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Dissociating pathomechanisms of depression with fMRI: bottom-up or top-down dysfunctions of the reward system

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Abstract

Depression is a debilitating psychiatric disorder characterized among other aspects by the inability to properly experience or respond to reward. However, it remains unclear whether patients with depression present impaired reward system due to abnormal modulatory mechanisms. We investigated the activation of the nucleus accumbens (NAcc), a crucial region involved in reward processing, with functional magnetic resonance imaging using the desire-reason-dilemma paradigm. This task allows tracking the activity of the NAcc during the acceptance or the rejection of previously conditioned reward stimuli. Patients were assigned into subgroups of lower (LA) or higher (HA) NAcc activation according to beta weights. LA patients presented significant hypoactivation in the ventral tegmental area in addition to bilateral ventral striatum, confirming impairments in the bottom-up input to the NAcc. Conversely, HA patients presented significant hyperactivation in prefrontal areas such as the rostral anterior cingulate cortex and the anterior ventral prefrontal cortex in addition to bilateral ventral striatum, suggesting disturbances in the top-down regulation of the NAcc. Demographic and clinical differences explaining the abnormal co-activations of midbrain and prefrontal regions were not identified. Therefore, we provide evidence for dysfunctional bottom-up processing in one potential neurobiological subtype of depression (LA) and dysfunctional top-down modulation in another subtype (HA). We suggest that the midbrain and prefrontal regions are more specific pathophysiological substrates for each depression subtype. Above all, our results encourage the segregation of patients by similar dysfunctional mechanisms of the dopaminergic system, which would finally contribute to disentangle more specific pathogeneses and guide the development of more personalized targets for future therapies.

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Abbreviations

AD:

Antidepressant

DC:

Desire Context

HA:

High NAcc Activity

LA:

Low NAcc Activity

OFC:

Orbitofrontal Cortex

NAcc:

Nucleus Accumbens

rACC:

Rostral Anterior Cingulate Cortex

RC:

Reason Context

VTA:

Ventral Tegmental Area

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Acknowledgments

We acknowledge our colleague Bernd Kraemer for constant support and all MR technicians for competent imaging acquisition. We are very grateful to our participants

Conflict of interest

The authors report no biomedical relationships with financial or commercial interests and identify no potential conflicts of interest.

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Author notes

  1. Esther Diekhof

    Present address: Neuroendocrinology Unit, Department of Human Biology, Biocenter Grindel and Zoological Museum, University of Hamburg, Hamburg, Germany

Authors and Affiliations

  1. Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Georg August University, Göttingen, Germany

    Roberto Goya-Maldonado, Kristina Weber, Sarah Trost, Esther Diekhof, Maria Keil & Oliver Gruber

  2. Research Group ‘MR-Research in Neurology and Psychiatry’, Department of Cognitive Neurology, University Medical Center, Georg August University, Göttingen, Germany

    Peter Dechent

Authors
  1. Roberto Goya-Maldonado
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  2. Kristina Weber
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  4. Esther Diekhof
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  5. Maria Keil
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  7. Oliver Gruber
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Corresponding author

Correspondence to Roberto Goya-Maldonado.

Electronic supplementary material

Below is the link to the electronic supplementary material.

406_2014_552_MOESM1_ESM.tif

Supplement 1. Small volumes created and displayed with Marsbar as described in the Methods section of the main text (TIFF 358 kb)

406_2014_552_MOESM2_ESM.tif

Supplement 2. Group differences between patients and controls (A) Results from the design matrix and contrast given supporting the heterogeneity in functional activation of the nucleus accumbens (NAcc) as presented in the main text; (B) Illustration of the results of a separate hypothesis of main effect of depression as an entire sample, which we did not set out to test a priori, with design matrix and contrast accordingly given; Note the absence of activation at NAcc with p<0.005 uncorrected (TIFF 218 kb)

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Goya-Maldonado, R., Weber, K., Trost, S. et al. Dissociating pathomechanisms of depression with fMRI: bottom-up or top-down dysfunctions of the reward system. Eur Arch Psychiatry Clin Neurosci 265, 57–66 (2015). https://doi.org/10.1007/s00406-014-0552-2

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  • DOI: https://doi.org/10.1007/s00406-014-0552-2

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