Social Deprivation,Inequality, and the Neighborhood-Level Incidence of Psychotic Syndromes in East London

Although urban birth, upbringing, and living are associated with increased risk of nonaffective psychotic disorders, few studies have used appropriate multilevel techniques accounting for spatial dependency in risk to investigate social, economic, or physical determinants of psychosis incidence. We adopted Bayesian hierarchical modeling to investigate the sociospatial distribution of psychosis risk in East London for DSM-IV nonaffective and affective psychotic disorders, ascertained over a 2-year period in the East London first-episode psychosis study. We included individual and environmental data on 427 subjects experiencing first-episode psychosis to estimate the incidence of disorder across 56 neighborhoods, having standardized for age, sex, ethnicity, and socioeconomic status. A Bayesian model that included spatially structured neighborhood-level random effects identified substantial unexplained variation in nonaffective psychosis risk after controlling for individual-level factors. This variation was independently associated with greater levels of neighborhood income inequality (SD increase in inequality: Bayesian relative risks [RR]: 1.25; 95% CI: 1.04–1.49), absolute deprivation (RR: 1.28; 95% CI: 1.08–1.51) and population density (RR: 1.18; 95% CI: 1.00–1.41). Neighborhood ethnic composition effects were associated with incidence of nonaffective psychosis for people of black Caribbean and black African origin. No variation in the spatial distribution of the affective psychoses was identified, consistent with the possibility of differing etiological origins of affective and nonaffective psychoses. Our data suggest that both absolute and relative measures of neighborhood social composition are associated with the incidence of nonaffective psychosis. We suggest these associations are consistent with a role for social stressors in psychosis risk, particularly when people live in more unequal communities.Key words: psychosis, epidemiology, urban, social environment, inequality, deprivation, Bayesian modeling, schizophrenia     

When the brain expects pain: common neural responses to pain anticipation are related to clinical pain and distress in fibromyalgia and osteoarthritis

Supraspinal processes in humans can have a top‐down enhancing effect on nociceptive processing in the brain and spinal cord. Studies have begun to suggest that such influences occur in conditions such as fibromyalgia (FM), but it is not clear whether this is unique to FM pain or common to other forms of chronic pain, such as that associated with osteoarthritis (OA). We assessed top‐down processes by measuring anticipation‐evoked potentials and their estimated sources, just prior (< 500 ms) to laser heat pain stimulation, in 16 patients with FM, 16 patients with OA and 15 healthy participants, by using whole‐brain statistical parametric mapping. Clinical pain and psychological coping factors (pain catastrophizing, anxiety, and depression) were well matched between the patient groups, such that these did not confound our comparisons between FM and OA patients. For the same level of heat pain, insula activity was significantly higher in FM patients than in the other two groups during anticipation, and correlated with the intensity and extent of reported clinical pain. However, the same anticipatory insula activity also correlated with OA pain, and with the number of tender points across the two patient groups, suggesting common central mechanisms of tenderness. Activation in the dorsolateral prefrontal cortex was reduced during anticipation in both patient groups, and was related to less effective psychological coping. Our findings suggest common neural correlates of pain and tenderness in FM and OA that are enhanced in FM but not unique to this condition.     

Neural correlates of endogenous attention,exogenous attention and inhibition of return in touch

Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event‐related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of expected targets both when the cue predicted targets at the same (endogenous predictive task) and opposite hand (endogenous counter‐predictive task), and these effects also correlated with ERP effects of endogenous attention. In an exogenous task, where the cue was non‐informative, inhibition of return (IOR) was observed. The electrophysiological results demonstrated early effects of exogenous attention followed by later endogenous attention modulations. These effects were independent in both the endogenous predictive and exogenous tasks. However, voluntarily directing attention away from a cued body part influenced the early exogenous marker (N80). This suggests that the two mechanisms are interdependent, at least when the task requires more demanding shifts of attention. The early marker of exogenous tactile attention, the N80, was not directly related to IOR, which may suggest that exogenous attention and IOR are not necessarily two sides of the same coin. This study adds valuable new insight into how we process and select information presented to our body, showing both independent and interdependent effects of endogenous and exogenous attention in touch.     

Systematic comparison of adeno‐associated virus and biotinylated dextran amine reveals equivalent sensitivity between tracers and novel projection targets in the mouse brain

As an anterograde neuronal tracer, recombinant adeno‐associated virus (AAV) has distinct advantages over the widely used biotinylated dextran amine (BDA). However, the sensitivity and selectivity of AAV remain uncharacterized for many brain regions and species. To validate this tracing method further, AAV (serotype 1) was systematically compared with BDA as an anterograde tracer by injecting both tracers into three cortical and 15 subcortical regions in C57BL/6J mice. Identical parameters were used for our sequential iontophoretic injections, producing injections of AAV that were more robust in size and in density of neurons infected compared with those of BDA. However, these differences did not preclude further comparison between the tracers, because the pairs of injections were suitably colocalized and contained some percentage of double‐labeled neurons. A qualitative analysis of projection patterns showed that the two tracers behave very similarly when injection sites are well matched. Additionally, a quantitative analysis of relative projection intensity for cases targeting primary motor cortex (MOp), primary somatosensory cortex (SSp), and caudoputamen (CP) showed strong agreement in the ranked order of projection intensities between the two tracers. A detailed analysis of the projections of two brain regions (SSp and MOp) revealed many targets that have not previously been described in the mouse or rat. Minor retrograde labeling of neurons was observed in all cases examined, for both AAV and BDA. Our results show that AAV has actions equivalent to those of BDA as an anterograde tracer and is suitable for analysis of neural circuitry throughout the mouse brain. J. Comp. Neurol. 522:1989–2012, 2014. © 2014 Wiley Periodicals, Inc.     

Predictive utility of cyclo-oxygenase-2 expression by colon and rectal cancer

Background

Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear.

Methods

Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated. COX-2 expression was assessed by immunohistochemistry. Univariate analysis was used to determine the predictive significance of clinicopathologic variables. Overall survival, disease-specific survival, and disease-free survival were the main outcomes examined.

Results

COX-2 was found to be expressed in 93% of colon cancers and 87% of rectal cancers. Decreased COX-2 expression was related to decreased disease-specific survival (P = .016) and decreased disease-free survival (P = .019) in the rectal cancer cohort but not in the colon cancer cohort.

Conclusions

COX-2 expression has predictive utility for management of rectal but not colon cancer.