Ventral Striatal Activation during Reward Processing in Subjects with Ultra-High Risk for Schizophrenia

Abstract

Background: Early dysfunction of the brain reward system in schizophrenia might be already recognized in the prodromal phase of this illness. We used functional magnetic resonance imaging to assess the blood oxygen level-dependent response in the ventral striatum (VS) of subjects with ultra-high risk for psychosis during the presentation of reward-indicating and loss-indicating stimuli. Methods: Thirteen prodromal patients (mean age: 25.5 ± 4.6 years) and 13 age-matched healthy volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus will gain money, avoid losing money or have no consequence. Results: Compared with the neutral condition, anticipation of reward loss-avoidance elicited significant activation of the VS in both healthy subjects and subjects with ultra-high risk for psychosis, but there was only a statistical tendency for less activation during loss-avoidance anticipation in prodromal compared to healthy subjects. Discussion: This study provides a first weak hint, as revealed by functional magnetic resonance imaging, for impaired activation of a central area of the mesolimbic dopaminergic brain reward system, the VS, already in subjects with ultra-high risk for psychosis, which is in line with results of patients with full-blown schizophrenic psychosis. This pilot study has, however, strong limitations, and its results need to be replicated first before they can be used e.g. for early recognition of patients in the schizophrenic prodrome.

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

“…[15][16][17][18] Other studies including patients with broadly defined first-episode psychosis (not restricted to schizophrenia and schizophreniform disorder) or individuals at-risk for psychosis did not report any group differences, but focused more on the relationship with symptom expression. [19][20][21][22][23] This work supports the idea that on a group level reduced activation of the striatum may be more strongly related to schizophrenia or chronic forms of psychosis than to psychotic disorders in general. Importantly, these divergent findings highlight the importance of using dimensional approaches to investigate the neural basis of psychosis rather than restricting research to group differences.…”

“…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).…”

Fronto-striatal Dysfunction During Reward Processing in Unaffected Siblings of Schizophrenia Patients

“…29 Our finding of decreased ventral striatal activation during reward anticipation in siblings of schizophrenia patients as compared to healthy controls is consistent with several studies in medicated schizophrenia patients, 19,21,49 but not with others. 27,50,51 The latter inconsistency may be partly due to the varying effects of antipsychotics on activation in the fronto-striatal network. 16,[52][53][54][55] Indeed, findings in medication-free 16,20 and medication-naïve patients 17,18 consistently show diminished ventral striatal activity during reward anticipation.…”

Mechanisms Underlying Motivational Deficits in Psychopathology: Similarities and Differences in Depression and Schizophrenia

“…On the one hand, depression and psychosis frequently co-occur and there are a number of ways in which motivational and hedonic impairments operate similarly in psychosis and mood pathology. For example, motivational/hedonic impairments can be present in individuals at risk for developing psychosis (Delawalla et al 2006;Glatt et al 2006;Juckel et al 2012;Grimm et al 2014;Schlosser et al 2014) or at risk for developing depression (Gotlib et al 2010;Foti et al 2011a, b, c;McCabe et al 2012;Kujawa et al 2014;Macoveanu et al 2014;Olino et al 2014;Sharp et al 2014). Further, there is evidence that the presence or severity of motivational/hedonic impairments is associated with the development of manifest illness for both psychosis (Chapman et al 1994;Kwapil et al 1997;Gooding et al 2005;Velthorst et al 2009) and depression (Bress et al 2013;Morgan et al 2013).…”