Neural correlates of reward processing in schizophrenia - Relationship to apathy and depression

Section of Experimental Psychopathology, Department of Psychiatry, University of Heidelberg, 69115 Heidelberg, Germany.
Schizophrenia Research (Impact Factor: 3.92). 12/2009; 118(1-3):154-61. DOI: 10.1016/j.schres.2009.11.007
Source: PubMed


The present study employs a new framework to categorise the heterogeneous findings on the relationship between impaired reward processing and negative and affective symptoms of schizophrenia. Based on previous behavioural and neuroimaging studies we postulate that "wanting" (i.e. anticipation) of a reward is specifically related to apathy, whereas "liking" (i.e. hedonic impact) is related to anhedonia and depression--symptoms commonly observed in schizophrenia. Fifteen patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic drugs and fifteen healthy controls performed a probabilistic monetary incentive delay task while undergoing functional magnetic resonance imaging. At the group level we found no significant differences between patients and controls in neural activation during anticipation or receipt of a reward. However, in patients with schizophrenia specific relationships between ventral-striatal activation and symptoms were observed. Ventral-striatal activation during reward anticipation was negatively correlated with apathy, while activation during receipt of reward was negatively correlated with severity of depressive symptoms. These results suggest that the link between negative symptoms and reward anticipation might specifically relate to apathy, i.e. a lack of motivation and drive. Impaired hedonic reward processing might contribute to the development of depressive symptoms in patients with schizophrenia, but it is not directly associated with self-rated anhedonia. These results indicate the necessity of more specifically differentiating negative and affective symptoms in schizophrenia in order to understand the role of the reward system in their pathogenesis.


Available from: Joe Simon, Feb 13, 2015
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    • "Moreover, neural correlates of reward processing seem to be associated with symptom severity in patients with schizophrenia. A negative correlation between VS activation and positive symptoms was found by Nielsen et al. (2012b) and negative symptoms were shown to be negatively correlated with VS activation (Robbins and Everitt, 1996; Juckel et al., 2006a,b; Schlagenhauf et al., 2008; Simon et al., 2010). More specifically, anhedonia is one of the symptoms that seems to be related to a decrease in activation in the striatum (Juckel et al., 2006a,b). "
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    ABSTRACT: Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be related to SZ. Studies in patients with SZ have found less activation in the ventral striatum (VS) during anticipation of reward, but these findings do not provide information on effect of the genetic load on reward processing. Therefore, this study investigated RP in healthy first-degree relatives of SZ patients. The sample consisted of 94 healthy siblings of SZ patients and 57 healthy controls. Participants completed a classic RP task, the Monetary Incentive Delay task, during functional magnetic resonance imaging (fMRI). As expected, there were no behavioral differences between groups. In contrast to our expectations, we found no differences in any of the anticipatory reward related brain areas (region of interest analyses). Whole-brain analyses did reveal group differences during both reward anticipation and reward consumption; during reward anticipation siblings showed less deactivation in the insula, posterior cingulate cortex (PCC) and medial frontal gyrus (MFG) than controls. During reward consumption siblings showed less deactivation in the PCC and the right MFG compared to controls and activation in contrast to deactivation in controls in the precuneus and the left MFG. Exclusively in siblings, MFG activity correlated positively with subclinical negative symptoms. These regions are typically associated with the default mode network (DMN), which normally shows decreases in activation during task-related cognitive processes. Thus, in contrast to prior literature in patients with SZ, the results do not point to altered brain activity in classical RP brain areas, such as the VS. However, the weaker deactivation found outside the reward-related network in siblings could indicate reduced task-related suppression (i.e., hyperactivation) of the DMN. The presence of DMN hyperactivation during reward anticipation and reward consumption might indicate that siblings of patients with SZ have a higher baseline level of DMN activation and possible abnormal network functioning.
    Frontiers in Human Neuroscience 09/2015; 9. DOI:10.3389/fnhum.2015.00504 · 3.63 Impact Factor
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    • "This supports the finding that antipsychotic medication may have a bigger impact on anticipatory rather than consummatory pleasure. It appears that reduced activation of the ventral striatum in response to rewarding cues may be more pronounced in those people taking typical antipsychotics but not those taking atypical antipsychotics; with this effect being correlated with negative symptom severity in those taking typical antipsychotics only (Juckel et al., 2006a; Kirsch et al., 2007; Schlagenhauf et al., 2008; Simon et al., 2010; Walter et al., 2009). The limited behavioural studies have consistently reported no association between medication type/dosage and anticipatory pleasure (Choi et al., 2013; Trémeau et al., 2010). "
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    ABSTRACT: Anhedonia and amotivation are substantial predictors of poor functional outcomes in people with schizophrenia and often present a formidable barrier to returning to work or building relationships. The Temporal Experience of Pleasure Model proposes constructs which should be considered therapeutic targets for these symptoms in schizophrenia e.g. anticipatory pleasure, memory, executive functions, motivation and behaviours related to the activity. Recent reviews have highlighted the need for a clear evidence base to drive the development of targeted interventions. To review systematically the empirical evidence for each TEP model component and propose evidence-based therapeutic targets for anhedonia and amotivation in schizophrenia. Following PRISMA guidelines, PubMed and PsycInfo were searched using the terms "schizophrenia" and "anhedonia". Studies were included if they measured anhedonia and participants had a diagnosis of schizophrenia. The methodology, measures and main findings from each study were extracted and critically summarised for each TEP model construct. 80 independent studies were reviewed and executive functions, emotional memory and the translation of motivation into actions are highlighted as key deficits with a strong evidence base in people with schizophrenia. However, there are many relationships that are unclear because the empirical work is limited by over-general tasks and measures. Promising methods for research which have more ecological validity include experience sampling and behavioural tasks assessing motivation. Specific adaptations to Cognitive Remediation Therapy, Cognitive Behavioural Therapy and the utilisation of mobile technology to enhance representations and emotional memory are recommended for future development. Copyright © 2015. Published by Elsevier B.V.
    Schizophrenia Research 09/2015; DOI:10.1016/j.schres.2015.08.013 · 3.92 Impact Factor
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    • "Moreover, reanalyzing data from a set of studies, Hägele and colleagues showed that depression, schizophrenia and alcohol disorders were all associated with reduced activity in the right ventral striatum with this effect correlated with depressive symptoms as measured by the Beck Depression Inventory (Hägele et al., 2015). However, given that patient groups were not matched to each other or to controls in age and gender in the study by Hägele and colleagues we sought to replicate and extend it using a specifically-designed study with matched groups; we also wished to relate neural responses to additional key symptoms, as previous work has indicated that ventral striatum (de)activation could also relate to other symptoms such as anhedonia (Simon et al., 2010; Stoy et al., 2012) and more generally, to positive (Nielsen et al., 2012), and negative (Juckel et al., 2006a; Waltz et al., 2009) symptoms. "
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    ABSTRACT: In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.
    Frontiers in Psychology 08/2015; 6. DOI:10.3389/fpsyg.2015.01280 · 2.80 Impact Factor
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