Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by defects in one of several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 90% of cases are caused by 21-hydroxylase deficiency, and the severity of the resulting clinical symptoms varies according to the level of 21-hydroxylase activity. 21-Hydroxylase deficiency is usually caused by mutations in the CYP21A2 gene, which is located on the RCCX module, a chromosomal region highly prone to genetic recombination events that can result in a wide variety of complex rearrangements, such as gene duplications, gross deletions and gene conversions of variable extensions. Molecular genotyping of CYP21A2 and the RCCX module has proved useful for a more accurate diagnosis of the disease, and prenatal diagnosis. This article summarises the clinical features of 21-hydroxylase deficiency, explains current understanding of the disease at the molecular level, and highlights recent developments, particularly in diagnosis.

Social Cognition, Negative Symptoms and Psychosocial Functioning in Schizophrenia.

Although functional recovery could be advocated as an achievable treatment goal, many effective interventions for the treatment of psychotic symptoms, such as antipsychotic drugs, may not improve functioning. The last two decades of cognitive and clinical research on schizophrenia were a turning point for the firm acknowledgment of how relevant social cognitive deficits and negative symptoms could be in predicting psychosocial functioning. The relevance of social cognition dysfunction in schizophrenia patients’ daily living is now unabated. In fact, social cognition deficits could be the most significant predictor of functionality in patients with schizophrenia, non-redundantly with neurocognition. Emerging evidence suggests that negative symptoms appear to play an indirect role, mediating the relationship between neurocognition and social cognition with functional outcomes. Further explorations of this mediating role of negative symptoms have revealed that motivational deficits appear to be particularly important in explaining the relationship between both neurocognitive and social cognitive dysfunction and functional outcomes in schizophrenia. In this paper we will address the relative contribution of two key constructs—social cognitive deficits and negative symptoms, namely how intertwined they could be in daily life functioning of patients with schizophrenia.