Neuropsychological function brain structure …

1 Neuropsychological function brain structure relationshipsand stage of illness : An investigation into chronicand first - episode schizophreniaPreethi Premkumara, , Veena Kumaria, Philip Corrb,Dominic Fannonc, Tonmoy SharmadaDepartment of Psychology, Institute of Psychiatry, King's College London, London, UKbDepartment of Psychology, University of Wales, Swansea, UKcDivision of Psychological Medicine, Institute of Psychiatry, King's College London, London, UKdThe Cognition Group, Newark, DE, USAR eceived 14 August 2007; accepted 23 August 2007 AbstractNeuropsychological function brain structure relationships may differ as a function of illness stage because of progressive brainmatter loss through the course of schizophrenia .

2 In this study, we tested whether Neuropsychological function brain structurerelationships differed as a function of illness stage. In addition, we tested whether these relationships differed between older andyoung healthy controls. function structure relationships were examined in 35 first - episode patients (31 with schizophrenia , 4 withschizoaffective disorder), 54 chronic schizophrenia patients, 21 older healthy controls and 20 young healthy controls. MRI volumesof frontal and temporal lobe structures, as well as the whole brain , were estimated using a region-of-interest approach. Hierarchicalmultiple regression analyses were performed between the MRI and Neuropsychological measures.

3 Stronger relationships ofimmediate memory-total prefrontal cortex (PFC) volume in chronic than first - episode patients, and in older than young controlswere observed. The abstract reasoning (WCST perseverative errors)-total temporal lobe volume relationship was stronger in olderthan young controls. These function structure relationships appeared unexplained by whole brain volume or age in chronicpatients. 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 .

4 2007 Elsevier Ireland Ltd. All rights :Magnetic resonance imaging; Neuropsychological function ; function structure relationships; illness stage1. IntroductionNeuropsychological function brain structure rela-tionships have been observed in both first - episode andchronic schizophrenia patients (Seidman et al., 1994;Bilder et al., 1995; Antonova et al., 2005). However, it isnot known whether similar function structure relation-ships occur at different stages of illness . DeterminingAvailable online at Research: Neuroimaging 162 (2008) 195 Corresponding author. Department of Psychology, Institute ofPsychiatry, De Crespigny Park, London SE5 8AF, UK.

5 Tel.: +44 207848 5102; fax: +44 207 848 Premkumar).0925-4927/$ - see front matter 2007 Elsevier Ireland Ltd. All rights different function structure relationships existat different illness stages would inform us about theemergent nature of function structure relationships inpeople with hypothesis that Neuropsychological function brain structure relationships may differ as a function ofillness stage is based on evidence for progressive brainmatter loss through the course of schizophrenia (DeLisiet al., 2004; Premkumar and Sharma, 2005; Premkumaret al., 2006), with reports of further volumetric reductionfollowing illness onset (Gur et al.

6 , 1998; Mathalon et al.,2001; Bachmann et al., 2004), but a neuropsychologicalimpairment that is relatively stable over time (seeAntonova et al., 2004for a detailed review and tableexploring the consistency of the relationship betweenspecific brain regional volumes and specific neuropsy-chological functions;Kurtz, 2005).In patients with chronic schizophrenia , fewer Wiscon-sin Card Sorting Test (WCST) perseverative errors andbetter Wechsler Memory Scale (WMS)-Logical Memoryimmediate recall and WMS Visual Reproduction-imme-diate recall scores have been associated with largerdorsolateral prefrontal cortex (DLPFC) volume (Seidmanet al.

7 , 1994). Better immediate verbal and visual memory(temporal lobe measures) and verbal fluence (frontal lobemeasure) have also been associated with larger prefrontalcortical (PFC) grey matter volume in patients with chronicschizophrenia (Baar et al., 1999). In males with first - episode schizophrenia , executive and motor functionassociated positively with anterior hippocampal volumeleading to the suggestion that abnormalities of the anteriorhippocampus predict frontal lobe dysfunction in schizo-phrenia (Bilder et al., 1995; Szeszko et al., 2002). Poorerexecutive function has been associated with smalleranterior cingluate gyrus volume in first - episode schizo-phrenia males (Szeszko et al.

8 , 2000). No associationbetween Neuropsychological function and the cerebellumhas been found in first - episode patients (Szeszko et al.,2003).In healthy individuals, function structure relationshipsare characterised by an age-related decline (Brickman et al.,2006; Zimmerman et al., 2006). Poorer executive functionis found to be associated with smaller lateral frontal greymatter volume in individuals older than 40 years, but not inindividuals younger than 40 years (Zimmerman et al.,2006). A high number of perseverative errors on the WCST hasbeenlinkedwithanage-relateddeclineinP FCvolumein middle-aged and older healthy individuals (Gunning-Dixon and Raz, 2003).

9 A meta-analysis of studies on therelationship between memory and hippocampal volumeacross the life-span suggestsa positive association only inolder adults and not in young adults (Van Petten, 2004).In the present study, we aimed to determine whetherthere are differences in function structure relationshipsbetween first - episode and chronic patients after control-ling for normal age-related differences in function structure relationships. We hypothesized that in first - episode patients, poorer executive function would berelated to smaller temporal lobe and hippocampalvolumes based on previous findings in first -episodepatients (Bilder et al.)

10 , 1995; Szeszko et al., 2002). Inchronic patients, we hypothesized that poorer executivefunction, attention and immediate memory would berelated to smaller PFC volume based on previousfindings in patients with chronic schizophrenia (Seidmanet al., 1994; Baar et al., 1999). In older healthy adults,we hypothesized that better executive function , attentionand immediate memory would be related to larger PFCvolume and that better delayed memory would be relatedto larger temporal lobe and hippocampal volumesbecause of a normal age-associated decline relatingthese functions to these structures (Gunning-Dixon andRaz, 2003; Zimmerman et al.