Gender differences in the associations between childhood adversity and psychopathology in the general population

PURPOSE: To explore gender differences of the associations between childhood adversity (CA) subtypes and psychiatric symptoms in the general population. METHODS: Data of 791 participants were retrieved from a general population twin cohort. The Symptom Checklist-90 Revised (SCL-90) and the Childhood Trauma Questionnaire were used to assess overall psychopathology with nine symptom domains scores and total CA with exposure to five CA subtypes, respectively. The associations between CA and psychopathology were analyzed in men and women separately and were subsequently compared. RESULTS: Total CA was associated with total SCL-90 and all symptom domains without significant gender differences. However, the analyses of CA subtypes showed that the association between emotional abuse and total SCL-90 was stronger in women compared to men [χ 2(1) = 4.10, P = 0.043]. Sexual abuse was significantly associated with total SCL-90 in women, but emotional neglect and physical neglect were associated with total SCL-90 in men. Exploratory analyses of CA subtypes and SCL-90 subdomains confirmed the pattern of gender-specific associations. In women, emotional abuse was associated with all symptom domains, and sexual abuse was associated with all except phobic anxiety and interpersonal sensitivity. In men, emotional neglect was associated with depression, and physical neglect was associated with phobic anxiety, anxiety, interpersonal sensitivity, obsessive-compulsive, paranoid ideation, and hostility subdomains. CONCLUSION: CA is a trans-syndromal risk factor regardless of gender. However, differential associations between CA subtypes and symptom manifestation might exist. Abuse might be particularly associated with psychopathology in women, whereas neglect might be associated with psychopathology in men

Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus

Orientia tsutsugamushi is the causal agent of scrub typhus, a public health problem in the Asia-Pacific region and a life-threatening disease. O. tsutsugamushi is an obligate intracellular bacterium that mainly infects endothelial cells. We demonstrated here that O. tsutsugamushi also replicated in monocytes isolated from healthy donors. In addition, O. tsutsugamushi altered the expression of more than 4,500 genes, as demonstrated by microarray analysis. The expression of type I interferon, interferon-stimulated genes and genes associated with the M1 polarization of macrophages was significantly upregulated. O. tsutsugamushi also induced the expression of apoptosis-related genes and promoted cell death in a small percentage of monocytes. Live organisms were indispensable to the type I interferon response and apoptosis and enhanced the expression of M1-associated cytokines. These data were related to the transcriptional changes detected in mononuclear cells isolated from patients with scrub typhus. Here, the microarray analyses revealed the upregulation of 613 genes, which included interferon-related genes, and some features of M1 polarization were observed in these patients, similar to what was observed in O. tsutsugamushi-stimulated monocytes in vitro. This is the first report demonstrating that monocytes are clearly polarized in vitro and ex vivo following exposure to O. tsutsugamushi. These results would improve our understanding of the pathogenesis of scrub typhus, during which interferon-mediated activation of monocytes and their subsequent polarization into an M1 phenotype appear critical. This study may give us a clue of new tools for the diagnosis of patients with scrub typhus

Development and validation of the Thai version of the 4 ‘A’s Test for delirium screening in hospitalized elderly patients with acute medical illnesses

Sanchai Kuladee, Thanavadee Prachason Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Background: The English version of the 4 ‘A’s Test (4AT) is a rapid screening tool for delirium with a high sensitivity and specificity among hospitalized elderly patients.Objective: To develop the Thai version of the 4AT (4AT-T) and assess its validity.Subjects and setting: A total of 97 elderly patients aged 60 years or above who were admitted to the general medical wards were included.Methods: Both authors independently translated the English version of the 4AT into Thai and thereafter developed a single reconciled forward translation by consensus. Back translation was performed by a bilingual native English speaker and it was then reviewed to ensure its agreement with the original one. After 24 hours of admission, subjects were enrolled and clinical data collected. Definite diagnosis of delirium was made by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text-Revision criteria and the 6-item Thai Delirium Rating Scale; the 4AT was then administered to participants by nurses within 30 minutes. A 4AT score ≥4 was considered positive for delirium screening. The optimal cut-off point of the 4AT-T was identified by Youden’s index.Results: In all, 24 out of 97 participants met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text-Revision criteria for delirium. At a cut-off score of 4 or greater, the 4AT-T exhibited satisfactory diagnostic performance with a sensitivity of 83.3% (95% confidence interval (CI): 62.6%–95.3%) and specificity of 86.3% (95% CI: 76.3%–93.2%). The area under the receiver operating characteristic curve was 0.92. The specified score provided maximal Youden’s index, suggesting an optimal criterion value for delirium screening.Conclusion: The 4AT-T is a valid delirium-screening instrument for hospitalized elderly patients with acute medical illnesses. Keywords: Thai, delirium, screening tool, delirium screening, acute medical illnesse

Activation of Indoleamine 2,3-Dioxygenase in Patients with Scrub Typhus and Its Role in Growth Restriction of <em>Orientia tsutsugamushi</em>

<div><h3>Background</h3><p>Our earlier genome-wide expression study revealed up-regulation of a tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO1), in patients with scrub typhus. This gene has been previously reported to have anti-microbial activity in a variety of infectious diseases; therefore, we aimed to prove whether it is also involved in host defense against <em>Orientia tsutsugamushi</em> (OT) infection.</p> <h3>Methodology/Principal Findings</h3><p>Using LC-MS, we observed an increased ratio of serum L-kynurenine to serum L-tryptophan in patients with scrub typhus, which suggests an active catalytic function of this enzyme upon the illness. To evaluate the effect of IDO1 activation on OT infection, a human macrophage-like cell line THP-1 was used as a study model. Although transcription of IDO1 was induced by OT infection, its functional activity was not significantly enhanced unless the cells were pretreated with IFN-γ, a potent inducer of IDO1. When the degree of infection was evaluated by quantitative real-time PCR, the relative number of OT 47 kDa gene per host genes, or infection index, was markedly reduced by IFN-γ treatment as compared to the untreated cultures at five days post-infection. Inhibition of IDO1 activity in IFN-γ treated cultures by 1-methyl-L-tryptophan, a competitive inhibitor of IDO1, resulted in partial restoration of infection index; while excessive supplementation of L-tryptophan in IFN-γ treated cultures raised the index to an even higher level than that of the untreated ones. Altogether, these data implied that IDO1 was partly involved in restriction of OT growth caused by IFN-γ through deprivation of tryptophan.</p> <h3>Conclusions/Significance</h3><p>Activation of IDO1 appeared to be a defensive mechanism downstream of IFN-γ that limited intracellular expansion of OT via tryptophan depletion. Our work provided not only the first link of in vivo activation of IDO1 and IFN-γ-mediated protection against OT infection but also highlighted the promise of this multifaceted gene in scrub typhus research.</p> </div

Kinetics of IDO1 expression in THP-1 cells.

<p>Before being infected with OT, THP-1 cells were treated with IFN-γ alone, IFN-γ combined with 1-MT, or neither. Mock-infected THP-1 cells were used as a control. Fold induction represents levels of IDO1 expression in each culture condition at indicated time points relative to that in mock-infected cells at 6 hours p.i.. For clearer illustration, data of OT-infected and mock-infected cultures are exclusively presented in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001731#pntd-0001731-g002" target="_blank">Figure 2A</a>, and those of all four culture conditions are shown in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001731#pntd-0001731-g002" target="_blank">Figure 2B</a>. Means ± SEM from triplicate cultures are shown.</p

Assessment of IDO1 activity in patients' sera.

<p>Serum concentrations of L-Trp (A) and L-Kyn (B) in patients with scrub typhus (n = 20) were compared with those in healthy donors (n = 10). L-Kyn/L-Trp ratios (C) were calculated to reflect IDO1 activity. Data were derived from triplicate measurement. Median and interquantile range are presented.</p

Clinical and laboratory characteristics of the patients with scrub typhus.

<p>IQR = interquantile range, DIC = disseminated intravascular coagulopathy, AST = aspartate aminotansferase, ALT = alanine aminotransferase.</p

Assessment of OT growth in THP-1 cultures.

<p>Before being infected with OT, THP-1 cells were treated with IFN-γ alone, IFN-γ combined with 1-MT, or IFN-γ supplemented with L-Trp at 400 µg/ml (A) or 1 mg/ml (B). The infection index represents the degree of OT growth in each culture condition at indicated time points relative to that in mock-infected cells at 1 day p.i.. Means ± SEM from triplicate cultures are shown.</p