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Original Article |

Toward Clinically Useful Neuroimaging in Depression Treatment:  Prognostic Utility of Subgenual Cingulate Activity for Determining Depression Outcome in Cognitive Therapy Across Studies, Scanners, and Patient Characteristics

Greg J. Siegle, PhD; Wesley K. Thompson, PhD; Amanda Collier, BS; Susan R. Berman, MEd; Joshua Feldmiller, BA; Michael E. Thase, MD; Edward S. Friedman, MD
Arch Gen Psychiatry. 2012;69(9):913-924. doi:10.1001/archgenpsychiatry.2012.65.
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Context  Among depressed individuals not receiving medication in controlled trials, 40% to 60% respond to cognitive therapy (CT). Multiple previous studies suggest that activity in the subgenual anterior cingulate cortex (sgACC; Brodmann area 25) predicts outcome in CT for depression, but these results have not been prospectively replicated.

Objective  To examine whether sgACC activity is a reliable and robust prognostic outcome marker of CT for depression and whether sgACC activity changes in treatment.

Design  Two inception cohorts underwent assessment with functional magnetic resonance imaging using different scanners on a task sensitive to sustained emotional information processing before and after 16 to 20 sessions of CT, along with a sample of control participants who underwent testing at comparable intervals.

Setting  A hospital outpatient clinic.

Patients  Forty-nine unmedicated depressed adults and 35 healthy controls.

Main Outcome Measures  Pretreatment sgACC activity in an a priori region in response to negative words was correlated with residual severity and used to classify response and remission.

Results  As expected, in both samples, participants with the lowest pretreatment sustained sgACC reactivity in response to negative words displayed the most improvement after CT (R2 = 0.29, >75% correct classification of response, >70% correct classification of remission). Other a priori regions explained additional variance. Response/remission in cohort 2 was predicted based on thresholds from cohort 1. Subgenual anterior cingulate activity remained low for patients in remission after treatment.

Conclusions  Neuroimaging provides a quick, valid, and clinically applicable way of assessing neural systems associated with treatment response/remission. Subgenual anterior cingulate activity, in particular, may reflect processes that interfere with treatment (eg, emotion generation) in addition to its putative regulatory role; alternately, its absence may facilitate treatment response.

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Figures

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Figure 1. CONSORT diagram. CT indicates cognitive therapy; fMRI, functional magnetic resonance imaging; HRSD, Hamilton Rating Scale for Depression; and SSRI, selective serotonin reuptake inhibitor.

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Figure 2. Correlation of decreased anatomically defined subgenual anterior cingulate cortex (sgACC) activity with a stronger clinical response (decreased residual Beck Depression Inventory [BDI]). A, A strong correlation is seen in cohort 1 (green squares indicate noncompleters whose final BDI scores were interpolated). B, A moderate association is seen in cohort 2. C, A stronger association is seen in the combined cohort. D, A stronger association is also seen in the combined cohort using z scores for sgACC and change in BDI as the outcome variable. E, Waveforms for hemodynamic responses for participants with nonremitting depression (nonremitters [n = 21]; final BDI score ≥ 10) compared with controls (n = 35) and participants with remitting depression (remitters [n = 22]; final BDI score < 10). Areas significant at P < .05 by means of analyses of variance at each scan are highlighted in gray.

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Figure 3. Decreased empirically defined subgenual anterior cingulate activity associated strongly with response. A, Pretreatment regions associated with decreased depressive severity from Siegle et al.4 B, The new cognitive therapy samples (n = 40; R2 > 0.40 [P < .001]). Green indicates the anatomical region of interest used as a mask; orange, regions only in the new data set; and red, voxels that overlap. C and D, These regions were reflected in predictive regions in cohorts 1 (R2 = 0.43-0.79 [P < .01]) and 2 (R2 = 0.26 [P < .01]), respectively.

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Figure 4. Relationships of pretreatment subgenual anterior cingulate cortex (sgACC) reactivity to posttreatment sgACC activity (low and high). A, Continuous change for the temporal region of interest. B-E, Waveforms in participants who were predicted to remit (pretreatment percentage change, <0.02) or not remit. Areas significant at P < .05 after analyses of variance at each scan are highlighted in gray.

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