The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain

Objectives. Antipsychotics with high weight gain-inducing propensities influence the expression of immune and neurotrophin genes, which have been independently related to obesity indices. Thus, we investigated whether variants in the genes encoding interleukin (IL)-1β, IL-2, and IL-6 and brain-derived neurotrophic factor (BDNF) Val66Met are associated with antipsychotic-induced weight gain (AIWG). Methods. Nineteen polymorphisms were genotyped using Taqman^® assays in 188 schizophrenia patients on antipsychotic treatment for up to 14 weeks. Mean weight change (%) from baseline was compared across genotypic groups using analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction. Results. In European patients, IL-1β rs16944*GA (P = 0.013, P_corrected = 0.182), IL-1β rs1143634*G (P = 0.001, P_corrected = 0.014), and BDNF Val66Met (Val/Val, P = 0.004, P_corrected = 0.056) were associated with greater AIWG, as were IL-1β rs4849127*A (P = 0.049, P_corrected = 0.784), and IL-1β rs16944*GA (P = 0.012, P_corrected = 0.192) in African Americans. BDNF Val66Met interacted with both IL-1β rs13032029 (Val/Met+ TT, P_Perm = 0.029), and IL-6 rs2069837 (Val/Val+ AA, P_Perm = 0.021) in Europeans, in addition to IL-1β rs16944 (Val/Val+ GA, P_Perm = 0.006) in African Americans. Conclusions. SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.     

Salvage therapy for acute myeloid leukemia with fludarabine,cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G‐CSF

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG‐IM) or without gemtuzumab ozogamicin (GO) (9 mg/m² on Day 8) (FLAG‐I) in relapsed/refractory AML. Three‐quarters of patients also received concurrent G‐CSF. Seventy‐one patients were treated, 23 with FLAG‐I and 48 with FLAG‐IM. The median duration of follow‐up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18–70) and 47 years (range 20–68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG‐I and FLAG‐IM. The complete remission (CR) rate in the FLAG‐I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG‐IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event‐free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG‐I over FLAG‐IM. The patients who received G‐CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G‐CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG‐I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G‐CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

Appreciating symptoms and deficits in schizophrenia: right posterior insula and poor insight

Poor insight is one of the most prominent clinical features of psychosis. Loss of insight in schizophrenia is characterised by abnormalities in awareness and attribution of the origin of pathological mental phenomena. Converging lines of investigations suggest that in healthy individuals, right posterior insula plays an important role in awareness and self-attribution of mental phenomena, contributing to the emergence of a sense of self (Craig, 2002; Farrer et al., 2003). In addition, neuroimaging studies investigating brain morphometry in schizophrenia have consistently reported deficits in the structure of insula (Glahn et al., 2008; Ellison-Wright and Bullmore, 2010). In the present study, we investigated the relationship between the morphometry of posterior insula and degree of insight in a sample of 57 patients in a stable phase of illness using high resolution Magnetic Resonance Imaging. We measured the cortical surface area and local white matter volume of posterior insula. A significant inverse relationship was found between right posterior insular structure and degree of insight in schizophrenia. No such relationship was noted for left posterior insula. Our results highlight the importance of a predominantly right-sided network that includes posterior insula as the neural basis of insight. Abnormalities in interoceptive awareness and self-appraisal of emotional states may contribute to the loss of insight seen in schizophrenia.     

Posttraumatic stress disorder and depression in heart transplantation recipients: the relationship with outcome and adherence to medical treatment

Objective

There is growing evidence of the importance of psychiatric risk factors for predicting the outcome of heart transplantation (HT) recipients. The aim of our study was to investigate the role of major depression and posttraumatic stress disorder (PTSD) in the prediction of the outcome of HT in a consecutive sample of 107 recipients.

Method

All subjects of the study underwent a structured diagnostic interview for assessing the presence of pretransplant and posttransplant major depression and transplantation-related PTSD 1 to 5 years after HT. The adherence to medical treatment was assessed some months after the structured interview. The medical outcome (acute rejections, cancer, mortality) was followed up for 8 years on average after the interview, using a prospective design.

Results

Estimated frequency of psychiatric diagnoses after HT was 12% for transplantation-related PTSD and 41% for major depression. The presence of an episode of major depression prior to HT is a significant independent risk factor for posttransplant malignancies. Age, posttransplant malignancies and poor adherence are significant predictors of mortality in the survival analyses.

Conclusions

The present study highlights the importance of the assessment of psychosocial variables and psychiatric diagnoses before and after transplantation in HT recipients. Our findings have important clinical implications and require replication with larger samples.     

Study of finger print patterns in leprosy

Finger print patterns of 150 male leprosy patients (100 paucibacillary and 50 multibacillary leprosy) were compared with 50 matched controls. Significant differences were found in finger print patterns of multibacillary leprosy patients and controls. No differences in dermatoglyphic patterns were observed between paucibacillary leprosy and controls. The total finger ridge count (TFRC) in both types of leprosy was slightly lower than controls. A significant difference in individual finger ridge count on digit 1 of right hand was noted in paucibacillary leprosy cases as compared to controls.