As one would expect in a complex

genetic disorder, subsequent investigations demonstrated a low prevalence of clinical pathophysiology in carriers of variant alleles of the HFE gene, despite high transferrin saturation levels.25,26 The HFE gene is thus recognized as a susceptibility gene in HH, possibly necessary, but insufficient, for expression of clinical hemochromatosis. This illustrates the principle Inhibitors,research,lifescience,medical that there are more unaffected carriers of susceptibility gene variant alleles than persons with the disorder. It is reasonable to expect insights gained from the study of somatic disorders will draw attention to promising molecular targets for effective therapeutic intervention in schizophrenia. Cognitive impairment: a core feature of schizophrenia Schizophrenia has been recognized clinically as a disorder of cognition since at least 1893, when Emil Kraepelin referred to this illness as “dementia praecox,” a chronic,

disabling disorder whose core Inhibitors,research,lifescience,medical feature was “a disorder of the will,” or an impairment of executive functions and working memory in current terminology. Recent clinical studies confirm the role of cognition in the disability of this disorder. For example, McGurk and colleagues27-29 studied Inhibitors,research,lifescience,medical the relationship of neuropsychological measures of executive function and psychiatric symptoms to work outcomes in 30 patients enrolled in Inhibitors,research,lifescience,medical a supported employment program. Surprisingly, over a 2-year period, patients’ work outcomes were more strongly predicted by levels of function in three key domains of cognitive function than by the severity of their psychotic symptoms; the greater the perturbation of working memory, attentional capacity, and processing speed, the less likely a patient was to remain employed. Similarly, Bryson and Bell30 studied the influence of cognitive function on work performance in 96 outpatients and found that measures of attention and verbal working memory were the strongest

predictors of work Inhibitors,research,lifescience,medical performance for the first 13 weeks, and measures of verbal working memory were the strongest predictors of continued employment over the second 13 weeks. Goldberg Cell press and colleagues18 identified specific cognitive measures of genetic risk in schizophrenia, describing large differences in cognitive performance as a whole between unaffected and affected members of discordant MZ twin pairs, and lesser differences in comparisons between the unaffected discordant twins and controls. Weickert and colleagues31 studied the Enzastaurin ic50 pattern of cognitive decline in a large sample of patients with schizophrenia and found that 51% experienced a 10-point or greater decline in IQ from premorbid status, while another 35% had cognitive deficits from early in life.