Affect fluctuations examined with ecological momentary assessment in patients with current or remitted depression and anxiety disorders.

BACKGROUND: There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders. METHODS: Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels. RESULTS: Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant. CONCLUSIONS: Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.

ATP and NADPH coated iron oxide nanoparticles for targeting of highly metabolic tumor cells.

The metabolic activity of tumor cells is known to be higher as compared to that of normal cells, which has been previously exploited to deliver nanomedicines to highly metabolic tumor cells. Unfortunately, current strategies, which are mostly based on complex energy sources, such as sugars, showed insufficient accumulation at the target sites. We here report the coating of IONPs with two essential units of cellular metabolism: adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH). ATP and NADPH were directly bound to the IONPs' surface using a simple aqueous method. Both molecules were used as coatings, i.e. as stabilizing agents, but also simultaneously as targeting molecules to deliver IONPs to highly metabolic tumor cells. Indeed, we found that the uptake of ATP-IONPs and NADPH-IONPs is correlated with the metabolic activity of tumor cells, especially regarding their cellular ATP levels and NADPH consumption. We also measured one of the highest MRI r2 relaxivities for both ATP-IONPs and NADPH-IONPs. With the direct coating of IONPs with ATP and NADPH, we therefore provide an optimal platform to stabilize IONPs and at the same time promising properties for the targeting and detection of highly metabolic tumor cells.

Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.

BACKGROUND: Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings. METHOD: A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined. RESULTS: In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%. CONCLUSIONS: Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.

Mental health problems are associated with low-frequency fluctuations in reaction time in a large general population sample. The TRAILS study.

BACKGROUND: Increased intra-subject reaction time variability (RT-ISV) as coarsely measured by the standard deviation (RT-SD) has been associated with many forms of psychopathology. Low-frequency RT fluctuations, which have been associated with intrinsic brain rhythms occurring approximately every 15-40s, have been shown to add unique information for ADHD. In this study, we investigated whether these fluctuations also relate to attentional problems in the general population, and contribute to the two major domains of psychopathology: externalizing and internalizing problems. METHODS: RT was monitored throughout a self-paced sustained attention task (duration: 9.1 ± 1.2 min) in a Dutch population cohort of young adults (n=1455, mean age: 19.0 ± 0.6 years, 55.1% girls). To characterize temporal fluctuations in RT, we performed direct Fourier Transform on externally validated frequency bands based on frequency ranges of neuronal oscillations: Slow-5 (0.010-0.027 Hz), Slow-4 (0.027-0.073 Hz), and three additional higher frequency bands. Relative magnitude of Slow-4 fluctuations was the primary predictor in regression models for attentional, internalizing and externalizing problems (measured by the Adult Self-Report questionnaire). Additionally, stepwise regression models were created to investigate (a) whether Slow-4 significantly improved the prediction of problem behaviors beyond the RT-SD and (b) whether the other frequency bands provided important additional information. RESULTS: The magnitude of Slow-4 fluctuations significantly predicted attentional and externalizing problems and even improved model fit after modeling RT-SD first (R(2) change=0.6%, P<.01). Subsequently, adding Slow-5 explained additional variance for externalizing problems (R(2) change=0.4%, P<.05). For internalizing problems, only RT-SD made a significant contribution to the regression model (R(2)=0.5%, P<.01), that is, none of the frequency bands provided additional information. CONCLUSIONS: Low-frequency RT fluctuations have added predictive value for attentional and externalizing, but not internalizing problems beyond global differences in variability. This study extends previous findings in clinical samples of children with ADHD to adolescents from the general population and demonstrates that deconstructing RT-ISV into temporal components can provide more distinctive information for different domains of psychopathology.

Evidence for mirror systems in emotions.

Why do we feel tears well up when we see a loved one cry? Why do we wince when we see other people hurt themselves? This review addresses these questions from the perspective of embodied simulation: observing the actions and tactile sensations of others activates premotor, posterior parietal and somatosensory regions in the brain of the observer which are also active when performing similar movements and feeling similar sensations. We will show that seeing the emotions of others also recruits regions involved in experiencing similar emotions, although there does not seem to be a reliable mapping of particular emotions onto particular brain regions. Instead, emotion simulation seems to involve a mosaic of affective, motor and somatosensory components. The relative contributions of these components to a particular emotion and their interrelationship are largely unknown, although recent experimental evidence suggests that motor simulation may be a trigger for the simulation of associated feeling states. This mosaic of simulations may be necessary for generating the compelling insights we have into the feelings of others. Through their integration with, and modulation by, higher cognitive functions, they could be at the core of important social functions, including empathy, mind reading and social learning.