Neuropsychological function–brain structure relationships and stage of illness: An investigation into chronic and first-episode schizophrenia

Neuropsychological function-brain structure relationships may differ as a function of illness stage because of progressive brain matter loss through the course of schizophrenia. In this study, we tested whether neuropsychological function-brain structure relationships differed as a function of illness stage. In addition, we tested whether these relationships differed between older and young healthy controls. Function-structure relationships were examined in 35 first-episode patients (31 with schizophrenia, 4 with schizoaffective disorder), 54 chronic schizophrenia patients, 21 older healthy controls and 20 young healthy controls. MRI volumes of frontal and temporal lobe structures, as well as the whole brain, were estimated using a region-of-interest approach. Hierarchical multiple regression analyses were performed between the MRI and neuropsychological measures. Stronger relationships of immediate memory-total prefrontal cortex (PFC) volume in chronic than first-episode patients, and in older than young controls were observed. The abstract reasoning (WCST perseverative errors)-total temporal lobe volume relationship was stronger in older than young controls. These function-structure relationships appeared unexplained by whole brain volume or age in chronic patients. A similar dissociation between young and older subjects of both healthy and patient groups suggests that a 'bigger-is-better' relationship style is present in older individuals regardless of a diagnosis of schizophrenia.