Jindra M Bakker1,2, Liesbet Goossens1, Poornima Kumar3,4, Iris M J Lange1, Stijn Michielse1, Koen Schruers1,5, Jojanneke A Bastiaansen6,7, Ritsaert Lieverse1, Machteld Marcelis1,8, Thérèse van Amelsvoort1, Jim van Os1,9,10, Inez Myin-Germeys2, Diego A Pizzagalli3,4, Marieke Wichers6. 1. Department of Psychiatry and Psychology, Maastricht University, Maastricht University Medical Centre, School for Mental Health and Neuroscience, Maastricht, The Netherlands. 2. Department of Neuroscience, KU Leuven, Center for Contextual Psychiatry, Leuven, Belgium. 3. McLean Hospital, Center for Depression, Anxiety and Stress Research, Belmont, MA, USA. 4. Department of Psychiatry, Harvard Medical School, Boston, MA, USA. 5. Department of Psychology, KU Leuven, Leuven, Belgium. 6. Department of Psychiatry (UCP), University of Groningen, University Medical Centre Groningen, Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), Groningen, The Netherlands. 7. Friesland Mental Health Care Services, Leeuwarden, The Netherlands. 8. Institute for Mental Health Care Eindhoven (GGzE), Eindhoven, the Netherlands. 9. Department of Psychiatry, Utrecht University, University Medical Center, Brain Center Rudolf Magnus, Utrecht, The Netherlands. 10. Department of Psychosis Studies, King's College, King's Health Partners, Institute of Psychiatry, London, UK.
Abstract
BACKGROUND: Depression has been associated with abnormalities in neural underpinnings of Reward Learning (RL). However, inconsistencies have emerged, possibly owing to medication effects. Additionally, it remains unclear how neural RL signals relate to real-life behaviour. The current study, therefore, examined neural RL signals in young, mildly to moderately depressed - but non-help-seeking and unmedicated - individuals and how these signals are associated with depressive symptoms and real-life motivated behaviour. METHODS: Individuals with symptoms along the depression continuum (n = 87) were recruited from the community. They performed an RL task during functional Magnetic Resonance Imaging and were assessed with the Experience Sampling Method (ESM), completing short questionnaires on emotions and behaviours up to 10 times/day for 15 days. Q-learning model-derived Reward Prediction Errors (RPEs) were examined in striatal areas, and subsequently associated with depressive symptoms and an ESM measure capturing (non-linearly) how anticipation of reward experience corresponds to actual reward experience later on. RESULTS: Significant RPE signals were found in the striatum, insula, amygdala, hippocampus, frontal and occipital cortices. Region-of-interest analyses revealed a significant association between RPE signals and (a) self-reported depressive symptoms in the right nucleus accumbens (b = -0.017, p = 0.006) and putamen (b = -0.013, p = .012); and (b) the quadratic ESM variable in the left (b = 0.010, p = .010) and right (b = 0.026, p = 0.011) nucleus accumbens and right putamen (b = 0.047, p < 0.001). CONCLUSIONS: Striatal RPE signals are disrupted along the depression continuum. Moreover, they are associated with reward-related behaviour in real-life, suggesting that real-life coupling of reward anticipation and engagement in rewarding activities might be a relevant target of psychological therapies for depression.
BACKGROUND:Depression has been associated with abnormalities in neural underpinnings of Reward Learning (RL). However, inconsistencies have emerged, possibly owing to medication effects. Additionally, it remains unclear how neural RL signals relate to real-life behaviour. The current study, therefore, examined neural RL signals in young, mildly to moderately depressed - but non-help-seeking and unmedicated - individuals and how these signals are associated with depressive symptoms and real-life motivated behaviour. METHODS: Individuals with symptoms along the depression continuum (n = 87) were recruited from the community. They performed an RL task during functional Magnetic Resonance Imaging and were assessed with the Experience Sampling Method (ESM), completing short questionnaires on emotions and behaviours up to 10 times/day for 15 days. Q-learning model-derived Reward Prediction Errors (RPEs) were examined in striatal areas, and subsequently associated with depressive symptoms and an ESM measure capturing (non-linearly) how anticipation of reward experience corresponds to actual reward experience later on. RESULTS: Significant RPE signals were found in the striatum, insula, amygdala, hippocampus, frontal and occipital cortices. Region-of-interest analyses revealed a significant association between RPE signals and (a) self-reported depressive symptoms in the right nucleus accumbens (b = -0.017, p = 0.006) and putamen (b = -0.013, p = .012); and (b) the quadratic ESM variable in the left (b = 0.010, p = .010) and right (b = 0.026, p = 0.011) nucleus accumbens and right putamen (b = 0.047, p < 0.001). CONCLUSIONS: Striatal RPE signals are disrupted along the depression continuum. Moreover, they are associated with reward-related behaviour in real-life, suggesting that real-life coupling of reward anticipation and engagement in rewarding activities might be a relevant target of psychological therapies for depression.
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