Functional Connectivity Bias of the Orbitofrontal Cortex in Drug-Free Patients with Major Depression

doi:10.1016/j.biopsych.2009.08.022

Biological Psychiatry

Volume 67, Issue 2, 15 January 2010, Pages 161-167

https://doi.org/10.1016/j.biopsych.2009.08.022 Get rights and content

Background

The orbitofrontal cortex (OFC) plays a crucial role in emotion-processing circuits and should therefore also be included in models of the pathophysiology of major depression. The aim of this study was to compare the functional connectivity of the OFC during emotion processing in patients with major depression and healthy control subjects.

Methods

Twenty-five untreated patients with major depression and 15 healthy control subjects were investigated using a functional magnetic resonance imaging face-matching task.

Results

Dorsal anterior cingulate cortex, precuneus, and cerebellum activity showed less connectivity with the OFC in patients than in control subjects. In contrast, functional connectivity between the OFC and the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal operculum, and left motor areas was increased in patients compared with healthy control subjects.

Conclusions

The OFC plays a key role in the pathophysiology of major depression. The observed imbalance of OFC connectivity seems to represent a neural mechanism of the processing bias. From a neurobiological point of view, the uncoupling of precuneus and gyrus cinguli activity from the OFC might be associated with problems in the regulation of self-schemas, whereas the increased connectivity of the DLPFC to the OFC might represent a higher neural response to negative stimuli.

Section snippets

Subjects

Twenty-five patients with major depression were recruited from the Department of Psychiatry of the Ludwig-Maximilian University, Munich (Table 1). Psychiatric diagnoses were based on DSM-IV criteria and the Structured Clinical Interview for DSM-IV and determined by a consensus of at least two psychiatrists. All patients were antidepressant free: 16 patients had never received antidepressant medication; nine patients had received antidepressant medications during a previous episode but not

Results

There were no significant differences in age, sex, or weight between the patients and healthy control subjects (Table 1). Patients and control subjects showed no differences in the number of correct responses or reaction time in the explicit, implicit or comparison conditions. No significant differences were detected between connectivity of the left and right OFC.

Discussion

Our study demonstrates an altered connectivity between the OFC and other brain regions of the emotion-processing circuit in untreated patients with major depression. In particular, we found that connectivity between the OFC and right dorsolateral prefrontal cortex, right inferior frontal operculum, left motor regions, and left angular cortex was increased in patients than in control subjects but lower in patients in the middle ACC, precuneus, cerebellum, and right thalamus.

Structural

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The neurocognitive mechanism by which automatic emotion regulation (AER) affects emotion processing remains understudied in the context of psychopathology, such as depression. Participants with sub-clinical depression and healthy controls were randomly assigned to an emotion regulation priming group or a neutral priming group. All participants completed an emotional Go/No-go task by judging the gender of angry or happy faces. During the Go/No-go task, each trial was preceded by subliminal presentation of words describing emotion regulation goals or neutral goals as a manipulation of priming. The behavioral results showed that compared with neutral priming, subliminal priming of regulation goals increased the accuracy in No-go trials with angry faces only for sub-clinically depressed participants. In the ERP results, the main effect of regulation priming was significant in sub-clinically depressed participants, such that showing subliminal priming of regulation goals decreased the amplitude of N2 compared to the neutral priming. Similarly, for the sub-clinically depressed participants, regulation goal priming evoked smaller P3 in response to angry faces than to happy faces. No such pattern was found in neutral goal priming condition or for healthy controls. According to the automotive model of emotion regulation, once goals or norms related to emotion regulations are formed in the mind, a related regulation response could be activated without awareness. Our results suggest that subliminal priming of regulation goals could change the response inhibition to angry faces in sub-clinically depressed participants.
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Archival ReportFunctional Connectivity Bias of the Orbitofrontal Cortex in Drug-Free Patients with Major Depression

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Prog Neurobiol

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Neuropsychologia

Neuroimage

Neuroimage

Trends Cogn Sci

Neuroimage

Biol Psychiatry

Deciding advantageously before knowing the advantageous strategy

Science

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: An MRI-based parcellation of the prefrontal cortex

Am J Psychiatry

The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans

Cereb Cortex

Attenuation of the neural response to sad faces in major depression by antidepressant treatment: A prospective, event-related functional magnetic resonance imaging study

Arch Gen Psychiatry

Neuronal correlates of emotional processing in patients with major depression

World J Biol Psychiatry

Functional coupling of the amygdala in depressed patients treated with antidepressant medication

Neuropsychopharmacology

Archival Report
Functional Connectivity Bias of the Orbitofrontal Cortex in Drug-Free Patients with Major Depression