Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment

Brain Mapping Unit, University of Cambridge, Department of Psychiatry, Addenbrooke's Hospital, Cambridge, UK.
Biological Psychiatry (Impact Factor: 9.47). 10/2007; 62(5):407-14. DOI: 10.1016/j.biopsych.2006.09.018
Source: PubMed

ABSTRACT It would be therapeutically useful to predict clinical response to antidepressant drugs. We evaluated structural magnetic resonance imaging (MRI) and functional MRI (fMRI) data as predictors of symptom change in people with depression.
Brain structure and function were measured with MRI in 17 patients with major depression immediately before 8 weeks treatment with fluoxetine 20 mg/day. For fMRI, patients were scanned during visual presentation of faces representing different intensities of sadness. Clinical response was measured by change in serial scores on the Hamilton Rating Scale for Depression. Symptom change scores (and baseline symptom severity) were regressed on structural and functional MRI data to map brain regions where grey matter volume, or activation by sad facial affect processing, was significantly associated with symptom change (or baseline severity).
Faster rates of symptom improvement were strongly associated with greater grey matter volume in anterior cingulate cortex, insula, and right temporo-parietal cortex. Patients with greater than median grey matter volume in this system had faster rates of improvement and significantly lower residual symptom scores after 8 weeks' treatment. Faster improvement was also predicted by greater functional activation of anterior cingulate cortex. Baseline symptom severity was negatively correlated with greater grey matter volume in dorsal prefrontal and anterior midcingulate regions anatomically distinct from the pregenual and subgenual cingulate regions predicting treatment response.
Structural MRI measurements of anterior cingulate cortex could provide a useful predictor of antidepressant treatment response.


Available from: John Suckling, Jun 12, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The amygdala plays a central role in various aspects of affect processing and mood regulation by its rich anatomical connections to other limbic and cortical regions. It is plausible that depressive disorders, and response to antidepressant drugs, may reflect changes in the physiological coupling between the amygdala and other components of affect-related large-scale brain systems. We explored this hypothesis by mapping the functional coupling of right and left amygdalae in functional magnetic resonance imaging data acquired from 19 patients with major depressive disorder and 19 healthy volunteers, each scanned twice (at baseline and 8 weeks later) during performance of an implicit facial affect processing task. Between scanning sessions, the patients received treatment with an antidepressant drug, fluoxetine 20 mg/day. We found that the amygdala was positively coupled bilaterally with medial temporal and ventral occipital regions, and negatively coupled with the anterior cingulate cortex. Antidepressant treatment was associated with significantly increased coupling between the amygdala and right frontal and cingulate cortex, striatum, and thalamus. Treatment-related increases in functional coupling to frontal and other regions were greater for the left amygdala than for the right amygdala. These results indicate that antidepressant drug effects can be measured in terms of altered coupling between components of cortico-limbic systems and that these effects were most clearly demonstrated by enhanced functional coupling of the left amygdala.
    Neuropsychopharmacology 08/2008; 33(8):1909-18. DOI:10.1038/sj.npp.1301593 · 7.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The integrity of decision-making under emotionally evocative circumstances is critical to navigating complex environments, and dysfunctions in these processes may play an important role in the emergence and maintenance of various psychopathologies. The goal of the present study was to examine the spatial and temporal dynamics of neural responses to emotional stimuli and emotion-modulated response inhibition. High-density event-related brain potentials (ERPs) were measured as participants (N=25) performed an emotional Go/NoGo task that required button presses to words of a "target" emotional valence (i.e., positive, negative, neutral) and response inhibition to words of a different "distractor" valence. Using scalp ERP analyses in conjunction with source-localization techniques, we identified distinct neural responses associated with affective salience and affect-modulated response inhibition, respectively. Both earlier (approximately 300 ms) and later (approximately 700 ms) ERP components were enhanced with successful response inhibition to emotional distractors. Only ERPs to target stimuli differentiated affective from neutral cues. Moreover, source localization analyses revealed right ventral lateral prefrontal cortex (VLPFC) activation in affective response inhibition regardless of emotional valence, whereas rostral anterior cingulate activation (rACC) was potentiated by emotional valence but was not modulated by response inhibition. This dissociation was supported by a significant Region x Trial Type x Emotion interaction, confirming that distinct regional dynamics characterize neural responses to affective valence and affective response-inhibition. The results are discussed in the context of an emerging affective neuroscience literature and implications for understanding psychiatric pathologies characterized by a detrimental susceptibility to emotional cues, with an emphasis on major depressive disorder.
    NeuroImage 06/2008; 42(2):988-97. DOI:10.1016/j.neuroimage.2008.04.248 · 6.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The anterior cingulate cortex (ACC) is implicated in the cognitive and affective abnormalities observed in mood disorders. Bilateral ACC volume reductions have been reported in patients with major depressive disorder (MDD) when compared to healthy controls. We compared regional brain volumes in the subgenual prefrontal cortex (SGPFC; Brodmann area (BA) 24(sg)), subcallosal gyrus (BA25), and paracingulate gyrus (BA32) in 65 patients receiving a first course of treatment for MDD and 93 healthy control subjects. Patients with more than three episodes of untreated MDD had smaller subcallosal gyrus volumes than healthy controls, while those with three or fewer past untreated episodes did not differ from controls. We also found preliminary evidence that medication-exposed patients had smaller SGPFC volumes than patients with no exposure to medication and healthy controls. There was no evidence that these effects related to mood state, duration of untreated illness, or to patient age. No differences were apparent in paracingulate gyrus volumes between patients and controls. These findings confirm the presence of ACC volume reductions in untreated patients with MDD and suggest that illness burden and short-term medication exposure mediate this change.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 04/2008; 33(13):3157-63. DOI:10.1038/npp.2008.40 · 7.83 Impact Factor