Childhood neglect and abuse as predictors of antidepressant response in adult depression

Background: Childhood neglect and abuse are recognized as risk factors for depression, but are not often studied as predictors of treatment response in depression. Methods: Clinically depressed outpatients (n=195) were asked about childhood experiences before beginning a randomized antidepressant trial with either fluoxetine or nortriptyline. Three treatment outcomes were measured: Adequate trial, six‐week response and two months sustained recovery. Results: Patients reporting low paternal care (paternal neglect), as measured by the Parental Bonding Instrument (PBI), were less likely to complete an adequate six‐week trial of medication. Patients who reported high maternal protection (maternal overprotection) on the PBI had poorer treatment response in the short‐term at six weeks, and longer term, for two months of sustained recovery. However, abuse, whether sexual, physical, or psychological in nature, did not predict treatment response. Conclusions: The experience of having a neglectful father or an overprotective mother was more predictive of response to treatment for depression than abuse, suggesting that the quality of ongoing intra‐familial relationships has a greater impact on treatment outcomes for depression than experiences of discrete abuse in childhood. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

Hierarchy of simulation models in predicting structure and energetics of the Src SH2 domain binding to tyrosyl phosphopeptides.

Structure and energetics of the Src Src Homology 2 (SH2) domain binding with the recognition phosphopeptide pYEEI and its mutants are studied by a hierarchical computational approach. The proposed structure prediction strategy includes equilibrium sampling of the peptide conformational space by simulated tempering dynamics with the simplified, knowledge-based energy function, followed by structural clustering of the resulting conformations and binding free energy evaluation of a single representative from each cluster, a cluster center. This protocol is robust in rapid screening of low-energy conformations and recovers the crystal structure of the pYEEI peptide. Thermodynamics of the peptide-SH2 domain binding is analyzed by computing the average energy contributions over conformations from the clusters, structurally similar to the predicted peptide bound structure. Using this approach, the binding thermodynamics for a panel of studied peptides is predicted in a better agreement with the experiment than previously suggested models. However, the overall correlation between computed and experimental binding affinity remains rather modest. The results of this study show that small differences in binding free energies between the Ala and Gly mutants of the pYEEI peptide are considerably more difficult to predict than the structure of the bound peptides, indicating that accurate computational prediction of binding affinities still remains a major methodological and technical challenge.     

PRIMARY MENINGOCOCCAL CONJUNCTIVITIS IN CHILDREN

SUMMARY Four cases of primary meningococcal conjunctivitis in children are reported. This represents an incidence of 2% of patients presenting with conjunctivitis to a paediatric A&E department. All were initially treated with topical chloramphenicol, followed by systemic rifampicin once the diagnosis had been established. No ocular or systemic complications developed, nor recolonisation of the conjunctiva or colonisation of the nasopharynx at follow-up (1–2 years).     

Blood transfusion exposure does not influence survival in patients with carcinoma of the breast

There is abundant evidence of immune modulation induced by exposure to blood transfusions. Some studies have demonstrated a detrimental effect of transfusion on the recurrence of malignant disease and survival. We retrospectively studied the impact of blood transfusion exposure on 229 patients with breast cancer who were seen from July 1973 to September 1980, had at least 5 years' follow-up and had been randomized by therapy at the time of diagnosis. The patients were divided into four groups according to transfusion history: Group 1 (111 patients), no transfusion; Group 2 (34 patients), first transfusion after mastectomy; Group 3 (41 patients), first transfusion at mastectomy; and Group 4 (43 patients), first transfusion before mastectomy. All transfused patients received red cells or whole blood or both. At the time of analysis, 124 (54%) of the patients had died. Only Group 2 was statistically associated with decreased survival; recurrence of disease was 85 percent in this group, compared with 53 percent to 61 percent in the other three groups (p = 0.006, log-rank test). In general, Group 2 patients received transfusions because of recurrent disease. We conclude that transfusions before or at mastectomy are not associated with increased recurrence or reduced survival in patients with breast cancer.     

Antihypertensive efficacy of metoprolol XL/Low dose chlorthalidone (6.25 mg) combination: a randomized,comparative study in Indian patients with mild-to-moderate essential hypertension

Objective

High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-tomoderate essential hypertension.

Methods

Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.

Results

The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na⁺, K⁺, Cl^-)and fasting blood sugar, evident across the treatment groups.

Conclusion

Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.     

Effects of childhood experiences on cortisol levels in depressed adults

OBJECTIVE: To evaluate the impact of childhood abuse and parental bonding on cortisol levels in depressed adults. METHODS: Mean afternoon cortisol levels were measured in 192 depressed adult patients at the beginning of a treatment trial. Childhood experiences of physical and sexual abuse were ascertained by interview, and perceived parenting by self-report. RESULTS: Maternal affectionless control, childhood sexual and physical abuse were all associated with cortisol levels. CONCLUSION: Childhood experiences, especially maternal affectionless control, appear to be related to hypothalamic pituitary adrenal axis function in depressed adults.