thinking, language, and creativity are specific for mankind. Intertwined with the evolution of these uniquely human capacities might be the emergence of a uniquely human conditionschizophrenia. Traditionally considered a chronic and debilitating disorder, schizophrenia manifests itself by a combination of psychotic symptoms (hallucinations and delusions), motivational difficulties, and cognitive dysfunctions. 1 Cognitive deficits, such as problems in abstract thinking, language, and executive functioning, are considered the core pathology in schizophrenia. 2 In fact, in persons with a nonaffective psychotic disorder, cognitive deficits can be traced back to childhood, as early as to 18 months of age, 3 suggesting that there is an intrinsic vulnerability to schizophrenia, present before its full-

Childhood trauma (CT) increases the risk for psychopathology through disturbed acquisition and extinction of fear. The effects of CT are mediated by abnormalities of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor (GR). Since, the alterations in GRα translational isoforms have been documented in psychiatric disorders we sought to: 1) explore whether multiple GRα isoforms in the human peripheral blood mononuclear cells of two independent cohorts (whole cell n = 40; and nuclear extracts n = 43, adult subjects) mediate the effect of CT on negative affectivity (NA) measured by Depression, Anxiety and Stress Scales (DASS), and 2) examine their role/function during fear extinction in the animal model. In multiple regression analysis, CT, nuclear 40-kDa GRα, their interactions and FKBP5 explained 22%−35% of variance in DASS scores. Structural equation modeling showed that CT had a significant direct effect on 40-kDa and DASS in both cohorts, and on the nuclear 25-kDa GRα. The association between 40-kDa and total DASS was significantly mediated by nuclear FKBP5, whereas on DASS anxiety, over FKBP5 in both cohorts and nuclear full length GRα. Nuclear 40-kDa GRα and its interaction with CT had a significant direct effect on DASS anxiety. In mice, the successful extinction learning was followed by nuclear translocation of 40-kDa GRα and induction of BDNF exon IV expression. Our data revealed that the association between CT and adult NA in non-clinical subjects is mediated by the GRα translational isoforms, in particular 40-kDa GRα, and emphasized its role in fear extinction and neural plasticity.

Among the highest incidences of schizophrenia is the one documented in second-generation migrants of African descent in the Western countries. Interestingly, people of African and European ancestry demonstrate significant genetic-based differences in immune system regulation and response. As a result, the pro-inflammatory phenotype is more pronounced in people of African descent than it is in Europeans. At the same time, the role of the immune system in the etiology of schizophrenia is gaining increased recognition. Here, we propose that the population-specific genetic variation within the immune system interacts with unfavourable environments to contribute to a higher risk of schizophrenia in people of African ancestry. Our hypothesis is supported by recent findings from two separate fields of research-population genetics and psychoneuroimmunology. Moreover, we highlight the need to include African populations in genetic studies of schizophrenia.