International Review of Psychiatry, August 2009; 21(4): 336–356 Cognitive functioning in patients with affective disorders and schizophrenia: A meta-analysis EVGENIA STEFANOPOULOU 1 , ANDIAPPAN MANOHARAN 2 , SABINE LANDAU 2 , JOHN R. GEDDES 3 , GUY GOODWIN 3 , & SOPHIA FRANGOU 1 1 Section of Neurobiology of Psychosis, Institute of Psychiatry and Biomedical Research Centre for Mental Health, King’s College London, London, UK, 2 Department of Biostatistics and Computing, Institute of Psychiatry, Kings College London, London, UK, and 3 Department of Psychiatry, University of Oxford, Oxford, UK Abstract There is considerable evidence for cognitive dysfunction in schizophrenia and affective disorders, but the pattern of potential similarities or differences between diagnostic groups remains uncertain. The objective of this study was to conduct a quantitative review of studies on cognitive performance in schizophrenia and affective disorders. Relevant articles were identified through literature search in major databases for the period between January 1980 and December 2005. Meta-analytic treatment of the original studies revealed widespread cognitive deficits in patients with schizophrenia and affective disorders in intellectual ability and speed of information processing, in encoding and retrieval, rule discovery and in response generation and response inhibition. Differences between diagnostic groups were quantitative rather than qualitative. Introduction Genetic factors are important in the aetiology of schizophrenia and mood disorders. The evidence is overwhelming for schizophrenia and bipolar disor- ders (BD) (Craddock, O’Donovan, & Owen, 2006) but more equivocal for major depressive disorder (MDD) (Hamet & Tremblay, 2005; Sullivan, Neale, & Kendler, 2000). Family studies have repeatedly shown that relatives of probands with schizophrenia and affective disorders have elevated lifetime risk for a number of psychiatric conditions (Shih, Belmonte, & Zandi, 2004). However, there is little evidence of specificity in familial aggregation for the clinical phenotypes of either schizophrenia or affective disorders. For example, first-degree relatives of patients with schizophrenia may have elevated rates of schizophrenia but also of schizoaffective and affective psychoses compared to healthy controls (Erlenmeyer-Kimling et al., 1997). Similarly, family members of BD probands are at increased risk not only for bipolar disorder but also for MDD and schizoaffective disorders (Gershon et al., 1982; Sadovnick et al., 1994; Weissman et al., 1984). The relationship between familial aggregation and clinical phenotypes is therefore complex even when heritability is very high (Cardno et al., 1999). This is perhaps to be expected as schizophrenia and mood disorders follow a multi-factorial polygenic inheri- tance model where multiple genes of small effect, together with non-genetic influences, contribute to increased risk for a disorder. Overt manifestation of the clinical phenotype only results if the com- bined and/or additive effects of gene and environ- ment cross a theoretical ‘threshold of liability’. This together with the absence of conclusive evidence for the validity and reliability of clinical phenotypes (Kendell, 1989; Kendell & Jablensky, 2003) has shifted the focus of research towards endophenotypes. Endophenotypes are indicators of processes med- iating between genotype and phenotype and may therefore reflect pathophysiological mechanisms associated with the different clinical syndromes. In this respect, examination of the profile of cognitive changes in affective disorders and schizophrenia may help us identify dysfunction within specific brain systems. Although it may not be possible to localize brain dysfunction solely on the basis of cognitive test performance, differences or similarities between disorders in the pattern of deficits observed informs on models of pathophysiology. Cognitive dysfunction is a recognized core dimen- sion of BD and schizophrenia, while comparatively less is known about such deficits in MDD patients. Correspondence: Dr Sophia Frangou, Section of Neurobiology of Psychosis, PO66, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK. Tel/Fax: 0044 20 7848 0903. E-mail: s.frangou@iop.kcl.ac.uk ISSN 0954–0261 print/ISSN 1369–1627 online ß 2009 Institute of Psychiatry DOI: 10.1080/09540260902962149 Int Rev Psychiatry Downloaded from informahealthcare.com by King's College London on 08/28/14 For personal use only.