-band activity in the PFC during late-stage happy face processing, suggesting inhibition of amygdala activity. Deep brain stimulation (DBS) targeting specific brain regions normalized atypical amygdala and PFC responses in TRD patients. These findings indicate dysregulated bottom-up processing in TRD, with potential therapeutic implications for DBS in modulating emotion.

2.Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson's disease

https://www.nature.com/articles/s41467-024-47552-6

This study investigates the electrophysiological signature of deep brain stimulation (DBS) in the subthalamic nucleus (STN), known as evoked resonant neural activity (ERNA), and its relation to treatment efficacy in Parkinson's disease. Key findings include: (i) association of ERNA peaks with temporally-locked neuronal inhibition in the STN; (ii) characterization of ERNA's temporal dynamics; (iii) identification of a putative mesocircuit architecture necessary for ERNA emergence; (iv) localization of ERNA to the dorsal STN; (v) assessment of spatial relevance of ERNA to DBS outcome using patient-wise hotspot locations; and (vi) characterization of the local fiber activation profile associated with ERNA. These findings shed light on the neural mechanisms underlying DBS treatment efficacy in Parkinson's disease.

3.The claustrum-prelimbic cortex circuit through dynorphin/κ-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology

DOI: 10.1038/s41467-023-43636-x

https://www.nature.com/articles/s41467-023-43636-x

This study unveils a mechanism underlying the stress-induced development of depression. Chronic social defeat stress (CSDS) reduces the excitatory output from the claustrum (CLA) to the prelimbic cortex (PL) via dynorphin/κ-opioid receptor (KOR) signaling in male mice. This attenuation, particularly affecting the connection between CLA and parvalbumin (PV) interneurons in the PL, disrupts PL micronetwork function by disinhibiting pyramidal neurons (PNs). Optogenetic modulation of this circuit influences depressive-like behaviors, with chemogenetic manipulation of PV neurons reversing these effects. Additionally, controlling dynorphin/KOR signaling in CLA-PL projections regulates depressive behaviors, highlighting a potential therapeutic target. This study enhances understanding of depression's stress origins and suggests interventions targeting the CLA-PL circuit may offer therapeutic benefits.

4.Distinct genomic signatures and modifiable risk factors underly the comorbidity between major depressive disorder and cardiovascular disease

https://www.medrxiv.org/content/10.1101/2023.09.01.23294931v2

This study investigates the genetic basis and causal pathways linking major depressive disorder (MDD) and cardiovascular disease (CVD) comorbidity. Genomic analysis reveals a substantial overlap in genetic risk factors between MDD and atherosclerotic CVD (ASCVD), leading to the identification of seven novel loci. Tissue and brain cell-type enrichments suggest involvement of the thalamus. Shared inflammatory, metabolic, and psychosocial/lifestyle risk factors contribute to this overlap. Causal effects of MDD genetic liability on CVD risk are observed, partly mediated by metabolic and psychosocial/lifestyle factors. The findings suggest an immunometabolic subtype of MDD associated more strongly with CVD. This study sheds light on biological mechanisms and modifiable risk factors for preventing CVD in individuals with MDD.

5.Psychological resilience mediates the relationship between diabetes distress and depression among persons with diabetes in a multi-group analysis

https://www.nature.com/articles/s41598-024-57212-w

This cross-sectional study investigates the relationship between diabetes distress and depression, along with the mediating role of psychological resilience, in individuals with Type 1 and Type 2 diabetes. Data from 181 participants were analyzed, revealing a significant positive correlation between diabetes distress and depression, with psychological resilience partially mediating this relationship. Additionally, differences were observed between Type 1 and Type 2 diabetes subgroups, with the relationship between diabetes distress and depression more pronounced in Type 1, and the relationship between psychological resilience and depression stronger in Type 2. These findings underscore the importance of considering diabetes type in interventions for individuals with comorbid depression, aiming for personalized approaches to enhance well-being.