Background The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental ...pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine. Hypothesis Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers. Methods We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP. Results (1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends. Conclusion ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant.
The current study examines the predictive validity of the Beck Depression Inventory (BDI) suicide item for death by suicide and suicide attempts.
The study included 2 samples: (1) 5,200 psychiatric ...outpatients who were evaluated between 1975 and 1995 and followed prospectively for up to 20 years (all psychiatric diagnoses based on DSM-III and DSM-III-R), and (2) 119 patients who, between 2000 and 2004, participated in a randomized controlled trial of outpatient Cognitive Therapy for Suicide Prevention after a suicide attempt and were followed for 18 months (all psychiatric diagnoses based on DSM-IV-TR). All patients completed structured diagnostic interviews, as well as the BDI and Scale for Suicide Ideation.
Cox regression models demonstrated that the BDI suicide item significantly predicted both deaths by suicide (Wald χ(2)1 = 35.67; P < .001 N = 5,200) and repeat suicide attempts (Wald χ(2)1 = 8.82; P < .01 N = 119), with each successive rating on the item conferring greater risk. Using receiver operating characteristic (ROC) curves, optimal cutoff scores of 1 and above for suicide and 2 and above for suicide attempts were identified as providing the best balance between sensitivity and specificity.
The BDI suicide item is associated with both risk of repeat suicide attempts and death by suicide. The use of the item as a brief, efficient screen for suicide risk in routine clinical care is recommended. Clinicians would then conduct a comprehensive suicide risk assessment in response to a positive screen. Future research examining the item's performance in other at-risk groups (ie, older adults, adolescents, inpatients, etc) is encouraged.
Non-ribosomal peptide synthetases are important enzymes for the assembly of complex peptide natural products. Within these multi-modular assembly lines, condensation domains perform the central ...function of chain assembly, typically by forming a peptide bond between two peptidyl carrier protein (PCP)-bound substrates. In this work, we report structural snapshots of a condensation domain in complex with an aminoacyl-PCP acceptor substrate. These structures allow the identification of a mechanism that controls access of acceptor substrates to the active site in condensation domains. The structures of this complex also allow us to demonstrate that condensation domain active sites do not contain a distinct pocket to select the side chain of the acceptor substrate during peptide assembly but that residues within the active site motif can instead serve to tune the selectivity of these central biosynthetic domains.
To determine the risk factors for suicide, 6,891 psychiatric outpatients were evaluated in a prospective study. Subsequent deaths for the sample were identified through the National Death Index. ...Forty-nine (1%) suicides were determined from death certificates obtained from state vital statistics offices. Specific psychological variables that could be modified by clinical intervention were measured using standardized scales. Univariate survival analyses revealed that the severity of depression, hopelessness, and suicide ideation were significant risk factors for eventual suicide. A multivariate survival analysis indicated that several modifiable variables were significant and unique risk factors for suicide, including suicide ideation, major depressive disorder, bipolar disorder, and unemployment status.
Clinicians working with youth exposed to trauma may be at increased risk for experiencing elevated levels of stress and symptoms of secondary traumatic stress, which can negatively impact clinician ...wellbeing and ultimately contribute to reduced access to quality care for clients. An innovative Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) training incorporating self-care practices (i.e., Practice What You Preach; PWYP) was developed to help facilitate the implementation of TF-CBT and to enhance clinicians’ coping and decrease stress. The primary purpose of this study was to determine whether the PWYP-augmented training met three Objectives: (1) increase clinicians’ feelings of TF-CBT competency; (2) improve clinicians’ coping abilities/reduce clinicians’ stress; and (3) increase clinicians’ insight into the benefits and/or challenges clients may experience in treatment. An exploratory aim was also developed to identify additional facilitators and barriers of TF-CBT implementation. The written reflections of 86 community-based clinicians who participated in the PWYP-augmented TF-CBT training were examined using qualitative methods. The majority of clinicians indicated increased feelings of competency and improved coping abilities and/or stress levels; almost half mentioned increased insight into clients’ experiences. The most frequently mentioned additional facilitators were related to elements of the TF-CBT treatment model. Anxiety/self-doubt was the barrier most frequently mentioned, though all clinicians who mentioned this barrier indicated it lessened or resolved over the course of the training. Incorporating self-care strategies into trainings may serve as a facilitator for TF-CBT implementation by enhancing the competency and well-being of clinicians. The additional insights into barriers and facilitators can be used to further improve the PWYP initiative and future training and implementation efforts.
Objective: To examine the differential efficacy of trauma-focused cognitive-behavioral therapy (TF-CBT) and child-centered therapy for treating posttraumatic stress disorder (PTSD) and related ...emotional and behavioral problems in children who have suffered sexual abuse. Method: Two hundred twenty-nine 8- to 14-year-old children and their primary caretakers were randomly assigned to the above alternative treatments. These children had significant symptoms of PTSD, with 89% meeting full DSM-IV PTSD diagnostic criteria. More than 90% of these children had experienced traumatic events in addition to sexual abuse. Results: A series analyses of covariance indicated that children assigned to TF-CBT, compared to those assigned to child-centered therapy, demonstrated significantly more improvement with regard to PTSD, depression, behavior problems, shame, and abuse-related attributions. Similarly, parents assigned to TF-CBT showed greater improvement with respect to their own self-reported levels of depression, abuse-specific distress, support of the child, and effective parenting practices. Conclusions: This study adds to the growing evidence supporting the efficacy of TF-CBT with children suffering PTSD as a result of sexual abuse and suggests the efficacy of this treatment for children who have experienced multiple traumas.
The etiology of autism spectrum disorders (ASD) is believed to involve genetic and environmental components. This study focused on the plasticizer, Bisphenol-A (BPA). The major pathway for BPA ...metabolism and excretion is via glucuronidation. To determine whether there was a relationship between BPA exposure and ASD, urine specimens were collected from 46 children with ASD and 52 controls. Free and total BPA concentrations were determined by mass spectrometry. The fraction glucuronidated was calculated from the difference. A metabolomics study was done to investigate metabolite distribution in the urine. (i) Most of the BPA excreted in the urine was as the glucuronide; (ii) about 20% of the ASD children had BPA levels beyond the 90th percentile (>50 ng/mL) of the frequency distribution for the total sample of 98 children; (iii) Mann-Whitney U tests and multiple regression analyses found significant differences (P < 0.05) between the groups in total and % bound BPA; and (iv) the metabolomics analyses showed the number of absolute partial correlations >|0.30| between metabolite concentrations and total BPA was ∼3 times greater with the ASD group than the controls (P < 0.001), and the number of absolute partial correlations > |0.30| for % bound BPA was ∼15 times higher with ASD (P < 0.001). The results suggest there is an association between BPA and ASD.
This pilot study evaluated the effectiveness of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) training programs augmented with a systematic “PRACTICE What You Preach” (PWYP) self-care focus, ...which has trainees personally utilize the coping skills they teach their clients. Participants were 115 clinicians/supervisors who completed a PWYP TF-CBT training program. Pre- to post-training analyses documented significant increases in participants’ competency and fidelity in implementing TF-CBT (
p
s < .001), significantly more frequent use of coping skills including instrumental social support (
p
< .01), active coping (
p
< .001), humor (
p
< .01), and restraint (
p
< .01), and significant decreases in secondary traumatic stress (STS;
p
< .001). Children’s symptoms of PTSD (
p
s < .001) and behavior problems (
p
< .05) also decreased significantly. This preliminary evidence suggests that training augmented with PWYP may enhance clinicians’/supervisors’ personal coping and reduce their levels of STS without compromising treatment implementation efforts and client outcomes.
Abstract This preliminary investigation assessed whether different aspects of personal resiliency improved for youth (7–17 years old) impacted by child sexual abuse (CSA) after completing ...trauma-focused cognitive behavioral therapy (TF-CBT). The Resiliency Scales for Children and Adolescents (RSCA; Prince-Embury, 2007) were administered to 157 youth before and after participating in TF-CBT with their nonoffending caregivers. Hierarchal regression analyses were performed to ascertain whether pretest RSCA resiliency scores moderated decreases in the posttraumatic stress and self-reported depressive symptoms at posttreatment. The RSCA scales did not moderate any of the improvements on the PTSD and depression outcome measures. Paired t -tests between the mean pre- and posttest RSCA Sense of Mastery (MAS), Sense of Relatedness (REL), and Emotional Reactivity (REA) scores demonstrated significant (ps < 0.001) improvements on these measures over time. Using residualized posttest scores for the three RSCA scales to assess improvement, significant correlations were found between changes in resiliency and various residualized outcome scores for posttraumatic stress disorder (PTSD) and depression measures. Decreases in the REA scores and increases in the MAS and REL scores were related to fewer symptoms of hypervigilance and less self-reported depression after completing TF-CBT. Only improvements in the REL scores were associated with fewer symptoms of re-experiencing after treatment. The results were discussed as indicating that significant improvements in personal resiliency had occurred over time with effect sizes less than those found for posttraumatic stress symptoms, but comparable to those found for self-reported depression reductions. Limitations and future research recommendations are discussed.
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