Developmental diversification of cortical inhibitory interneurons, bioRxiv, 2017-02-03

ABSTRACTDiverse subsets of cortical interneurons play a particularly important role in the stability of the neural circuits underlying cognitive and higher order brain functions, yet our understanding of how this diversity is generated is far from complete. We applied massively parallel single-cell RNA-seq to profile a developmental time course of interneuron development, measuring the transcriptomes of over 60,000 progenitors during their maturation in the ganglionic eminences and embryonic migration into the cortex. While diversity within mitotic progenitors is largely driven by cell cycle and differentiation state, we observed sparse eminence-specific transcription factor expression, which seeds the emergence of later cell diversity. Upon becoming postmitotic, cells from all eminences pass through one of three precursor states, one of which represents a cortical interneuron ground state. By integrating datasets across developmental timepoints, we identified transcriptomic heterogeneity in interneuron precursors representing the emergence of four cardinal classes (Pvalb, Sst, Id2 and Vip), which further separate into subtypes at different timepoints during development. Our analysis revealed that the ASD-associated transcription factor Mef2c discriminates early Pvalb-precursors in E13.5 cells, and removal of Mef2c confirms its essential role for Pvalb interneuron development. These findings shed new light on the molecular diversification of early inhibitory precursors, and suggest gene modules that may link developmental specification with the etiology of neuropsychiatric disorders.

biorxiv neuroscience 100-200-users 2017

Untangling intelligence, psychopathy, antisocial personality disorder, & conduct problems A meta-analytic review, bioRxiv, 2017-01-18

AbstractSubstantial research has investigated the association between intelligence and psychopathic traits. The findings to date have been inconsistent and have not always considered the multi-dimensional nature of psychopathic traits. Moreover, there has been a tendency to confuse psychopathy with other closely related, clinically significant disorders. The current study represents a meta-analysis conducted to evaluate the direction and magnitude of the association of intelligence with global psychopathy, as well as its factors and facets, and related disorders (Antisocial Personality Disorder, Conduct Disorder, and Oppositional Defiant Disorder). Our analyses revealed a small, significant, negative relationship between intelligence and total psychopathy (r = -.07, p = .001). Analysis of factors and facets found differential associations, including both significant positive (e.g., interpersonal facet) and negative (e.g., affective facet) associations, further affirming that psychopathy is a multi-dimensional construct. Additionally, intelligence was negatively associated with Antisocial Personality Disorder (r = -.13, p = .001) and Conduct Disorder (r = -.11, p = .001), but positively with Oppositional Defiant Disorder (r = .06, p = .001). There was significant heterogeneity across studies for most effects, but the results of moderator analyses were inconsistent. Finally, bias analyses did not find significant evidence for publication bias or outsized effects of outliers.

biorxiv neuroscience 0-100-users 2017

 

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