Network Analysis of the Symptoms of Depressive Disorders Over the Course of Therapy: Changes in Centrality Measures.

OBJECTIVE: Network analysis can be used in terms of a novel psychopathological approach for depressive syndrome. We aimed to estimate the successive network structures of depressive symptoms in patients with depressive disorder using data from the Clinical Research Center for Depression study. METHODS: We enrolled 1,152 South Korean adult patients with depressive disorders who were beginning treatment for first-onset or recurrent depressive episodes. We examined the network structure of the severities of the items on the Hamilton Depression Rating Scale (HAMD) at baseline and at weeks 2, 12, 25, and 52. The node strength centrality of all the HAMD items at baseline and at week 2, 12, 25, and 52 in terms of network analysis. RESULTS: In the severity networks, the anxiety (psychic) item was the most centrally situated in the initial period (baseline and week 2), while loss of weight was the most centrally situated item in the later period (weeks 25 and 52). In addition, the number of strong edges (i.e., edges representing strong correlations) increased in the late period compared to the initial period. CONCLUSION: Our findings support a period-specific and symptom-focused therapeutic approach that can provide complementary information to the unidimensional total HAMD score.

A single gene of a commensal microbe affects host susceptibility to enteric infection.

Indigenous microbes inside the host intestine maintain a complex self-regulating community. The mechanisms by which gut microbes interact with intestinal pathogens remain largely unknown. Here we identify a commensal Escherichia coli strain whose expansion predisposes mice to infection by Vibrio cholerae, a human pathogen. We refer to this strain as 'atypical' E. coli (atEc) because of its inability to ferment lactose. The atEc strain is resistant to reactive oxygen species (ROS) and proliferates extensively in antibiotic-treated adult mice. V. cholerae infection is more severe in neonatal mice transplanted with atEc compared with those transplanted with a typical E. coli strain. Intestinal ROS levels are decreased in atEc-transplanted mice, favouring proliferation of ROS-sensitive V. cholerae. An atEc mutant defective in ROS degradation fails to facilitate V. cholerae infection when transplanted, suggesting that host infection susceptibility can be regulated by a single gene product of one particular commensal species.

Contributions of rat Ctr1 to the uptake and toxicity of copper and platinum anticancer drugs in dorsal root ganglion neurons.

Dorsal root ganglion (DRG) neurons are affected by platinum-induced neurotoxicity and neurodegenerative processes associated with disturbed copper homeostasis and transport. This study aimed to understand the role of copper transporter 1 (Ctr1) in the uptake and toxicity of copper and platinum drugs in cultured rat DRG neurons, and the functional activities of rat Ctr1 (rCtr1) as a membrane transporter of copper and platinum drugs. Heterologous expression of rCtr1 in HEK293 cells (HEK/rCtr1 cells) increased the uptake and cytotoxicity of copper, oxaliplatin, cisplatin and carboplatin, in comparison to isogenic vector-transfected control cells. Cultured rat DRG neurons endogenously expressed rCtr1 protein on their neuronal cell body plasma membranes and cytoplasm, and displayed substantial capacity for taking up copper, but were resistant to copper toxicity. The uptake of copper by both cultured rat DRG neurons and HEK/rCtr1 cells was saturable and inhibited by cold temperature, silver and zinc, consistent with it being mediated by rCtr1. Cultured rat DRG neurons accumulated platinum during their exposure to oxaliplatin and were sensitive to oxaliplatin cytotoxicity. The accumulation of platinum by both cultured rat DRG neurons and HEK/rCtr1 cells, during oxaliplatin exposure, was saturable and temperature dependent, but was inhibited by copper only in HEK/rCtr1 cells. In conclusion, rCtr1 can transport copper and platinum drugs, and sensitizes cells to their cytotoxicities. DRG neurons display substantial capacity for accumulating copper via a transport process mediated by rCtr1, but appear able to resist copper toxicity and use alternative mechanisms to take up oxaliplatin.