Self-reference in psychosis and depression: a language marker of illness.

BACKGROUND: Language use is of increasing interest in the study of mental illness. Analytical approaches range from phenomenological and qualitative to formal computational quantitative methods. Practically, the approach may have utility in predicting clinical outcomes. We harnessed a real-world sample (blog entries) from groups with psychosis, strong beliefs, odd beliefs, illness, mental illness and/or social isolation to validate and extend laboratory findings about lexical differences between psychosis and control subjects. METHOD: We describe the results of two experiments using Linguistic Inquiry and Word Count software to assess word category frequencies. In experiment 1, we compared word use in psychosis and control subjects in the laboratory (23 per group), and related results to subject symptoms. In experiment 2, we examined lexical patterns in blog entries written by people with psychosis and eight comparison groups. In addition to between-group comparisons, we used factor analysis followed by clustering to discern the contributions of strong belief, odd belief and illness identity to lexical patterns. RESULTS: Consistent with others' work, we found that first-person pronouns, biological process words and negative emotion words were more frequent in psychosis language. We tested lexical differences between bloggers with psychosis and multiple relevant comparison groups. Clustering analysis revealed that word use frequencies did not group individuals with strong or odd beliefs, but instead grouped individuals with any illness (mental or physical). CONCLUSIONS: Pairing of laboratory and real-world samples reveals that lexical markers previously identified as specific language changes in depression and psychosis are probably markers of illness in general.

The doxastic shear pin: delusions as errors of learning and memory.

We reconsider delusions in terms of a "doxastic shear pin", a mechanism that errs so as to prevent the destruction of the machine (brain) and permit continued function (in an attenuated capacity). Delusions may disable flexible (but energetically expensive) inference. With each recall, delusions may be reinforced further and rendered resistant to contradiction. We aim to respond to deficit accounts of delusions - that delusions are only a problem without any benefit - by considering delusion formation and maintenance in terms of predictive coding. We posit that brains conform to a simple computational principle: to minimize prediction error (the mismatch between prior top-down expectation and current bottom-up input) across hierarchies of brain regions and psychological representation. Recent data suggest that delusions may form in the absence of constraining top-down expectations. Then, once formed, they become new priors that motivate other beliefs, perceptions, and actions by providing strong (sometimes overriding) top-down expectation. We argue that delusions form when the shear-pin breaks, permitting continued engagement with an overwhelming world, and ongoing function in the face of paralyzing difficulty. This crucial role should not be ignored when we treat delusions: we need to consider how a person will function in the world without them..

Word use in first-person accounts of schizophrenia.

BACKGROUND: Language use is often disrupted in patients with schizophrenia; novel computational approaches may provide new insights. AIMS: To test word use patterns as markers of the perceptual, cognitive and social experiences characteristic of schizophrenia. METHOD: Word counting software was applied to first-person accounts of schizophrenia and mood disorder. RESULTS: More third-person plural pronouns ('they') and fewer first-person singular pronouns ('I') were used in schizophrenia than mood disorder accounts. Schizophrenia accounts included fewer words related to the body and ingestion, and more related to religion. Perceptual and causal language were negatively correlated in schizophrenia accounts but positively correlated in mood disorder accounts. CONCLUSIONS: Differences in pronouns suggest decreased self-focus or perhaps even an understanding of self as other in schizophrenia. Differences in how perceptual and causal words are correlated suggest that long-held delusions represent a decreased coupling of explanations with sensory experience over time.

Dicer is required for proliferation, viability, migration and differentiation in corticoneurogenesis.

In mice, microRNAs (miRNAs) are required for embryonic viability, and previous reports implicate miRNA participation in brain cortical neurogenesis. Here, we provide a more comprehensive analysis of miRNA involvement in cortical brain development. To accomplish this we used mice in which Dicer, the RNase III enzyme necessary for canonical miRNA biogenesis, is depleted from Nestin-expressing progenitors and progeny cells. We systematically assessed how Dicer depletion impacts proliferation, cell death, migration and differentiation in the developing brain. Using markers for proliferation and in vivo labeling with thymidine analogs, we found reduced numbers of proliferating cells, and altered cell cycle kinetics from embryonic day 15.5 (E15.5). Progenitor cells were distributed aberrantly throughout the cortex rather than restricted to the ventricular and subventricular zones. Activated Caspase3 was elevated, reflecting increased cortical cell death as early as E15.5. Cajal-Retzius-positive cells were more numerous at E15.5 and were dysmorphic relative to control cortices. Consistent with this, Reelin levels were enhanced. Doublecortin and Rnd2 were also increased and showed altered distribution, supporting a strong regulatory role for miRNAs in both early and late neuronal migration. In addition, GFAP staining at E15.5 was more intense and disorganized throughout the cortex with Dicer depletion. These results significantly extend earlier works, and emphasize the impact of miRNAs on neural progenitor cell proliferation, apoptosis, migration, and differentiation in the developing mammalian brain.

Application of newer concepts in diabetes.

The changing definition of diabetes, brought up to date, includes the concepts of premellitus as well as mellitus, and of an enzymatically impaired or otherwise ineffective insulin as the possible cause of the full syndrome. Another current concept holds that an increased amount of this lipogenically active but glycolytically impaired insulin is the mechanism producing obesity in diabetes as a premellitic sign. Despite changed concepts the importance and effectiveness of prophylactic weight control in the premellitic stage, and as the fundamental treatment in all stages of obesity-diabetes remains the same. The order of preference in the addition of specific drugs to the dietary treatment of obesity-diabetes is anorexigenic agents, phenformin, single sulfonylureas, and combined chlorpropamide-phenformin. Insulin is the therapy of last resort in this usually mild form of diabetes. There is great potential usefulness for oral hypoglycemic combination therapy (with steroids temporarily if necessary) as a replacement for insulin in the treatment of immunologically-produced insulin resistance.