MicroRNAs (miRNAs) are endogenously expressed noncoding RNAs that regulate mRNA expression. In vertebrates, more distinct miRNAs are expressed in the brain than in any other tissue, where they are hypothesized to function in neural development. Recent reports describing the effects of specific miRNAs during development, and studies employing miRNA depletion as neural commitment proceeds in the embryo, support a requisite role for miRNAs in cell-fate decisions and provide clues to their function in other aspects of nervous system development.

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.

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.

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One aspect of selfhood that may have relevance for borderline personality disorder (BPD) is variation in sense of body ownership. We employed the rubber hand illusion to manipulate sense of body ownership in BPD. We extended previous research on illusory body ownership in BPD by testing: (i) two illusion conditions: asynchronous and synchronous stimulation, (ii) relationship between illusion experience and BPD symptoms, and (iii) relationship between illusion experience and maladaptive personality traits. We measured illusion strength (questionnaire responses), proprioceptive drift (perceived shift in physical hand position), BPD symptoms (Revised Diagnostic Interview for Borderlines score), and maladaptive personality traits (Personality Inventory for DSM-5) in 24 BPD and 21 control participants. For subjective illusion strength, we found main effects of group (BPD > healthy control, F(1, 43) = 11.94, P = 0.001) and condition (synchronous > asynchronous, F(1, 43) = 22.80, P < 0.001). There was a group × condition interaction for proprioceptive drift (F(1, 43) = 6.48, P = 0.015) such that people with BPD maintained illusion susceptibility in the asynchronous condition. Borderline symptom severity correlated with illusion strength within the BPD group, and this effect was specific to affective (r = 0.45, P < 0.01) and cognitive symptoms (r = 0.46, P < 0.01). Across all participants, trait psychoticism correlated with illusion strength (r = 0.44, P < 0.01). People with BPD are more susceptible to illusory body ownership than controls. This is consistent with the clinical literature describing aberrant physical and emotional experiences of self in BPD. A predictive coding framework holds promise to develop testable mechanistic hypotheses for disrupted bodily self in BPD.