Time to Re-focus onto Cognitive Symptoms in Schizophrenia.

Abstract

Byline: M. Reddy, S. Mythri INTRODUCTION Clinicians always feel helpless when faced with a person with residual symptoms of schizophrenia. Though the available antipsychotic agents have definitely reduced the disease burden and disability due to psychotic symptoms, the cognitive symptoms keep the affected person disabled and lead to poor functional outcomes. It is a cause of concern in routine clinical psychiatric practice. It has led to the FDA/NIMH initiative of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) in 2004. [sup][1] The multidisciplinary group which convened for MATRICS initiative proposed the clinical trial guidelines for the development of novel cognitive-enhancing agents in schizophrenia. They also designed the MATRICS Consensus Cognitive Battery, as a measurement tool [sup][2] in research to find novel procognitive agents. In this article, we will review the current status of research into cognitive symptoms of schizophrenia and their management. CONCEPTUAL ISSUES What's in a Name? An awful lot! Recently, Kahn and Keefe [sup][3] argued to call-a-spade-a-spade by reaffirming that schizophrenia is a cognitive illness. They discussed that the erstwhile name Dementia Praecox suited schizophrenia best and that both Kraepelin and Bleuler gave prominence to the cognitive decline or cognitive deficits in its diagnosis and gave only a secondary (or, accessory) status to what we today call as positive symptoms. The later emphasis on psychotic symptoms as the core of schizophrenia was an outcome of factors such as push for a psychological explanation of schizophrenia by Freudian school, Kurt Schneider's proposal to give prominence to first rank symptoms to aid reliability, and the excitement related to symptom resolution by dopamine antagonists. Kahn and Keefe's proposal to refocus is based on four threads of evidence. *Low IQ and poor scholastic performance increase the risk for developing schizophrenia in a dose-response fashion *There is a progressive cognitive decline between the ages 7 and 13 in people who go onto develop schizophrenia, which starts at least a decade before the onset of psychotic symptoms *There is significantly lesser increase in cognition in patients compared to controls and larger degree of cognitive impairment in patients than that is observed before the onset of psychosis suggesting that cognitive performance may continue to decline after the onset of psychotic symptoms *The mean cognitive underperformance during adolescence and at the onset of psychotic symptoms differentiates schizophrenia from the other major psychotic illness and bipolar disorder. The proposal to view schizophrenia as a cognitive illness will impact the way, we formulate the diagnosis, treatment guidelines, and risk phenotype in research. This perspective will radically influence the discourse on at-risk psychosis and also encourage the use of (and research into) early interventions such as cognitive and behavioral therapies. Change in drug target Dopamine hypothesis which was the focus of drug discovery over the last six decades has now given place to newer hypothesis such as the N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis and the modified dopamine hypothesis which give importance to glutamine and serotonin function, respectively. Newer drugs which are studied for the potential benefit in relieving cognitive symptoms are either those who act on novel serotonin receptors like 5HT1A or those who act on NMDAR. There is also a serious consideration to develop drugs which can be combined for the treatment of schizophrenia, similar to the multidrug therapy in tuberculosis or cancer. [sup][4] Recovery model The newer and nuanced use of the term recovery does not refer to the older clinical use which focuses only on the reduction of symptoms but refers to an emphasis on a renewed sense of self and encouragement to return to a more meaningful and self-directed life. …