Overview

Overview of Impaired Cognition in Schizophrenia

Schizophrenia is associated with a range of impairments in neurocognitive domains that include memory, attention, executive functioning, and psychomotor performance. These impairments appear to be a core feature of schizophrenia because such deficits are found in attenuated form in first-degree relatives of patients and because they are independent of the psychotic symptoms of the illness. Cognitive impairments are common at the onset of schizophrenia and can frequently be identified in childhood, well before psychotic symptoms emerge. In contrast to psychotic symptoms which are typically episodic, impairments in cognition appear to be a stable feature of the illness. Most contemporary models for conceptualizing schizophrenia recognize that impairments in neurocognition should be included as a distinct feature of the disorder, in addition to negative symptoms, positive symptoms, and thought disorganization.

Given the wide range of cognitive deficits in schizophrenia, there is uncertainty about which domains are the most important to measure and to treat. One of the key goals of the NIMH Contract: Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), is to identify the cognitive domains to be assessed in the NIMH consensus battery that will be used in TURNS, and in other clinical trials of pro-cognitive medications for schizophrenia. Based on a review of existing data sets, the MATRICS Neurocognition Committee concluded that there was empirical support for six separable cognitive domains: Verbal Learning and Memory, Speed of Processing, Working Memory, Reasoning and Problem Solving, Attention/ Vigilance, and Visual Learning and Memory. Based on responses from participants at the first MATRICS consensus meeting, held in April 2003, one additional domain was considered important to assess in the MATRICS battery: Social Cognition.

Cognitive impairments are important as a treatment target because they have a substantial impact on the outcome of schizophrenia. Literature reviews by Green and colleagues have demonstrated that there are consistent relationships between cognitive deficits measured in the laboratory and functional outcome in schizophrenia, including social outcome, vocational outcome, and success in rehabilitation programs. These relationships between neurocognitive deficits and functional outcome are found in both cross sectional and longitudinal studies. In contrast to cognitive deficits, clinical symptoms are only weakly related to functional outcome in schizophrenia. The magnitudes for the relationships between cognitive deficits and functional outcome are medium for individual cognitive constructs (such as those identified as separable factors by the MATRICS Neurocognition Committee) and the relationships can be large when summary scores (e.g., composites of several cognitive functions) are used. This literature on cognitive linkages to functional outcome provides a rather compelling rationale for intervention at the level of cognition.

Antipsychotic medications may lead to some improvement in cognition in schizophrenia, although the overall effects are relatively weak. A body of research suggests that second generation antipsychotic medications appear to have beneficial effects on cognition, at least when compared with first generation agents. However, patients with schizophrenia often perform two or three standard deviations below the mean of controls on neurocognitive tests and newer antipsychotic drugs only make up a fraction of that difference. This gap in the effectiveness of antipsychotic drugs for neurocognition has inspired a search for co-treatments that can be added to an antipsychotic to improve cognition.