Striatal reactivity to reward under threat-of-shock and working memory load in adults at increased familial risk for major depression: A preliminary study.

Gaillard, Claudie; Guillod, Matthias; Ernst, Monique; Federspiel, Andrea; Schoebi, Dominik; Recabarren, Romina Evelyn; Ouyang, Xinyi; Mueller-Pfeiffer, Christoph; Horsch, Antje; Homan, Philipp; Wiest, Roland; Hasler, Gregor; Martin-Soelch, Chantal (2020). Striatal reactivity to reward under threat-of-shock and working memory load in adults at increased familial risk for major depression: A preliminary study. NeuroImage: Clinical, 26, p. 102193. Elsevier 10.1016/j.nicl.2020.102193

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Anhedonia, a core symptom of Major Depressive Disorder (MDD), manifests as a lack or loss of motivation as reflected by decreased reward responsiveness, at both behavioral and neural (i.e., striatum) levels. Exposure to stressful life events is another important risk factor for MDD. However, the mechanisms linking reward-deficit and stress to MDD remain poorly understood. Here, we explore whether the effects of stress exposure on reward processing might differentiate between Healthy Vulnerable adults (HVul, i.e., positive familial MDD) from Healthy Controls (HCon). Furthermore, the well-described reduction in cognitive resources in MDD might facilitate the stress-induced decrease in reward responsiveness in HVul individuals. Accordingly, this study includes a manipulation of cognitive resources to address the latter possibility.


16 HVul (12 females) and 16 gender- and age-matched HCon completed an fMRI study, during which they performed a working memory reward task. Three factors were manipulated: reward (reward, no-reward), cognitive resources (working memory at low and high load), and stress level (no-shock, unpredictable threat-of-shock). Only the reward anticipation phase was analyzed. Imaging analyses focused on striatal function.


Compared to HCon, HVul showed lower activation in the caudate nucleus across all conditions. The HVul group also exhibited lower stress-related activation in the nucleus accumbens, but only in the low working memory (WM) load condition. Moreover, while stress potentiated putamen reactivity to reward cues in HVul when the task was more demanding (high WM load), stress blunted putamen reactivity in both groups when no reward was at stake.


Findings suggest that HVul might be at increased risk of developing anhedonic symptoms due to weaker encoding of reward value, higher difficulty to engage in goal-oriented behaviors and increased sensitivity to negative feedback, particularly in stressful contexts. These findings open new avenues for a better understanding of the mechanisms underlying how the complex interaction between the systems of stress and reward responsiveness contribute to the vulnerability to MDD, and how cognitive resources might modulate this interaction.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Translational Research Center
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic and Interventional Neuroradiology

UniBE Contributor:

Federspiel, Andrea, Wiest, Roland Gerhard Rudi


600 Technology > 610 Medicine & health








Martin Zbinden

Date Deposited:

03 Mar 2020 12:25

Last Modified:

02 Mar 2023 23:33

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Major depressive disorder Reward Stress Striatum Vulnerability fMRI




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