Modulation of Tcf7l2 Expression Alters Behavior in Mice

The comorbidity of type 2 diabetes (T2D) with several psychiatric diseases is well established. While environmental factors may partially account for these co-occurrences, common genetic susceptibilities could also be implicated in the confluence of these diseases. In support of shared genetic burdens, TCF7L2, the strongest genetic determinant for T2D risk in the human population, has been recently implicated in schizophrenia (SCZ) risk, suggesting that this may be one of many loci that pleiotropically influence both diseases. To investigate whether Tcf7l2 is involved in behavioral phenotypes in addition to its roles in glucose metabolism, we conducted several behavioral tests in mice with null alleles of Tcf7l2 or overexpressing Tcf7l2. We identified a role for Tcf7l2 in anxiety-like behavior and a dose-dependent effect of Tcf7l2 alleles on fear learning. None of the mutant mice showed differences in prepulse inhibition (PPI), which is a well-established endophenotype for SCZ. These results show that Tcf7l2 alters behavior in mice. Importantly, these differences are observed prior to the onset of detectable glucose metabolism abnormalities. Whether these differences are related to human anxiety-disorders or schizophrenia remains to be determined. These animal models have the potential to elucidate the molecular basis of psychiatric comorbidities in diabetes and should therefore be studied further

Cognition and multiple sclerosis: a historical analysis of medical perceptions

The earliest descriptions of multiple sclerosis (MS) rarely distinguished cognitive impairment from the general category of "mental symptoms", which also encompassed a broad range of affective disorders. Case-study methods led to disputes about the extent and nature of these symptoms, exacerbated by different national medical traditions. Appropriate scientific methods were only used to investigate cognitive performance in a modest number of studies up to the 1960s, and it was being argued as late as the mid 1970s that affective processes rather than cognitive processes were the key to understanding the psychological aspects of MS. However, the early 1980s, saw major developments in test procedures for the detection of subtle and selective cognitive changes, in the use of brain imaging techniques, and in collaboration between neurologists and neuropsychologists. Pressure to use research findings to improve patients' daily lives suggests a need to reconsider the connection between affective and cognitive processes in MS

Schizotaxia: current status and future directions

Schizophrenia is a biologic disorder whose etiology involves a combination of genetic and environmental risk factors. In this review, the authors update the conceptual basis of schizotaxia, consider evidence for its validity, and look toward its likely evolution in the future