Depression,anxiety and loss of resilience after multiple traumas: an illustration of a mediated moderation model of sensitization in a group of children who survived the Nazi Holocaust

Background

Depressive and anxiety disorders (DAD) have become a major public health problem. Multiple trauma is known to increase the risk of DAD through a sensitization mechanism. We investigate the hypothesis that resilience is a mediator of this mechanism.

Methods

Former Hidden Children (FHC), the Jewish youths who spent World War II in various hideaway shelters across Nazi-occupied Europe, were compared with a control group. In each group, we measured the presence of multiple traumas, the resilience with the Resilience Scale for Adults, which has a six factors solution, and the DAD with the Hopkins Symptoms Checklist. We test a mediated moderation model with childhood trauma as the predictor; Later trauma as the moderator; Resilience as the mediator; and DAD as the outcome variable.

Results

Results are consistent with a sensitization model of DAD mediated by resilience: confrontation with a primary trauma during childhood followed by secondary trauma(s) after childhood damages resilience, which, in turn, results in higher level of DAD.

Limitations

We are unable to differentiate if the sensitization process is a consequence of the nature of the trauma endured by FHC (long-standing exposure to extreme external events) or a consequence of the fact that this first trauma occurred during childhood.

Conclusions

Resilience construct is multi-factorial and a limited damaging of some of the factors is sufficient to lead to DAD even if other factors remain unaltered. Resilience can be altered by multiple traumas and, therefore, needs to be bolstered in therapy sessions.     

Reduced plasticity and mild cognitive impairment-like deficits after entorhinal lesions in hAPP/APOE4 mice

Mild cognitive impairment (MCI) is a clinical condition that often precedes Alzheimer disease (AD). Compared with apolipoprotein E-ε3 (APOE3), the apolipoprotein E-ε4 (APOE4) allele is associated with an increased risk of developing MCI and spatial navigation impairments. In MCI, the entorhinal cortex (EC), which is the main innervation source of the dentate gyrus, displays partial neuronal loss. We show that bilateral partial EC lesions lead to marked spatial memory deficits and reduced synaptic density in the dentate gyrus of APOE4 mice compared with APOE3 mice. Genotype and lesion status did not affect the performance in non-navigational tasks. Thus, partial EC lesions in APOE4 mice were sufficient to induce severe spatial memory impairments and synaptic loss in the dentate gyrus. In addition, lesioned APOE4 mice showed no evidence of reactional increase in cholinergic terminals density as opposed to APOE3 mice, suggesting that APOE4 interferes with the ability of the cholinergic system to respond to EC input loss. These findings provide a possible mechanism underlying the aggravating effect of APOE4 on the cognitive outcome of MCI patients.     

Attempted Passive Prophylaxis with a Monoclonal Anti-Burkholderia Pseudomallei Exopolysaccharide Antibody in a Murine Model of Melioidosis

Melioidosis is a severe gram-negative infection caused by the facultative intracellular bacterium Burkholderia pseudomallei, which is responsible for a broad spectrum of symptoms in both humans and animals. No licensed vaccine currently exists. This study evaluated the protective effect of a monoclonal antibody (Mab Ps6F6) specific to B. pseudomallei exopolysaccharide in an outbred murine model of sub-acute melioidosis. When administered before the infectious challenge, Ps6F6 significantly increased resistance to infection and restrained bacterial burden in the spleen over a 30-days period. Patterns of IFN-γ production were similar in the treated and non treated groups of mice. However, Ps6F6 lowered IFN-γ levels over the duration of the assay period, except on day 1, suggesting a transient and rapid production of IFN-γ under Ps6F6 control. Minor but persisting increases occurred in IL-12 levels while TNF-α was detected only in the controls at the later stages of infection. No IL-10 secretion was detected in both groups of mice. These data suggest that passive prophylaxis with Mab Ps6F6 provide a moderate and transient induction of inflammatory responses in infected mice but failed to trigger a sterilizing protective immunity.     

Long-term serological follow-up after primary Coxiella burnetii infection in patients with vascular risk factors for chronic Q fever

We evaluated the long-term serological follow-up of patients with vascular risk factors for chronic Q fever that were previously Coxiella burnetii seropositive. C. burnetii phase I IgG titers were reevaluated in patients that gave informed consent or retrospectively collected in patients already deceased or lost to follow-up. Of 107 patients, 25 (23.4%) became seronegative, 77 (72.0%) retained a profile of past resolved Q fever infection, and five (4.7%) developed chronic Q fever. We urge clinicians to stay vigilant for chronic Q fever beyond two years after primary infection and perform serological testing based on clinical presentation.

     

Whole Exome Sequencing Reveals Uncommon Mutations in the Recently Identified Fanconi Anemia Gene SLX4/FANCP

Fanconi anemia (FA) is a rare genetic disorder characterized by congenital malformations, progressive bone marrow failure (BMF), and susceptibility to malignancies. FA is caused by biallelic or hemizygous mutations in one of 15 known FA genes, whose products are involved in the FA/BRCA DNA damage response pathway. Here, we report on a patient with previously unknown mutations of the most recently identified FA gene, SLX4/FANCP. Whole exome sequencing (WES) revealed a nonsense mutation and an unusual splice site mutation resulting in the partial replacement of exonic with intronic bases, thereby removing a nuclear localization signal. Immunoblotting detected no residual SLX4 protein, which was consistent with abrogated interactions with XPF/ERCC1 and MUS81/EME1. This cellular finding did not result in a more severe clinical phenotype than that of previously reported FA‐P patients. Our study additionally exemplifies the versatility of WES for the detection of mutations in heterogenic disorders such as FA.     

Blastic Transformation of Mouse Spleen Lymphocytes by a Water-Soluble Mitogen Extracted from Nocardia

A water-soluble extract of Nocardia markedly increased in vitro [(3)H]thymidine incorporation by mouse spleen lymphocytes. The blastogenic activity of the extract and lipopolysaccharide was studied comparatively on various mouse lymphocyte subpopulations. The data obtained by [(3)H]thymidine incorporation and by electron microscopy have demonstrated that this preparation stimulates selectively mouse bone-marrow-derived cortisone-sensitive lymphocytes. This stimulation is related neither to a natural infection of mice with Nocardia organisms nor to the presence in Nocardia water-soluble mitogen of a lipopolysaccharide contaminant or of a lipopolysaccharide-like material.