Elsevier

Biological Psychiatry

Volume 62, Issue 5, 1 September 2007, Pages 429-437
Biological Psychiatry

Original Article
Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus

https://doi.org/10.1016/j.biopsych.2006.09.020Get rights and content

Background

Positron emission tomography (PET) studies of major depression have revealed resting-state abnormalities in the prefrontal and cingulate cortices. Recently, fMRI has been adapted to examine connectivity within a specific resting-state neural network—the default-mode network—that includes medial prefrontal and anterior cingulate cortices. The goal of this study was to examine resting-state, default-mode network functional connectivity in subjects with major depression and in healthy controls.

Methods

Twenty-eight subjects with major depression and 20 healthy controls underwent 5-min fMRI scans while resting quietly. Independent component analysis was used to isolate the default-mode network in each subject. Group maps of the default-mode network were compared. A within-group analysis was performed in the depressed group to explore effects of depression refractoriness on functional connectivity.

Results

Resting-state subgenual cingulate and thalamic functional connectivity with the default-mode network were significantly greater in the depressed subjects. Within the depressed group, the length of the current depressive episode correlated positively with functional connectivity in the subgenual cingulate.

Conclusions

This is the first study to explore default-mode functional connectivity in major depression. The findings provide cross-modality confirmation of PET studies demonstrating increased thalamic and subgenual cingulate activity in major depression. Further, the within-subject connectivity analysis employed here brings these previously isolated regions of hypermetabolism into the context of a disordered neural network. The correlation between refractoriness and subgenual cingulate functional connectivity within the network suggests that a quantitative, resting-state fMRI measure could be used to guide therapy in individual subjects.

Section snippets

Subjects

Subjects were recruited through inpatient and outpatient facilities at Stanford University or self-referred from online and print study advertisements. Eligibility screening procedures included the Structured Clinical Interview for the DSM-IV (SCID) (First et al. 1997), the 21-item Hamilton Depression Rating Scale (HDRS) (Hamilton 1980), the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1961), and clinical laboratory tests (complete blood count, comprehensive metabolic panel,

Subjects

The control group had a mean age of 35.4 with 11 women and 9 men. The depressed group had a mean age of 38.5 with 16 women and 12 men. Groups did not differ significantly in mean age (t-test p = .46) or gender distribution (chi-square p = .88). The mean HDRS score was 25.4 in the depressed group with a standard deviation (SD) of 4. The mean HDRS score in the control group was .4 (SD .5).

Regarding exposure to psychotropic medications, control subjects and 8 of 28 depressed subjects were not

Discussion

This is the first study to describe default-mode network abnormalities in major depression. The finding of increased subgenual cingulate functional connectivity in major depression provides cross-modality support for the growing body of evidence implicating this region as a dysfunctional node in a distributed limbic and paralimbic neural network (Botteron et al 2002, Drevets et al 1997, Drevets et al 2002, Hirayasu et al 1999, Kennedy et al 2001, Mayberg et al 2000, Ongur et al 1998, Osuch et

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