•Stronger PGI skills predict earlier entry to treatment for depression.•PGI skills improve during treatment as usual for depression.•Reliable improvement in PGI skills predicts treatment ...outcome.•Clinically significant improvement in PGI skills predicts treatment outcome.
Current methods for treating depressive disorders ineffectively treat large portions of patients. We need to identify malleable factors that predict treatment outcome and can be modified prior to or concurrently with treatment to enhance outcomes. We examined personal growth initiative (PGI) as a malleable predictor of treatment outcome for depressed patients in partial hospital treatment.
Archival data were extracted from medical records of 521 adult patients with depression diagnoses (67.2% women) in a partial hospital program (2008 – 2010). Demographic data and admission and discharge scores for depression and PGI were extracted. ANCOVA assessed the extent to which reliable or clinically significant change in PGI predicted level of depression at discharge, controlling for admission depression levels.
PGI and depression were significantly correlated at admission. PGI scores increased significantly from admission to discharge. Reliable and clinically significant improvement in PGI each significantly, uniquely, and negatively predicted depression at discharge, adjusting for admission depression.
The correlational nature of the longitudinal design precludes definitive statements regarding causality. A large portion of the initial sample was dropped due to substantial missing data, yielding the final N = 521. Dropped patients had higher levels of depression at discharge and increased likelihood of leaving treatment against medical advice, raising concerns about potential other, unmeasured differences.
Our findings confirm the utility of PGI as a malleable predictor of treatment outcome for depressed patients in partial hospital treatment and may have implications for using PGI-based interventions to enhance treatment outcomes.
In this study, we report on the use of differential mobility spectrometry (DMS) as a tool for studying tautomeric species, allowing a more in-depth interrogation of these elusive isomers using ...ion/molecule reactions and tandem mass spectrometry. As an example, we revisit a case study in which gas-phase hydrogen-deuterium exchange (HDX)—a probe of ion structure in mass spectrometry—actually altered analyte ion structure by tautomerization. For the N- and O-protonated tautomers of 4-aminobenzoic acid, when separated using DMS and subjected to subsequent HDX with trace levels of D
2
O, the anticipated difference between the exchange rates of the two tautomers is observed. However, when using higher levels of D
2
O or a more basic reagent, equivalent and almost complete exchange of all labile protons is observed. This second observation is a result of the interconversion of the N-protonated tautomer to the O-protonated form during HDX. We can monitor this transformation experimentally, with support from detailed molecular dynamics and electronic structure calculations. In fact, calculations suggest the onset of bulk solution phase properties for 4-aminobenzoic acid upon solvation with eight CH
3
OH molecules. These findings also underscore the need for choosing HDX reagents and conditions judiciously when separating interconvertible isomers using DMS.
Graphical Abstract
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Chimeric RNAs and their encoded proteins have been traditionally viewed as unique features of neoplasia, and have been used as biomarkers and therapeutic targets for multiple cancers. Recent studies ...have demonstrated that chimeric RNAs also exist in non-cancerous cells and tissues, although large-scale, genome-wide studies of chimeric RNAs in non-diseased tissues have been scarce. Here, we explored the landscape of chimeric RNAs in 9495 non-diseased human tissue samples of 53 different tissues from the GTEx project. Further, we established means for classifying chimeric RNAs, and observed enrichment for particular classifications as more stringent filters are applied. We experimentally validated a subset of chimeric RNAs from each classification and demonstrated functional relevance of two chimeric RNAs in non-cancerous cells. Importantly, our list of chimeric RNAs in non-diseased tissues overlaps with some entries in several cancer fusion databases, raising concerns for some annotations. The data from this study provides a large repository of chimeric RNAs present in non-diseased tissues, which can be used as a control dataset to facilitate the identification of true cancer-specific chimeras.
Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized ...double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality.
The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less.
At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4-6 and significantly lower depression scores (9.2 SD=6.6 compared with 14.9 SD=9.2; adjusted β=-5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them.
The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.
Rationale
Caffeine is widely consumed in foods and beverages and is also used for a variety of medical purposes. Despite its widespread use, relatively little is understood regarding how genetics ...affects consumption, acute response, or the long-term effects of caffeine.
Objective
This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson’s and cardiovascular diseases in habitual caffeine consumers.
Results
Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Analysis of polysubstance use shows that predisposition to caffeine use is highly specific to caffeine itself and shares little common disposition to use of other substances. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users.
Conclusion
Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine.
This study evaluated the biological dimension of meditation and self-transcendent states. A convenience sample of 513 participants was drawn from attendees at a 4-day guided meditation workshop. Half ...were randomly assigned to an active placebo control intervention. All were assessed on a variety of measures, both psychological anxiety, pain, posttraumatic stress disorder (PTSD), positive emotions, and transcendent states, and physiological (physical functioning). Additional biological assessments including salivary immunoglobulin-A (SIgA), cortisol, and Quantitative Electroencephalography (qEEG) were obtained from subset of the Experimental group (
N
= 117). No significant difference in psychological symptoms or positive emotions was observed between Experimental and placebo groups at baseline. At post-test, significant improvements were noted in the Experimental group, including a 49.5% median increase in SIgA (
p
= 0.01), though cortisol remained unchanged. qEEG z-score analysis identified sustained stress reduction, including delta frequency band amplitude increases, high beta decreases, and faster acquisition of sustained alpha states (all
p
< 0.001). Psychological symptoms also improved on all measures. At 6-month follow-up (
N
= 140), PTSD and somatic symptoms significantly improved from baseline, and post-test versus 6-month follow-up results indicated significant increases in happiness and spiritual and physical oneness, along with decreases in depressive symptoms. These findings suggest that autonomic self-regulation and transcendent states may be measured in both biological and psychological dimensions and are associated with pervasive health benefits.
The Integrated Stress Response (ISR) helps metazoan cells adapt to cellular stress by limiting the availability of initiator methionyl-tRNA for translation. Such limiting conditions paradoxically ...stimulate the translation of ATF4 mRNA through a regulatory 5' leader sequence with multiple upstream Open Reading Frames (uORFs), thereby activating stress-responsive gene expression. Here, we report the identification of two critical regulators of such ATF4 induction, the noncanonical initiation factors eIF2D and DENR. Loss of eIF2D and DENR in Drosophila results in increased vulnerability to amino acid deprivation, susceptibility to retinal degeneration caused by endoplasmic reticulum (ER) stress, and developmental defects similar to ATF4 mutants. eIF2D requires its RNA-binding motif for regulation of 5' leader-mediated ATF4 translation. Consistently, eIF2D and DENR deficient human cells show impaired ATF4 protein induction in response to ER stress. Altogether, our findings indicate that eIF2D and DENR are critical mediators of ATF4 translational induction and stress responses in vivo.
We conducted a consented pilot newborn screening (NBS) for Pompe, Gaucher, Niemann-Pick A/B, Fabry, and MPS 1 to assess the suitability of these lysosomal storage disorders (LSDs) for public health ...mandated screening.
At five participating high-birth rate, ethnically diverse New York City hospitals, recruiters discussed the study with postpartum parents and documented verbal consent. Screening on consented samples was performed using multiplexed tandem mass spectrometry. Screen-positive infants underwent confirmatory enzymology, DNA testing, and biomarker quantitation when available. Affected infants are being followed for clinical management and long-term outcome.
Over 4 years, 65,605 infants participated, representing an overall consent rate of 73%. Sixty-nine infants were screen-positive. Twenty-three were confirmed true positives, all of whom were predicted to have late-onset phenotypes. Six of the 69 currently have undetermined disease status.
Our results suggest that NBS for LSDs is much more likely to detect individuals at risk for late-onset disease, similar to results from other NBS programs. This work has demonstrated the feasibility of using a novel consented pilot NBS study design that can be modified to include other disorders under consideration for public health implementation as a means to gather critical evidence for evidence-based NBS practices.
Despite evidence for the benefits of exercise in Parkinson's disease (PD), many patients remain sedentary for undefined reasons.
To compare exercise habits, perceptions about exercise, and barriers ...to exercise in 'low' (<3 h/week) and 'high' (≥3 h/week) exercisers with PD.
A 48-item survey was administered to PD patients at an outpatient academic center. Chi-squared tests were used to compare the percentage differences between low- and high-exercisers with two-sided tests and a significant level of 0.05.
243 surveys were collected over three months; 28 were excluded due to incomplete data, leaving 215 to be analyzed. 49.3% reported 'low'-exercise and 50.7% reported 'high'-exercise. High-exercisers participated in higher intensity exercise regimens (83.4% versus 32.1%, p≤0.001). High-exercisers were more likely to start exercising after being diagnosed (54.2% versus 27.8%, p < 0.001), whereas low-exercisers were more likely to reduce their amount of exercise (40.2% versus 15.9%, p < 0.001). Low-exercisers required more motivating factors. Both groups benefited from having a significant other or a personal trainer motivate them, and both were more likely to exercise if their neurologist encouraged them. Low-exercisers reported twice as many barriers as high-exercisers (p = 0.001). Barriers that were significantly more common in low-exercisers were: lacking someone to motivate them (33.3% versus 10.5%, p < 0.001), fatigue (20.8% versus 15.2%, p = 0.005), and depression (16.7% versus 7.6%, p = 0.045).
There are significant differences between people with PD who exercise regularly and those who do not in terms of motivators and barriers. These findings should be considered when tailoring recommendations for PD patients to encourage exercise, and in designing future interventions.
Breastfeeding is associated with numerous health benefits to offspring and mothers and may improve maternal-infant bonding. Ample evidence suggests breastfeeding can improve child neurodevelopment, ...but more research is needed to establish whether breastfeeding is linked to the development of child psychopathology. This paper aims to explore the effects of both breastfeeding and mother-child interactions on child behavioral outcomes at a later age. Children from the China Jintan Child Cohort Study (N=1267), at age six years old were assessed, along with their parents. Children who were breastfed exclusively for a period of time in the presence of active bonding were compared to those who were breastfed in the absence of active bonding as well as to children who were not exclusively breastfed, with or without active bonding. Results from ANOVA and GLM, using SPSS20, indicate that children who were breastfed and whose mothers actively engaged with them displayed the lowest risk of internalizing problems (mean=10.01, SD=7.21), while those who were neither exclusively breastfed nor exposed to active bonding had the least protection against later internalizing problems (mean=12.79, SD=8.14). The effect of breastfeeding on internalizing pathology likely represents a biosocial and holistic effect of physiological, and nutritive, and maternal-infant bonding benefits.
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