Open Access Research article

Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy

Ilya A Lipkovich1*, Walter Deberdt2, John G Csernansky3, Bernard Sabbe4, Richard SE Keefe5 and Sara Kollack-Walker6

Author Affiliations

1 Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, USA

2 Eli Lilly Benelux, Eli Lilly and Company, Brussels, Belgium

3 Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA

4 CAPRI (Collaborative Antwerp Psychiatric Research Institute), Department of Psychiatry, University of Antwerp, Antwerp B-2610, Antwerpen, Belgium

5 Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, USA

6 Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, USA

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BMC Psychiatry 2009, 9:44  doi:10.1186/1471-244X-9-44

Published: 14 July 2009



Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs.


Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms.


At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied.


Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and following 24 weeks of antipsychotic treatment.