Elsevier

Biological Psychiatry

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

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

https://doi.org/10.1016/j.biopsych.2009.08.022Get 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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