Abstract
The revised dopamine hypothesis of schizophrenia postulates that dopamine metabolism is impacted differently with increased dopamine in the subcortical mesolimbic system and decreased dopamine in prefrontal cortical regions. Recently, we described findings supporting this hypothesis using a financial reward task in patients with schizophrenia (Walter et al., 2009). In addition to analysing prediction and prediction error coding, we found in this study evidence for aberrant cortical representation of salience in the right ventrolateral prefrontal cortex (VLPFC) in patients. Here, we reanalysed data of four other published reward studies of our group in order to investigate (i) whether we could replicate this finding in an independent cohort of patients with schizophrenia and (ii) how dopaminergic modulation impacts on cortical salience representation. Our main result was that we could replicate the finding of aberrant salience coding in the right VLPFC in patients with schizophrenia. Furthermore, we found evidence that the degree of salience coding in this region was correlated inversely with negative symptoms (anhedonia). Results of dopaminergic modulation showed tentative evidence for an influence of dopaminergic stimulation, but were not conclusive. In summary, we conclude that the right VLPFC might play a crucial role in salience coding and is impaired in schizophrenia.
Highlights
The dopamine hypothesis of schizophrenia (Carlsson and Lindqvist, 1963; Carlsson et al, 2000) assumes a central role for dopamine in the development of psychotic symptoms based on the mechanisms of antipsychotic drug action and PET studies on dopamine release in patients with schizophrenia following amphetamine intake
STUDY 2 (REPLICATION STUDY) Like in the index study, we found activation in the right ventrolateral prefrontal cortex (VLPFC) and adjacent anterior insula and anterior cingulate in controls but not in patients with schizophrenia
Aberrant salience coding proved to be related to negative symptoms as evidenced by negative correlations with anhedonia, which is in line with the revised dopamine hypothesis
Summary
The dopamine hypothesis of schizophrenia (Carlsson and Lindqvist, 1963; Carlsson et al, 2000) assumes a central role for dopamine in the development of psychotic symptoms based on the mechanisms of antipsychotic drug action and PET studies on dopamine release in patients with schizophrenia following amphetamine intake. In its revised form hyperactivation of the mesolimbic dopamine system via D2-receptors is suggested to explain positive symptoms like delusions or hallucinations, while hypoactivation of the mesocortical system via D1-receptors is suggested to explain negative symptoms including anhedonia and cognitive impairment (Guillin et al, 2007). This view has recently been reframed as the aberrant salience hypothesis (Kapur, 2003; Kapur et al, 2006), for similar approaches compare (Spitzer, 1997; Heinz, 2002). The anhedonia hypothesis of dopamine function (Wise et al, 1978) suggests a link between mesolimbic–mesocortical hypoactivation and negative symptoms
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