Negative symptoms and cognitive deficits in schizophrenia share many features and are correlated in their severity on a cross-sectional basis. The question arises as to the nature of this relationship: are these symptoms the same, caused by the same factor (or factors); or is the nature of their relationship determined by other factors, such as definitional issues and common correlates? In this article we provide a conceptual overview for addressing this question and provide a selective review of the literature on the cross-sectional and longitudinal relationships between these two features of the illness. We describe 4 different models of the "true" relationship between these variables. Some data suggest that the relationship between these variables is determined by the definition of negative symptoms employed and that, in general, the correlation is moderate at the most. Further, path modeling suggests the possibility, to be addressed with later research, that correlations between negative and cognitive symptoms and everyday functional outcomes may influence the observed correlations between these variables. Thus, we conclude that negative and cognitive symptoms may be separable, if not conceptually independent, domains of the illness and that it might be possible to develop treatments that target negative symptoms and cognitive deficits independently.

/pdf/negative-symptoms-and-cognitive-deficits-what-is-the-nature-587cjqo481.pdf

Negative Symptoms and Cognitive Deficits: What Is the Nature of Their Relationship?

The discovery of the pathophysiology(ies) for schizophrenia is necessary to direct rational treatment directions for this brain disorder. Firm knowledge about this illness is limited to areas of phenomenology, clinical electrophysiology, and genetic risk; some aspects of dopamine pharmacology, cognitive symptoms, and risk genes are known. Basic questions remain about diagnostic heterogeneity, tissue neurochemistry, and in vivo brain function. It is an illness ripe for molecular characterization using a rational approach with a confirmatory strategy; drug discovery based on knowledge is the only way to advance fully effective treatments. This paper reviews the status of general knowledge in this area and proposes an approach to discovery, including identifying brain regions of dysfunction and subsequent localized, hypothesis-driven molecular screening.

Phenotype of schizophrenia: a review and formulation

Molecular profiles of schizophrenia in the CNS at different stages of illness.

Despite effective pharmacological treatments for psychotic symptoms (eg, hallucinations, delusions), functional outcomes for people with psychotic disorders are often disappointing. Although it is not included in the diagnostic criteria for psychotic disorders, cognitive impairment is one of the strongest determinants of community functioning in this clinical population, and thus it is an important target for intervention. In this review, we discuss the major areas of research regarding impaired cognition in psychotic illness. The specific topics covered include: (i) the prevalence of cognitive impairment in psychotic disorders; (ii) the profile and magnitude of cognitive impairment in psychotic disorders; (iii) the developmental course of cognitive impairment; (iv) the longitudinal stability of cognitive impairment; and (v) treatment approaches to improve cognitive performance in people with psychotic disorders. .

/pdf/cognitive-impairment-in-psychotic-illness-prevalence-profile-268ksunn11.pdf

Cognitive impairment in psychotic illness: prevalence, profile of impairment, developmental course, and treatment considerations .

OBJECTIVE: This study assessed the relationship between symptoms and cognitive measures at intake and functional outcome 2–8 years later (average 3 years) in first-episode and previously treated schizophrenia patients. METHOD: A composite cognitive score was assessed at intake to determine the influence of cognition on later functional outcome. At intake and follow-up, positive and negative symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, and affective symptoms were assessed with the Hamilton Depression Rating Scale. Level of function in seven domains (social function, occupational function, independent living, symptom severity, fullness of life, extent of psychiatric hospitalization, and overall level of function) at intake and follow-up was assessed with the Strauss-Carpenter Level of Function scale. The contributions of sex, education, and duration of illness to functional outcome were also examined. RESULTS: The result...

https://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.163.3.433

Prognostic variables at intake and long-term level of function in schizophrenia.

Objective: Authors sought to use a cognitive assessment instrument validated for assessing low-functioning patients to broaden knowledge about the rate and correlates of functional decline. Methods: Patients were examinedacross a wide range of baseline cognitive and functional statute, and changes in cognitive and functional status were examined. A group of 424 elderly patients with schizophrenia were followed up over a 6-year period; 280 of these manifested severe cognitive impairment at baseline. Patients were examined with an instrument designed for cognitive and functional assessment of severe cognitive impairment: the Alzbeimer's Disease Assessment Scale-Late (ADAS-L). Results: Patients with higher and lower baseline scores manifested equivalent declines in the ADAS-L cognitive subscale, but differences in decline on basic activities of daily living. Random-effects regression analysis indicated that functional changes were significantly correlated with cognitive changes for the sample as whole and that cognitive changes were the best predictor of changes in functional status over time. Baseline cognitive status was not a statistically significant covariate for functional change, nor was the course of negative symptoms over the follow-up period. Conclusions: Cognitive change appears very similar in magnitude across older; poor-outcome patients with different baselines of cognitive impairment. In contrust, functional decline was limited to patients with lower levels of functioning at baseline. These findings suggest that cognitive thresholds for impairments in different aspects of functional status may exist in patients with schizophrenia. Basic activities of daily living decline only in patients with very low levels of baseline cognitive functioning.

The course of functional decline in geriatric patients with schizophrenia: cognitive-functional and clinical symptoms as determinants of change.

P542. Perfusion and Diffusion Abnormalities in the Hippocampal Subfields in Psychotic Spectrum Disorders Associate With Memory Deficits

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The course of functional decline in geriatric patients with schizophrenia: cognitive-functional and clinical symptoms as determinants of change.

P542. Perfusion and Diffusion Abnormalities in the Hippocampal Subfields in Psychotic Spectrum Disorders Associate With Memory Deficits