title: Serotonin and dopamine receptors in motivational and cognitive disturbances of schizophrenia.
abstract: Negative symptoms (e.g., decreased spontaneity, social withdrawal, blunt affect) and disturbances of cognitive function (e.g., several types of memory, attention, processing speed, executive function, fluency) provide a major determinant of long-term outcome in patients with schizophrenia. Specifically, motivation deficits, a type of negative symptoms, have been attracting interest as (1) a moderator of cognitive performance in schizophrenia and related disorders, and (2) a modulating factor of cognitive enhancers/remediation. These considerations suggest the need to clarify neurobiological substrates regulating motivation. Genetic studies indicate a role for the monoamine systems in motivation and key cognitive domains. For example, polymorphism of genes encoding catecholamine-O-methyltransferase, an enzyme catabolizing dopamine (DA), affects performance on tests of working memory and executive function in a phenotype (schizophrenia vs. healthy controls)-dependent fashion. On the other hand, motivation to maximize rewards has been shown to be influenced by other genes encoding DA-related substrates, such as DARPP-32 and DA-D2 receptors. Serotonin (5-HT) receptors may also play a significant role in cognitive and motivational disabilities in psychoses and mood disorders. For example, mutant mice over-expressing D2 receptors in the striatum, an animal model of schizophrenia, exhibit both decreased willingness to work for reward and up-regulation of 5-HT2C receptors. Taken together, genetic predisposition related to 5-HT receptors may mediate the diversity of incentive motivation that is impaired in patients receiving biological and/or psychosocial treatments. Thus, research into genetic and neurobiological measures of motivation, in association with 5-HT receptors, is likely to facilitate intervention into patients seeking better social consequences.
authors.affiliation: Department of Clinical Research Promotion, National Center Hospital, National Center of Neurology and Psychiatry Tokyo, Japan.
authors.forename: Tomiki
authors.initials: T
authors.lastname: Sumiyoshi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.affiliation: National Center Hospital, National Center of Neurology and Psychiatry Tokyo, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakagome
keywords: 5-HT receptors; cognition; dopamine; motivation; negative symptoms; psychosis; schizophrenia; serotonin