The high societal and individual cost of schizophrenia necessitates finding better, more effective treatment, diagnosis, and prevention strategies. One of the obstacles in this endeavor is the diverse set of etiologies that comprises schizophrenia. A substantial body of evidence has grown over the last few decades to suggest that schizophrenia is a heterogeneous syndrome with overlapping symptoms and etiologies. At the same time, an increasing number of clinical, epidemiological, and experimental studies have shown links between schizophrenia and inflammatory conditions. In this review, we analyze the literature on inflammation and schizophrenia, with a particular focus on comorbidity, biomarkers, and environmental insults. We then identify several mechanisms by which inflammation could influence the development of schizophrenia via the two-hit hypothesis. Lastly, we note the relevance of these findings to clinical applications in the diagnosis, prevention, and treatment of schizophrenia.

No abstract

Debates about the function of the prefrontal cortex are as old as the field of neuropsychology-often dated to Paul Broca's seminal work. Theories of the functional organization of the prefrontal cortex can be roughly divided into those that describe organization by process and those that describe organization by material. Recent studies of the function of the posterior, left inferior frontal gyrus (pLIFG) have yielded two quite different interpretations: One hypothesis holds that the pLIFG plays a domain-specific role in phonological processing, whereas another hypothesis describes a more general function of the pLIFG in cognitive control. In the current study, we distinguish effects of increasing cognitive control demands from effects of phonological processing. The results support the hypothesized role for the pLIFG in cognitive control, and more task-specific roles for posterior areas in phonology and semantics. Thus, these results suggest an alternative explanation of previously reported phonology-specific effects in the pLIFG. whereas another hypothesis describes a more general function of the pLIFG in cognitive control. In the current study, we distinguish effects of increasing cognitive control demands from effects of phonological processing. The results support the hypothesized role for the pLIFG in cognitive control, and more task-specific roles for posterior areas in phonology and semantics. Thus, these results suggest an alternative explanation of previously reported phonology-specific effects in the pLIFG. &

Introduction: In the Ebbinghaus illusion, a shape appears larger than its actual size when surrounded by small shapes and smaller than its actual size when surrounded by large shapes. Resistance to this visual illusion has been previously reported in schizophrenia, and linked to disorganized symptoms and poorer prognosis in cross-sectional studies. It is unclear, however, when in the course of illness this resistance first emerges or how it varies longitudinally with illness phase.Method: We addressed these issues by having first-episode psychosis patients, multiple-episode schizophrenia patients and healthy controls complete a psychophysical task at two different time points, corresponding to hospital admission and discharge for patients. The task required judging the relative size of two circular targets centered on either side of the screen. Targets were presented without context (baseline), or were surrounded by shapes that made the size judgment harder or easier (misleading and helpful contexts, respectively). Context sensitivity was operationalized as the amount of improvement relative to baseline in the helpful condition minus the amount of decrement relative to baseline in the misleading condition.Results: At hospital admission, context sensitivity was lower in the multiple-episode group than in the other groups, and was marginally less in the first episode than in the control group. In addition, schizophrenia patients were significantly more and less accurate than the other groups in the misleading and helpful conditions, respectively. At discharge, all groups exhibited similar context sensitivity. In general, poorer context sensitivity was related to higher levels of disorganized symptoms, and lower level of depression, excitement, and positive symptoms.Discussion: Resistance to the Ebbinghaus illusion, as a characteristic of the acute phase of illness in schizophrenia, increases in magnitude after the first episode of psychosis. This suggests that visual context processing is a state-marker in schizophrenia and a biomarker of relapse and recovery.

OLs (oligodendrocytes) are the myelinating cells of the CNS (central nervous system), wrapping axons in conductive sheathes to ensure effective transmission of neural signals. The regulation of OL development, from precursor to mature myelinating cell, is controlled by a variety of inhibitory and inductive signalling factors. The dorsal spinal cord contains signals that inhibit OL development, possibly to prevent premature and ectopic precursor differentiation. The Wnt and BMP (bone morphogenic protein) signalling pathways have been identified as dorsal spinal cord signals with overlapping temporal activity, and both have similar inhibitory effects on OL differentiation. Both these pathways feature prominently in many developmental processes and demyelinating events after injury, and they are known to interact in complex inductive, inhibitive and synergistic manners in many developing systems. The interaction between BMP and Wnt signalling in OL development, however, has not been extensively explored. In the present study, we examine the relationship between the canonical Wnt and BMP pathways. We use pharmacological and genetic paradigms to show that both Wnt3a and BMP4 will inhibit OL differentiation in vitro. We also show that when the canonical BMP signalling pathway is blocked, neither Wnt3a nor BMP4 have inhibitory effects on OL differentiation. In contrast, abrogating the Wnt signalling pathway does not alter the actions of BMP4 treatment. Our results indicate that the BMP signalling pathway is necessary for the canonical Wnt signalling pathway to exert its effects on OL development, but not vice versa, suggesting that Wnt signals upstream of BMP.