Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders

Abstract

RationaleA dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.ObjectivesWe compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment.MethodsWe used functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task to study the functional correlates of reward anticipation across major psychiatric disorders in 184 subjects, with the diagnoses of alcohol dependence (n = 26), schizophrenia (n = 44), major depressive disorder (MDD, n = 24), bipolar disorder (acute manic episode, n = 13), attention deficit/hyperactivity disorder (ADHD, n = 23), and healthy controls (n = 54). Subjects’ individual Beck Depression Inventory-and State-Trait Anxiety Inventory-scores were correlated with clusters showing significant activation during reward anticipation.ResultsDuring reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation.ConclusionOur findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-014-3662-7) contains supplementary material, which is available to authorized users.

Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression

“…Thus, reward system pathology may contribute to clinical reward dysfunction across multiple psychiatric disorders. Further confirmation comes from an important recent study by Hägele et al (2014), which demonstrated that depressive symptoms are associated with a similar blunting of reward responses in a large sample of patients with diverse diagnoses.…”

“…However, only one study to our knowledge has examined reward-related signaling in bipolar depression: Chase et al (2013) who did not find differences in ventral striatum prediction error responses between controls and subjects with bipolar or unipolar depression. Additionally, an important recent study by Hägele et al (2014) demonstrated that depressive symptoms are associated with a similar blunting of reward responses in a large and diverse sample of subjects including unipolar depression, bipolar disorder, ADHD, alcoholism, and schizophrenia.…”

“…Specifically, given prior research relating anhedonia to reward system dysfunction in multiple psychiatric disorders (Juckel et al, 2006;Wolf, 2006;Harvey et al, 2007;Wolf et al, 2008;Pizzagalli et al, 2009;Treadway and Zald, 2011;Gabbay et al, 2013;Hägele et al, 2014) anhedonia was examined using a sub-set of anhedonia-related items from the BDI (Joiner et al, 2003). Furthermore, we similarly examined the relationship with BDI items unrelated to anhedonia.…”

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

“…In humans, neuroimaging has been widely used to study brain signals related to reward anticipation. Functional MRI experiments probing reward anticipation in the ventral striatum with MID tasks reveal decreased striatal activation in drug-naïve and unmedicated schizophrenia patients Hägele et al, 2015;Juckel et al, 2006b) as well as in participants at high clinical risk for psychosis (Juckel et al, 2012;Wotruba et al, 2014). The degree of reduced reward anticipation is linked to symptom severity (Juckel et al, 2006a;Kring and Barch, 2014;Nielsen et al, 2012) and altered dopamine activity, as suggested by the observation that treatment with atypical antipsychotics partially normalizes ventral striatal dysfunction in schizophrenia (Nielsen et al, 2012;Walter et al, 2009).…”

“…Such a perspective could suggest a common pathophysiologic mechanism for related and often co-occurring psychiatric disorders. One example of a transdiagnostic perspective comes from a recent study by Hägele et al (2015) which used the same MID task in patients with schizophrenia, major depression, alcohol addiction, bipolar manic episode, or ADHD and found commonly reduced reward anticipation signals in schizophrenia, major depression and alcohol addiction.…”