Neuropsychological correlates of psychotic features in major depressive disorders: a review and meta-analysis Shelley K. Fleming a,b, *, Christine Blasey a , Alan F. Schatzberg a a Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, Stanford, CA 94305, USA b Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA 94304, USA Received 12 September 2002; received in revised form 29 May 2003; accepted 15 June 2003 Abstract Neuropsychological functioning has been a focus of study in psychotic disorders for many decades. These studies have focused primarily on schizophrenia, and less so on the affective psychoses, including psychotic major depression PMD. Several studies have provided evidence of cognitive dysfunction in PMD. However, these studies have utilized different assessment methods and instruments. Consequently, a clear picture of the nature and severity of cognitive impairment in PMD has yet to emerge in the literature.Thecurrentreviewseekstoprovideasummaryoftheliteraturebycomposingaquantitativeandqualitativereviewofthe research to date on the cognitive impairment in psychotic major depression, specifically as it contrasts to those deficits observed in nonpsychotic depression. This review also provides a summary model of the pathophysiology of PMD to provide the necessary context to understanding the biological mechanisms of these impairments. Published by Elsevier Ltd. Keywords: Neuropsychology; Cognitive; Psychotic; Depression; Cortisol 1. Introduction Neuropsychological functioning has been a focus of study in psychotic disorders for many decades. The vast majority of these studies have focused on schizophrenia and have been primarily descriptive in nature. Investi- gators have described the neurocognitive ‘‘profile’’ of schizophreniaatdifferentphasesoftheillness,including pre-onset vulnerability markers, deficits associated with acute psychosis, and residual deficits that remain as the acute symptoms abate (Spaulding et al., 1996). Researchers have correlated neuropsychological deficits with functional impairment in social and occupational skills, highlighting the real-world consequences of cog- nitive deficits for patients. These deficits have also been correlated with structural and functional brain anoma- lies with the goal of delineating the pathophysiology of schizophrenia and other psychotic disorders. Fewerstudieshavefocusedontheneuropsychological deficitsobservedinaffectivepsychoticdisorders,suchas major depression with psychotic features and bipolar disorder with psychotic features. As much of the work that does exist focuses on non-psychotic major depres- sion (NPMD) and psychotic major depression (PMD), the current review will concentrate on these specific affective disorders. The literature is qualitatively and quantitatively reviewed. Lessons from the schizophrenia literature are incorporated where applicable, especially regarding the future directions of this research. 2. Clinical features and diagnosis of psychotic major depression Approximately 25% of consecutively admitted depressed patients exhibit psychotic symptoms (Coryell et al., 1984). These symptoms usually consist of non- bizarre nihilistic, somatic, or guilty delusional beliefs and less often hallucinations or formal thought dis- order. Considerable evidence supports PMD as a distinct subtype of depression, including stability of psychotic symptoms across depressive episodes 0022-3956/$ - see front matter Published by Elsevier Ltd. doi:10.1016/S0022-3956(03)00100-6 Journal of Psychiatric Research 38 (2004) 27–35 www.elsevier.com/locate/jpsychires * Corresponding author at current address: VAPAHCS, 116B Psy- chology,3801MirandaAvenue,PaloAlto,CA94304,USA.Tel.:+1- 650-493-5000x63025. E-mail address: shelleyf@stanford.edu (S.K. Fleming).