Ventral Striatal Activation During Reward Processing in Psychosis

Abstract

IMPORTANCE Abnormal reward processing is suggested to underlie the formation of psychotic symptoms, likely driven by elevated ventral striatal (VS) dopamine levels. Functional magnetic resonance imaging studies reveal alterations of VS activity during reward processing in patients with chronic psychosis and first episode of psychosis, as well as individuals at high risk for psychosis, but findings are inconclusive, conflicting, and difficult to subject to meta-analysis without introducing bias because several studies reported that findings were not statistically significant but did not report statistics. OBJECTIVE To assess the differences between patients with schizophrenia spectrum disorders and healthy controls in VS activation during reward processing. DATA SOURCES Web of Knowledge database (incorporating Web of Science and MEDLINE) until July 2015, including references of eligible articles and reviews. STUDY SELECTION Functional magnetic resonance imaging studies comparing VS activity during monetary reward processing between patients with schizophrenia spectrum disorders or clinical or genetic high-risk state for psychosis and healthy controls. DATA EXTRACTION AND SYNTHESIS Statistics and thresholds related to the main outcome measures and potential moderators were independently retrieved by 2 investigators. Effect sizes were analyzed using MetaNSUE, a random-effects method that enables the unbiased inclusion of nonstatistically significant unreported effects. MAIN OUTCOMES AND MEASURES Effect size of the group differences in VS activity, and correlation between VS activity and negative and positive symptom scores in patients. RESULTS The meta-analysis included 23 studies (917 patients) for reward anticipation, 9 studies (358 patients) for reward feedback, and 8 studies (314 patients) for reward prediction error. We found significant bilateral VS hypoactivation during reward anticipation (23 studies, n = 917) in patients compared with healthy controls (left/right Cohen d, −0.50/−0.70; P< .001). Left VS abnormality was more severe in patients with high scores of negative symptoms during reward anticipation (r=−0.41; P< .001). Patients also showed hypoactivation during reward feedback (left/right d, −0.57/−0.56; P< .001). Simulations showed that exclusion of studies with nonstatistically significant unreported effects was associated with a strong bias (d bias=0.22), whereas estimations using MetaNSUE were unbiased even when statistics were seldom reported (d bias < 0.001). CONCLUSIONS AND RELEVANCE This meta-analysis provides evidence that patients with psychosis demonstrate VS hypoactivation during reward anticipation. The assessment of VS prediction errors seems to be promising, but more studies are needed to draw valid conclusions.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

“…Such findings may help to explain the high prevalence of avolition and anhedonia in schizophrenia, two core dimensions of negative symptomatology. In line with this, aberrant neural responses to reward feedback was observed in medial prefrontal areas of patients with schizophrenia (Schlagenhauf et al 2009), although results from this and several other studies also emphasize the relevance of ventral striatal pathways pointing towards an involvement of a wider striatal-prefrontal network in reward feedback (Schlagenhauf et al 2014;Mørch-Johnsen et al 2015;Radua et al 2015).…”

Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis

“…9 Again, the most consistent evidence comes from studies in schizophrenia reporting an association between negative symptoms and blunted striatal activity during reward anticipation mainly in chronic medicated patients. [24][25][26][27] In addition, this association has also been observed in first-degree relatives of patients with schizophrenia. 18 Concerning positive symptoms, the literature strongly suggests an association with diminished striatal activity to relevant stimuli in unmedicated first-episode psychosis patients and individuals at ultra-high risk, which is consistent with the aberrant salience model of psychosis.…”

“…19,53 At the group level, we found no differences between HCs and individuals with SPT or first-episode psychosis in VS activation, which is consistent with previous results in broadly defined FEP patients and individuals at-risk for psychosis. [19][20][21][22] In contrast, there is now meta-analytic support for reduced VS activation in patients with established schizophrenia, 24 but results on the individual study level are very inconsistent. 15,16,23,25,31,35,59,62,63 These mixed findings support the notion that striatal alterations in psychosis do not solely consist of hypo-activation but vary between different stages (early vs chronic) and different forms of psychosis (schizophrenia vs non-schizophrenia).…”

“…15,21 However, on a meta-analytic level including studies with unmedicated and medicated patients the association of neural alterations during reward processing and positive symptoms is less clearly delineated. 24 Furthermore, the association between striatal dysfunction and depressive symptoms is well described within depressive disorders 28,29 but data are limited for schizophrenia. 30,31 Most research did not take into account the neural basis of symptom dimensions on a psychosis continuum with broadly defined first-episode psychosis patients or individuals with schizotypal personality traits (SPT).…”

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

“…To date, the most reliable decreases in ventral striatal activity have been observed during periods of reward anticipation (for a recent meta-analysis, see Radua et al, 2015), which have also been linked to reduced effortful behavior in schizophrenia (Wolf et al, 2014). In addition, recent work has demonstrated both a blunting of neural prediction errors to contextually relevant cues (Morris et al, 2011) as well as behavioral evidence for enhanced prediction error learning for irrelevant stimuli (Hannestad et al, 2012b;Williams et al, 2013).…”