Generalized and specific neurocognitive deficits in psychotic disorders: Utility for evaluating pharmacological treatment effects and as intermediate phenotypes for gene discovery

James L. Reilly, John A. Sweeney

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

A growing body of research suggests that schizophrenia and bipolar disorder share overlapping clinical, neurobiological, and genetic features, raising important questions about the boundaries and distinctiveness of these 2 major psychiatric disorders. A generalized cognitive impairment has long been understood to be a core feature of schizophrenia. More recently, it has become apparent that cognitive impairment also occurs in bipolar disorder, particularly in those patients with a history of psychotic symptoms. Whether a generalized deficit exists across a spectrum of psychotic disorders is less clearly established. Additionally, in the context of a broad impairment, it remains a significant challenge to identify deficits in specific cognitive processes that may have distinct neurochemical or regional brain substrates and linkages to particular risk-associated genetic factors. In this article, we review the findings from neuropsychological studies across a spectrum that includes schizophrenia, schizoaffective and bipolar disorders, and conclude the available evidence strongly supports that a generalized deficit is present across psychotic disorders that differs in severity more so than form. We then consider the implications of generalized and specific deficits in psychosis for 2 areas of research - the evaluation of pharmacological treatments targeting cognitive deficits, and the investigation of cognitive intermediate phenotypes in family genetic studies. Examples from the literature that touch on the relevance of the generalized deficit in these contexts are provided, as well as consideration for the continued need to identify specific impairments that are separable from the generalized deficit in order to advance drug and gene discovery.

Original languageEnglish (US)
Pages (from-to)516-522
Number of pages7
JournalSchizophrenia Bulletin
Volume40
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Genetic Association Studies
Psychotic Disorders
Bipolar Disorder
Pharmacology
Phenotype
Schizophrenia
Drug Discovery
Therapeutics
Psychiatry
Brain
Research
Cognitive Dysfunction

Keywords

  • bipolar disorder
  • cognition
  • endophenotype
  • neuropsychology
  • schizoaffective disorder
  • schizophrenia
  • treatment effects

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Medicine(all)

Cite this

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