1.Transcriptional dissection of symptomatic profiles across the brain of men and women with depression

https://www.nature.com/articles/s41467-023-42686-5

This study investigates the molecular underpinnings of major depressive disorder (MDD) and their association with specific symptom domains. Analyzing gene expression in six brain regions, sex-specific gene modules related to MDD expression were identified. Varying levels of network homology were observed between males and females, yet associations with MDD expression remained sex-specific. Transcriptional signatures linked to GABAergic and glutamatergic neurotransmission, metabolic processes, and signal transduction pathways were identified, exhibiting region-specific symptomatic profiles. These associations were predominantly sex-specific, although some modules were linked to common symptoms in both sexes. Overall, the study highlights sex-specific transcriptional structures across brain regions associated with distinct MDD symptom domains, offering insights into the heterogeneous nature of MDD.

2.Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses

DOI: 10.1038/s41591-023-02352-1

https://www.nature.com/articles/s41591-023-02352-1

This study conducted a genome-wide association meta-analysis involving over 1.3 million individuals to investigate the genetic basis of depression. They identified 243 risk loci, including 64 new ones, implicating genes related to neurotransmitter receptors targeted by antidepressants. Functional genomics analysis highlighted prenatal brain cell types involved. The study revealed depression's highly polygenic nature, with variants influencing other psychiatric disorders and educational attainment. They found distinct genetic architectures across depression subgroups, with higher polygenic burden associated with increased recurrence risk and psychiatric comorbidity, especially in women. These findings deepen our understanding of depression biology, disease progression, and support precision medicine approaches.

3.Impact of trauma exposure and depression comorbidity on response to transdiagnostic behavioral therapy for pediatric anxiety and depression

https://www.nature.com/articles/s44184-023-00049-4

This study explored the impact of trauma history and clinically significant depression on treatment outcomes in the Brief Behavioral Therapy (BBT) trial, a large study of transdiagnostic psychotherapy for youth aged 8-16 years. Participants received either BBT or assisted referral to outpatient community care (ARC). Results showed that BBT was effective for most of the sample, but for youth with comorbid anxiety and depression who had a history of trauma, BBT did not significantly outperform ARC. These findings suggest that trauma history and depression may moderate treatment outcomes in transdiagnostic therapies, highlighting the need for tailored interventions for this subgroup. The study's implications for intervention development and learning models are discussed.

4.Cingulate dynamics track depression recovery with deep brain stimulation

DOI: 10.1038/s41586-023-06541-3

https://www.nature.com/articles/s41586-023-06541-3

This study investigates the effectiveness of deep brain stimulation (DBS) of the subcallosal cingulate (SCC) for treatment-resistant depression (TRD) and explores the development of objective biomarkers to guide clinical decisions. Ten TRD participants underwent SCC DBS, with 90% showing robust clinical response and 70% achieving remission at 24 weeks. Using SCC local field potentials, an artificial intelligence approach identified changes indicative of the patient's clinical state, distinct from transient stimulation effects. Preoperative damage to white matter integrity and connectivity predicted variable recovery trajectories. Objective facial expression changes detected by video analysis matched these findings. These results highlight the potential of biomarkers in personalized SCC DBS management and shed light on TRD pathology variability, encouraging further research.

5.Preliminary evidence for preserved synaptic density in late-life depression

DOI: 10.1038/s41398-024-02837-8

https://www.nature.com/articles/s41398-024-02837-8

The study aimed to explore whether synaptic deficits contribute to lower gray matter volume in late-life depression, similar to what has been observed in early-onset depression and Alzheimer's Disease. The researchers conducted PET imaging using the synaptic vesicle glycoprotein 2A receptor radioligand 11C-UCB-J in 24 individuals with late-life depression and 36 healthy controls. They also performed MRI to assess gray matter volume in specific brain regions implicated in depression. While trends of lower gray matter volume were observed in the depression group, no differences in synaptic density, as measured by 11C-UCB-J binding, were found between the two groups. These results suggest that, unlike Alzheimer's Disease, synaptic density may not be altered in late-life depression, which could have implications for treatment strategies targeting synaptic function.