Theory of mind deficits in chronically depressed patients

Background: Poor theory of mind (ToM) performance has been found in patients with mood disorders, but it has not been examined in the subgroup of chronic depression where ToM deficits may be even more persistent than in acute depressive episodes. The aim of this study was to compare the ToM performance of chronically depressed patients with a healthy control group and to clarify the relation of ToM to other cognitive functions. Methods: ToM performance was assessed in 30 chronically depressed patients and 30 matched healthy controls by two cartoon picture story tests. In addition, logical memory, alertness, and executive functioning were evaluated. Results: Chronically depressed patients were markedly impaired in all ToM‐ and neuropsychological tasks compared to healthy controls. Performance in the different ToM tests was significantly correlated with at least one other cognitive variable. After controlling for logical memory and working memory, no ToM tasks predicted being a patient. Conclusions: Patients with chronic depression present significant deficits in “reading” social interactions, which may be associated with general cognitive impairments. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

The functional relevance of affect recognition errors in schizophrenia.

To evaluate the clinical and ecological validity of affect recognition (AR) measures in a sample of community-dwelling schizophrenic outpatients (N = 40), we analyzed the relation of facial and vocal AR to intellectual, symptomatic, and quality-of-life criteria. Facial and vocal AR showed virtually identical patterns of association with these criteria, suggesting that both modalities of AR draw on the same underlying heteromodal capacity. Specifically, AR was correlated with a subset of intellectual abilities (verbal-semantic, executive-attentional), but was unrelated to age, education, or neuroleptic dose. In terms of clinical and ecological criteria, AR errors correlated with more severe psychotic symptoms (positive and disorganized) and with lower quality of life (relationships, community participation, and richness of intrapsychic experience). Even after controlling for subjects' intellectual abilities and illness severity, inaccurate AR was associated with bizarre behaviors (involving sociosexual interactions, clothing, appearance) and with impoverished interpersonal relations. Thus, while difficulty identifying basic affective cues is related to general cognitive and illness-severity factors, it appears to have specific functional implications that do not depend on generalized impairment. Assessment of AR may identify a subgroup of schizophrenic patients who have a central defect in the heteromodal monitoring of emotional-social displays, associated with dysregulation of social behaviors and disruption of interpersonal relations.     

The Role of Ultrasound for the Personalized Botulinum Toxin Treatment of Cervical Dystonia

The visualization of the human body has frequently been groundbreaking in medicine. In the last few years, the use of ultrasound (US) imaging has become a well-established procedure for botulinum toxin therapy in people with cervical dystonia (CD). It is now undisputed among experts that some of the most relevant muscles in this indication can be safely injected under visual US guidance. This review will explore the method from basic technical considerations, current evidence to conceptual developments of the phenomenology of cervical dystonia. We will review the implications of introducing US to our understanding of muscle function and anatomy of common cervical dystonic patterns. We suggest a flow chart for the use of US to achieve a personalized treatment of people with CD. Thus, we hope to contribute a resource that is useful in clinical practice and that stimulates the ongoing development of this valuable technique.     

Association of Urinary Concentrations of Bisphenol A and Phthalate Metabolites with Risk of Type 2 Diabetes: A Prospective Investigation in the Nurses’ Health Study (NHS) and NHSII Cohorts

Background: Prospective evidence regarding associations for exposures to bisphenol A (BPA) and phthalates with type 2 diabetes (T2D) is lacking.Objective: We prospectively examined urinary concentrations of BPA and phthalate metabolites with T2D risk.Methods: We measured BPA and eight major phthalate metabolites among 971 incident T2D case–control pairs from the Nurses’ Health Study (NHS) (mean age, 65.6 years) and NHSII (mean age, 45.6 years).Results: In the NHSII, BPA levels were not associated with incident T2D in multivariate-adjusted analysis until body mass index was adjusted: odds ratio (OR) comparing extreme BPA quartiles increased from 1.40 (95% CI: 0.91, 2.15) to 2.08 (95% CI: 1.17, 3.69; p_trend = 0.02) with such an adjustment. In contrast, BPA concentrations were not associated with T2D in the NHS (OR = 0.81; 95% CI: 0.48, 1.38; p_trend = 0.45). Likewise, urinary concentrations of total phthalate metabolites were associated with T2D in the NHSII (OR comparing extreme quartiles = 2.14; 95% CI: 1.19, 3.85; p_trend = 0.02), but not in the NHS (OR = 0.87; 95% CI: 0.49, 1.53; p_trend = 0.29). Summed metabolites of butyl phthalates or di-(2-ethylhexyl) phthalates were significantly associated with T2D only in the NHSII; ORs comparing extreme quartiles were 3.16 (95% CI: 1.68, 5.95; p_trend = 0.0002) and 1.91 (95% CI: 1.04, 3.49; p_trend = 0.20), respectively.Conclusions: These results suggest that BPA and phthalate exposures may be associated with the risk of T2D among middle-aged, but not older, women. The divergent findings between the two cohorts might be explained by menopausal status or simply by chance. Clearly, these results need to be interpreted with caution and should be replicated in future studies, ideally with multiple urine samples collected prospectively to improve the measurement of these exposures with short half-lives.Citation: Sun Q, Cornelis MC, Townsend MK, Tobias DK, Eliassen AH, Franke AA, Hauser R, Hu FB. 2014. Association of urinary concentrations of bisphenol A and phthalate metabolites with risk of type 2 diabetes: a prospective investigation in the Nurses’ Health Study (NHS) and NHSII Cohorts. Environ Health Perspect 122:616–623; http://dx.doi.org/10.1289/ehp.1307201     

EF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells

EF-hand Ca²⁺-binding proteins are thought to shape the spatiotemporal properties of cellular Ca²⁺ signaling and are prominently expressed in sensory hair cells in the ear. Here, we combined genetic disruption of parvalbumin-α, calbindin-D28k, and calretinin in mice with patch-clamp recording, in vivo physiology, and mathematical modeling to study their role in Ca²⁺ signaling, exocytosis, and sound encoding at the synapses of inner hair cells (IHCs). IHCs lacking all three proteins showed excessive exocytosis during prolonged depolarizations, despite enhanced Ca²⁺-dependent inactivation of their Ca²⁺ current. Exocytosis of readily releasable vesicles remained unchanged, in accordance with the estimated tight spatial coupling of Ca²⁺ channels and release sites (effective “coupling distance” of 17 nm). Substitution experiments with synthetic Ca²⁺ chelators indicated the presence of endogenous Ca²⁺ buffers equivalent to 1 mM synthetic Ca²⁺-binding sites, approximately half of them with kinetics as fast as 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). Synaptic sound encoding was largely unaltered, suggesting that excess exocytosis occurs extrasynaptically. We conclude that EF-hand Ca²⁺ buffers regulate presynaptic IHC function for metabolically efficient sound coding.Intracellular Ca²⁺ signaling regulates a multitude of cellular processes. In sensory hair cells, Ca²⁺ is crucial for electrical frequency tuning, afferent synaptic transmission, and efferent modulation (reviewed in ref. 1). To separate these signaling pathways and maintain high temporal fidelity of neurotransmission, Ca²⁺ signals must be temporally limited and spatially confined to the site of action. Cells typically achieve this by localizing Ca²⁺ entry and by rapidly removing free Ca²⁺ ions via binding to cytosolic “buffers” and finally Ca²⁺ extrusion (2–4). Of the various EF-hand Ca²⁺-binding proteins, some seem to function primarily as Ca²⁺-dependent signaling proteins (e.g., calmodulin and Ca²⁺-binding proteins 1–8, CaBP1–8), whereas others [parvalbumin-α (PVα), calbindin-D28k (CB), and calretinin (CR)] are thought to mainly serve as mobile Ca²⁺ buffers.Hair cells of various species strongly express the Ca²⁺-binding proteins PV, CB, and, in some cases, CR. This possibly reflects the need for buffers with different biophysical properties to functionally isolate different Ca²⁺ signaling mechanisms, which are spatially not well separated in these compact epithelial cells. Ca²⁺-binding proteins are particularly abundant in frog and chicken hair cells, which contain millimolar concentrations of parvalbumin-3 (5) as well as of CR (6, 7). An immune-EM study in rats indicated hundreds of micromolar of proteinaceous Ca²⁺-binding sites in inner hair cells (IHCs) (8). A patch-clamp study in gerbil IHCs reported endogenous buffers equivalent to approximately 0.4 mM 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) (9). Genetic deletion of the EF-hand Ca²⁺-binding proteins PVα, CB, and CR in mice has facilitated the analysis of their function (10–13; reviewed in ref. 14), but the combined deletion of these proteins remains to be studied. IHCs provide an experimentally well-accessible presynaptic preparation that uses all three. Here, we studied IHC function and hearing in mice lacking the three buffers [triple buffer KO (TKO); Pv^−/−Cb^−/−Cr^−/−]. By using perforated and ruptured-patch recordings, we analyzed voltage-gated Ca²⁺ currents and exocytosis of Pv^−/−Cb^−/−Cr^−/− IHCs, in which we also substituted the deleted endogenous buffers with the synthetic Ca²⁺ chelators EGTA or BAPTA. Auditory systems function was probed by measuring otoacoustic emissions and auditory brainstem responses (ABRs) as well as by recordings from single spiral ganglion neurons (SGNs). We performed mathematical modeling to estimate concentrations of the endogenous mobile Ca²⁺ buffers and to better understand how these proteins control exocytosis at IHC synapses. We conclude that the endogenous buffer capacity of IHCs is well approximated by 1 mM synthetic Ca²⁺-binding sites with different kinetics. A tight spatial coupling between Ca²⁺ channels and sensors of exocytosis (Ca²⁺ channel-exocytosis coupling) precludes interference of PVα, CB, and CR with fusion of the readily releasable pool of vesicles (RRP). Instead, we suggest that these buffers jointly regulate IHC presynaptic function by restricting neurotransmitter release to active zones (AZs).     

Testing Skype as an interview method in epidemiologic research: response and feasibility

Introduction

Despite its popularity, Skype has not been tested as a tool for epidemiologic research. We examined its feasibility in Germany.

Methods

A population-based sample of young adults was randomly invited to a Skype (n?=?150) or a phone interview (n?=?150). Response and duration of interviews were analysed to evaluate the feasibility of Skype interviews.

Results

Response was low and, with 10 % (95 % CI 5–15 %), even worse among Skype candidates, compared to 22 % (15–28 %) in the phone group. A third of the Skype group asked for being interviewed by phone. Median duration was 34.0 minutes for Skype interviews and 37.0 minutes for phone interviews.

Conclusions

Skype is not yet a feasible tool for data collection in Germany.