Determinants of different aspects of everyday outcome in schizophrenia: The roles of negative symptoms, cognition, and functional capacity

Cognition, negative symptoms, and depression are potential predictors of disability in schizophrenia. We present analyses of pooled data from four separate studies (all n>169; total n=821) that assessed differential aspects of disability and their potential determinants. We hypothesized that negative symptoms would predict social outcomes, but not vocational functioning or everyday activities and that cognition and functional capacity would predict vocational functioning and everyday activities but not social outcomes. The samples were rated by clinician informants for their everyday functioning in domains of social and vocational outcomes, and everyday activities, examined with assessments of cognition and functional capacity, rated clinically with the Positive and Negative Syndrome Scale (PANSS) and self-reporting depression. We computed a model that tested the hypotheses described above and compared it to a model that predicted that negative symptoms, depression, cognition, and functional capacity had equivalent influences on all aspects of everyday functioning. The former, specific relationship model fit the data adequately and we subsequently confirmed a similar fit within all four samples. Analyses of the relative goodness of fit suggested that this specific model fit the data better than the more general, equivalent influence predictor model. We suggest that treatments aimed at cognition may not affect social functioning as much as other aspects of disability, a finding consistent with earlier research on the treatment of cognitive deficits in schizophrenia, while negative symptoms predicted social functioning. These relationships are central features of schizophrenia and treatment efforts should be aimed accordingly

Esmethadone-HCl (REL-1017): a promising rapid antidepressant

This review article presents select recent studies that form the basis for the development of esmethadone into a potential new drug. Esmethadone is a promising member of the pharmacological class of uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists that have shown efficacy for major depressive disorder (MDD) and other diseases and disorders, such as Alzheimer's dementia and pseudobulbar affect. The other drugs in the novel class of NMDAR antagonists with therapeutic uses that are discussed for comparative purposes in this review are esketamine, ketamine, dextromethorphan, and memantine. We present in silico, in vitro, in vivo, and clinical data for esmethadone and other uncompetitive NMDAR antagonists that may advance our understanding of the role of these receptors in neural plasticity in health and disease. The efficacy of NMDAR antagonists as rapid antidepressants may advance our understanding of the neurobiology of MDD and other neuropsychiatric diseases and disorders.ISSN:0940-1334ISSN:1433-849

Determinants of different aspects of everyday outcome in schizophrenia: The roles of negative symptoms, cognition, and functional capacity

Cognition, negative symptoms, and depression are potential predictors of disability in schizophrenia. We present analyses of pooled data from four separate studies (all n>169; total n=821) that assessed differential aspects of disability and their potential determinants. We hypothesized that negative symptoms would predict social outcomes, but not vocational functioning or everyday activities and that cognition and functional capacity would predict vocational functioning and everyday activities but not social outcomes. The samples were rated by clinician informants for their everyday functioning in domains of social and vocational outcomes, and everyday activities, examined with assessments of cognition and functional capacity, rated clinically with the Positive and Negative Syndrome Scale (PANSS) and self-reporting depression. We computed a model that tested the hypotheses described above and compared it to a model that predicted that negative symptoms, depression, cognition, and functional capacity had equivalent influences on all aspects of everyday functioning. The former, specific relationship model fit the data adequately and we subsequently confirmed a similar fit within all four samples. Analyses of the relative goodness of fit suggested that this specific model fit the data better than the more general, equivalent influence predictor model. We suggest that treatments aimed at cognition may not affect social functioning as much as other aspects of disability, a finding consistent with earlier research on the treatment of cognitive deficits in schizophrenia, while negative symptoms predicted social functioning. These relationships are central features of schizophrenia and treatment efforts should be aimed accordingly